bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of E-Cigarette Exposure on Prenatal Life and Childhood Respiratory Health: A Review of Current Evidence
Authors: Mescolo Federica , Ferrante Giuliana , La Grutta Stefania
Published: September 2021

In the last decade, widespread use of E-cigarettes (EC) has occurred all over the world. Whereas, a large amount of evidence on harm to children from conventional cigarette exposure is available, data on health effects in this population throughout different vulnerability windows are still a matter of concern. Exposure to EC during pregnancy may compromise placental function, resulting in fetal structural abnormalities. Specifically, this may cause physio-pathologic changes in the developing lung, which in turn may impair respiratory health later in life. Furthermore, there is evidence that using EC can cause both short- and long-term respiratory problems in the pediatric population and there is great concern for future young people with nicotine addiction. The low parental perception of the risks connected to EC exposure for children increases their susceptibility to harmful effects from passive vaping. This minireview aims to summarize the current evidence focusing on: (i) prenatal effects of EC passive exposure; (ii) post-natal respiratory effects of EC exposure in youth; (iii) parental attitudes toward EC use and perception of children's health risks connected to EC exposure; and (iv) addressing gaps in our current evidence.
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway
Authors: Liang Li , Gu Xin , Shen Hai Ji , Shi Yu Heng , Li Yao , Zhang Jie , Chen Yan Yan , Chen Zhen He , Ma Jia Yun , Li Qing Yun
Published: September 2021

Aims

Obstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma.

Main Methods

The effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-β treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse (n= 6) and ASMCs models (n= 6), which were both treated with the p38 MAPK inhibitor SB239063.

Key Findings

Under CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice (p< 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group (P< 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In thein vitrostudy, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-β combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription (p< 0.05).

Significance

These results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway.
Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism
Authors: Montanari Chiara , Parolisi Sara , Borghi Elisa , Putignani Lorenza , Bassanini Giulia , Zuvadelli Juri , Bonfanti Cristina , Tummolo Albina , Dionisi Vici Carlo , Biasucci Giacomo , Burlina Alberto , Carbone Maria Teresa , Verduci Elvira
Published: September 2021

Inborn errors of metabolism (IEMs) represent a complex system model, in need of a shift of approach exploring the main factors mediating the regulation of the system, internal or external and overcoming the traditional concept of biochemical and genetic defects. In this context, among the established factors influencing the metabolic flux, i.e., diet, lifestyle, antibiotics, xenobiotics, infectious agents, also the individual gut microbiota should be considered. A healthy gut microbiota contributes in maintaining human health by providing unique metabolic functions to the human host. Many patients with IEMs are on special diets, the main treatment for these diseases. Hence, IEMs represent a good model to evaluate how specific dietary patterns, in terms of macronutrients composition and quality of nutrients, can be related to a characteristic microbiota associated with a specific clinical phenotype (“enterophenotype”). In the present review, we aim at reporting the possible links existing between dysbiosis, a condition reported in IEMs patients, and a pro-inflammatory status, through an altered “gut-liver” cross-talk network and a major oxidative stress, with a repercussion on the health status of the patient, increasing the risk of non-communicable diseases (NCDs). On this basis, more attention should be paid to the nutritional status assessment and the clinical and biochemical signs of possible onset of comorbidities, with the goal of improving the long-term wellbeing in IEMs. A balanced intestinal ecosystem has been shown to positively contribute to patient health and its perturbation may influence the clinical spectrum of individuals with IEMs. For this, reaching eubiosis through the improvement of the quality of dietary products and mixtures, the use of pre-, pro- and postbiotics, could represent both a preventive and therapeutic strategy in these complex diseases.
Use of RNAi With OsMYB76R as a Reporter for Candidate Genes Can Efficiently Create and Verify Gametophytic Male Sterility in Rice
Authors: Chen Yun , Zhu Wenping , Shi Shudan , Wu Lina , Du Shuanglin , Jin Liangshen , Yang Kuan , Zhao Wenjia , Yang Jiaxin , Guo Longbiao , Wang Zhongwei , Zhang Yi
Published: September 2021

Gametophytic male sterility (GMS) plays an important role in the study of pollen development and seed propagation of recessive nuclear male sterile lines insensitive to the environmental conditions in hybrid rice breeding. Since the inherent phenotypic and genetic characteristics of GMS, it is very difficult to find and identify the GMS mutants. However, due to the abundance of gene transcription data, a large number of pollen-specific genes have been found, and most of them may be associated with GMS. To promote the study of these genes in pollen development and heterosis utilization, in this study, an easy and efficient method of creating and identifying GMS was established using RNAi and OsMYB76R as a reporter. First, the OsC1/OsMYB76 gene involved in anthocyanin synthesis was modified, and we have validated that the modified OsMYB76R is workable as the same as the pre-modified OsMYB76 gene. Then, the ascorbic acid oxidase gene OsPTD1 was downregulated using RNAi, driven by its own promoter that resulted in abnormal pollen tube growth. Finally, the RNAi elements were linked with OsMYB76R and transformed into an osmyb76 mutant, and the distortion of purple color segregation was found in T1 and F1 generations. This indicates that the OsPTD1 GMS was prepared successfully. Compared to current methods, there are several advantages to this method. First, time is saved in material preparation, as one generation less needs to be compared than in the conventional method, and mutation screening can be avoided. In addition, for identification, the cost is lower; PCR, electrophoresis, and other processes are not needed; and no expensive chemicals or instruments are required. Finally, the results are more accurate, with much lower background effects, and no damage to the plant. The result is an easy, efficient, low-cost, and accurate method of preparing and identifying GMS genes.
Embodiment in Virtual Reality Intensifies Emotional Responses to Virtual Stimuli
Authors: Gall Dominik , Roth Daniel , Stauffert Jan-Philipp , Zarges Julian , Latoschik Marc Erich
Published: September 2021

Modulating emotional responses to virtual stimuli is a fundamental goal of many immersive interactive applications. In this study, we leverage the illusion of illusory embodiment and show that owning a virtual body provides means to modulate emotional responses. In a single-factor repeated-measures experiment, we manipulated the degree of illusory embodiment and assessed the emotional responses to virtual stimuli. We presented emotional stimuli in the same environment as the virtual body. Participants experienced higher arousal, dominance, and more intense valence in the high embodiment condition compared to the low embodiment condition. The illusion of embodiment thus intensifies the emotional processing of the virtual environment. This result suggests that artificial bodies can increase the effectiveness of immersive applications psychotherapy, entertainment, computer-mediated social interactions, or health applications.
Preferred Place of Death in Adult Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Fereidouni Armin , Rassouli Maryam , Salesi Mahmood , Ashrafizadeh Hadis , Vahedian-Azimi Amir , Barasteh Salman
Published: September 2021

Background: Identifying the preferred place of death is a key indicator of the quality of death in cancer patients and one of the most important issues for health service policymakers. This study was done to determine the preferred place of death and the factors affecting it for adult patients with cancer.

Methods: In this systematic review and meta-analysis study four online databases (PubMed, Scopus, web of science, ProQuest) were searched by relevant keywords. Quality assessment of papers was conducted using Newcastle-Ottawa (NOS) criterion. Odds ratios, relative risks, and 95% confidence intervals were determined for each of the factors extracted from the investigations.

Results: A total of 14,920 participants of 27 studies were included into the meta-analysis. Based on the results, 55% of cancer patients with a confidence interval [95% CI (41–49)] preferred home, 17% of patients with a confidence interval [95% CI (−12%) 23)] preferred hospital and 10% of patients with confidence interval [95% CI (13–18)] preferred hospices as their favored place to die. Effective factors were also reported in the form of demographic characteristics, disease-related factors and psychosocial factors.

Conclusions: This study showed that more than half of cancer patients chose home as their preferred place of death. Therefore, guided policies need to ensure that the death of the patients in the preferred place should be considered with priority.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020218680, identifier: CRD42020218680.
Social Capital, Financial Literacy, and Rural Household Entrepreneurship: A Mediating Effect Analysis
Authors: Zhao Jingmei , Li Tiancheng
Published: September 2021

In rural areas, entrepreneurship helps lift households out of poverty by alleviating unemployment and increasing income, and financial literacy plays an important role in promoting entrepreneurship. Social capital is a resource embedded in social relationships, the boundaries of which have been expanded by the development of information communications technologies (ICTs). This article aims to link social capital, financial literacy, and rural entrepreneurship through a partial mediating effect analysis. Using data from the 2015 China Household Finance Survey (CHFS), we analyze how social capital affects rural entrepreneurship and the role of local ICTs development in this effect while also accounting for reverse causality. We construct a social capital indicator, mainly referring to bridging social capital, and two financial literacy indicators to make the conclusions robust. The empirical results show that social capital promotes rural entrepreneurship by sharing financial literacy. Furthermore, the spread of ICTs enhances this mediating effect. Our study provides empirical evidence for encouraging entrepreneurship and promoting knowledge sharing and implies the importance of ICTs in promoting entrepreneurship in rural areas.
A Review of the Effectiveness of Foreign Language Enjoyment and Foreign Language Classroom Anxiety on Learners' Engagement and Attainment
Authors: Shen Jingping
Published: September 2021

Cognitive factors are not the fundamental determinants of success in language learning. Foreign language attainment depends on both cognitive and affective factors, highlighting the deeper impacts of the former. Some scholars started to investigate affective issues, particularly negative emotions in language learning studies; nevertheless, reducing negative emotions such as anxiety should be accompanied by the development of positive emotions (e.g., well-being, autonomy, and enjoyment). Since then, a great number of researchers have examined the impact of anxiety and enjoyment in foreign language literature, particularly after the introduction of reliable and valid foreign language classroom anxiety (FLCA) and foreign language enjoyment (FLE) scales. So, the present study aims to review contemporary scholarly articles and books in this regard. Findings suggest that there has been a major interest in the evaluation of FLCA and FLE across a variety of dimensions including personality traits, interpersonal characteristics, and classroom conditions. The central issues are summarized into three categories of the relationship between FLCA and FLE, the robustness of respective scales, and the impact of individual and interpersonal factors. Hence, this research attempts to highlight probable gaps and areas for further examinations to help enrich the literature and improve the theoretical knowledge.
Epidemiology, Hot Spots, and Sociodemographic Risk Factors of Alcohol Consumption in Indian Men and Women: Analysis of National Family Health Survey-4 (2015-16), a Nationally Representative Cross-Sectional Study
Authors: Balasubramani Karuppusamy , Paulson Winnie , Chellappan Savitha , Ramachandran Ramakrishnan , Behera Sujit Kumar , Balabaskaran Nina Praveen
Published: September 2021

Objectives: To map the alcohol hot spots and understand the Sociodemographic Indices (SDI) affecting alcohol consumption in Indian men and women.

Methods: Data from National Family Health Survey-4 carried out from 2015 to 2016 with a sample size of 103,411 men and 699,686 women were used for Geographic Information System mapping, and hot spot identification by spatial statistics (Getis-Ord Gi*). Bivariate analyses and multiple logistic regressions were used to analyze SDI.

Results: India has three major alcohol hot spots: (1) North-East (NE) states, (2) Eastern Peninsular states formed by Chhattisgarh, Odisha, Jharkhand, and Telangana, and (3) Southern states of Tamil Nadu and Kerala. Hot spot analysis strongly correlated with region-wise analysis of SDI. Respondents who consumed tobacco have higher odds (men adjusted odds ratio [aOR]: 5.42; women aOR: 4.30) of consuming alcohol. Except for religion and social category, other socioeconomic factors have a low to moderate effect on alcohol consumption.

Conclusions: Hot spots and high-risk districts of alcohol consumption identified in this study can guide public health policies for targeted intervention. Alcohol use is at the discretion of individual states and union territories, and stringent anti-alcohol policies strictly enforced across India are the keys to control alcohol use.
Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru
Authors: Diaz Monica M. , Custodio Nilton , Montesinos Rosa , Lira David , Herrera-Perez Eder , Pintado-Caipa Maritza , Cuenca-Alfaro Jose , Gamboa Carlos , Lanata Serggio
Published: September 2021

Background: Reversible etiologies of cognitive impairment are common and treatable, yet the majority of mild cognitive impairment (MCI) and dementia research in Latin America has focused on irreversible, neurodegenerative etiologies.

Objective: We sought to determine if thyroid dysfunction and vitamin B12 and folate deficiencies are associated with cognitive disorders among older adults with memory complaints in Lima, Peru.

Methods: This was a retrospective review of patients who presented for cognitive evaluations to a multidisciplinary neurology clinic in Lima, Peru from January 2014 to February 2020. We included individuals aged ≥60 years, native Spanish-speakers, with at least a primary school educational level and a complete clinical assessment. Patients had either subjective cognitive decline (SCD), MCI, or dementia. One-way ANOVA and multiple logistic regression analyses were performed.

Results: We included 720 patients (330 SCD, 154 MCI, and 236 dementia); the dementia group was significantly older [mean age SCD 69.7 ± 4.1, dementia 72.4 ± 3.7 (p = 0.000)] and had lower folate levels than SCD patients. The MCI group had higher free T3 levels compared with SCD patients. Those with lower TSH had greater dementia risk (OR = 2.91, 95%CI: 1.15–6.86) but not MCI risk in unadjusted models. B12 deficiency or borderline B12 deficiency was present in 34% of the dementia group, yet no clear correlation was seen between neuropsychological test results and B12 levels in our study. There was no association between MCI or dementia and thyroid hormone, B12 nor folate levels in adjusted models.

Conclusion: Our findings do not support an association between metabolic and endocrine disorders and cognitive impairment in older Peruvians from Lima despite a high prevalence of B12 deficiency. Future work may determine if cognitive decline is associated with metabolic or endocrine changes in Latin America.
Vitamin A Levels Among Pre-School Children of Central and Western China
Authors: Chen Qian , Liu Yongfang , Chen Li , Chen Jie , Yang Ting , Cheng Qian , Li Tingyu
Published: September 2021

Objective: To investigate vitamin A deficiency of pre-school children in central and western China for developing strategies to prevent and control vitamin A deficiency (VAD) among children.

Design: From November 2018 to September 2019, a total of 2,194 healthy children aged 2–6 years were enrolled. Serum retinol levels in the children were detected by liquid-phase tandem mass spectrometry. In addition, social demographic and dietary questionnaires were collected through interviews with children's caregivers.

Setting: The participants were enrolled in 12 cities or their subordinate jurisdictions in the central and western regions of China.

Participants: Two thousand one hundred and ninety four healthy children aged 2–6 years old.

Results: Overall, 35.51% (779/2,194) of the children were found to be vitamin A insufficient (VAI, serum retinol < 1.05 μmol/L). Elder children had a higher risk to suffer from VAI, with proportions of 25.00% (87/348), 28.92% (142/491), 38.38% (256/667), and 42.73% (294/688) among children aged 2, 3, 4, and 5 years, respectively. Vitamin A levels were also positively correlated with per capita income (AOR = 1.18) and regional economic level (0.71), and the frequency of milk intake (0.91).

Conclusions: The incidence of VAI was higher among children aged 2–6 years, and the incidence of VAI increases with age. VA levels were positively correlated with levels of economic development in the family and region. So prevention strategies for VAD need to focus on pre-school children, especially dairy intake and developing regions.
Nanopore Sequencing Provides Rapid and Reliable Insight Into Microbial Profiles of Intensive Care Units
Authors: de Siqueira Guilherme Marcelino Viana , Pereira-dos-Santos Felipe Marcelo , Silva-Rocha Rafael , Guazzaroni María-Eugenia
Published: September 2021

Fast and accurate identification of pathogens is an essential task in healthcare settings. Second-generation sequencing platforms such as Illumina have greatly expanded the capacity with which different organisms can be detected in hospital samples, and third-generation nanopore-driven sequencing devices such as Oxford Nanopore's minION have recently emerged as ideal sequencing platforms for routine healthcare surveillance due to their long-read capacity and high portability. Despite its great potential, protocols and analysis pipelines for nanopore sequencing are still being extensively validated. In this work, we assess the ability of nanopore sequencing to provide reliable community profiles based on 16S rRNA sequencing in comparison to traditional Illumina platforms using samples collected from Intensive Care Units of a hospital in Brazil. While our results demonstrate that lower throughputs may be a shortcoming of the method in more complex samples, we show that the use of single-use Flongle flowcells in nanopore sequencing runs can provide insightful information on the community composition in healthcare settings.
Community Readiness for Local COVID-19 Management
Authors: Pozzo Riccardo , Virgili Vania
Published: September 2021

The experience of COVID-19 has highlighted the strategic role of local administrations, in all areas of service, in directing and coordinating actions to contain the pandemic. In this brief research report, we have interpreted the theme of the issue Open when, why, to whom? Changing challenges, perspectives, and practices in a new research culture by transferring it into a local context, namely in Italy’s inner areas, whose communities had already endured the 2016–2017 seismic swarm. We will look into the issue pragmatically, because we think that in front of a COVID-19 induced fast-changing institutional environment, science and technology studies researchers have some ideas to offer. These days, we are learning important lessons in citizen science. Today, local administrators must equip themselves with the management of infrastructures (unimaginable before COVID-19) for enforcing social distance and tracking positive cases. One of the tasks that we wish to take up is determining the levels of societal readiness and the levels of integration in society of new technologies, products, and services. The pandemic requires social and cultural innovation policies that make communities ready to respond to catastrophic events on their territory—our case-study is Italy’s inner areas—through access to data, communities of practice, co-creation, reflection, and inclusion. Finally, COVID-19 ought not to undermine the work done so far to achieve Sustainable Development Goal 1 (Poverty), 3 (Health), 4 (Education), 5 (Gender), 6 (Water), 8 (Work), 10 (Inequalities) and 16 (Peace). Pope Francis has made it clear: “This is the moment to see the poor.”
Changes in Motivation, Socialization, Wellness and Mental Health in Youth Long-Distance Runners During COVID-19 Social Distancing Restrictions
Authors: Bazett-Jones David M. , Garcia Micah C. , Taylor-Haas Jeffery A. , Long Jason T. , Rauh Mitchell J. , Paterno Mark V. , Ford Kevin R.
Published: September 2021

Purpose: The COVID-19 pandemic impacted the sporting and exercise activities of millions of youth. Running is an activity that could be maintained while social distancing restrictions were implemented during the pandemic. However, a recent study has indicated that youth runners reported lower running distance, frequency, and intensity during COVID-19. The reason for this reduction and the impact on overall well-being is unknown. Therefore, the purpose of this study was to determine if the social distancing restrictions during the 2020 COVID-19 pandemic influenced running motives, socialization, wellness and mental health in youth long-distance runners.

Methods: A customized, open online questionnaire was provided to runners 9–19 years of age who participated in long-distance running activities including team/club cross-country, track and field (distances ≥800 m), road races, or recreational running. Participants responded to questions about demographics, motive for running, and wellness (sleep quality, anxiety, running enjoyment, food consumption quality) 6-months before as well as during social distancing restrictions due to COVID-19. Wilcoxon signed rank tests compared differences for ratio data and Chi-square tests were used to compare proportions before and during COVID-19 social distancing restrictions. Statistical significance was set at p ≤ 0.05.

Results: A total of 287 youth long-distance runners (male = 124, female = 162, unspecified = 1; age = 15.3 ± 1.7 years; running experience = 5.0 ± 2.3 years) participated. Compared to their pre-COVID-19 responses, youth long-distance runners reported lower overall motivation to run (p < 0.001) and changes to most motive rankings (p < 0.001 to p = 0.71). The proportion of youth running alone increased during COVID-19 (65.8%) compared to pre-COVID-19 (13.8%, p < 0.001). Youth long-distance runners also reported less running enjoyment (p = 0.001), longer sleep duration (p < 0.001), lower sleep quality (p = 0.05), more anxiety (p = 0.043), and lower food quality consumed (p < 0.001) during COVID-19 social distance restrictions.

Conclusion: The COVID-19 social distancing restrictions resulted in significant decreases in motivation and enjoyment of running. The removal of competition and team-based interactions likely had a role in these decreases for this population. Continuing team-based activities (e.g., virtual) during social distancing may help with maintaining motivation of youth long-distance runners. Reduced running occurred concurrently with reduced overall well-being of youth long-distance runners during the COVID-19 pandemic.
Characterization and Evaluation of Layered Bi2WO6 Nanosheets as a New Antibacterial Agent
Authors: Leandro Maria Karollyna do Nascimento Silva , Moura João Victor Barbosa , Freire Paulo de Tarso Cavalcante , Vega Maria Leticia , Lima Cleânio da Luz , Hidalgo Ángel Alberto , Araújo Ana Carolina Justino de , Freitas Priscilla Ramos , Paulo Cicera Laura Roque , Sousa Amanda Karine de , Rocha Janaina Esmeraldo , Leandro Lívia Maria Garcia , Silva Rakel Olinda Macedo da , Cruz-Martins Natália , Coutinho Henrique Douglas Melo
Published: September 2021

Background: Pathogenic microorganisms are causing increasing cases of mortality and morbidity, along with alarming rates of ineffectiveness as a result of acquired antimicrobial resistance. Bi2WO6 showed good potential to be used as an antibacterial substance when exposed to visible light. This study demonstrates for the first time the dimension-dependent antibacterial activity of layered Bi2WO6 nanosheets. Materials and methods: The synthesized layered Bi2WO6 nanosheets were prepared by the hydrothermal method and characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman and Fourier transform infrared spectroscopy (FTIR). Antibacterial and antibiotic-modulation activities were performed in triplicate by the microdilution method associated with visible light irradiation (LEDs). Results: Bi2WO6 nanosheets were effective against all types of bacteria tested, with MIC values of 256 μg/mL against Escherichia coli standard and resistant strains, and 256 μg/mL and 32 μg/mL against Staphylococcus aureus standard and resistant strains, respectively. Two-dimensional (2D) Bi2WO6 nanosheets showed antibacterial efficiency against both strains studied without the presence of light. Conclusions: Layered Bi2WO6 nanosheets revealed dimension-dependent antibacterial activity of the Bi2WO6 system.
How Do We Determine the Efficacy of an Antibacterial Surface? A Review of Standardised Antibacterial Material Testing Methods
Authors: Cunliffe Alexander J. , Askew Peter D. , Stephan Ina , Iredale Gillian , Cosemans Patrick , Simmons Lisa M. , Verran Joanna , Redfern James
Published: September 2021

Materials that confer antimicrobial activity, be that by innate property, leaching of biocides or design features (e.g., non-adhesive materials) continue to gain popularity to combat the increasing and varied threats from microorganisms, e.g., replacing inert surfaces in hospitals with copper. To understand how efficacious these materials are at controlling microorganisms, data is usually collected via a standardised test method. However, standardised test methods vary, and often the characteristics and methodological choices can make it difficult to infer that any perceived antimicrobial activity demonstrated in the laboratory can be confidently assumed to an end-use setting. This review provides a critical analysis of standardised methodology used in academia and industry, and demonstrates how many key methodological choices (e.g., temperature, humidity/moisture, airflow, surface topography) may impact efficacy assessment, highlighting the need to carefully consider intended antimicrobial end-use of any product.
Chemical Constituents and Biological Activities of Croton heliotropiifolius Kunth
Authors: Fernandes Priscilla Augusta de Sousa , Silva Josefa Carolaine Pereira da , Lima Sales Débora , Ribeiro Paulo Riceli Vasconcelos , Sousa de Brito Edy , Kerntopf Marta Regina , Delmondes Gyllyandeson de Araújo , Andrade Pinheiro Jacqueline Cosmo , Salazar Gerson Javier Torres , Batista Francisco Lucas Alves , Alves Magalhães Francisco Ernani , Gomez Maria Celeste Vega , Rolón Míriam , Coronel Cathia , Ribeiro-Filho Jaime , Almeida-Bezerra José Weverton , Siyadatpanah Abolghasem , Nissapatorn Veeranoot , Pereira Maria de Lourdes , Coutinho Henrique Douglas Melo , Morais-Braga Maria Flaviana Bezerra
Published: September 2021

Croton heliotropiifolius Kunth (Euphorbiaceae), whose occurrence has already been registered in the most varied Brazilian biomes, is commonly found in the Chapada do Araripe, Ceará. The species is traditionally used to treat fungal, parasitic, and degenerative diseases. This study investigated the chemical composition and pharmacological potential (antioxidant, antifungal, antiparasitic, and cytotoxic) of an aqueous extract obtained from the roots of C. heliotropiifolius. Following a qualitative phytochemical screening, the chemical constituents were identified by ultra-efficiency liquid chromatography coupled witha quadrupole/time-of-flight system (UPLC-QTOF). The antioxidant potential was verified by thin-layer chromatography (TLC). The direct and combined antifungal activity of the extract against opportunistic Candida strains was investigated using the microdilution method. The minimal fungicidal concentration (MFC) was determined by subculture, while the modulation of the morphological transition (fungal virulence) was evaluated by light microscopy. The in vitro antiparasitic activity was analyzed using epimastigotes of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and Leishmania infantum, while cytotoxicity was determined in cultures of mouse fibroblasts. The phytochemical analysis identified the presence of acids, terpenes, flavonoids, lignans, and alkaloids. Among these constituents, the presence of polar and non-polar phenolic compounds with known antioxidant action was highlighted. While the extract showed clinically ineffective antifungal effects, it could enhance the effectiveness of fluconazole, in addition to inhibiting the morphological transition associated with increased virulence in Candida strains. Although the extract showed low cytotoxicity against fibroblasts, it also had weak antiparasitic effects. In conclusion, Croton heliotropiifolius is a source of natural products with antifungal and antioxidant potential.
Non-Uniform Circumferential Expansion of Cylindrical Li-Ion Cells—The Potato Effect
Authors: Hemmerling Jessica , Guhathakurta Jajnabalkya , Dettinger Falk , Fill Alexander , Birke Kai Peter
Published: September 2021

This paper presents the non-uniform change in cell thickness of cylindrical Lithium (Li)-ion cells due to the change of State of Charge (SoC). Using optical measurement methods, with the aid of a laser light band micrometer, the expansion and contraction are determined over a complete charge and discharge cycle. The cell is rotated around its own axis by an angle of α=10° in each step, so that the different positions can be compared with each other over the circumference. The experimental data show that, contrary to the assumption based on the physical properties of electrode growth due to lithium intercalation in the graphite, the cell does not expand uniformly. Depending on the position and orientation of the cell coil, there are different zones of expansion and contraction. In order to confirm the non-uniform expansion around the circumference of the cell in 3D, X-ray computed tomography (CT) scans of the cells are performed at low and at high SoC. Comparison of the high resolution 3D reconstructed volumes clearly visualizes a sinusoidal pattern for non-uniform expansion. From the 3D volume, it can be confirmed that the thickness variation does not vary significantly over the height of the battery cell due to the observed mechanisms. However, a slight decrease in the volume change towards the poles of the battery cells due to the higher stiffness can be monitored.
Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy
Authors: Park Min Ho , Jo Gayoung , Lee Bo Young , Kim Eun Jeong , Hyun Hoon
Published: September 2021

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)–ZW800-1 conjugate (INH–ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH–ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH–ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH–ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.
Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies
Authors: D'Amelio Raffaele , Asero Riccardo , Cassatella Marco Antonio , Laganà Bruno , Lunardi Claudio , Migliorini Paola , Nisini Roberto , Parronchi Paola , Quinti Isabella , Racanelli Vito , Senna Gianenrico , Vacca Angelo , Maggi Enrico
Published: September 2021

The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient’s clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants.
Comparison of Outcomes between 3 Monthly Brolucizumab and Aflibercept Injections for Polypoidal Choroidal Vasculopathy
Authors: Fukuda Yoshiko , Sakurada Yoichi , Matsubara Mio , Hasebe Yuka , Sugiyama Atsushi , Kikushima Wataru , Kashiwagi Kenji
Published: September 2021

We compared the short-term outcomes between 3-monthly aflibercept and brolucizumab injections for treatment-naïve polypoidal choroidal vasculopathy (PCV). A total of 52 eyes were included. Patients received 3 monthly intravitreal aflibercept (n = 38) or intravitreal brolucizumab (n = 14). Indocyanine green angiography (ICGA) was performed at baseline and at the 3-month visit. Selection of anti-VEGF agents depended on time. In the brolucizumab-treated group, best-corrected visual acuity (BCVA) improved from 0.27 ± 0.34 (log MAR unit) at baseline to 0.20 ± 0.24 at 3-month visit, which is comparable with the aflibercept-treated group (p = 0.87), after adjustment of confounding factors. Central retinal thickness significantly decreased by 43%−44% in both groups. Subfoveal choroidal thickness also significantly decreased by 20.5% during this interval in the brolucizumab-treated group, which was greater than the aflibercept-treated group. The complete resolution rate of polypoidal lesions on ICGA was significantly higher (p = 0.043) in the brolucizumab-treated group (78.6%) than in the aflibercept-treated group (42.1%). Intraocular inflammation was observed in 14.3% (2/14) in the brolucizumab-treated group only. In short-term follow-up, intravitreal injection of 3-monthly brolucizumab was comparable with aflibercept in terms of BCVA and morphological improvement along with higher resolution of polypoidal lesion(s) on ICGA.
Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas
Authors: Cooper Isabella D. , Brookler Kenneth H. , Crofts Catherine A. P.
Published: September 2021

Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures. Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
Insights into the Pathogenesis of HS and Therapeutical Approaches
Authors: Rosi Elia , Fastame Maria Thais , Scandagli Ilaria , Di Cesare Antonella , Ricceri Federica , Pimpinelli Nicola , Prignano Francesca
Published: September 2021

Hidradenitis suppurativa (HS) is a debilitating, chronic, (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. Although pathogenic mechanisms responsible for HS have not yet been fully elucidated, it is a multifactorial process whose main target is the terminal follicle. The role of the inflammatory process (and consequently of cytokine milieu) and of several other factors (genetics, lifestyle, hormonal status, microbiome, innate and adaptive immune systems) involved in HS pathogenesis has been investigated (and often defined) over the years with a view to transferring research results from bench to bedside and describing a unique and universally accepted pathogenetic model. This review will update readers on recent advances in our understanding of HS pathogenesis and novel (potential) medical therapies for patients with moderate-to-severe HS.
Myeloma–Bone Interaction: A Vicious Cycle via TAK1–PIM2 Signaling
Authors: Harada Takeshi , Hiasa Masahiro , Teramachi Jumpei , Abe Masahiro
Published: September 2021

Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL–NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. Thus, MM cells alter the microenvironments through bone destruction in the bone where they reside, which in turn potentiates tumor growth and survival, thereby generating a vicious loop between tumor progression and bone destruction. The serine/threonine kinases PIM2 and TAK1, an upstream mediator of PIM2, are overexpressed in bone marrow stromal cells and osteoclasts as well in MM cells in bone lesions. Upregulation of the TAK1–PIM2 pathway plays a critical role in tumor expansion and bone destruction, posing the TAK1–PIM2 pathway as a pivotal therapeutic target in MM.
Normalizing Tumor Vasculature to Reduce Hypoxia, Enhance Perfusion, and Optimize Therapy Uptake
Authors: Matuszewska Kathy , Pereira Madison , Petrik Duncan , Lawler Jack , Petrik Jim
Published: September 2021

A basic requirement of tumorigenesis is the development of a vascular network to support the metabolic requirements of tumor growth and metastasis. Tumor vascular formation is regulated by a balance between promoters and inhibitors of angiogenesis. Typically, the pro-angiogenic environment created by the tumor is extremely aggressive, resulting in the rapid vessel formation with abnormal, dysfunctional morphology. The altered morphology and function of tumor blood and lymphatic vessels has numerous implications including poor perfusion, tissue hypoxia, and reduced therapy uptake. Targeting tumor angiogenesis as a therapeutic approach has been pursued in a host of different cancers. Although some preclinical success was seen, there has been a general lack of clinical success with traditional anti-angiogenic therapeutics as single agents. Typically, following anti-angiogenic therapy, there is remodeling of the tumor microenvironment and widespread tumor hypoxia, which is associated with development of therapy resistance. A more comprehensive understanding of the biology of tumor angiogenesis and insights into new clinical approaches, including combinations with immunotherapy, are needed to advance vascular targeting as a therapeutic area.
LAG3 and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma
Authors: Souri Zahra , Wierenga Annemijn P. A. , Kroes Wilma G. M. , van der Velden Pieter A. , Verdijk Robert M. , Eikmans Michael , Luyten Gregorius P. M. , Jager Martine J.
Published: September 2021

Uveal melanoma (UM) is a rare ocular malignancy which originates in the uveal tract, and often gives rise to metastases. Potential targets for immune checkpoint inhibition are lymphocyte-activation gene 3 (LAG3) and its ligands. We set out to analyse the distribution of these molecules in UM. The expression of mRNA was determined using an Illumina array in 64 primary UM from Leiden. The T lymphocyte fraction was determined by digital droplet PCR. In a second cohort of 15 cases from Leiden, mRNA expression was studied by Fluidigm qPCR, while a third cohort consisted of 80 UM from TCGA. In the first Leiden cohort, LAG3 expression was associated with the presence of epithelioid cells (p = 0.002), monosomy of chromosome 3 (p = 0.004), and loss of BAP1 staining (p = 0.001). In this Leiden cohort as well as in the TCGA cohort, LAG3 expression correlated positively with the expression of its ligands: LSECtin, Galectin-3, and the HLA class II molecules HLA-DR, HLA-DQ, and HLA-DP (all p < 0.001). Furthermore, ligands Galectin-3 and HLA class II were increased in monosomy 3 tumours and the expression of LAG3 correlated with the presence of an inflammatory phenotype (T cell fraction, macrophages, HLA-A and HLA-B expression: all p < 0.001). High expression levels of LAG3 (p = 0.01), Galectin-3 (p = 0.001), HLA-DRA1 (p = 0.002), HLA-DQA1 (p = 0.04), HLA-DQB2 (p = 0.03), and HLA-DPA1 (p = 0.007) were associated with bad survival. We conclude that expression of the LAG ligands Galectin-3 and HLA class II strongly correlates with LAG3 expression and all are increased in UM with Monosomy 3/BAP1 loss. The distribution suggests a potential benefit of monoclonal antibodies against LAG3 or Galectin-3 as adjuvant treatment in patients with high-risk UM.
Clinical Importance of Regimens in Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Macrovascular Invasion
Authors: Niizeki Takashi , Iwamoto Hideki , Shirono Tomotake , Shimose Shigeo , Nakano Masahito , Okamura Shusuke , Noda Yu , Kamachi Naoki , Hiroyuki Suzuki , Sakai Miwa , Kuromatsu Ryoko , Koga Hironori , Torimura Takuji
Published: September 2021

Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child–Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively (p < 0.05, p < 0.05). The complete response (29%) and objective response rate (76%) of New FP were significantly higher than those of LFP (p < 0.001, p < 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC.