bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Gene Rearrangements: Unique Signatures for Tracing Physiological Lymphocytes and Leukemic Cells
Authors: Kotrova Michaela , Darzentas Nikos , Pott Christiane , Baldus Claudia D. , Brüggemann Monika
Published: June 2021

The tremendous diversity of the human immune repertoire, fundamental for the defense against highly heterogeneous pathogens, is based on the ingenious mechanism of immune gene rearrangements. Rearranged immune genes encoding the immunoglobulins and T-cell receptors and thus determining each lymphocyte’s antigen specificity are very valuable molecular markers for tracing malignant or physiological lymphocytes. One of their most significant applications is tracking residual leukemic cells in patients with lymphoid malignancies. This so called ‘minimal residual disease’ (MRD) has been shown to be the most important prognostic factor across various leukemia subtypes and has therefore been given enormous attention. Despite the current rapid development of the molecular methods, the classical real-time PCR based approach is still being regarded as the standard method for molecular MRD detection due to the cumbersome standardization of the novel approaches currently in progress within the EuroMRD and EuroClonality NGS Consortia. Each of the molecular methods, however, poses certain benefits and it is therefore expectable that none of the methods for MRD detection will clearly prevail over the others in the near future.
Post-Operative All-Cause Mortality in Elderly Patients Undergoing Abdominal Emergency Surgery: Role of Charlson Comorbidity Index
Authors: Fabbian Fabio , De Giorgi Alfredo , Ferro Silvia , Lacavalla Domenico , Andreotti Dario , Ascanelli Simona , Volpato Stefano , Occhionorelli Savino
Published: June 2021

(1) Background: The Charlson comorbidity index (CCI) score has been shown to predict 10-year all-cause mortality, but its validity is a matter of debate in surgical patients. We wanted to evaluate CCI on predicting all-cause mortality in elderly patients undergoing emergency abdominal surgery (EAS); (2) Methods: This retrospective single center study included all patients aged 65 years or older consecutively admitted from January 2017 to December 2019, who underwent EAS and were discharged alive. CCI was calculated by using of the International Classification of Diseases, 9th Revision, Clinical Modification codes. Our outcome was all-cause death recorded during the 20.8 ± 8.8 month follow-up; (3) Results: We evaluated 197 patients aged 78.4 ± 7.2 years of whom 47 (23.8%) died. Mortality was higher in patients who underwent open abdominal surgery than in those treated with laparoscopic procedure (74% vs. 26%, p < 0.001), and in those who needed colon, small bowel, and gastric surgery. Mean CCI was 4.98 ± 2.2, and in subjects with CCI ≥ 4 survival was lower. Cox regression analysis showed that CCI (HR 1.132, 95% CI 1.009–1.270, p = 0.035), and open surgery (HR 10.298, 95%CI 1.409–75.285, p = 0.022) were associated with all-cause death independently from age and sex; (4) Conclusions: Calculation of CCI, could help surgeons in the preoperative stratification of risk of death after discharge in subjects aged ≥65 years who need EAS. CCI ≥ 4, increases the risk of all-causes mortality independently from age.
Factors Associated with Medication Non-Adherence in Patients with Dyslipidemia
Authors: Alefishat Eman , Jarab Anan S. , Al-Qerem Walid , Abu-Zaytoun Lina
Published: June 2021

Lack of medication adherence among patients with dyslipidemia negatively affects health-related outcomes. This study aims to evaluate medication adherence; we also aim to investigate the predictors of non-adherence among patients with dyslipidemia in Jordan. Medication adherence was evaluated in a total of 228 dyslipidemia patients. The Beliefs about Medicines Questionnaire was also used to assess patients’ beliefs about medications. The majority of the current study participants (73.2%) reported non-adherence to the prescribed medications. There were significant negative associations between medication adherence and concerns of prescription drug use (B = −0.41, p-value < 0.01), duration of dyslipidemia (B = −0.22, p-value < 0.01), and the number of medications (B = −0.64, p-value < 0.01). Positive associations were found between medication adherence and the necessity of prescription drug use (B = 0.43, p-value < 0.01), taking statin and fibrate (B = 2.04, p-value < 0.01), and moderate-intensity statin (B = 2.34, p-value < 0.01). As for patients’ beliefs about medications, the item “My medicine to lower my cholesterol disrupted my life” had the highest mean (3.50 ± 0.99). This study revealed a low adherence rate to medication among patients with dyslipidemia. It also demonstrates modifiable factors such as beliefs regarding perceived risk, medication harms, treatment duration, and the number of medications associated with poor adherence in patients with dyslipidemia.
Effect of Message Approach and Image Size on Pictorial Health Warning Effectiveness on Cigarette Pack in Indonesia: A Mixed Factorial Experiment
Authors: Yuliati Reny , Sarwono Billy Koernianti , Ahsan Abdillah , Wibhisono I Gusti Lanang Agung Kharisma , Kusuma Dian
Published: June 2021

Background: Cigarette consumption remains high and increasing in Indonesia. The government implemented a pictorial health warnings requirement of 40% cover of the pack (front and back) using fear appeal messages. Objective: Our study aims to assess the effectiveness of cigarette pictorial health warnings by message and size. Methods: We conducted a mixed factorial experiment online study using three messaging approaches (fear vs. guilt vs. financial loss) and two picture sizes (40% vs. 75%) among 209 smoking participants. Sociodemographic variables included gender, education, income, employment status, and marital status. Data analysis used a mixed model ANOVA to see the main effect and interaction effect on dependent variables. For subgroup analysis, we used t-test and one-way ANOVA. All analyzes were in SPSS 22. Results: We found significant differences in the three message types, in which fear and guilt have higher effectiveness than financial loss. By subgroup, the guilt message was more compelling among female smokers and married smokers. The financial loss message was effective among lower-income smokers. We found no difference in pictorial health warning effectiveness by image size, potentially because participants could zoom in/out the cigarette pack image on the screen. Conclusions: Our finding supports more diverse message types in pictorial health warnings in Indonesia and other countries.
Exploring the Effect of Social Support and Empathy on User Engagement in Online Mental Health Communities
Authors: Chen Yixin , Xu Yang
Published: June 2021

It is known that social support and empathy are beneficial for mental health. As a result of the widespread development of social media, online social support and empathy could also influence user behaviors during the development of online communities. However, few studies have examined these effects from the perspective of online mental health communities. These communities appear to be a crucial source for mental health related support, but the spread of online empathy in these communities is not well-understood. This study focused on 22 mental health related subreddits, and matched and compared users (1) who received social support with those who did not receive social support, and users (2) who received more empathic social support with those who received less empathic social support. The results showed that social support and empathy are “contagious”. That is, users who received social support at their first post would be more likely to post again and provide support for others; in addition, users who received more empathic support would subsequently express a higher level of empathy to others in the future. Our findings indicate the potential chain reaction of social support and empathy in online mental health communities. Our study also provides insights into how online mental health communities might better assist people to deliver social support that can help others to deal with mental problems.
Continuous Performance Improvement Framework for Sustainable Wastewater Treatment Facilities in Arid Regions: Case of Wadi Rumah in Qassim, Saudi Arabia
Authors: Haider Husnain , AlHetari Mohammed , Ghumman Abdul , Al-Salamah Ibrahim , Thabit Hussein , Shafiquzzaman Md.
Published: June 2021

In arid regions such as Saudi Arabia, wastewater treatment (WWT) facilities (meeting promulgated standards) need to adapt their continuous performance improvement (CPI) for long-term sustainability. To achieve this, the facilities need to improve their performance to comply with more strict objectives for broader reuse applications of treated effluent. The present research proposes a CPI framework based on performance benchmarking process for the stepwise improvement of WWT facilities. A grey rational analysis water quality index (GWQI) based on exceedance probability was developed. For weights’ estimation of 11 physical, chemical, and biological water quality parameters, the entropy method effectively accommodated the changes in relative importance of the parameters with including additional future reuse applications. For existing effluent reuse scenarios of restricted and unrestricted irrigation, the GWQI values were found consistent with the modified version of the Canadian WQI (CWQI). The indices’ values (ranged between 0 and 100) greater than 80 showed the efficient operation of four WWT plants in the Qassim Region of Saudi Arabia. Two hypothetical CPI scenarios with future reuse applications (fish, livestock drinking, and recreation) showed an overall decline in the average (of four plants) values of the GWQI (97 to 78) and CWQI (85 to 60). CWQI predicted stricter results for the facilities with parameters’ concentrations exceeding the targets with larger margins and was found applicable for the CPI of WWT facilities in arid regions. For existing scenarios, the assessment results suggest the facilities to control and monitor the chlorination practice. For future targets, tertiary treatment needs to be enhanced for desired nutrients and total dissolved solids removal. The proposed CPI framework provides a platform to initiate the performance benchmarking process for WWT facilities at local or regional levels in Saudi Arabia and elsewhere.
Factors Influencing Unmet Healthcare Needs among Older Korean Women
Authors: Choi Jung A. , Kim Oksoo
Published: June 2021

The purpose of this study was to determine factors that influence the unmet healthcare needs of older women in Korea and to examine differences in the reasons for these unmet healthcare needs according to age and residential area. We analyzed data from the 2018 Korea Community Health Survey and enrolled 42,698 older Korean women in this study. Residential area, living arrangement, income, education, basic livelihood subsidy, activity of daily living, subjective health status, hypertension and diabetes, unmet healthcare needs, and the reasons healthcare needs were not met were assessed. Logistic regression analysis was performed to identify factors that influenced unmet healthcare needs. Chi-square tests were used to identify reasons for unmet healthcare needs according to age group and residential area. Of the participants, 4151 (9.7%) reported unmet healthcare needs over the past year. The primary reason participants could not use health services was “inconvenient transportation” (38.4%), followed by “financial burden” (28.4%) and “symptoms not severe” (16.8%). There were significant differences in “financial burden”, “difficulty making appointments”, “inconvenient transportation”, and “symptoms not severe” according to both age group and residential area. Factors that influenced unmet healthcare needs were residential area, living alone, lower family income, lower educational level, basic livelihood subsidy, difficult activities of daily living, hypertension and diabetes, and poor subjective health. Older women in Korea living alone in urban and rural areas had more unmet healthcare needs of than those who lived with other people. To address the unmet healthcare needs of older Korean women, transportation and medical facilities need to be improved or established.
Age Differences in Attitudes towards Older People in Poland
Authors: Krajewska-Kułak Elżbieta , Cybulski Mateusz , Aniśko Paulina , Popławska Magda
Published: June 2021

Introduction: The attitudes towards older people is essential. Society’s perception of older adults is often unpleasant. Inappropriate treatment of older people in society causes a decrease in self-esteem, a sense of control over one’s own life, a decrease in the quality of life, an increase in anxiety, depression, anger, and sadness. The aim of this study was to compare the attitudes of young people and seniors towards older people in relation to their satisfaction with life and self-esteem. Materials and Methods: The study was conducted online in groups of young adults under 35 years of age (Group I) and over 65 years of age (group II), with 177 people each. Method: The study used the following questionnaires: Satisfaction with Life Scale (SWLS), Self-Assessment of Own Person (SOP), and Kogan’s Attitude Towards Old People Scale (KATOPS). Results: The satisfaction of life in both groups was average. The mean value of self-esteem was significantly (p < 0.001) lower in the group of seniors. Both groups of respondents had negative attitudes towards seniors in the KATOPS. There was a statistically significant correlation between life satisfaction and self-esteem in seniors. Gender, age, education, or place of residence of respondents had no impact on negative attitudes in both groups. Conclusions: Both groups showed negative attitudes towards seniors. No significant correlation was found between the groups and gender of the respondents, and the influence of the respondent’s age, education, marital status, or place of residence. There was a correlation between the respondents’ attitudes in the subscale of negative attitudes and their satisfaction with life. No correlation between self-esteem and age and marital status were found with no dependence on gender, education, or place of residence.
Assessing the Country-Level Excess All-Cause Mortality and the Impacts of Air Pollution and Human Activity during the COVID-19 Epidemic
Authors: Meng Yuan , Wong Man Sing , Xing Hanfa , Kwan Mei-Po , Zhu Rui
Published: June 2021

The impact of Coronavirus Disease 2019 (COVID-19) on cause-specific mortality has been investigated on a global scale. However, less is known about the excess all-cause mortality and air pollution-human activity responses. This study estimated the weekly excess all-cause mortality during COVID-19 and evaluated the impacts of air pollution and human activities on mortality variations during the 10th to 52nd weeks of 2020 among sixteen countries. A SARIMA model was adopted to estimate the mortality benchmark based on short-term mortality during 2015–2019 and calculate excess mortality. A quasi-likelihood Poisson-based GAM model was further applied for air pollution/human activity response evaluation, namely ground-level NO2 and PM2.5 and the visit frequencies of parks and workplaces. The findings showed that, compared with COVID-19 mortality (i.e., cause-specific mortality), excess all-cause mortality changed from −26.52% to 373.60% during the 10th to 52nd weeks across the sixteen countries examined, revealing higher excess all-cause mortality than COVID-19 mortality in most countries. For the impact of air pollution and human activities, the average country-level relative risk showed that one unit increase in weekly NO2, PM2.5, park visits and workplace visits was associated with approximately 1.54% increase and 0.19%, 0.23%, and 0.23% decrease in excess all-cause mortality, respectively. Moreover, compared with the impact on COVID-19 mortality, the relative risks of weekly NO2 and PM2.5 were lower, and the relative risks of weekly park and workplace visits were higher for excess all-cause mortality. These results suggest that the estimation based on excess all-cause mortality reduced the potential impact of air pollution and enhanced the influence of human activities compared with the estimation based on COVID-19 mortality.
Difference in Incontinence Pad Use between Patients after Radical Prostatectomy and Cancer-Free Population with Subgroup Analysis for Open vs. Minimally Invasive Radical Prostatectomy: A Descriptive Analysis of Insurance Claims-Based Data
Authors: Mun Dong-Ho , Yang Lin , Shariat Shahrokh F. , Reitter-Pfoertner Sylvia , Gredinger Gerald , Waldhoer Thomas
Published: June 2021

Purpose: to quantify and compare pre- and post-surgical incontinence pad use between men treated with radical prostatectomy (RP) for prostate cancer (PCa) and cancer-free controls, using population-based Austrian insurance claims data. Methods: Men who underwent RP for treating PCa between 2013–2015 were identified. Cancer-free men ≥45 years with and without benign prostate hyperplasia (BPH) were used as controls. Longitudinal data on ICD-diagnoses, type of surgery, prescribed incontinence pads, and hospitals’ surgery volumes were aggregated between 2011–2018 to capture pre- and up to three years post-RP follow-up. Monthly rates of pad use were calculated and compared between RP types and cancer-free controls. Results: A total of 6248 RP patients, 7158 cancer-free men with BPH, and 50,257 cancer-free men without BPH were analyzed. Comparing to pre-RP (0.03, 95%CI: 0.02–0.05), RP resulted in significantly higher rates of prescribed pads (at 3 months: 12.61, 95%CI: 11.59–13.65; 12 months: 6.71, 95%CI: 6.10–7.34; 36 months: 4.91, 95%CI: 3.76–4.62). These rates were also higher than those for cancer free controls (with BPH:0.06, 95%CI: 0.04–0.09; without BPH:0.12, 95%CI: 0.10–0.14). The rate of prescribed pads after surgery continued to decline over time and remained higher among men who underwent minimally invasive RP compared to those who underwent an open procedure. Conclusion: Despite progress in surgical techniques, post-RP incontinence remains a prevalent adverse event. The rate of pad usage steadily improved over the first three years post RP. The rate of patients with incontinence needing pads was higher among those who were treated minimally invasive compared to open approach.
COVID-19 Mortality Rate and Its Incidence in Latin America: Dependence on Demographic and Economic Variables
Authors: Cifuentes-Faura Javier
Published: June 2021

The pandemic caused by COVID-19 has left millions infected and dead around the world, with Latin America being one of the most affected areas. In this work, we have sought to determine, by means of a multiple regression analysis and a study of correlations, the influence of population density, life expectancy, and proportion of the population in vulnerable employment, together with GDP per capita, on the mortality rate due to COVID-19 in Latin American countries. The results indicated that countries with higher population density had lower numbers of deaths. Population in vulnerable employment and GDP showed a positive influence, while life expectancy did not appear to significantly affect the number of COVID-19 deaths. In addition, the influence of these variables on the number of confirmed cases of COVID-19 was analyzed. It can be concluded that the lack of resources can be a major burden for the vulnerable population in combating COVID-19 and that population density can ensure better designed institutions and quality infrastructure to achieve social distancing and, together with effective measures, lower death rates.
A Psychological Perception Mechanism and Factor Analysis in Landsenses Ecology: A Case Study of Low-Carbon Harmonious Discourse
Authors: Zhang Lan , Huang Guowen , Li Yongtao , Bao Shitai
Published: June 2021

Landsenses ecology has been widely applied in research into sustainable consciousness and behavior and the notion of landsense creation realizes the unity of the macro physical senses and micro psychological perceptions. However, a great deal of current research about landsenses ecology has concentrated on the dimension of the physical senses, while there have been relatively few studies on the dimension of its psychological perception. This paper begins by clarifying the concept of self and explaining out that the psychological perception mechanism of landsense creation represents a process of guiding people to know themselves and realize their ecological self. It then utilizes the example of low-carbon discourse to explore the factors contributing to the resonance of ecological self-vision. Our results show that the perceived self-efficacy, environmental concern and environmental knowledge triggered by ecological discourse are the main factors contributing to the resonance of sustainable vision, thus clarifying the indicators of landsenses ecology at the level of psychological perception. Our purpose is to effectively guide the landsense creation of harmonious discourse and promote people to engage in potentially more sustainable behavior.
Estimating the Total Number of Residential Fire-Related Incidents and Underreported Residential Fire Incidents in New South Wales, Australia by Using Linked Administrative Data
Authors: Ghassempour Nargess , Tannous W. Kathy , Avsar Gulay , Agho Kingsley E. , Harvey Lara A.
Published: June 2021

The rate of fires, and particularly residential fires, is a serious concern in industrialized countries. However, there is considerable uncertainty regarding the reported numbers of residential fire incidents as official figures are based on fires reported to fire response agencies only. This population-based study aims to quantify the total number of residential fire incidents regardless of reporting status. The cohort comprised linked person-level data from Fire and Rescue New South Wales (FRNSW) and health system and death records. It included all persons residing at a residential address in New South Wales, Australia, that experienced a fire between 1 January 2005 and 31 December 2014. The capture-recapture method was used to estimate the underreporting number of residential fire-related incidents. Over the study period, 43,707 residential fire incidents were reported to FRNSW, and there were 2795 residential fire-related health service utilizations, of which 2380 were not reported. Using the capture-recapture method, the total number of residential fire incidents was estimated at 267,815 to 319,719, which is more than six times the official records. This study found that 15% of residential fire incidents that were identified in health administrative dataset were reported. The residential fire incidents that were not reported occurred mainly in socio-economically disadvantaged areas among males and adults.
Asbestos Exposure Level and the Carcinogenic Risk Due to Corrugated Asbestos-Cement Slate Roofs in Korea
Authors: Lee Eun-Soo , Kim Young-Ki
Published: June 2021

Asbestos-cement slate roofs are one of the most common environmental causes of asbestos exposure. However, few studies have examined residential asbestos-cement slate-related exposure and its effects on human health. This study was performed to evaluate cumulative asbestos exposure levels and to calculate the Excess Lifetime Cancer Risk (ELCR) of residents of asbestos-cement slate-roofed houses. We reviewed previous Korean literature to estimate the concentration of airborne asbestos from asbestos-cement slate roofed buildings. Finally, eight studies were selected, and a pooled analysis was performed. The results derived from the pooled analysis were combined with the data from a health impact survey conducted from 2009 to 2016 at the Environmental Health Center for Asbestos (EHCA) of the Yangsan Pusan National University Hospital, and a carcinogenic risk assessment was performed. As a result, the representative value of the indoor exposure concentration related to asbestos-cement slate was found to be 0.0032 f/cc on average, and the representative value of the exposure related to occupational asbestos-cement slate dismantling and demolition was found to be 0.0034 f/cc. In addition, the ELCR of asbestos-cement slate related indoor exposure and occupational dismantling and demolition was found to be of medium risk, and the ELCR of residential dismantling and demolition of asbestos-cement slate was less than 10−6, indicating that the risk was low. Since there is no threshold for carcinogenicity related to asbestos, this should not be ignored even if the risk appears low, and it would be reasonable to calculate the carcinogenic risk based on total lifetime exposure. More studies on asbestos exposure scenarios and the scope of similar exposure groups through additional data collection and further analysis of risk are needed.
Exploring Equity in Healthcare Services: Spatial Accessibility Changes during Subway Expansion
Authors: Liu Maohua , Luo Siqi , Du Xishihui
Published: June 2021

The unequal allocation of healthcare resources raises many fundamental problems, one of which is how to address inequity in population health. This paper focuses on disparities in public transport healthcare accessibility, with a special focus on an expanding subway system. Based on a vulnerability index, including factors that are likely to limit healthcare opportunities, a two-step floating catchment area method was used to assess the distribution of supply and demand for healthcare. Quantity, quality, and walking distance accessibility were aggregated into hexagonal grids. The Theil index was used to measure inequity and understand the influence of subways on spatial disparities in healthcare accessibility. The ongoing construction of the subway has heterogeneous impacts on healthcare accessibility for different parts of the city and exacerbates spatial inequity in many areas. In an environment where people in peri-urban areas are excluded from healthcare access because of low subway coverage, the results suggest that the potential for subways to address inaccessibility is limited. The findings highlight the requirement of efficient public transport services and are relevant to researchers, planners, and policymakers aiming to improve accessibility to healthcare, especially for populations who dwell in winter cities.
The Effect of Exogenous Application of Quercetin Derivative Solutions on the Course of Physiological and Biochemical Processes in Wheat Seedlings
Authors: Jańczak-Pieniążek Marta , Migut Dagmara , Piechowiak Tomasz , Buczek Jan , Balawejder Maciej
Published: June 2021

Quercetin, classified as a flavonoid, is a strong antioxidant that plays a significant role in the regulation of physiological processes in plants, which is particularly important in the case of biotic and abiotic stresses. The study investigated the effect of the use of potassium quercetin solutions in various concentrations (0.5%, 1.0%, 3.0% and 5.0%) on the physiological and biochemical properties of wheat seedlings. A pot experiment was carried out in order to determine the most beneficial dose of this flavonoid acting as a bio-stimulant for wheat plants. Spraying with quercetin derivative solutions was performed twice, and physiological measurements (chlorophyll content and fluorescence as well as gas exchange) were carried out on the first and seventh days after each application. The total phenolic compounds content and the total antioxidant capacity were also determined. It was shown that the concentrations of potassium quercetin applied have a stimulating effect on the course of physiological processes. In the case of most of the tested physiological parameters (chlorophyll content and fluorescence and gas exchange) and the total antioxidant capacity, no significant differences were observed in their increase as a result of application with concentrations of 3.0 and 5.0%. Therefore, the beneficial effect of quercetin on the analysed parameters is already observed when spraying with a concentration of 3.0%.
Coregulation Analysis of Mechanistic Biomarkers in Autosomal Dominant Polycystic Kidney Disease
Authors: Leierer Johannes , Perco Paul , Hofer Benedikt , Eder Susanne , Dzien Alexander , Kerschbaum Julia , Rudnicki Michael , Mayer Gert
Published: June 2021

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation.
Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
Authors: Sharapova Tatiana N. , Romanova Elena A. , Ivanova Olga K. , Yashin Denis V. , Sashchenko Lidia P.
Published: June 2021

The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70–TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Moreover, incubation of PBMCs with Hsp70 leads to an appearance of cytotoxic lymphocyte subpopulations active against the MHC-negative tumor cells. In addition, both the CD4+ T-lymphocytes and CD14+ monocytes are necessary for the Hsp70 signal transduction and a consequent activation of the cytotoxic lymphocytes. We believe that data presented in this study will broaden the views on the involvement of Hsp70 in the antitumor immunity.
Plant Secondary Metabolites with an Overview of Populus
Authors: Movahedi Ali , Almasi Zadeh Yaghuti Amir , Wei Hui , Rutland Paul , Sun Weibo , Mousavi Mohaddeseh , Li Dawei , Zhuge Qiang
Published: June 2021

Populus trees meet continuous difficulties from the environment through their life cycle. To warrant their durability and generation, Populus trees exhibit various types of defenses, including the production of secondary metabolites. Syntheses derived from the shikimate-phenylpropanoid pathway are a varied and plentiful class of secondary metabolites manufactured in Populus. Amongst other main classes of secondary metabolites in Populus are fatty acid and terpenoid-derivatives. Many of the secondary metabolites made by Populus trees have been functionally described. Any others have been associated with particular ecological or biological processes, such as resistance against pests and microbial pathogens or acclimatization to abiotic stresses. Still, the functions of many Populus secondary metabolites are incompletely understood. Furthermore, many secondary metabolites have therapeutic effects, leading to more studies of secondary metabolites and their biosynthesis. This paper reviews the biosynthetic pathways and therapeutic impacts of secondary metabolites in Populus using a genomics approach. Compared with bacteria, fewer known pathways produce secondary metabolites in Populus despite P. trichocarpa having had its genome sequenced.
Amino Acid-Mediated Intracellular Ca2+ Rise Modulates mTORC1 by Regulating the TSC2-Rheb Axis through Ca2+/Calmodulin
Authors: Amemiya Yuna , Nakamura Nao , Ikeda Nao , Sugiyama Risa , Ishii Chiaki , Maki Masatoshi , Shibata Hideki , Takahara Terunao
Published: June 2021

Mechanistic target of rapamycin complex 1 (mTORC1) is a master growth regulator by controlling protein synthesis and autophagy in response to environmental cues. Amino acids, especially leucine and arginine, are known to be important activators of mTORC1 and to promote lysosomal translocation of mTORC1, where mTORC1 is thought to make contact with its activator Rheb GTPase. Although amino acids are believed to exclusively regulate lysosomal translocation of mTORC1 by Rag GTPases, how amino acids increase mTORC1 activity besides regulation of mTORC1 subcellular localization remains largely unclear. Here we report that amino acids also converge on regulation of the TSC2-Rheb GTPase axis via Ca2+/calmodulin (CaM). We showed that the amino acid-mediated increase of intracellular Ca2+ is important for mTORC1 activation and thereby contributes to the promotion of nascent protein synthesis. We found that Ca2+/CaM interacted with TSC2 at its GTPase activating protein (GAP) domain and that a CaM inhibitor reduced binding of CaM with TSC2. The inhibitory effect of a CaM inhibitor on mTORC1 activity was prevented by loss of TSC2 or by an active mutant of Rheb GTPase, suggesting that a CaM inhibitor acts through the TSC2-Rheb axis to inhibit mTORC1 activity. Taken together, in response to amino acids, Ca2+/CaM-mediated regulation of the TSC2-Rheb axis contributes to proper mTORC1 activation, in addition to the well-known lysosomal translocation of mTORC1 by Rag GTPases.
The Role of Fatty Acids in Non-Alcoholic Fatty Liver Disease Progression: An Update
Authors: Hliwa Aleksandra , Ramos-Molina Bruno , Laski Dariusz , Mika Adriana , Sledzinski Tomasz
Published: June 2021

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.
Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis
Authors: Nishimura Norihisa , Kaji Kosuke , Kitagawa Koh , Sawada Yasuhiko , Furukawa Masanori , Ozutsumi Takahiro , Fujinaga Yukihisa , Tsuji Yuki , Takaya Hiroaki , Kawaratani Hideto , Moriya Kei , Namisaki Tadashi , Akahane Takemi , Fukui Hiroshi , Yoshiji Hitoshi
Published: June 2021

Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called “leaky gut”. Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.
Molecular Complexes at Euchromatin, Heterochromatin and Centromeric Chromatin
Authors: Morrison Olivia , Thakur Jitendra
Published: June 2021

Chromatin consists of a complex of DNA and histone proteins as its core components and plays an important role in both packaging DNA and regulating DNA metabolic pathways such as DNA replication, transcription, recombination, and chromosome segregation. Proper functioning of chromatin further involves a network of interactions among molecular complexes that modify chromatin structure and organization to affect the accessibility of DNA to transcription factors leading to the activation or repression of the transcription of target DNA loci. Based on its structure and compaction state, chromatin is categorized into euchromatin, heterochromatin, and centromeric chromatin. In this review, we discuss distinct chromatin factors and molecular complexes that constitute euchromatin—open chromatin structure associated with active transcription; heterochromatin—less accessible chromatin associated with silencing; centromeric chromatin—the site of spindle binding in chromosome segregation.
Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma
Authors: García-Marín Rocío , Reda Sara , Riobello Cristina , Cabal Virginia N. , Suárez-Fernández Laura , Vivanco Blanca , Álvarez-Marcos César , López Fernando , Llorente José L. , Hermsen Mario A.
Published: June 2021

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30–50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)—CD8high (>10%); and 39/57 (68%)—CD8low (1–10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.
Dissecting the Interplay Mechanism between Epigenetics and Gut Microbiota: Health Maintenance and Disease Prevention
Authors: Wu Yuqi , Wang Chong-Zhi , Wan Jin-Yi , Yao Haiqiang , Yuan Chun-Su
Published: June 2021

The gut microbiota exists throughout the full life cycle of the human body, and it has been proven to have extensive impacts on health and disease. Accumulating evidence demonstrates that the interplay between gut microbiota and host epigenetics plays a multifaceted role in health maintenance and disease prevention. Intestinal microflora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification. Moreover, epigenetic factors can serve as mediators to coordinate gut microbiota within the host. Aiming to dissect this interplay mechanism, the present review summarizes the research profile of gut microbiota and epigenetics in detail, and further interprets the biofunctions of this interplay, especially the regulation of intestinal inflammation, the improvement of metabolic disturbances, and the inhibition of colitis events. This review provides new insights into the interplay of epigenetics and gut microbiota, and attempts to reveal the mysteries of health maintenance and disease prevention from this new perspective.
Substituent Effect in the Cation Radicals of Monosubstituted Benzenes
Authors: Dobrowolski Jan Cz. , Dudek Wojciech M. , Karpińska Grażyna , Baraniak Anna
Published: June 2021

In 30 monosubstituted benzene cation radicals, studied at the ωB97XD/aug-cc-pVTZ level, the phenyl rings usually adopt a compressed form, but a differently compressed form—equivalent to an elongated one—may coexist. The computational and literature ionization potentials are well correlated. The geometrical and magnetic aromaticity, estimated using HOMA and NICS indices, show the systems to be structurally aromatic but magnetically antiaromatic or only weakly aromatic. The partial charge is split between the substituent and ring and varies the most at C(ipso). In the ring, the spin is 70%, concentrated equally at the C(ipso) and C(p) atoms. The sEDA(D) and pEDA(D) descriptors of the substituent effect in cation radicals, respectively, were determined. In cation radicals, the substituent effect on the σ-electron system is like that in the ground state. The effect on the π-electron systems is long-range, and its propagation in the radical quinone-like ring is unlike that in the neutral molecules. The pEDA(D) descriptor correlates well with the partial spin at C(ipso) and C(p) and weakly with the HOMA(D) index. The correlation of the spin at the ring π-electron system and the pEDA(D) descriptor shows that the electron charge supplied to the ring π-electron system and the spin flow oppositely.
The Felicitous Success of the Subsection Molecular Oncology of International Journal of Molecular Sciences
Authors: Welsh Michael
Published: June 2021

The evolvement of the newly started subsection IJMS molecular oncology is discussed. The breadth and depth of the journal articles is alluded to. A bright future for this subsection is anticipated, developing into a top tier cancer journal.
Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) Is a Prognostic Biomarker and Associated with Chemotherapy Responsiveness in Colorectal Cancer
Authors: Chen Hung-Ming , Lin Chun-Chi , Chen Wei-Shone , Jiang Jeng-Kai , Yang Shung-Haur , Chang Shih-Ching , Ho Ching-Liang , Yang Chung-Chi , Huang Shih-Ching , Chao Yee , Liao Tsai-Tsen , Hwang Wei-Lun , Teng Hao-Wei
Published: June 2021

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an RNA-binding protein and serves as a post-transcriptional fine-tuner regulating the expression of mRNA targets. However, the clinicopathological roles of IGF2BP1 in colorectal cancer (CRC) remains limited. Thus, we aimed to elucidate the clinical significance and biomarker potentials of IGF2BP1 in CRC. A total of 266 specimens from two sets of CRC patients were collected. IGF2BP1 expression was studied by immunohistochemical (IHC) staining. The Kaplan-Meier survival plot and a log-rank test were used for survival analysis. The Cox proportional hazards model was applied to determine the survival impact of IGF2BP1. Public datasets sets from The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB), receiver operating characteristic (ROC) plotter, and two CRC cell lines, HCT-116 and DLD-1, were used for validating our findings. We showed that IGF2BP1 was overexpressed in tumor specimens compared to 13 paired normal parts by examining the immunoreactivity of IGF2BP1 (p = 0.045). The increased expression of IGF2BP1 in primary tumor parts was observed regardless of metastatic status (p < 0.001) in HCMDB analysis. IGF2BP1 expression was significantly associated with young age (59.6% vs. 46.7%, p-value = 0.043) and advanced stage (61.3% vs. 40.0%, p-value = 0.001). After controlling for confounding factors, IGF2BP1 remained an independent prognostic factor (HR = 1.705, p-value = 0.005). TCGA datasets analysis indicated that high IGF2BP1 expression showed a lower 5-year survival rate (58% vs. 65%) in CRC patients. The increased expression of IGF2BP1 in chemotherapy non-responder rectal cancer patients was observed using a ROC plotter. Overexpression of IGF2BP1 promoted the colony-forming capacity and 5-fluorouracil and etoposide resistance in CRC cells. Here, IGF2BP1 was an independent poor prognostic marker in CRC patients and contributed to aggressive phenotypes in CRC cell lines.
Evolution of Terpene Synthases in Orchidaceae
Authors: Huang Li-Min , Huang Hsin , Chuang Yu-Chen , Chen Wen-Huei , Wang Chun-Neng , Chen Hong-Hwa
Published: June 2021

Terpenoids are the largest class of plant secondary metabolites and are one of the major emitted volatile compounds released to the atmosphere. They have functions of attracting pollinators or defense function, insecticidal properties, and are even used as pharmaceutical agents. Because of the importance of terpenoids, an increasing number of plants are required to investigate the function and evolution of terpene synthases (TPSs) that are the key enzymes in terpenoids biosynthesis. Orchidacea, containing more than 800 genera and 28,000 species, is one of the largest and most diverse families of flowering plants, and is widely distributed. Here, the diversification of the TPSs evolution in Orchidaceae is revealed. A characterization and phylogeny of TPSs from four different species with whole genome sequences is available. Phylogenetic analysis of orchid TPSs indicates these genes are divided into TPS-a, -b, -e/f, and g subfamilies, and their duplicated copies are increased in derived orchid species compared to that in the early divergence orchid, A. shenzhenica. The large increase of both TPS-a and TPS-b copies can probably be attributed to the pro-duction of different volatile compounds for attracting pollinators or generating chemical defenses in derived orchid lineages; while the duplications of TPS-g and TPS-e/f copies occurred in a species-dependent manner.