bluuebunny/crossref_metadata_2025 huggingface dataset:
Allicin Promoted Reducing Effect of Garlic Powder through Acrylamide Formation Stage
Authors: Li Xiude , Teng Wendi , Liu Guangmin , Guo Fengyu , Xing Hanzhu , Zhu Yahui , Li Jinwang
Published: August 2022

Background: Acrylamide is formed during food heating and is neurotoxic to animals and potentially carcinogenic to humans. It is important to reduce acrylamide content during food processing. Researchers have suggested that garlic powder could reduce acrylamide content, but the key substance and acrylamide reduction pathway of garlic powder was unclear. Methods: The inhibitory effect of garlic powder on acrylamide in asparagine/glucose solution and a fried potato model system were firstly evaluated. Furthermore, the effect of allicin on the amount of produced acrylamide in the asparagine/glucose solution model system and fried potatoes was studied with kinetic analysis. Results: The freeze-dried garlic powder had a higher inhibition rate (41.0%) than oven-dried garlic powder (maximum inhibition rate was 37.3%), and allicin had a 71.3% attribution to the reduction of acrylamide content. Moreover, the inhibition rate of allicin had a nonlinear relationship with the addition level increase. The kinetic analysis indicated that garlic powder and allicin could reduce acrylamide content through the AA formation stage, but not the decomposition stage. Conclusions: Allicin was the key component of garlic powder in reducing acrylamide content during acrylamide formation stage. This research could provide a new method to reduce acrylamide content during food processing and expand the application area of garlic.
Characterization of a Nattokinase from the Newly Isolated Bile Salt-Resistant Bacillus mojavensis LY-06
Authors: Li Yuan , Tang Xiyu , Chen Liangqi , Xu Xinran , Li Jinyao
Published: August 2022

Nattokinase is a potential new thrombolytic drug because of its strong thrombolytic effect, high safety, and low cost. However, there is no research reporting on bile salt-tolerant nattokinase-producing probiotics. In this study, the bile salt-tolerant nattokinase-producing strain Bacillus mojavensis LY-06 was isolated from local Xinjiang douchi, and the fermentation yield of nattokinase of 1434.64 U/mL was obtained by both a single factor experiment and an orthogonal experiment. A gene responsible for fibrinolysis (aprY) was cloned from the genome of strain Bacillus mojavensis LY-06, and the soluble expression of this gene in Escherichia coli (rAprY, fused with His-tag at C-terminus) was achieved; molecular docking elucidates the cause of insoluble expression of rAprY. The optimal pH and temperature for the fibrinolysis activity of nattokinase AprY fermented by Bacillus mojavensis LY-06 were determined to be pH 6.0 and 50 °C, respectively. However, the optimal pH of rAprY expressed in Escherichia coli was 8, and its acid stability, thermal stability, and fibrinolytic activity were lower than those of AprY. Bioinformatics analysis found that the His-tag carried at the C-terminus of rAprY could affect its acidic stability by changing the isoelectric point and surface charge of the enzyme; in contrast to AprY, changes in the number of internal hydrogen bonds and the flexibility of the loop region in the structure of rAprY resulted in lower fibrinolytic activity and poorer thermal stability.
A Game-Theoretic Model of Voluntary Yellow Fever Vaccination to Prevent Urban Outbreaks
Authors: Caasi Jovic Aaron S. , Joseph Brian M. , Kodiyamplakkal Heera J. , Manibusan Jaelene Renae U. , Camacho Aquino Leslie J. , Oh Hyunju , Rychtář Jan , Taylor Dewey
Published: August 2022

Yellow fever is a vector-borne acute viral hemorrhagic disease. It is endemic in tropical areas of Africa and Latin America but demonstrated the potential for international spread during the 2016 outbreak in Luanda, Angola. Yellow fever can be prevented by vaccination, vector control, and avoiding mosquito bites. To account for human behavior in disease dynamics, we add a game-theoretic component to a recent compartmental model of yellow fever transmission. The self-interested individuals evaluate the risks of contracting yellow fever and choose to vaccinate or avoid the bites to minimize the overall costs. We find the Nash equilibria, the optimal levels of vaccination and bite protections if the individuals can decide on the use of only one of the prevention methods as well as when they can decide on the use of both of them. In the later case, we show that vaccination is the preferred method of protection from the individual standpoint and, in the Nash equilibrium, individuals use vaccination only. Our model predicts the vaccination coverage in Angola to be around 65%, which is in reasonable agreement with the empirical value of 68%. We also study whether voluntary prevention can lead to the elimination of the disease in endemic areas. We show that voluntary vaccination alone is not enough to mitigate the risks of outbreaks, suggesting that a mandatory vaccination policy is necessary.
microRNA Expression Profile of Purified Alveolar Epithelial Type II Cells
Authors: Dehmel Stefan , Weiss Katharina J. , El-Merhie Natalia , Callegari Jens , Konrad Birte , Mutze Kathrin , Eickelberg Oliver , Königshoff Melanie , Krauss-Etschmann Susanne
Published: August 2022

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways. We purified “untouched by antibodies” ATII cells using a flow cytometric sorting method with a highly autofluorescent population of lung cells. TaqMan® miRNA low-density arrays were performed on sorted cells and intersected with miRNA profiles of ATII cells isolated according to a previously published protocol. Of 293 miRNAs expressed in both ATII preparations, 111 showed equal abundances. The target mRNAs of bona fide ATII miRNAs were used for pathway enrichment analysis. This analysis identified nine signaling pathways with known functions in fibrosis and/or epithelial-to-mesenchymal transition (EMT). In particular, a subset of 19 miRNAs was found to target 21 components of the TGF-β signaling pathway. Three of these miRNAs (miR-16-5p, -17-5p and -30c-5p) were down-modulated by TGF-β1 stimulation in human A549 cells, and concomitant up-regulation of associated mRNA targets (BMPR2, JUN, RUNX2) was observed. These results suggest an important role for miRNAs in maintaining the homeostasis of the TGF-β signaling pathway in ATII cells under physiological conditions.
SINE Insertion May Act as a Repressor to Affect the Expression of Pig LEPROT and Growth Traits
Authors: Wang Xiaoyan , Chi Chengling , He Jia , Du Zhanyu , Zheng Yao , D’Alessandro Enrico , Chen Cai , Moawad Ali Shoaib , Asare Emmanuel , Song Chengyi
Published: August 2022

Retrotransposon is an important component of the mammalian genome. Previous studies have shown that the expression of protein-coding genes was affected by the insertion of retrotransposon into the proximal genes, and the phenotype variations would be related to the retrotransposon insertion polymorphisms (RIPs). In this study, leptin (LEP), leptin receptor (LEPR), and leptin receptor overlapping transcript (LEPROT), which play important roles in the regulation of fat synthesis and body weight, were screened to search for the RIPs and their effect on phenotype and gene expression, as well as to further study the function of the insertion. The results showed that three RIPs located in intron 1 of LEPROT and intron 2 and 21 of LEPR were identified, and they were all SINEA1, which was one type of retrotransposon. The SINE insertion at the LEPROT was the dominant allele in native pig breeds. The age of 100 kg body weight of SINE+/+ Large White individuals was significantly higher than those of SINE+/− and SINE−/− individuals (p < 0.05). The LEPROT gene expression in the liver and suet of 30-day-old SINE−/− Sujiang piglets were significantly higher than those of SINE+/+ and SINE+/− piglets (p < 0.01). The dual-luciferase reporter gene assay showed that SINE insertion in PK15 and 3T3-L1 cells significantly reduced the promoter activity of the LEPROT gene (p < 0.01). Therefore, SINE insertion can be a repressor to reduce the expression of LEPROT and could be a useful molecular marker for assisted selection of growth traits in pig breeding.
Promoting Comfort: A Clinician Guide and Evidence-Based Skin Care Plan in the Prevention and Management of Radiation Dermatitis for Patients with Breast Cancer
Authors: Sherman Deborah Witt , Walsh Sandra M.
Published: August 2022

Patients with breast cancer may be offered adjuvant radiation therapy (RT) after surgery. Up to 95% of these patients develop radiation dermatitis (RD) during or following RT. Randomized clinical trials and other literature provide evidence that RD can be prevented or reduced. The aim of this article is to propose a Clinician Guide and Evidence-based Skin Care Plan to prevent and/or reduce radiation dermatitis and promote the comfort of breast cancer patients receiving RT. As an integrative review, the databases searched were CINAHL and Medline, using the key terms: breast cancer, skin care, radiation, radiation therapy, radiotherapy, radiation dermatitis, and radiation skin reaction, prevention, and management. Search criteria included English language, full text, published between 2012 through 2020, and peer-reviewed. The search yielded 320 articles. Relevant articles were evaluated using the Quality Assessment Tool (QAT), and highly rated articles were selected to be included in the review of literature. The outcomes were the development of a Clinician Guide to offer holistic, patient-centered care and an Evidence-based Skin Care Plan. The research literature supports a standard skin care regimen, along with use of an emollient cream to the treatment area, use of deodorants depending on patient preferences, and application of a topical steroid cream daily throughout treatment and two weeks post RT. Clinician’s weekly assessments of patients offers therapeutic support and ensures optimal skin care during and post-RT. The comfort of breast cancer patients receiving RT requires the best level of evidence regarding the efficacy of interventions, coupled with clinician’s judgement, and patient’s preferences and wishes. The clinician-patient relationship is essential in addressing the physical, emotional, social, spiritual, and functional challenges associated with a cancer diagnosis and adjunctive radiation therapy to improve long-term survival.
Concurrent Validity of GAITRite and the 10-m Walk Test to Measure Gait Speed in Adults with Chronic Ankle Instability
Authors: Kim Ho , Kum Dongmin , Lee Insu , Choi Jongduk
Published: August 2022

Since there are many different assessments related to gait speed, it is important to determine the concurrent validity of each measure so that they can be used interchangeably. Our study aimed to investigate the concurrent validity of gait speed measured by the 10 m walk test (10 MWT) and the gold standard gait analysis system, the GAITRite system, for people with chronic ankle instability (CAI). For 16 people with CAI, 4 evaluations of the 10 MWT and 4 evaluations of the GAITRite system were performed (a comfortable gait speed for 2 evaluations; a maximal gait speed for 2 evaluations). We used intraclass correlations [ICC (2,1), absolute agreement] and Bland–Altman plots to analyze the relationship between the gait speed of the two measures. The absolute agreement between the 10 MWT and the GAITRite system is at the comfortable gait speed [ICC = 0.66; p < 0.001)], and the maximal gait speed [ICC = 0.68; p < 0.001)] showed fair to good agreement. Both gait speeds had a proportional bias; the limit of agreement (LOA) was large (0.50 at the comfortable gait speed and 0.60 at the maximal gait speed). Regression-based Bland–Altman plots were created for the comfortable gait speed (R2 = 0.54, p < 0.001) and the maximal gait speed (R2 = 0.78, p < 0.001). The regression-based LOA ranged from 0.45 to 0.66 m/s for the comfortable gait speed and 1.09 to 1.37 m/s for the maximal gait speed. Our study suggests that it is undesirable to mix the 10 MWT and the GAITRite system gait speed measurements in people with CAI. Each measure should not be recorded by the same evaluation tool and referenced to normative data.
Willingness to Work during Public Health Emergencies: A Systematic Literature Review
Authors: Santinha Gonçalo , Forte Teresa , Gomes Ariana
Published: August 2022

The identification of the factors underlying the willingness or lack thereof to respond to public health emergencies is paramount to informing more capable health services. The interest in this topic appears renewed with each surge of threat, either referring to natural disasters, man-made violence, or epidemic and pandemics. However, there is no systematic approach to the research patterns and related main findings concerning individual and contextual determinants. The present article contributes to this theme through a systematic literature review of a sample of 150 articles published in the last 30 years on the subject of willingness and preparedness of health professionals to deal with public health threats. Our findings show that the research is mainly phenomena and contextual driven, responding to whichever emergency threat is more salient in a given period. Geographically, research on this topic is led by USA and China, mostly solely, while European countries invest in collaborations that are more international. Universities, including health institutes and schools, and researchers at hospitals conduct most of the research on the topic. The main research areas are medicine, psychology, and psychiatry. Pandemics, including COVID-19, influenza, and natural disasters, are the phenomena gauging more attention as opposed to terrorism events and biological accidents. The specific role of health professionals within the institution, their belief in ethical duties, preparation training, and concerns regarding infection of self and family are the main variables influencing the willingness and ability to report to work in public health emergencies.
Analysis of Factors Related to Mental Health, Suppression of Emotions, and Personality Influencing Coping with Stress among Nurses
Authors: Cybulska Anna Maria , Rachubińska Kamila , Stanisławska Marzanna , Grochans Szymon , Cymbaluk-Płoska Aneta , Grochans Elżbieta
Published: August 2022

(1) The specificity of a nurse’s work, apart from performing medical procedures, is characterized by intensive contacts with other people. Stress is an inevitable part of a nurse’s job and can affect their physical and mental health. Thus, strategies for coping with stress play an important role in improving health or well-being by reducing the level of stress. (2) The aim of the study was to evaluate the impact of coping strategies in predicting the overall health of nurses. The study also assessed the impact of personality traits and emotional control (anger, depression, anxiety) on the choice of coping with stress among nurses. (3) The study included 811 nurses from the West Pomeranian Voivodeship, with an average age of 40 (SD = 9.8), working mainly in hospitals (82%). The research was carried out with a diagnostic survey method, using the Coping Inventory for Stressful Situations questionnaire, NEO-Five Factor Inventor, Courtland Emotional Control Care Scale, General Health Questionnaire 30, and a demographic questionnaire. (4) Among the surveyed nurses, the dominant style of coping with stress was the style focused on emotions (MT 0.43), followed by the style focused on avoidance (MT 0.42). There were mental problems among 46.1% of the respondents. Nurses with mental problems according to GHQ-30 were characterized by a high intensity of coping styles focused on emotions (30.2%), avoiding (18.7%), and engaging in alternative activities (32.3%) (p = 0.000). (5) Most of the surveyed nurses have a tendency to cope with stress through an emotional-focused style, which may be associated with a higher level of occupational stress.
Changes in Nutrition-Intake Method and Oral Health through a Multidisciplinary Team Approach in Malnourished Older Patients Admitted to an Acute Care Hospital
Authors: Suzuki Hiroyuki , Furuya Junichi , Nakagawa Kazuharu , Hidaka Rena , Nakane Ayako , Yoshimi Kanako , Shimizu Yukue , Saito Keiko , Itsui Yasuhiro , Tohara Haruka , Sato Yuji , Minakuchi Shunsuke
Published: August 2022

Malnourished older inpatients referred to a nutrition support team (NST) usually receive multidisciplinary oral health management during NST intervention. However, the effects of multidisciplinary oral health management on the nutrition-intake method and oral health in these patients remain unclear. This longitudinal study aimed to investigate the effects of NST-mediated multidisciplinary oral health management on the nutrition-intake methods, oral health, and the systemic and oral factors influencing the changes in the nutrition-intake method. A total of 117 inpatients (66 men, 51 women, mean age, 71.9 ± 12.5 years) who underwent NST-mediated multidisciplinary oral health management between April 2016 and July 2019 were enrolled. Demographic data and Functional Oral Intake Scale (FOIS), Dysphagia Severity Scale (DSS), and Oral Health Assessment Tool (OHAT) scores at the time of referral to the NST and completion of the NST intervention were evaluated. After multidisciplinary NST intervention, FOIS, DSS, and OHAT scores showed significant improvements (p < 0.001). Even after adjusting the results for systemic parameters, FOIS score improvement correlated positively with the length of NST intervention (p = 0.030) and DSS score improvement (p < 0.001) as well as OHAT score improvement (p = 0.047). NST interventions with multidisciplinary oral health management could improve the nutrition-intake method.
Breast Cancer Disparities in Asian Women: The Need for Disaggregated Research
Authors: Fane Lauren , Biswas Tithi , Jindal Charulata , Choi Yuk Ming , Efird Jimmy T.
Published: August 2022

Asian (AZN) women are a heterogeneous group, comprising a wide array of cultural beliefs, languages, and healthcare needs. Yet, studies of breast cancer (BCa) risks and outcomes predominately consider AZNs in aggregate, assuming that the distinct ethnicities have similar disease profiles and homogeneous responses to treatment. This stereotypical portrayal of AZNs as a homogenous group tends to mask disparities. For example, healthcare-seeking behaviors and attitudes of medical providers toward AZN BCa patients frequently differ within this group and from other races. Misconceptions may arise that significantly influence the prevention, detection, treatment, and post-therapeutic care of AZN women. In addition to low BCa screening rates among AZN women, disparities also exist in various stages of BCa treatment—omission of radiation after breast-conserving surgery, less access to hypofractionation, underutilization of hormonal therapy, and higher-cost treatment owing to high HER2+ incidence. In this perspective, we highlight the need for disaggregated research of BCa among AZN women and advocate for comprehensive, culturally sensitive strategies to address health disparities in this priority population. Improving BCa literacy and awareness, access to care, and equitable recruitment into clinical trials are a few amelioratory goals to consider in the future.
Immersive Therapy for Improving Anxiety in Health Professionals of a Regional Hospital during the COVID-19 Pandemic: A Quasi-Experimental Pilot Study
Authors: Linares-Chamorro Marta , Domènech-Oller Neus , Jerez-Roig Javier , Piqué-Buisan Joel
Published: August 2022

Background: Immersive therapy through virtual reality represents a novel strategy used in psychological interventions, but there is still a need to strengthen the evidence on its effects on health professionals’ mental health. Objective: To analyze the results of immersive therapy through virtual reality on the levels of anxiety and well-being of the health professionals working in a regional hospital in Olot (Spain). Methods: Pilot quasi-experimental study including a group of 35 female (mean age = 45.7, SD = 8.43) health professionals who undertook immersive therapy for 8 weeks. The intervention was implemented through virtual reality, and its effect on anxiety levels and well-being was evaluated through the Hamilton and Eudemon scales, respectively. Data on age, gender, active pharmacological or psychological treatment, mental health disorders and number of sessions were also collected. Results: A statistically significant (p < 0.001) improvement in anxiety and well-being was found, with large and moderate effect sizes (0.90 and 0.63 respectively). In addition, these changes were clinically significant. No significant associations were found between the improvements and the different variables, but a greater trend was identified among the group of professionals with untreated or unidentified levels of anxiety. Conclusion: This group of health professionals showed a statistically and clinically significant improvement in anxiety and well-being after the application of immersive therapy using virtual reality. Further studies with a control group are necessary to further analyze this novel intervention.
A Work-Related Musculoskeletal Disorders (WMSDs) Risk-Assessment System Using a Single-View Pose Estimation Model
Authors: Kwon Young-Jin , Kim Do-Hyun , Son Byung-Chang , Choi Kyoung-Ho , Kwak Sungbok , Kim Taehong
Published: August 2022

Musculoskeletal disorders are an unavoidable occupational health problem. In particular, workers who perform repetitive tasks onsite in the manufacturing industry suffer from musculoskeletal problems. In this paper, we propose a system that evaluates the posture of workers in the manufacturing industry with single-view 3D human pose-estimation that can estimate the posture in 3D using an RGB camera that can easily acquire the posture of a worker in a complex workplace. The proposed system builds a Duckyang-Auto Worker Health Safety Environment (DyWHSE), a manufacturing-industry-specific dataset, to estimate the wrist pose evaluated by the Rapid Limb Upper Assessment (RULA). Additionally, we evaluate the quality of the built DyWHSE dataset using the Human3.6M dataset, and the applicability of the proposed system is verified by comparing it with the evaluation results of the experts. The proposed system provides quantitative assessment guidance for working posture risk assessment, assisting the continuous posture assessment of workers.
Identifying and Predicting Healthcare Waste Management Costs for an Optimal Sustainable Management System: Evidence from the Greek Public Sector
Authors: Sepetis Anastasios , Zaza Paraskevi N. , Rizos Fotios , Bagos Pantelis G.
Published: August 2022

The healthcare sector is an ever-growing industry which produces a vast amount of waste each year, and it is crucial for healthcare systems to have an effective and sustainable medical waste management system in order to protect public health. Greek public hospitals in 2018 produced 9500 tons of hazardous healthcare wastes, and it is expected to reach 18,200 tons in 2025 and exceed 18,800 tons in 2030. In this paper, we investigated the factors that affect healthcare wastes. We obtained data from all Greek public hospitals and conducted a regression analysis, with the management cost of waste and the kilos of waste as the dependent variables, and a number of variables reflecting the characteristics of each hospital and its output as the independent variables. We applied and compared several models. Our study shows that healthcare wastes are affected by several individual-hospital characteristics, such as the number of beds, the type of the hospital, the services the hospital provides, the number of annual inpatients, the days of stay, the total number of surgeries, the existence of special units, and the total number of employees. Finally, our study presents two prediction models concerning the management costs and quantities of infectious waste for Greece’s public hospitals and proposes specific actions to reduce healthcare wastes and the respective costs, as well as to implement and adopt certain tools, in terms of sustainability.
Does Involution Cause Anxiety? An Empirical Study from Chinese Universities
Authors: Yi Da , Wu Jingwen , Zhang Minqiang , Zeng Qing , Wang Jinqing , Liang Jingdan , Cai Yashi
Published: August 2022

The debate over whether involution causes anxiety has persisted because no studies have attempted to quantify introversion and study its relationship to anxiety. This study quantified involution and explored its relationship with anxiety, provided evidence about whether involution was related to anxiety, and created a foundation for other scholars to carry out research on involution. Interviews and questionnaires were conducted to investigate the characteristics of 535 Chinese college students’ involution behavior and its relationship with anxiety. We found that involution was not necessarily positively related to anxiety. The specific results were as follows: (1) The involution behavior of the Chinese college students could be divided into three types: the passive involution, reward-oriented involution, and achievement-motivated involution; (2) Significant differences in the involvement of involution existed at the college level; (3) Three motivations that resulted in involution, from primary to secondary, were achievement-motivation, reward-orientation, and passive engagement; and (4) Passive involution, reward-oriented involution, and the total scores for the involution behavior of the college students were significantly and positively correlated with anxiety. Among the three types of involution behavior, the college students’ passive involution had a significant and positive predictive effect on their anxiety, while achievement-motivated involution had a significant and negative predictive effect.
A Randomized Controlled Trial of a Research-Tested Mobile Produce Market Model Designed to Improve Diet in Under-Resourced Communities: Rationale and Design for the Veggie Van Study
Authors: Vermont Leah , Kasprzak Christina , Lally Anne , Claudio Alicia , Tumiel-Berhalter Laurene , Haynes-Maslow Lindsey , Ammerman Alice , Raja Samina , Leone Lucia
Published: August 2022

Mobile produce markets are increasingly popular retail vendors used for providing access to fresh fruits and vegetables (F&V) in under-resourced communities; however, evaluation is limited due to design and implementation challenges. This protocol presents the original design of a randomized control trial aimed at assessing the effectiveness of the evidence-based Veggie Van (VV) mobile market model. Nine US community partner organizations were asked to partner with four community sites serving lower-income areas. Sites are randomized to either intervention or control. Intervention sites will host a mobile market for one year while the control sites will host planning events, with the goal to open a market afterward. Eligible participants are aged ≥ 18, the primary household shopper, live nearby/regularly frequent the site, and have expressed interest in learning about a mobile market. The primary outcome, F&V consumption, will be assessed via dietary recall at baseline and 12 months and compared between the intervention and control sites. This research advances work on the VV model and methods for mobile market evaluation with the addition of more robust measures and the study design. Determining the effectiveness of the VV model is imperative to justify taking it to scale to enhance the impact of mobile markets.
Correction: Tischer, M.; Roitzsch, M. Estimating Inhalation Exposure Resulting from Evaporation of Volatile Multicomponent Mixtures Using Different Modelling Approaches. Int. J. Environ. Res. Public Health 2022, 19, 1957
Authors: Tischer Martin , Roitzsch Michael
Published: August 2022

There was an error in the original publication [...]
Brazilian Strategy for Breastfeeding and Complementary Feeding Promotion: A Program Impact Pathway Analysis
Authors: Melo Daiane , Venancio Sonia , Buccini Gabriela
Published: August 2022

Background: The Brazilian Breastfeeding and Complementary Feeding Strategy (Estratégia Amamenta e Alimenta Brasil—EAAB) aims to improve Primary Health Care (PHC) workers’ counseling skills to promote and support infant and young children feeding (IYCF). However, the maintenance and scaling up of the EAAB has been challenging. The theory-driven Program Impact Pathway (PIP) is recommended to assess and enhance the large-scale implementation of IYCF programs. The purpose of this study was to document barriers and facilitators to scale up the EAAB using a PIP analysis. Methods: First, we reviewed EAAB documents to develop an initial PIP diagram. Then, we interviewed EAAB key informants to identify Critical Quality Control Points (CCP) in the PIP. We revised and analyzed the PIP to inform the EAAB core functions and pathways. Results: Six CCPs for EAAB maintenance were identified: CCP1—Definition and strengthening of the coordination in states and municipalities; CCP2—Maintenance of tutors’ work; CCP3—Feasibility of the certification process; CCP 4—Quality improvement of IYCF activities in PHC units; CCP 5—Adequate use of monitoring systems; and CCP 6—Consistent implementation monitoring. Four implementation pathways and seven core functions identified may assist with scaling up the EAAB in Brazil. Conclusion: The PIP analysis proved to be useful for documenting the factors that influence the maintenance and scaling up of the EAAB.
The Effect of Environmental Policy Uncertainty on Enterprises’ Pollution Emissions: Evidence from Chinese Industrial Enterprise
Authors: Le Dong , Ren Fei , Tang Yiding , Zhu Yuke
Published: August 2022

In response to the global call for emission reduction, China has assumed international responsibility for energy conservation and emission reduction by enacting several environmental policies to save energy and reduce consumption. However, it is debatable whether the increased uncertainty in environmental policies negatively affects firms’ emission reduction. Few studies have examined this relationship based on micro-level data. Therefore, this study constructs a theoretical framework of environmental policy uncertainty affecting firms’ pollution emissions. Based on comprehensive data from the Chinese Industrial Enterprise Database, the Chinese Industrial Enterprise Pollution Emission Database, and the Chinese Patent Database from 2002 to 2014, we empirically analyzed the impact of environmental policy uncertainty on firms’ pollution emissions. The results show that (1) environmental policy uncertainty significantly aggravates the pollution emission intensity of industrial enterprises; (2) environmental policy uncertainty inhibits the improvement of enterprises’ innovation capacity, reduces their human capital stock and foreign investment, and aggravates their pollution emission; (3) environmental policy uncertainty has significant heterogeneity on enterprise pollution emissions, that is, environmental policy uncertainty has a greater impact on non-export enterprises, large enterprises, young enterprises, capital-intensive enterprises, state-owned enterprises, and enterprises in polluting industries and central regions. This study provides a useful reference for the improvement of environmental policy and the green transformation of enterprises.
Spatiotemporal Analysis and Risk Assessment Model Research of Diabetes among People over 45 Years Old in China
Authors: Wang Zhenyi , Dong Wen , Yang Kun
Published: August 2022

Diabetes, which is a chronic disease with a high prevalence in people over 45 years old in China, is a public health issue of global concern. In order to explore the spatiotemporal patterns of diabetes among people over 45 years old in China, to find out diabetes risk factors, and to assess its risk, we used spatial autocorrelation, spatiotemporal cluster analysis, binary logistic regression, and a random forest model in this study. The results of the spatial autocorrelation analysis and the spatiotemporal clustering analysis showed that diabetes patients are mainly clustered near the Beijing–Tianjin–Hebei region, and that the prevalence of diabetes clusters is waning. Age, hypertension, dyslipidemia, and smoking history were all diabetes risk factors (p < 0.05), but the spatial heterogeneity of these factors was weak. Compared with the binary logistic regression model, the random forest model showed better accuracy in assessing diabetes risk. According to the assessment risk map generated by the random forest model, the northeast region and the Beijing–Tianjin–Hebei region are high-risk areas for diabetes.
The Experience of Patients in Chronic Care Management: Applications in Health Technology Assessment (HTA) and Value for Public Health
Authors: Pennestrì Federico , Banfi Giuseppe
Published: August 2022

Frail chronic patients consume the largest share of resources in advanced healthcare systems, with more hospitals waiting to receive them in the acute phase (awaiting paradigm) than there are effective public health interventions to keep them out of hospitals as much as possible. Effective chronic care management (CCM) requires organizational research as much as biomedical research (and, in some cases, perhaps more). Otherwise, excellent clinical care is wasted by poor coordination among professionals and institutions, with frail patients and their families paying the most expensive price. Comprehensive health technology assessment (HTA) procedures include organizational, social, and ethical dimensions to precisely capture the environmental factors that make medical interventions effective, accessible, and sustainable. Clinical outcomes and financial data are used extensively to evaluate care pathways from the providers’ perspective, but much remains to be done to capture equally important indicators from the perspective of patients and society. The authors hypothesize that the ordinary use of patient-reported experience measurement (PREMs) in HTA can help reduce gaps and inequalities by identifying frail patients on time, curbing the risks of isolation and the burden on care givers, preventing complications and inappropriate emergency care use, improving adherence, health communication and behavior, supporting risk assessment, and relieving the frequency of the healthcare environment.
Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration
Authors: Guerrini Giuditta , Gioria Sabrina , Sauer Aisha V. , Lucchesi Simone , Montagnani Francesca , Pastore Gabiria , Ciabattini Annalisa , Medaglini Donata , Calzolai Luigi
Published: August 2022

PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.
Prostate Infiltration by Treg and Th17 Cells as an Immune Response to Propionibacterium acnes Infection in the Course of Benign Prostatic Hyperplasia and Prostate Cancer
Authors: Radej Sebastian , Szewc Monika , Maciejewski Ryszard
Published: August 2022

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) belong to the most frequent diseases in ageing men. It has been proposed that prostate chronic inflammation is a risk factor for the development of both BPH and PCa. However, potential stimuli that cause or maintain inflammation in the prostate gland are still poorly characterized. Bacterial infections seems to be one of the potential sources of prostatitis. Recent studies show that Propionibacterium acnes (P. acnes) is the most prevalent microorganism in the prostate gland and may be a predisposing factor for inflammation of prostatic tissue. It indicates that P. acnes may contribute to cancer development by enhancing proinflammatory responses, as well as by modifying the prostate extracellular environment. In this review, we discuss the potential role of P. acnes in the development of BPH and PCa and highlight the importance of regulatory T CD4(+)FoxP3(+) (Treg) and Th17 cells in response to P. acnes infection in the context of both prostate diseases.
New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation
Authors: Ivan Beatrice-Cristina , Barbuceanu Stefania-Felicia , Hotnog Camelia Mia , Anghel Adriana Iuliana , Ancuceanu Robert Viorel , Mihaila Mirela Antonela , Brasoveanu Lorelei Irina , Shova Sergiu , Draghici Constantin , Olaru Octavian Tudorel , Nitulescu George Mihai , Dinu Mihaela , Dumitrascu Florea
Published: August 2022

The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, 1H-NMR and 13C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna Straus). The potential antitumor activity of several of the pyrrole derivatives was studied by performing in vitro cytotoxicity assays on human adenocarcinoma-derived cell lines (i.e., LoVo (colon), MCF-7 (breast), and SK-OV-3 (ovary)) and normal human umbilical vein endothelial cells (HUVECs). The obtained results of the cytotoxicity assessment indicated that the tested compounds had nontoxic activity on Triticum aestivum L., while on Artemia franciscana Kellogg nauplii, only compounds 2c and 4c had moderate toxicity. On Daphnia magna, 4b and 4c showed high toxicity; 2a, 2b, and 2c moderate to high toxicity; only 4a and 4d were nontoxic. The compound-mediated cytotoxicity assays showed that several pyrrole compounds demonstrated dose- and time-dependent cytotoxic activity against all tested tumor cell lines, the highest antitumor properties being achieved by 4a and its homologue 4d, especially against LoVo colon cells.
Contributions of Titin and Collagen to Passive Stress in Muscles from mdm Mice with a Small Deletion in Titin’s Molecular Spring
Authors: Hettige Pabodha , Mishra Dhruv , Granzier Henk , Nishikawa Kiisa , Gage Matthew J.
Published: August 2022

Muscular dystrophy with myositis (mdm) is a naturally occurring mutation in the mouse Ttn gene that results in higher passive stress in muscle fibers and intact muscles compared to wild-type (WT). The goal of this study was to test whether alternative splicing of titin exons occurs in mdm muscles, which contain a small deletion in the N2A-PEVK regions of titin, and to test whether splicing changes are associated with an increase in titin-based passive tension. Although higher levels of collagen have been reported previously in mdm muscles, here we demonstrate alternative splicing of titin in mdm skeletal muscle fibers. We identified Z-band, PEVK, and C-terminus Mex5 exons as splicing hotspots in mdm titin using RNA sequencing data and further reported upregulation in ECM-associated genes. We also treated skinned mdm soleus fiber bundles with trypsin, trypsin + KCl, and trypsin + KCL + KI to degrade titin. The results showed that passive stress dropped significantly more after trypsin treatment in mdm fibers (11 ± 1.6 mN/mm2) than in WT fibers (4.8 ± 1 mN/mm2; p = 0.0004). The finding that treatment with trypsin reduces titin-based passive tension more in mdm than in WT fibers supports the hypothesis that exon splicing leads to the expression of a stiffer and shorter titin isoform in mdm fibers. After titin extraction by trypsin + KCl + KI, mdm fibers (6.7 ± 1.27 mN/mm2) had significantly higher collagen-based passive stress remaining than WT fibers (2.6 ± 1.3 mN/mm2; p = 0.0014). We conclude that both titin and collagen contribute to higher passive tension of mdm muscles.
A γ-Secretase Inhibitor Attenuates Cell Cycle Progression and Invasion in Human Oral Squamous Cell Carcinoma: An In Vitro Study
Authors: Pongjantarasatian Sarai , Nowwarote Nunthawan , Rotchanakitamnuai Varumporn , Srirodjanakul Watcharee , Saehun Ritmongkol , Janebodin Kajohnkiart , Manokawinchoke Jeeranan , Fournier Benjamin P. J. , Osathanon Thanaphum
Published: August 2022

Notch signaling is associated with many human malignancies, including oral squamous cell carcinoma (OSCC). However, the exact function of Notch signaling in OSCC remains unclear. Here, we investigated the effect of Notch signaling inhibition using a γ-secretase inhibitor (DAPT) on OSCC behaviours in vitro. Bioinformatic analysis of public-available gene expression profiles revealed the dysregulation of the Notch signaling pathway in OSCC compared with normal tissues, indicating the role of Notch signaling in OSCC regulation. RNA sequencing analysis of DAPT-treated human OSCC cells revealed the dysregulation of genes related to cell cycle-related pathways. Blocking Notch signaling significantly inhibited cell proliferation. DAPT-induced G0/G1 cell cycle arrest induced cell apoptosis. Furthermore, cell migration and invasion were also reduced in DAPT-treated cells. These findings indicate that Notch signaling activation participates in OSCC regulation by promoting cell growth, cell cycle progression, cell migration, and invasion. These mechanisms could facilitate OSCC progression. These results imply the potential use of Notch signaling inhibitors as a candidate adjuvant treatment in OSCC patients.
Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
Authors: Man Yang Kee Stella , Aguirre-Hernandez Carmen , Fernandez Adrian , Martin-Duque Pilar , González-Pastor Rebeca , Halldén Gunnel
Published: August 2022

Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells in preclinical models. Further modifications are required to enable systemic delivery in patients due to the rapid hepatic elimination and neutralisation by blood factors and antibodies. Here, we show data that support the use of coating OAds with gold nanoparticles (AuNPs) as a possible new method of virus modification to help augment tumour uptake. The pre-incubation of cationic AuNPs with AdΔΔ, Ad-3∆-A20T and wild type adenovirus (Ad5wt) was performed prior to infection of prostate/pancreatic cancer cell lines (22Rv, PC3, Panc04.03, PT45) and a pancreatic stellate cell line (PS1). Levels of viral infection, replication and cell viability were quantified 24–72 h post-infection in the presence and absence of AuNPs. Viral spread was assessed in organotypic cultures. The presence of AuNPs significantly increased the uptake of Ad∆∆, Ad-3∆-A20T and Ad5wt in all the cell lines tested (ranging from 1.5-fold to 40-fold), compared to virus alone, with the greatest uptake observed in PS1, a usually adenovirus-resistant cell line. Pre-coating the AdΔΔ and Ad-3∆-A20T with AuNPs also increased viral replication, leading to enhanced cell killing, with maximal effect in the most virus-insensitive cells (from 1.4-fold to 5-fold). To conclude, the electrostatic association of virus with cationic agents provides a new avenue to increase the dose in tumour lesions and potentially protect the virus from detrimental blood factor binding. Such an approach warrants further investigation for clinical translation.
Acetylation-Specific Interference by Anti-Histone H3K9ac Intrabody Results in Precise Modulation of Gene Expression
Authors: Lisi Simonetta , Trovato Matteo , Vitaloni Ottavia , Fantini Marco , Chirichella Michele , Tognini Paola , Cornuti Sara , Costa Mario , Groth Marco , Cattaneo Antonino
Published: August 2022

Among Histone post-translational modifications (PTMs), lysine acetylation plays a pivotal role in the epigenetic regulation of gene expression, mediated by chromatin modifying enzymes. Due to their activity in physiology and pathology, several chemical compounds have been developed to inhibit the function of these proteins. However, the pleiotropy of these classes of proteins represents a weakness of epigenetic drugs. Ideally, a new generation of epigenetic drugs should target with molecular precision individual acetylated lysines on the target protein. We exploit a PTM-directed interference, based on an intrabody (scFv-58F) that selectively binds acetylated lysine 9 of histone H3 (H3K9ac), to test the hypothesis that targeting H3K9ac yields more specific effects than inhibiting the corresponding HAT enzyme that installs that PTM. In yeast scFv-58F modulates, gene expression in a more specific way, compared to two well-established HAT inhibitors. This PTM-specific interference modulated expression of genes involved in ribosome biogenesis and function. In mammalian cells, the scFv-58F induces exclusive changes in the H3K9ac-dependent expression of specific genes. These results suggest the H3K9ac-specific intrabody as the founder of a new class of molecules to directly target histone PTMs, inverting the paradigm from inhibiting the writer enzyme to acting on the PTM.