bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Outdoor Air Pollution on Indoor Air Quality in Low-Income Homes during Wildfire Seasons
Authors: Shrestha Prateek M. , Humphrey Jamie L. , Carlton Elizabeth J. , Adgate John L. , Barton Kelsey E. , Root Elisabeth D. , Miller Shelly L.
Published: September 2019

Indoor and outdoor number concentrations of fine particulate matter (PM2.5), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were monitored continuously for two to seven days in 28 low-income homes in Denver, Colorado, during the 2016 and 2017 wildfire seasons. In the absence of indoor sources, all outdoor pollutant concentrations were higher than indoors except for CO. Results showed that long-range wildfire plumes elevated median indoor PM2.5 concentrations by up to 4.6 times higher than outdoors. BC, CO, and NO2 mass concentrations were higher indoors in homes closer to roadways compared to those further away. Four of the homes with mechanical ventilation systems had 18% higher indoor/outdoor (I/O) ratios of PM2.5 and 4% higher I/O ratios of BC compared to other homes. Homes with exhaust stove hoods had PM2.5 I/O ratios 49% less than the homes with recirculating hoods and 55% less than the homes with no stove hoods installed. Homes with windows open for more than 12 hours a day during sampling had indoor BC 2.4 times higher than homes with windows closed. This study provides evidence that long-range wildfire plumes, road proximity, and occupant behavior have a combined effect on indoor air quality in low-income homes.
Internet Interpersonal Connection Mediates the Association between Personality and Internet Addiction
Authors: Chang Yun-Hsuan , Lee Yun-Ting , Hsieh Shulan
Published: September 2019

Backgrounds: The development of the Internet has changed interpersonal interactions, so that people no longer need to physically meet each other. However, some people are more vulnerable to becoming addicted to Internet activities, something to which the ease of Internet access and usage has contributed. In this study, we examined the association between personality traits and feelings about online interpersonal interactions to predict Internet addiction. This was accomplished using an online advertisement that asked participants to complete the questionnaires in the laboratory. Methods: Two hundred and twenty-three participants with a mean age of 22.50 years were recruited for this study and asked to complete the following questionnaires: the Beck Depressive Inventory (BDI), the Beck Anxiety Inventory (BAI), the Chen Internet Addiction Scale (CIAS), the Eysenck Personality Questionnaire (EPQ), the Internet Usage Questionnaire (IUQ) and the Feelings of Internet Interpersonal Interaction Questionnaire (FIIIQ). Results: The results showed that people with a neurotic personality and anxious feelings about Internet interpersonal interactions are more likely to become addicted to the Internet. In addition, people with neuroticism and who are more anxious about Internet interpersonal relationships are more likely to develop Internet addiction. Conclusions: People who tend to develop new interpersonal relationships via the Internet and be anxious about online interpersonal relationships are more vulnerable to becoming addicted to the Internet. The individuals who are more anxious about Internet interpersonal interaction and tend to develop new interpersonal relationships via the Internet are more likely to develop Internet addiction.
Assessing the Retail Food Environment in Madrid: An Evaluation of Administrative Data against Ground Truthing
Authors: Díez Julia , Cebrecos Alba , Galán Iñaki , Pérez-Freixo Hugo , Franco Manuel , Bilal Usama
Published: September 2019

Previous studies have suggested that European settings face unique food environment issues; however, retail food environments (RFE) outside Anglo-Saxon contexts remain understudied. We assessed the completeness and accuracy of an administrative dataset against ground truthing, using the example of Madrid (Spain). Further, we tested whether its completeness differed by its area-level socioeconomic status (SES) and population density. First, we collected data on the RFE through the ground truthing of 42 census tracts. Second, we retrieved data on the RFE from an administrative dataset covering the entire city (n = 2412 census tracts), and matched outlets using location matching and location/name matching. Third, we validated the administrative dataset against the gold standard of ground truthing. Using location matching, the administrative dataset had a high sensitivity (0.95; [95% CI = 0.89, 0.98]) and positive predictive values (PPV) (0.79; [95% CI = 0.70, 0.85]), while these values were substantially lower using location/name matching (0.55 and 0.45, respectively). Accuracy was slightly higher using location/name matching (k = 0.71 vs 0.62). We found some evidence for systematic differences in PPV by area-level SES using location matching, and in both sensitivity and PPV by population density using location/name matching. Administrative datasets may offer a reliable and cost-effective source to measure retail food access; however, their accuracy needs to be evaluated before using them for research purposes.
Unequal Associations between Educational Attainment and Occupational Stress across Racial and Ethnic Groups
Authors: Assari Shervin , Bazargan Mohsen
Published: September 2019

Background: Although other mechanisms are also involved, at least one reason high educational attainment (EA) is associated with better health is lower employment stress in individuals with high EA. Minorities’ Diminished Returns, however, refer to the smaller protective health effects of EA for racial- and ethnic-minority individuals, particularly African Americans (AAs) and Hispanics, as compared to Whites. We are, however, not aware of many studies that have explored differential associations between EA and work-related stress across racial and ethnic groups. Aims: We aimed to compare racial and ethnic groups for the association between EA and occupational stress in a national sample of American adults. Methods: The National Health Interview Survey (NHIS 2015), a cross-sectional survey, included 15,726 employed adults. Educational attainment was the independent variable. Occupational stress was the outcome. Race and ethnicity were the moderators. Age, gender, number of jobs, and years in the job were the covariates. Results: Overall, higher EA was associated with lower levels of occupational stress. Race and ethnicity both interacted with EA, suggesting that the association between high EA and reduced occupational stress is systemically smaller for AAs and Hispanics than it is for Whites. Conclusions: In the United States, race and ethnicity limit the health gains that follow EA. While EA helps individuals avoid environmental risk factors, such as occupational stress, this is more valid for non-Hispanic Whites than AAs and Hispanics. The result is additional physical and mental health risks in highly educated AAs and Hispanics. The results are important, given racial and ethnic minorities are the largest growing section of the US population. We should not assume that EA is similarly protective across all racial and ethnic groups. In this context, EA may increase, rather than reduce, health disparities.
Effect of Time-of-Day-Exercise in Group Settings on Level of Mood and Depression of Former Elite Male Athletes
Authors: Irandoust Khadijah , Taheri Morteza , Chtourou Hamdi , Nikolaidis Pantelis Theo , Rosemann Thomas , Knechtle Beat
Published: September 2019

Since the prevalence of depression is high among athletes at the end of their athletic career, the purpose of this study was to investigate the effect of time-of-day-exercise in group settings on the level of the mood and depression of former elite male athletes.Out of 187 volunteers referring to the sports counseling clinic, 71 retired male athletes who had a national championship record were randomly divided into two morning and evening exercise groups. The inclusion criteria were severe depression (high score in the Beck Depression Inventory-II), the age range of 50 to 60 years, the absence of metabolic syndrome, and the body mass index (BMI) between 28 and 35. All body composition variables were measured using body composition analysis (In Body 320; Korea). The second stage was the collection of data after three months (completion of the training protocol). After data collection, independent and dependent t-tests were used to analyze the data. The results indicated that both groups had a significant improvement in depression compared to the pre-test (p ≤ 0.05), while there was no significant difference between the two groups (p ≥ 0.05). The overall conclusion is that exercise at different times of the morning or evening can improve the psychological state and reduce depression.
Injury Severity and Contributing Driver Actions in Passenger Vehicle–Truck Collisions
Authors: Xu Jingjing , Wali Behram , Li Xiaobing , Yang Jiaqi
Published: September 2019

Large-scale truck-involved crashes attract great attention due to their increasingly severe injuries. The majority of those crashes are passenger vehicle–truck collisions. This study intends to investigate the critical relationship between truck/passenger vehicle driver’s intentional or unintentional actions and the associated injury severity in passenger vehicle–truck crashes. A random-parameter model was developed to estimate the complicated associations between the risk factors and injury severity by using a comprehensive Virginia crash dataset. The model explored the unobserved heterogeneity while controlling for the driver, vehicle, and roadway factors. Compared with truck passengers, occupants in passenger vehicles are six times and ten times more likely to suffer minor injuries and serious/fatal injuries, respectively. Importantly, regardless of whether passenger vehicle drivers undertook intentional or unintentional actions, the crashes are more likely to associate with more severe injury outcomes. In addition, crashes occurring late at night and in early mornings are often correlated with more severe injuries. Such associations between explanatory factors and injury severity are found to vary across the passenger vehicle–truck crashes, and such significant variations of estimated parameters further confirmed the validity of applying the random-parameter model. More implications based on the results and suggestions in terms of safe driving are discussed.
Varicella Seroprevalence in Healthcare Workers at a Medical Center Following Changes in National and Local Hospital Vaccination Policies
Authors: Tsou Meng-Ting , Shao Hsin-Hui
Published: September 2019

Background: Varicella seroprevalence in healthcare workers at a tertiary care hospital in Taiwan was assessed following the inclusion of varicella zoster vaccination in the national vaccination schedule in 2004 and was made a hospital policy in 2008. Methods: Seroprevalence data were extracted from records of pre-employment health check-ups performed between 2008 and 2018 at a single medical center. Staff with complete medical records and anti-varicella zoster virus immunoglobulin G (VZV IgG) titers were included. Sex and age group differences in terms of geometric mean titer (GMT) were compared using analysis of variance and chi-squared tests. The significance of the correlation between age and the anti-VZV IgG titer was tested by linear regression. The odds of significant associations among age, sex, vocation, and the years of national and hospital adoption of vaccination were determined using univariate and multivariate analyses. p < 0.05 was considered statistically significant. Results: Of the 7314 eligible participants, 5625 (76.90%) were women, and the mean patient age was 26.80 ± 8.00 years. The lowest VZV-positivity rates were in 18–20-year-old women (85.16%; GMT, 362.89 mIU/mL) and men (87.59%; GMT, 288.07 mIU/mL). VZV positivity increased with age (p < 0.001). Participants born before 2002 were more likely to be seropositive than those born after 2003 (odds ratio, 2.51 vs. 1.0; p < 0.001). The lowest seropositive rate was found in the nursing staff (88.91%; 95% confidence interval, 87.74%–90.05%). Varicella vaccine boosters have been required at pre-employment health check-ups since 2008 if anti-VZV antibodies were not detectable. A follow-up evaluation found marginal significant differences in the odds ratios of seropositivity after 2007 (p = 0.052), especially in 2008 and 2014 (p < 0.05) after the hospital policy launched. Conclusions: Despite public health efforts, a small number of healthcare workers were inadequately protected, and antibody titers were lower than required to maintain herd immunity. For effective prevention of nosocomial infection, VZV IgG status should be documented for all HCWs, and susceptible HCWs should be vaccinated to avoid outbreaks. Pre-employment screening and vaccination have increased immunity and need to be conducted to ensure protection of vulnerable patients.
The Needs of LGBTI People Regarding Health Care Structures, Prevention Measures and Diagnostic and Treatment Procedures: A Qualitative Study in a German Metropolis
Authors: Lampalzer Ute , Behrendt Pia , Dekker Arne , Briken Peer , Nieder Timo
Published: September 2019

(1) Background: Studies indicate that lesbian, gay, bisexual, transgender and intersex (LGBTI) people constantly face challenges and disadvantages in the health care system that prevent them from getting the best possible patient-centered care. However, the present study is the first to focus on LGBTI-related health in a major German metropolis. It aimed to investigate health care structures, prevention measures and diagnostic as well as treatment procedures that LGBTI individuals need in order to receive appropriate patient-centered health care and health promotion. (2) Methods: Following a participatory approach, five expert interviews with LGBTI people with multiplier function, i.e., people who have a key role in a certain social milieu which makes them able to acquire and spread information in and about this milieu, and three focus groups with LGBTI people and/or health professionals were conducted. Qualitative data were analyzed according to the principles of content analysis. (3) Results: The specific needs of LGBTI individuals must be recognized as a matter of course in terms of depathologization, sensitization, inclusion, and awareness. Such an attitude requires both basic knowledge about LGBTI-related health issues, and specific expertise about sufficient health care services for each of the minorities in the context of sex, sexual orientation and gender identity. (4) Conclusions: For an appropriate approach to LGBTI-centered health care and health promotion, health professionals will need to adopt a better understanding of specific soft and hard skills.
Threshold Effects of PM2.5 Exposure on Particle-Related Mortality in China
Authors: Tran Bao-Linh , Chang Ching-Cheng , Hsu Chia-Sheng , Chen Chi-Chung , Tseng Wei-Chun , Hsu Shih-Hsun
Published: September 2019

Ambient air pollution from energy use and other sources is a major environmental risk factor in the incidence and progression of serious diseases, such as cardiovascular and respiratory diseases. This study elucidates the health effects of energy consumption from air pollution in China based on multiple threshold effects of the population-weighted exposure to PM2.5 (fine particles less than 2.5 microns in diameter) on particle-related mortality rate. We firstly estimate the causal relationship between coal consumption and PM2.5 in China for 2004–2010 using a panel regression model. Panel threshold models are applied to access the non-linear relationships between PM2.5 and cause-specific mortality rates that indicate the health effects are dependent on the PM2.5 ranges. By combining these steps, we calculate the health impacts of coal consumption based on threshold effects of PM2.5. We find that a 1% coal consumption increase induces a 0.23% increase in PM2.5. A triple threshold effect is found between PM2.5 and cardiovascular mortality; for example, increasing PM2.5 exposure causes cardiovascular mortality rate to increase when PM2.5 lies in 17.7–21.6 μg/m3 and 21.6–34.3 μg/m3, with the estimated increments being 0.81% and 0.26%, respectively, corresponding to 1% PM2.5 increase. A single threshold effect of SO2 on respiratory mortality rate is identified and allows the estimation of the mortality effects of PM2.5 regarding the two regimes of SO2. Finally, we access the health impacts of coal consumption under specific estimated thresholds. This study provides a better understanding of sources contributing to related-air pollution mortality. The multi-threshold effect of PM2.5 could be considered for further applications in harmonizing emission standards in China and other developing countries.
Elemental Contamination in Indoor Floor Dust and Its Correlation with PAHs, Fungi, and Gram+/− Bacteria
Authors: Arar Sharif , Al-Hunaiti Afnan , Masad Mohanad H. , Maragkidou Androniki , Wraith Darren , Hussein Tareq
Published: September 2019

In this study, we performed elemental analysis for floor dust samples collected in Jordanian microenvironments (dwellings and educational building). We performed intercorrelation and cluster analysis between the elemental, polyaromatic hydrocarbon (PAH), and microorganism concentrations. In general, the educational building workshops had the highest elemental contamination. The age of the dwelling and its occupancy played a role on the elemental contamination level: older and more occupied dwellingshad greater contamination. The elemental contamination at a dwelling entrance was observed to be higher than in the living room. We found exceptionally high concentrations for Fe and Mn in the educational workshop and additionally, Hg, Cr, and Pb concentrations exceeded the limits set by the Canadian Council of Ministers of the Environment. According to the cluster analysis, we found three major groups based on location and contamination. According to the enrichment factor (EF) assessment, Al, Co, Mn, Ti, and Ba had EF < 2 (i.e., minimal enrichment) whereas P, S, Pb, Sb, Mo, Zn, Hg, and Cu had EF > 40 (i.e., extremely enriched). In contrast, Ca and P were geogenically enriched. Furthermore, significant Spearman correlations indicated nine subgroups of elemental contamination combined with PAHs and microbes.
Drama Therapy Counseling as Mental Health Care of College Students
Authors: Chang Wen-Lung , Liu Yu-Shiuan , Yang Cheng-Fu
Published: September 2019

(1) Background: This study aims to apply drama therapy to a counseling group to address the mental health problems of college students in Taiwan due to the increasingly serious psychological problems that have happened in recent times. Based on the healing factors in drama therapy, we applied such therapy activities to four counseling groups composed of 12 high-risk students from Taiwan. (2) Methods: “Questionnaire-based assessment, participant self-assessment and participant attitude assessment” methods were used to evaluate the six mental health indicators of the participants in the evaluation of drama therapy’s effect and the groups’ pre-test and post-test (the first group and the last group). The six indicators were self-awareness, self-expression, interpersonal and communication skills, self-cognitive reconstruction ability, social role ability, and decision-making ability. Data were collected and assessed for the frequencies and percentages of each indicator item. Sets of paired-samples t-tests, independent t-tests, and two-way repeated measures ANOVAs were employed to evaluate the different designs. (3) Results: The results revealed that drama therapy could deliver significantly positive effects for and improve the six mental health indicators of the participants. Males’ self-awareness and decision-making actions were more positively affected than females. (4) Conclusions: The study helps to provide a path of establishing the mental health module of drama therapy in the education sector in Taiwan.
Importance of Subjective Financial Knowledge and Perceived Credit Score in Payday Loan Use
Authors: Lee Jae Min , Park Narang , Heo Wookjae
Published: September 2019

This study examined the factors associated with consumers’ decisions to use payday loans. Using a sample of 24,201 respondents from the 2015 National Financial Capability Study (NFCS), structural equation modeling was used to analyze the relationships among the variables. The results indicated that payday loan use was associated with a series of consumers’ socio-psychological factors, including financial knowledge, perceived credit score, credit-card payment problems, and having emergency funds. The findings suggested that, to improve borrowing decisions and industry practices, discussions about consumers’ payday loan use and its underlying repayment problems should encompass policy intervention and institutional attention, rather than focusing on behavioral modification at the individual level alone.
The Role of Political Connections on Family Firms’ Performance: Evidence from Indonesia
Authors: Harymawan Iman , Nasih Mohammad , Madyan Muhammad , Sucahyati Diarany
Published: September 2019

The purpose of this study is to investigate the relationship of firms with family ownership and their performance in Indonesia and further examine on how political connections affect this relationship. This study used 933 samples from 413 companies listed on the Indonesia Stock Exchange (IDX) in the period between 2014 and 2016. Using ordinary least square (OLS) regression, the results shows that firms without family ownership (non-family firms) have better performance than firms with family ownership (family firms) in Indonesia. Furthermore, the findings also show that the performance of family firms significantly improve when the firms are affiliated with political connections. Our findings imply that establishing political connections in family firms will increase the performance of the firms.
Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice
Authors: Mizuno Yu , Yamamotoya Takeshi , Nakatsu Yusuke , Ueda Koji , Matsunaga Yasuka , Inoue Masa-Ki , Sakoda Hideyuki , Fujishiro Midori , Ono Hiraku , Kikuchi Takako , Takahashi Masahiro , Morii Kenichi , Sasaki Kensuke , Masaki Takao , Asano Tomoichiro , Kushiyama Akifumi
Published: September 2019

Hyperuricemia has been recognized as a risk factor for insulin resistance as well as one of the factors leading to diabetic kidney disease (DKD). Since DKD is the most common cause of end-stage renal disease, we investigated whether febuxostat, a xanthine oxidase (XO) inhibitor, exerts a protective effect against the development of DKD. We used KK-Ay mice, an established obese diabetic rodent model. Eight-week-old KK-Ay mice were provided drinking water with or without febuxostat (15 μg/mL) for 12 weeks and then subjected to experimentation. Urine albumin secretion and degrees of glomerular injury judged by microscopic observations were markedly higher in KK-Ay than in control lean mice. These elevations were significantly normalized by febuxostat treatment. On the other hand, body weights and high serum glucose concentrations and glycated albumin levels of KK-Ay mice were not affected by febuxostat treatment, despite glucose tolerance and insulin tolerance tests having revealed febuxostat significantly improved insulin sensitivity and glucose tolerance. Interestingly, the IL-1β, IL-6, MCP-1, and ICAM-1 mRNA levels, which were increased in KK-Ay mouse kidneys as compared with normal controls, were suppressed by febuxostat administration. These data indicate a protective effect of XO inhibitors against the development of DKD, and the underlying mechanism likely involves inflammation suppression which is independent of hyperglycemia amelioration.
Robust Sampling of Defective Pathways in Multiple Myeloma
Authors: Fernández-Martínez Juan Luis , de Andrés-Galiana Enrique J. , Fernández-Ovies Francisco Javier , Cernea Ana , Kloczkowski Andrzej
Published: September 2019

We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher’s ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of the disease, such as the existing difference between bone marrow stromal cells in MM and healthy controls (HC), the gene expression profiling of CD34+ cells in MM and HC, the difference between hyperdiploid and non-hyperdiploid myelomas, and the prediction of the chromosome 13 deletion, to provide a deeper insight into the molecular mechanisms involved in the disease. Our analysis has shown the importance of different altered pathways related to glycosylation, infectious disease, immune system response, different aspects of metabolism, DNA repair, protein recycling and regulation of the transcription of genes involved in the differentiation of myeloid cells. The main difference in genetic pathways between hyperdiploid and non-hyperdiploid myelomas are related to infectious disease, immune system response and protein recycling. Our work provides new insights on the genetic pathways involved in this complex disease and proposes novel targets for future therapies.
Active DNA Demethylation in Plants
Authors: Parrilla-Doblas Jara Teresa , Roldán-Arjona Teresa , Ariza Rafael R. , Córdoba-Cañero Dolores
Published: September 2019

Methylation of cytosine (5-meC) is a critical epigenetic modification in many eukaryotes, and genomic DNA methylation landscapes are dynamically regulated by opposed methylation and demethylation processes. Plants are unique in possessing a mechanism for active DNA demethylation involving DNA glycosylases that excise 5-meC and initiate its replacement with unmodified C through a base excision repair (BER) pathway. Plant BER-mediated DNA demethylation is a complex process involving numerous proteins, as well as additional regulatory factors that avoid accumulation of potentially harmful intermediates and coordinate demethylation and methylation to maintain balanced yet flexible DNA methylation patterns. Active DNA demethylation counteracts excessive methylation at transposable elements (TEs), mainly in euchromatic regions, and one of its major functions is to avoid methylation spreading to nearby genes. It is also involved in transcriptional activation of TEs and TE-derived sequences in companion cells of male and female gametophytes, which reinforces transposon silencing in gametes and also contributes to gene imprinting in the endosperm. Plant 5-meC DNA glycosylases are additionally involved in many other physiological processes, including seed development and germination, fruit ripening, and plant responses to a variety of biotic and abiotic environmental stimuli.
SNPs rs11240569, rs708727, and rs823156 in SLC41A1 Do Not Discriminate Between Slovak Patients with Idiopathic Parkinson’s Disease and Healthy Controls: Statistics and Machine-Learning Evidence
Authors: Cibulka Michal , Brodnanova Maria , Grendar Marian , Grofik Milan , Kurca Egon , Pilchova Ivana , Osina Oto , Tatarkova Zuzana , Dobrota Dusan , Kolisek Martin
Published: September 2019

Gene SLC41A1 (A1) is localized within Parkinson’s disease-(PD)-susceptibility locus PARK16 and encodes for the Na+/Mg2+-exchanger. The association of several A1 SNPs with PD has been studied. Two, rs11240569 and rs823156, have been associated with reduced PD-susceptibility primarily in Asian populations. Here, we examined the association of rs11240569, rs708727, and rs823156 with PD in the Slovak population and their power to discriminate between PD patients and healthy controls. The study included 150 PD patients and 120 controls. Genotyping was performed with the TaqMan® approach. Data were analyzed by conventional statistics and Random Forest machine-learning (ML) algorithm. Individually, none of the three SNPs is associated with an altered risk for PD-onset in Slovaks. However, a combination of genotypes of SNP-triplet GG(rs11240569)/AG(rs708727)/AA(rs823156) is significantly (p < 0.05) more frequent in the PD (13.3%) than in the control (5%) cohort. ML identified the power of the tested SNPs in isolation or of their singlets (joined), duplets and triplets to discriminate between PD-patients and healthy controls as zero. Our data further substantiate differences between diverse populations regarding the association of A1 polymorphisms with PD-susceptibility. Lack of power of the tested SNPs to discriminate between PD and healthy cases render their clinical/diagnostic relevance in the Slovak population negligible.
Rapid Microfluidic Preparation of Niosomes for Targeted Drug Delivery
Authors: Ag Seleci Didem , Maurer Viktor , Stahl Frank , Scheper Thomas , Garnweitner Georg
Published: September 2019

Niosomes are non-ionic surfactant-based vesicles with high promise for drug delivery applications. They can be rapidly prepared via microfluidics, allowing their reproducible production without the need of a subsequent size reduction step, by controlled mixing of two miscible phases of an organic (lipids dissolved in alcohol) and an aqueous solution in a microchannel. The control of niosome properties and the implementation of more complex functions, however, thus far are largely unknown for this method. Here we investigate microfluidics-based manufacturing of topotecan (TPT)-loaded polyethylene glycolated niosomes (PEGNIO). The flow rate ratio of the organic and aqueous phases was varied and optimized. Furthermore, the surface of TPT-loaded PEGNIO was modified with a tumor homing and penetrating peptide (tLyp-1). The designed nanoparticular drug delivery system composed of PEGNIO-TPT-tLyp-1 was fabricated for the first time via microfluidics in this study. The physicochemical properties were determined through dynamic light scattering (DLS) and zeta potential analysis. In vitro studies of the obtained formulations were performed on human glioblastoma (U87) cells. The results clearly indicated that tLyp-1-functionalized TPT-loaded niosomes could significantly improve anti-glioma treatment.
Efficient Epidermal Growth Factor Receptor Targeting Oligonucleotide as a Potential Molecule for Targeted Cancer Therapy
Authors: Wang Tao , Philippovich Svetlana , Mao Jun , Veedu Rakesh N.
Published: September 2019

Epidermal growth factor receptor (EGFR) is associated with the progression of a wide range of cancers including breast, glioma, lung, and liver cancer. The observation that EGFR inhibition can limit the growth of EGFR positive cancers has led to the development of various EGFR inhibitors including monoclonal antibodies and small-molecule inhibitors. However, the reported toxicity and drug resistance greatly compromised the clinical outcome of such inhibitors. As a type of chemical antibodies, nucleic acid aptamer provides an opportunity to overcome the obstacles faced by current EGFR inhibitors. In this study, we have developed and investigated the therapeutic potential of a 27mer aptamer CL-4RNV616 containing 2′-O-Methyl RNA and DNA nucleotides. Our results showed that CL-4RNV616 not only displayed enhanced stability in human serum, but also effectively recognized and inhibited the proliferation of EGFR positive Huh-7 liver cancer, MDA-MB-231 breast cancer, and U87MG glioblastoma cells, with an IC50 value of 258.9 nM, 413.7 nM, and 567.9 nM, respectively. Furthermore, TUNEL apoptosis assay revealed that CL-4RNV616 efficiently induced apoptosis of cancer cells. In addition, clinical breast cancer biopsy-based immunostaining assay demonstrated that CL-4RNV616 had a comparable detection efficacy for EGFR positive breast cancer with commonly used commercial antibodies. Based on the results, we firmly believe that CL-4RNV616 could be useful in the development of targeted cancer therapeutics and diagnostics.
Directed Evolution of Clostridium thermocellum β-Glucosidase A Towards Enhanced Thermostability
Authors: Yoav Shahar , Stern Johanna , Salama-Alber Orly , Frolow Felix , Anbar Michael , Karpol Alon , Hadar Yitzhak , Morag Ely , Bayer Edward A.
Published: September 2019

β-Glucosidases are key enzymes in the process of cellulose utilization. It is the last enzyme in the cellulose hydrolysis chain, which converts cellobiose to glucose. Since cellobiose is known to have a feedback inhibitory effect on a variety of cellulases, β-glucosidase can prevent this inhibition by hydrolyzing cellobiose to non-inhibitory glucose. While the optimal temperature of the Clostridium thermocellum cellulosome is 70 °C, C. thermocellum β-glucosidase A is almost inactive at such high temperatures. Thus, in the current study, a random mutagenesis directed evolutionary approach was conducted to produce a thermostable mutant with Kcat and Km, similar to those of the wild-type enzyme. The resultant mutant contained two mutations, A17S and K268N, but only the former was found to affect thermostability, whereby the inflection temperature (Ti) was increased by 6.4 °C. A17 is located near the central cavity of the native enzyme. Interestingly, multiple alignments revealed that position 17 is relatively conserved, whereby alanine is replaced only by serine. Upon the addition of the thermostable mutant to the C. thermocellum secretome for subsequent hydrolysis of microcrystalline cellulose at 70 °C, a higher soluble glucose yield (243%) was obtained compared to the activity of the secretome supplemented with the wild-type enzyme.
The Impact of Lactoferrin on the Growth of Intestinal Inhabitant Bacteria
Authors: Vega-Bautista Alan , de la Garza Mireya , Carrero Julio César , Campos-Rodríguez Rafael , Godínez-Victoria Marycarmen , Drago-Serrano Maria Elisa
Published: September 2019

Lactoferrin (Lf) is an iron-binding milk glycoprotein that promotes the growth of selected probiotic strains. The effect of Lf on the growth and diversification of intestinal microbiota may have an impact on several issues, including (i) strengthening the permeability of the epithelial cell monolayer, (ii) favoring the microbial antagonism that discourages the colonization and proliferation of enteric pathogens, (iii) enhancing the growth and maturation of cell-monolayer components and gut nerve fibers, and (iv) providing signals to balance the anti- and pro-inflammatory responses resulting in gut homeostasis. Given the beneficial role of probiotics, this contribution aims to review the current properties of bovine and human Lf and their derivatives in in vitro probiotic growth and Lf interplay with microbiota described in the piglet model. By using Lf as a component in pharmacological products, we may enable novel strategies that promote probiotic growth while conferring antimicrobial activity against multidrug-resistant microorganisms that cause life-threatening diseases, especially in neonates.
Immunomonitoring of Tacrolimus in Healthy Volunteers: The First Step from PK- to PD-Based Therapeutic Drug Monitoring?
Authors: in ‘t Veld Aliede E. , Grievink Hendrika W. , Saghari Mahdi , Stuurman Frederik E. , de Kam Marieke L. , de Vries Aiko P. J. , de Winter Brenda C. M. , Burggraaf Jacobus , Cohen Adam F. , Moerland Matthijs
Published: September 2019

Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of the relationship between tacrolimus dose, tacrolimus concentration, and its effect on the target cell, we developed functional immune tests for the quantification of the tacrolimus effect. Twelve healthy volunteers received a single dose of tacrolimus, after which intracellular and whole blood tacrolimus concentrations were measured and were related to T cell functionality. A significant correlation was found between tacrolimus concentrations in T cells and whole blood concentrations (r = 0.71, p = 0.009), while no correlation was found between tacrolimus concentrations in peripheral blood mononuclear cells (PBMCs) and whole blood (r = 0.35, p = 0.27). Phytohemagglutinin (PHA) induced the production of IL-2 and IFNγ, as well as the inhibition of CD71 and CD154 expression on T cells at 1.5 h post-dose, when maximum tacrolimus levels were observed. Moreover, the in vitro tacrolimus effect of the mentioned markers corresponded with the ex vivo effect after dosing. In conclusion, our results showed that intracellular tacrolimus concentrations mimic whole blood concentrations, and that PHA-induced cytokine production (IL-2 and IFNγ) and activation marker expression (CD71 and CD154) are suitable readout measures to measure the immunosuppressive effect of tacrolimus on the T cell.
Cytogenetics and Cytogenomics Evaluation in Cancer
Authors: Ribeiro Ilda Patrícia , Melo Joana Barbosa , Carreira Isabel Marques
Published: September 2019

The availability of cytogenetics and cytogenomics technologies improved the detection and identification of tumor molecular signatures as well as the understanding of cancer initiation and progression. The use of large-scale and high-throughput cytogenomics technologies has led to a fast identification of several cancer candidate biomarkers associated with diagnosis, prognosis, and therapeutics. The advent of array comparative genomic hybridization and next-generation sequencing technologies has significantly improved the knowledge about cancer biology, underlining driver genes to guide targeted therapy development, drug-resistance prediction, and pharmacogenetics. However, few of these candidate biomarkers have made the transition to the clinic with a clear benefit for the patients. Technological progress helped to demonstrate that cellular heterogeneity plays a significant role in tumor progression and resistance/sensitivity to cancer therapies, representing the major challenge of precision cancer therapy. A paradigm shift has been introduced in cancer genomics with the recent advent of single-cell sequencing, since it presents a lot of applications with a clear benefit to oncological patients, namely, detection of intra-tumoral heterogeneity, mapping clonal evolution, monitoring the development of therapy resistance, and detection of rare tumor cell populations. It seems now evident that no single biomarker could provide the whole information necessary to early detect and predict the behavior and prognosis of tumors. The promise of precision medicine is based on the molecular profiling of tumors being vital the continuous progress of high-throughput technologies and the multidisciplinary efforts to catalogue chromosomal rearrangements and genomic alterations of human cancers and to do a good interpretation of the relation genotype—phenotype.
Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment
Authors: Bæk Møller Nanna , Budolfsen Cecilie , Grimm Daniela , Krüger Marcus , Infanger Manfred , Wehland Markus , E. Magnusson Nils
Published: September 2019

This paper reviews current treatments for renal cell carcinoma/cancer (RCC) with the multikinase inhibitors (MKIs) sorafenib, sunitinib, lenvatinib and axitinib. Furthermore, it compares these drugs regarding progression-free survival, overall survival and adverse effects (AE), with a focus on hypertension. Sorafenib and sunitinib, which are included in international clinical guidelines as first- and second-line therapy in metastatic RCC, are now being challenged by new-generation drugs like lenvatinib and axitinib. These drugs have shown significant clinical benefits for patients with RCC, but all four induce a variety of AEs. Hypertension is one of the most common AEs related to MKI treatment. Comparing sorafenib, sunitinib and lenvatinib revealed that sorafenib and sunitinib had the same efficacy, but sorafenib was safer to use. Lenvatinib showed better efficacy than sorafenib but worse safety. No trials have yet been completed that compare lenvatinib with sunitinib. Although axitinib promotes slightly higher hypertension rates compared to sunitinib, the overall discontinuation rate and cardiovascular complications are favourable. Although the mean rate of patients who develop hypertension is similar for each drug, some trials have shown large differences, which could indicate that lifestyle and/or genetic factors play an additional role.
Effects of Extract of Arrabidaea chica Verlot on an Experimental Model of Osteoarthritis
Authors: Vasconcelos Cleydlenne Costa , Lopes Alberto Jorge Oliveira , Sousa Emerson Lucas Frazão , Camelo Darleno Sousa , Lima Fernando César Vilhena Moreira , Rocha Cláudia Quintino da , Silva Gyl Eanes Barros , Garcia João Batista Santos , Cartágenes Maria do Socorro de Sousa
Published: September 2019

The aim of this study was to analyze the analgesic potential of Arrabidaea chica extract (EHA) as an alternative to osteoarthritis (OA) treatment. Thus, the extract was initially evaluated by the cyclooxygenase inhibition test. The analgesic effect of the extract, in vivo, was also verified in a model of OA induced by sodium monoiodoacetate (2 mg). EHA was administered to rats at doses of 50, 150, and 450 mg/kg between 3 and 25 days after OA induction. The animals were clinically evaluated every 7 days, euthanized at 29 days, and the liver, spleen, kidney and knee collected for histopathological analysis. The chemical composition of EHA was identified by HPLC-MS and the identified compounds submitted to molecular docking study. The results showed that the extract promoted cyclooxygenase inhibition and produced significant improvements in disability, motor activity, hyperalgesia, and OA-induced allodynia parameters, in addition to improvements in the radiological condition of the knees (but not observed in the histopathological study). Chemically the extract is rich in flavonoids. Among them, we evidence that amentoflavone showed very favorable interactions with the enzyme COX-2 in the in silico analysis. Thus, it is concluded that A. chica has important analgesic properties for the treatment of OA.
Advances Towards How Meiotic Recombination Is Initiated: A Comparative View and Perspectives for Plant Meiosis Research
Authors: Jing Ju-Li , Zhang Ting , Wang Ya-Zhong , He Yan
Published: September 2019

Meiosis is an essential cell-division process for ensuring genetic diversity across generations. Meiotic recombination ensures the accuracy of genetic interchange between homolous chromosomes and segregation of parental alleles. Programmed DNA double-strand breaks (DSBs), catalyzed by the evolutionarily conserved topoisomerase VIA (a subunit of the archaeal type II DNA topoisomerase)-like enzyme Spo11 and several other factors, is a distinctive feature of meiotic recombination initiation. The meiotic DSB formation and its regulatory mechanisms are similar among species, but certain aspects are distinct. In this review, we introduced the cumulative knowledge of the plant proteins crucial for meiotic DSB formation and technical advances in DSB detection. We also summarized the genome-wide DSB hotspot profiles for different model organisms. Moreover, we highlighted the classical views and recent advances in our knowledge of the regulatory mechanisms that ensure the fidelity of DSB formation, such as multifaceted kinase-mediated phosphorylation and the consequent high-dimensional changes in chromosome structure. We provided an overview of recent findings concerning DSB formation, distribution and regulation, all of which will help us to determine whether meiotic DSB formation is evolutionarily conserved or varies between plants and other organisms.
Investigation of Phospholipase Cγ1 Interaction with SLP76 Using Molecular Modeling Methods for Identifying Novel Inhibitors
Authors: Tripathi Neha , Vetrivel Iyanar , Téletchéa Stéphane , Jean Mickaël , Legembre Patrick , Laurent Adèle D.
Published: September 2019

The enzyme phospholipase C gamma 1 (PLCγ1) has been identified as a potential drug target of interest for various pathological conditions such as immune disorders, systemic lupus erythematosus, and cancers. Targeting its SH3 domain has been recognized as an efficient pharmacological approach for drug discovery against PLCγ1. Therefore, for the first time, a combination of various biophysical methods has been employed to shed light on the atomistic interactions between PLCγ1 and its known binding partners. Indeed, molecular modeling of PLCγ1 with SLP76 peptide and with previously reported inhibitors (ritonavir, anethole, daunorubicin, diflunisal, and rosiglitazone) facilitated the identification of the common critical residues (Gln805, Arg806, Asp808, Glu809, Asp825, Gly827, and Trp828) as well as the quantification of their interaction through binding energies calculations. These features are in agreement with previous experimental data. Such an in depth biophysical analysis of each complex provides an opportunity to identify new inhibitors through pharmacophore mapping, molecular docking and MD simulations. From such a systematic procedure, a total of seven compounds emerged as promising inhibitors, all characterized by a strong binding with PLCγ1 and a comparable or higher binding affinity to ritonavir (∆Gbind < −25 kcal/mol), one of the most potent inhibitor reported till now.
Visualizing Air Motion Involving Isolated Subsurface Structures: A Critical Tool for Understanding Ventilation Induced by Natural Forces
Authors: McManus Thomas Neil , Haddad Assed
Published: September 2019

Worldwide, infrastructure contains millions of isolated subsurface structures. Most, if not all, meet requirements for classification as confined spaces. Workers routinely enter and work in these structures. Ventilation of these spaces by air exchange induced by natural forces was documented first in 1936. The mechanism of the process remains to be discovered. This investigation utilized ‘smoke’ tubes to visualize air motion and video capture techniques to record the process. Air moved across the surface of the ground and unpredictably entered the airspace when a single opening in the manhole cover was present. The process is discrete and not continuous. Air moved downward linearly or in circular motion, and moved across the underside of the manhole cover in the direction opposite airflow and down the sidewall of the structure. This produced the rapid mixing in the airspace observed instrumentally. For two openings, entry was more aggressive and predictable. Separation between the openings influenced exchange. Closer spacing (center + circumference) produced better ventilation than wider spacing (circumferential openings opposite each other). Optimizing naturally induced ventilation of these structures has profound importance to minimize risk to passersby and workers who enter and work in them.