bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel miR-146a-POU3F2/SMARCA5 Pathway Regulates Stemness and Therapeutic Response in Glioblastoma
Authors: Cui Tiantian , Bell Erica H. , McElroy Joseph , Liu Kevin , Sebastian Ebin , Johnson Benjamin , Gulati Pooja Manchanda , Becker Aline Paixao , Gray Ashley , Geurts Marjolein , Subedi Depika , Yang Linlin , Fleming Jessica L. , Meng Wei , Barnholtz-Sloan Jill S. , Venere Monica , Wang Qi-En , Robe Pierre A. , Haque S. Jaharul , Chakravarti Arnab
Published: September 2020

Rapid tumor growth, widespread brain-invasion, and therapeutic resistance critically contribute to glioblastoma (GBM) recurrence and dismal patient outcomes. Although GBM stem cells (GSC) are shown to play key roles in these processes, the molecular pathways governing the GSC phenotype (GBM-stemness) remain poorly defined. Here, we show that epigenetic silencing of miR-146a significantly correlated with worse patient outcome and importantly, miR-146a level was significantly lower in recurrent tumors compared with primary ones. Further, miR-146a overexpression significantly inhibited the proliferation and invasion of GBM patient-derived primary cells and increased their response to temozolomide (TMZ), both in vitro and in vivo. Mechanistically, miR-146a directly silenced POU3F2 and SMARCA5, two transcription factors that mutually regulated each other, significantly compromising GBM-stemness and increasing TMZ response. Collectively, our data show that miR-146a–POU3F2/SMARCA5 pathway plays a critical role in suppressing GBM-stemness and increasing TMZ-response, suggesting that POU3F2 and SMARCA5 may serve as novel therapeutic targets in GBM.

Implications:

miR-146a predicts favorable prognosis and the miR-146a–POU3F2/SMARCA5 pathway is important for the suppression of stemness in GBM.
A Rare Chromosome Abnormality with der(16)t(1;16)(q12;q11.2) in Blast Crisis of Chronic Myeloid Leukemia
Authors: Yanagiya Ryo , Ishikawa Daisuke , Toubai Tomomi , Ichikawa Tsubasa , Kawaguchi Naofumi , Sugasawa Kunie , Ishizawa Kenichi , Saito Soichi
Published: September 2020

Although tyrosine kinase inhibitors markedly improve the clinical outcome of chronic myeloid leukemia (CML), blast crisis in CML (CML-BC) still has a poor prognosis. Many chromosomal abnormalities have been reported in CML-BC and may contribute to therapeutic resistance, disease progression, and prognosis. Herein, we report a rare chromosome abnormality with der(16)t(1;16)(q12;q11.2) in CML-BC. It has been demonstrated that this chromosomal abnormality is associated with disease progression and poor prognosis in other malignancies, such as Ewing sarcoma. A 70-year-old man with CML who had been treated with imatinib and dasatinib was admitted to our hospital after complaining for several weeks of fatigue and dyspnea and diagnosed with CML-BC. His tumor cells presented additional chromosomal abnormality with der(16)t(1;16)(q12;q11.2), which has never been reported in CML cases. We successfully treated him using cytotoxic agents combined with ponatinib, and this chromosome abnormality was detected via G-banding. Our patient has lived for over 8 months without any progression with ponatinib treatment alone. Although the biological function of this chromosomal abnormality remains unclear, the satellite DNA of 1q12, which induces genomic instability in other malignancies, and the loss of 16q may contribute to the disease progression of CML in this case. In conclusion, this paper is the first to report on the case of CML-BC with der(16)t(1;16)(q12;q11.2).
What Information Are Patients Receiving from the Internet about the Operative and Nonoperative Management of Acute Appendicitis?
Authors: Conlon Luke , Baig Zarrukh , Moser Michael A.J.
Published: September 2020

Introduction: Recent studies suggest that nonoperative management of appendicitis (NOMA) may be a reasonable option for managing uncomplicated acute appendicitis. We examined the Internet to see if patients are likely to find the information they need to make an informed decision between the 2 options. Methods: A list of 29 search terms was established by a focus group and then entered into Google, resulting in 49 unique webpages, each reviewed by 3 reviewers. Consensus was obtained for bias (surgery, NOMA, or balanced), webpage type, JAMA score, reading grade, and DISCERN score, a measure of quality of written information for patients. Results: Thirty of the 49 websites (61%) favored surgery, while 13 (27%) favored NOMA, and 6 sites (12%) provided balanced information. Twelve of 49 sites (24%) did not list NOMA as an option. The majority of patient-directed (11/12 = 92%) and physician-directed (7/9 = 78%) webpages favored surgery, whereas academic webpages presented a more balanced distribution. Academic and physician-directed webpages ranked higher than commercial and news webpages (median ranks 3 and 4 vs. 7.5 and 8). Only 8/49 sites (16%) mentioned that the presence of a fecalith predicts the failure of NOMA. Reading grades were almost all well above the recommended grade 8 level. Conclusion: Most of the webpages available on the Internet do not provide enough information, nor are they sufficiently understandable to allow most patients to make an informed decision about the current options for the management of acute appendicitis.
Differential Risk Factors and Outcomes of Ischemic Stroke due to Cervical Artery Dissection in Young Adults
Authors: Garg Aayushi , Bathla Girish , Molian Vaelan , Limaye Kaustubh , Hasan David , Leira Enrique C. , Derdeyn Colin P. , Adams Harold P. , Shaban Amir
Published: September 2020

Introduction: Cervical artery dissection (CeAD) is a major cause of ischemic stroke in young adults. Our understanding of the specific risk factors and clinical course of CeAD is still evolving. In this study, we evaluated the differential risk factors and outcomes of CeAD-related strokes among young adults. Methods: The study population consisted of young patients 15–45 years of age consecutively admitted with acute ischemic stroke to our comprehensive stroke center between January 1, 2010, and November 30, 2016. Diagnosis of CeAD was based on clinical and radiological findings. Univariate and multivariable logistic regression analyses were used to assess the risk factors and clinical outcomes associated with CeAD-related strokes. Results: Of the total 333 patients with acute ischemic stroke included in the study (mean ± SD age: 36.4 ± 7.1 years; women 50.8%), CeAD was identified in 79 (23.7%) patients. As compared to stroke due to other etiologies, patients with CeAD were younger in age, more likely to have history of migraine and recent neck manipulation and were less likely to have hypertension, diabetes, and previous history of stroke. Clinical outcomes of CeAD were comparable to strokes due to other etiologies. Within the CeAD group, higher initial stroke severity and history of tobacco use were associated with higher modified Rankin Scale score at follow-up. Conclusions: While history of migraine and neck manipulation are significantly associated with CeAD, most of the traditional vascular risk factors for stroke are less prevalent in this group when compared to strokes due to other etiologies. For CeAD-related strokes, higher initial stroke severity and history of tobacco use may be associated with higher stroke-related disability, but overall, patients with CeAD have similar outcomes as compared to strokes due to other etiologies.
RBC Transfusion Triggers: Is There Anything New?
Authors: Tomic Mahecic Tina , Dünser Martin , Meier Jens
Published: September 2020

For many years, in daily clinical practice, the traditional 10/30 rule (hemoglobin 10 g/dL – hematocrit 30%) has been the most commonly used trigger for blood transfusions. Over the years, this approach is believed to have contributed to a countless number of unnecessary transfusions and an unknown number of overtransfusion-related deaths. Recent studies have shown that lower hemoglobin levels can safely be accepted, even in critically ill patients. However, even these new transfusion thresholds are far beyond the theoretical limits of individual anemia tolerance. For this reason, almost all publications addressing the limits of acute anemia recommend physiological transfusion triggers to indicate the transfusion of erythrocyte concentrates as an alternative. Although this concept appears intuitive at first glance, no solid scientific evidence supports the safety and benefit of physiological transfusion triggers to indicate the optimal time point for transfusion of allogeneic blood. It is therefore imperative to continue searching for the most sensitive and specific parameters that can guide the clinician when to transfuse in order to avoid anemia-induced organ dysfunction while avoiding overtransfusion-related adverse effects. This narrative review discusses the concept of anemia tolerance and critically compares hemoglobin-based triggers with physiological transfusion for various clinical indications.
Multiomics Screening Identifies Molecular Biomarkers Causally Associated With the Risk of Coronary Artery Disease
Authors: Nikpay Majid , Soubeyrand Sebastien , Tahmasbi Rasool , McPherson Ruth
Published: September 2020

Background:

In this study, we aimed to investigate functional mechanisms underlying coronary artery disease (CAD) loci and find molecular biomarkers for CAD.

Methods:

We devised a multiomics data analysis approach based on Mendelian randomization and utilized it to search for molecular biomarkers causally associated with the risk of CAD within genomic regions known to be associated with CAD.

Results:

Through our CAD-centered multiomics data analysis approach, we identified 33 molecular biomarkers (probes) that were causally associated with the risk of CAD. The majority of these (N=19) were methylation probes; moreover, methylation was often behind the causal effect of expression/protein probes. We identified a number of novel loci that have a causal impact on CAD including
C5orf38
,
SF3A3
,
DHX36
, and
MRPL33
. Furthermore, by integrating the risk factors of CAD in our analysis, we were able to investigate the clinical pathways whereby several of our probes exert their effect. We found that the SELE protein level in the blood is under the trans-regulatory impact of methylation sites within the
ABO
gene and that SELE exerts its effect on CAD through immune, glycemic, and lipid metabolism, making it a candidate of interest for therapeutic interventions. We found the methylation site, cg05126514 within the
BSN
gene exert its effect on CAD through central nervous system-lifestyle risk factors. Finally, genes with a transcriptional regulatory role (
SF3A3
,
ILF3
, and
N4BP2L2
) exert their effect on CAD through height.

Conclusions:

We demonstrate that multiomics data analysis is a powerful approach to unravel the functional mechanisms underlying CAD loci and to identify novel molecular biomarkers. Our results indicate epigenetic modifications are important in the pathogenesis of CAD and identifying and targeting these sites is of potential therapeutic interest to address the detrimental effects of both environmental and genetic factors.
Shocks versus Menu Costs: Patterns of Price Rigidity in an Estimated Multisector Menu-Cost Model
Authors: Gautier Erwan , Le Bihan Hervé
Published: September 2020

Sectoral heterogeneity matters for monetary policy. Using CPI microdata, we estimate for 227 products a time-varying menu-cost model to investigate the quantitative relevance of this heterogeneity. We find a substantial degree of cross-sectoral heterogeneity in all structural parameters. Heterogeneity in the Calvo component of the pricing friction is, however, the main source of heterogeneity in price rigidity. Cross-sectoral heterogeneity amplifies the output effect of a monetary shock by a factor of about 2.5, compared to a single-sector model estimated with mean moments. Heterogeneity in the Calvo parameter plays a key role in this amplification.
Election by Community Consensus: Effects on Political Selection and Governance
Authors: Arora Ashna
Published: September 2020

This paper evaluates the effects of encouraging the selection of local politicians in India via community consensus, as opposed to a secret ballot election. Using village-level data on candidates, elected politicians, government budgets, and workfare employment, I show that incentives for consensus elections lead to politicians who are more educated but less likely to be drawn from historically marginalized castes and increase how regressively workfare employment is targeted. These results are supported by qualitative evidence that shows that consensus elections are prone to capture by the local elite, which may reduce the need for clientelistic transfers to the non-elite.
Species relationship and population structure analysis in Allochrusa (Caryophylloideae, Caryophyllaceae) using ISSR molecular markers

Authors: DONG ZHEN , QI JING , ZHANG YONGJIE , LI GUIQIN , MINAEIFAR AMIR ABBAS
Published: September 2020

Allochrusa is a genus of subfamily Caryophylloideae comprising about 8 species distributed in Turkey, Central Asia, Afghanistan, Caucasus, and Iran. Four species of A. versicolor, A. bungei, A. lutea, and A. persica occur in Iran and show overlaps in morphology, which make critical their identification. In this study, we used 49 randomly collected specimens belonging to seven populations. AMOVA test provide important genetic variation among the examined populations and showed that 70% of the overall genetic difference was due to within population diversity, while 30% is because genetic population variability. Overall, 150 groups were distinguished through ISSR marker, in which 137 (90%) bands with a normal of 13.7 bands marker were polymorphic. Percentage of Polymorphic bands (PPB) ranging from 77% (ISSR-7) to 100% (ISSR-1, ISSR-4 and ISSR-5). The average Polymorphic Information Content (PIC), Shannon’s Information index (I), and Number of effective alleles (Ne) were 0.59, 0.27, and 1.8, respectively.
Nomenclator botanicus for Appendicularia DC. (Melastomataceae, Marcetieae)

Authors: SILVA DIEGO NUNES DA , ROCHA MARIA JOSÉ REIS DA , GUIMARÃES PAULO JOSÉ FERNANDES
Published: September 2020

Appendicularia is a neotropical genus of annual herbs, currently with four accepted species after a recent inclusion of three species that were formerly placed in Ernestia. However, during nomenclatural studies on Marcetieae, we observed that the combination A. rubra was mistaken, since its basionym Ernestia rubra belongs to the clade “Ernestia incertae sedis”. Here we exclude A. rubra from the genus, reinstating it to Ernestia, and consequently recognizing Appendicularia with three species. The type collections and nomenclatural comments are provided, as well as lectotypifications for A. thymifolia and E. rubra. Finally, Brachypremna has been listed as a synonym under Ernestia by previous treatments, but is synonymized here under Appendicularia.
Styrax carranzae, a new name for extant Styrax lanceolatus P.W. Fritsch non Engelhardt (Styracaceae)

Authors: DOWELD ALEXANDER B.
Published: September 2020

In revising fossil records of the genus Styrax Linnaeus (1753: 444) for the International Fossil Plant Names Index (IFPNI, 2014 onwards) with the aim of listing all fossil plant species (Doweld 2015, 2016a), it became apparent that a few fossil-species are later illegitimate homonyms of the extant species of Styrax, and their nomenclature was recently resolved by proposing new replacement names for them (Doweld 2016b). However, an additional case of the homonymy of an extant species by a preoccupied name in fossils remained unsettled.
High-Gravity-Assisted Green Synthesis of NiO-NPs Anchored on the Surface of Biodegradable Nanobeads with Potential Biomedical Applications
Authors: Rabiee Navid , Bagherzadeh Mojtaba , Ghadiri Amir Mohammad , Kiani Mahsa , Ahmadi Sepideh , Aldhaher Abdullah , Varma Rajender S. , Webster Thomas J.
Published: September 2020

Here, an unprecedented synthesis method for nickel oxide nanoparticles (NiO-NPs) was facilitated using Salvia hispanica leaf extracts with the assistance of a high gravity rotating packed bed (RPB) system that enabled fast mass transfer and molecular mixing. The synthesized nanoparticles
were anchored on the surface of biodegradable chitosan nanobeads and their photocatalytic activity was evaluated by the degradation of methylene blue. Additionally, the potential biological activities of NiO-NPs in terms of antibacterial (Staphylococcus aureus and Escherichia coli
for 24 hours), cytotoxicity (using the PC12 cell line for 24 and 72 hours), and antioxidant activities (based on the discoloration of the methanolic solution of DPPH) were assessed. This novel approach for NiO-NPs@Chitosan synthesis as mediated by a renewable plant extract and facilitated
by a high-gravity method, led to the greener synthesis of nanoparticles with significant antibacterial and photocatalytic properties.
Green Synthesis of ZnO NPs via Salvia hispanica: Evaluation of Potential Antioxidant, Antibacterial, Mammalian Cell Viability, H1N1 Influenza Virus Inhibition and Photocatalytic Activities
Authors: Rabiee Navid , Bagherzadeh Mojtaba , Ghadiri Amir Mohammad , Kiani Mahsa , Aldhaher Abdullah , Ramakrishna Seeram , Tahriri Mohammadreza , Tayebi Lobat , Webster Thomas J.
Published: September 2020

Among different forms of metallic nanoparticles (NPs), zinc oxide (ZnO) NPs with a very special bandgap of 3.37 eV and considerable binding energy of excitation (60 meV at room temperature), have been classified as high-tech nanoparticles. This study aimed to synthesize ZnO NPs using
the extract from Salvia hispanica leaves. The synthesized nanoparticles were fully characterized and the photocatalytic activity was evaluated through the degradation of methylene blue. Additionally, the potential in vitro biological activities of such ZnO NPs in terms of their
antibacterial activity were determined, as well as their antioxidant (30 minutes), antiviral (48 hours) and mammalian cell viability properties (48 and 72 hours). This study is the first investigation into the synthesis of such green ZnO NPs mediated by this plant extract, in which both photocatalytic
and biomedical properties were found to be promising. The IC50 values for the antibacterial activities were found to be around 17.4 μg mL–1 and 28.5 μg mL–1 for S. aureus and E. coli, respectively, and the antioxidant activity
was comparable with the standard BHT. However, the H1N1 inhibition rate using the present green ZnO NPs was lower than oseltamivir (up to about 40% for ZnO NPs and above 90% for oseltamivir) which was expected since it is a drug, but was higher than many synthetic nanoparticles reported in
the literature. In addition, the mammalian cell viability assay showed a higher than 80% cellular viability in the presence of 5, 10 and 20 μg mL–1 nanoparticles, and showed a higher than 50% cellular viability in the presence of 50 and 75 μg mL–1
nanoparticles. In this manner, this study showed that these green ZnO NPs should be studied for a wide range of medical applications.
Severe Convective Storms across Europe and the United States. Part I: Climatology of Lightning, Large Hail, Severe Wind, and Tornadoes
Authors: Taszarek Mateusz , Allen John T. , Groenemeijer Pieter , Edwards Roger , Brooks Harold E. , Chmielewski Vanna , Enno Sven-Erik
Published: September 2020

As lightning-detection records lengthen and the efficiency of severe weather reporting increases, more accurate climatologies of convective hazards can be constructed. In this study we aggregate flashes from the National Lightning Detection Network (NLDN) and Arrival Time Difference long-range lightning detection network (ATDnet) with severe weather reports from the European Severe Weather Database (ESWD) and Storm Prediction Center (SPC) Storm Data on a common grid of 0.25° and 1-h steps. Each year approximately 75–200 thunderstorm hours occur over the southwestern, central, and eastern United States, with a peak over Florida (200–250 h). The activity over the majority of Europe ranges from 15 to 100 h, with peaks over Italy and mountains (Pyrenees, Alps, Carpathians, Dinaric Alps; 100–150 h). The highest convective activity over continental Europe occurs during summer and over the Mediterranean during autumn. The United States peak for tornadoes and large hail reports is in spring, preceding the maximum of lightning and severe wind reports by 1–2 months. Convective hazards occur typically in the late afternoon, with the exception of the Midwest and Great Plains, where mesoscale convective systems shift the peak lightning threat to the night. The severe wind threat is delayed by 1–2 h compared to hail and tornadoes. The fraction of nocturnal lightning over land ranges from 15% to 30% with the lowest values observed over Florida and mountains (~10%). Wintertime lightning shares the highest fraction of severe weather. Compared to Europe, extreme events are considerably more frequent over the United States, with maximum activity over the Great Plains. However, the threat over Europe should not be underestimated, as severe weather outbreaks with damaging winds, very large hail, and significant tornadoes occasionally occur over densely populated areas.
Students’ Expectations and Students’ Satisfaction: The Mediating Role of Excellent Teacher Behaviors
Authors: Geier Michael T.
Published: September 2020

This study sought to investigate whether teacher behaviors, within the Teacher Behavior Checklist dimensions of caring and supportive and professional competency and communication skills, relate to students’ satisfaction. Additionally, it assessed the influence of the importance students set on teacher behaviors on students’ satisfaction. Cross-sectional survey data were analyzed using hierarchical linear regression and mediation analysis. Results suggested teacher behaviors within the caring and supportive dimension is the dominant predictor of students’ satisfaction. Behaviors according to professional competency and communication skills were also related to students’ satisfaction but to a lesser degree. Results showed that students’ importance for behaviors did mediate the relationship between teacher behaviors and students’ satisfaction with both caring and supportive and professional competency and communication skills. Theoretical and practical implications for excellent teacher behaviors are discussed including recommendations for future research.
What Do Students Think When Asked About Psychology as a Science?
Authors: Richardson Lindsay , Lacroix Guy
Published: September 2020

Research has shown that undergraduate courses in psychology often fail to make students accept the discipline as a science. It may be that explicit instruction is not sufficient to modify students’ conceptualization of psychology as something other than science. The goal of this study was to examine introductory psychology students’ conceptualizations of psychology and science. Five hundred and seventy participants completed a free association task for disciplines that included psychology and other sciences. They also provided ratings for these disciplines on relevant dimensions (e.g., important and scientific) and were asked “Is psychology a science?” Students tended to agree that psychology was a science but rated it to be less scientific than the natural sciences. Moreover, the free association results suggested that psychology was semantically distant from the other sciences. Thus, successful pedagogy will need to focus on conceptual change if students are to accept psychology as a science.
Inequality and Employment Resilience: An Analysis of Spanish Municipalities during the Great Recession
Authors: Geelhoedt Fabian , Royuela Vicente , Castells-Quintana David
Published: September 2020

In this paper we study an association almost neglected in the literature, that between income inequality and resilience. In particular, we explore the response of employment rates in the face of the crisis of 2008 and how income inequality levels may have affected this response. To do so, we construct two measures of employment resilience—resistance and recoverability—using data on total employment and self-employment for 995 Spanish municipalities during the Great Recession. Our results provide evidence of the threats that high levels of inequality pose for employment resilience, showing that average income is the most important mediating factor of this association.
Voices from the Margins: Low-income Fatherhood in the Era of Neoliberalism
Authors: Black Timothy , Keyes Sky
Published: September 2020

The norms and expectations of “father involvement” have changed rapidly within a generation, and yet, the labor force and state institutions have not supported low-income families in a way to achieve this. In this article, we examine the narratives of 138 socially and economically marginalized fathers to identify the frames that they adopt to represent themselves as fathers, tell a coherent story about their lives, and project an identity of themselves into their futures. Despite the political–economic forces that have dramatically increased inequality in an era of neoliberal capitalism, fathers rarely alluded to structural explanations for family instability, father absence, marital dissolution, and gender distrust in low-income communities. Instead, fathers attempted to adopt socially valued identities along three symbolic boundaries that distinguished themselves from their own fathers, from welfare frauds, and from the iconic deadbeat dad. They also adopted individualistic frames that took the form of therapeutic narratives and life-course transitional narratives. In general, despite harsh structural constraints, the men imagined themselves doing better, and, in nearly all cases, being engaged fathers was at the center of these hopeful constructions. Without structural change, however, these aspirational frames are likely to become little more than false hopes.
Loosely displaced formation-keeping control for satellite swarm with continuous low-thrust
Authors: Zhao Lin , Zhao Kun , Li Hui , Huang Weiquan , Zhang Xinyu , Zeng Xiangxi
Published: September 2020

Aiming at a long-term formation-keeping problem for the satellite swarm, the concept of a loosely displaced formation is proposed in this article. On this basis, a continuous low-thrust control strategy for maintaining the loosely displaced formation is designed. The control objective is to reduce more fuel consumption during the formation-keeping. For achieving that, we proposed a forward-feedback control strategy by using pseudo-spectral method and sliding mode theory. To be specific, the control strategy includes two parts: a forward control and a feedback control. For the forward control, a numerical optimization with the Legendre pseudo-spectral method is attempted to convert the optimal control problem into a nonlinear programming problem and fuel consumption is selected as the optimization index. For stability issue, the feedback control via adaptive finite-time sliding mode theory is introduced as an additional control component. Finally, the numerical results demonstrate that propellant mass is effectively saved as well as the formation can be tracked accurately with this control strategy proposed in this article.
Arsenic trioxide as a novel anti-glioma drug: a review
Authors: Fang Yi , Zhang Zhen
Published: September 2020

Arsenic trioxide has shown a strong anti-tumor effect with little toxicity when used in the treatment of acute promyelocytic leukemia (APL). An effect on glioma has also been shown. Its mechanisms include regulation of apoptosis and autophagy; promotion of the intracellular production of reactive oxygen species, causing oxidative damage; and inhibition of tumor stem cells. However, glioma cells and tissues from other sources show different responses to arsenic trioxide. Researchers are working to enhance its efficacy in anti-glioma treatments and reducing any adverse reactions. Here, we review recent research on the efficacy and mechanisms of action of arsenic trioxide in the treatment of gliomas to provide guidance for future studies.
Multi-spatial contamination of environmental aquatic matrices with Cryptosporidium: a climate, health, and regulatory framework for the Philippines
Authors: Masangkay Frederick R. , Milanez Giovanni D. , Somsak Voravuth , Kotepui Manas , Tangpong Jitbanjong , Karanis Panagiotis
Published: September 2020

Background

Cryptosporidium is a waterborne global pathogen causing diarrhea primarily in infants and immunocompromised individuals. The Philippines is a tropical country susceptible to the influences of climate change and water crises. To date, the country has no existing epidemiologic data, regulation, or strategy for monitoring Cryptosporidium in freshwater systems. We, therefore, endeavored to provide evidence on the multi-spatial contamination of Cryptosporidium in environmental aquatic matrices using low-cost, user-friendly, and sustainable strategies and submit implications on the presence of Cryptosporidium in freshwater systems in a climate, health, and regulatory framework.

Results

Here, we present the microscopic detection of Cryptosporidium oocysts in low-volume (50 mL) environmental samples of surface water (SW), sediments (BW), and substrate-associated biofilm (SAB) and in 1 L bulk SW investigated by PCR. The multi-spatial distribution of Cryptosporidium oocysts in the low-volume (50 ml) aquatic matrices based on microscopy was highest at 69% (20/29) in SW and lowest at 50% (13/26) in BW. Immunofluorescence technique provided the highest microscopic positivity rate with 59% (17/29), 38% (10/26), and 50% (10/20) detection in SW, BW, and SAB, respectively. The detection and identification of Cryptosporidium in 1 L bulk SW by PCR and sequence analysis was recorded in total at 21% (6/29) in sampling sites where the differential identification of C. parvum, C. hominis, and Cryptosporidium spp. was 7% (2/29), 10% (3/29), and 3% (1/29), respectively.

Conclusions

We report the microscopical and first molecular epidemiologic data of Cryptosporidium from the most significant environmental freshwater systems in the Philippines. The presence of the two main human and animal pathogenic species C. parvum and C. hominis from the largest lakes and major water reservoirs in the country calls for sustainable solutions in safeguarding the quality of freshwater resources in a climate, health, and regulatory approach.
Iranian’s healthcare system challenges during natural disasters: the qualitative case study of Kermanshah earthquake
Authors: Mohammadpour Mohammadtaghi , Sadeghkhani Omid , Bastani Peivand , Ravangard Ramin , Rezaee Rita
Published: September 2020

Background

In order to the significance of lessons learned from the natural disasters for health care systems particularly in developing and under-developed countries, the main purpose of this study was to identify challenges and limitations in light of the earthquake experience in Kermanshah Province.

Methods

The present study was conducted in 2019 as a qualitative research using content analysis method. In this regard, 19 key informants were selected using snowball sampling. To enhance the accuracy of the study, the four validation criteria for qualitative studies in data coding developed by Guba and Lincoln including credibility, transferability, dependability and confirmability were used. Data was analyzed applying Graneheim and Lundman (2004) approach for analyzing the qualitative content of an interview text.

Results

Analysis of the data led to the identification of 2 main themes, 5 sub- themes and 17 main categories. The first main theme was health system oriented challenges containing challenges of medication supply and preparation, structural challenges, challenges in crisis-scene management and challenges of service delivery and the second main theme was non-health system oriented challenges including social and psychosocial challenges.

Conclusion

According to the results, along with health system oriented challenges with the inter-sectoral or intra-sectoral nature, the non-health system oriented challenges the same as social, cultural and psychological factors can be considered as the major challenges of Iran’s healthcare system in the face of crises. This complicated context can shed the light to policy makers that not only attention to the medicine and medical equipment supply chain, manpower preparation and service delivery system can be considered as an emergency, but also careful attention to the structural challenges and crisis-scene management should be planned and considered as a priority. Besides, the policy makers and the local managers should try to plan and act in a contingent situation according to the social and cultural characteristics of the region and the psychological condition and the mental needs of the people.
The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue
Authors: Rezaei Marzieh , Mostafaei Shayan , Aghaei Amir , Hosseini Nayyerehalsadat , Darabi Hassan , Nouri Majid , Etemadi Ashkan , Neill Andrew O’. , Nahand Javid Sadri , Mirzaei Hamed , Donnelly Seamas C. , Doroudian Mohammad , Moghoofei Mohsen
Published: September 2020

Background

Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus.

Methods

In this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases.

Results

HPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR = 3.37, 95% C.I = 1.58–7.22, P = 0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples.

Conclusion

Our study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer.
Supporting patient access to medicines in community palliative care: on-line survey of health professionals’ practice, perceived effectiveness and influencing factors
Authors: Latter Sue , Campling Natasha , Birtwistle Jacqueline , Richardson Alison , Bennett Michael I. , Ewings Sean , Meads David , Santer Miriam
Published: September 2020

Background

Patient access to medicines at home during the last year of life is critical for symptom control, but is thought to be problematic. Little is known about healthcare professionals’ practices in supporting timely medicines access and what influences their effectiveness. The purpose of the study was to evaluate health professionals’ medicines access practices, perceived effectiveness and influencing factors.

Methods

On-line questionnaire survey of health care professionals (General Practitioners, Community Pharmacists, community-based Clinical Nurse Specialists and Community Nurses) delivering end-of-life care in primary and community care settings in England. Quantitative data were analysed using descriptive statistics.

Results

One thousand three hundred twenty-seven responses were received. All health professional groups are engaged in supporting access to prescriptions, using a number of different methods. GPs remain a predominant route for patients to access new prescriptions in working hours. However, nurses and, increasingly, primary care-based pharmacists are also actively contributing. However, only 42% (160) of Clinical Nurse Specialists and 27% (27) of Community Nurses were trained as prescribers. The majority (58% 142) of prescribing nurses and pharmacists did not have access to an electronic prescribing system. Satisfaction with access to shared patient records to facilitate medicines access was low: 39% (507) were either Not At All or only Slightly satisfied. Out-of-hours specialist cover was reported by less than half (49%; 656) and many General Practitioners and pharmacists lacked confidence advising about out-of-hours services. Respondents perceived there would be a significant improvement in pain control if access to medicines was greater. Those with shared records access reported significantly lower pain estimates for their caseload patients.

Conclusions

Action is required to support a greater number of nurses and pharmacists to prescribe end-of-life medicines. Solutions are also required to enable shared access to patient records across health professional groups. Coverage and awareness of out-of-hours services to access medicines needs to be improved.
Comparison of different feedback modalities for the training of procedural skills in Oral and maxillofacial surgery: a blinded, randomized and controlled study
Authors: Seifert Lukas B. , Herrera-Vizcaino Carlos , Herguth Philipp , Sterz Jasmina , Sader Robert
Published: September 2020

Background

The feedback given to students plays an important role in their efficiency related to learning practical skills. In the present study, diverse feedback modalities have been investigated. Our hypothesis is that individualized and unsupervised video feedback can produce a similar learning experience as performing practical skills in an oral and maxillofacial surgery setting with conventional direct expert feedback (control group).

Methods

This prospective, randomized, controlled, and blinded study compared direct expert feedback (DEF), individualized video feedback (IVF) and unsupervised video feedback (UVF). The participants were fourth-year dental students from University Goethe in Frankfurt. The students were assigned to one of the three feedback methods (n = 20 per group) using simple randomization. All participants watched an instruction video for an interdental (‘Ernst’) ligature and periphery venous catheterization. Next, the students were video recorded performing the tasks by themselves (pre-test). Following this, every student received feedback using one of the above-mentioned feedback modalities. The participants then performed the same task again while being video recorded (post-test) to measure the acquired competence. Six weeks later, the students participated in an objective structured clinical examination (OSCE) to evaluate their long-term knowledge retention. All examiners were blinded regarding the students’ instructional approach and their affiliation in terms of the learning group.

Results

For the interdental ligature, we found significant improvements in performance in each feedback modality group between the pre-test and post-test (p < 0.001). UVF had the strongest effect on performance time. The comparison between each group in the post-test showed no significant differences between the three groups.

Conclusion

This study showed that IVF and UVF can be considered an alternative or adjunct to conventional methods (i.e. DEF) when learning procedural skills in oral and maxillofacial surgery. However, DEF showed to be the most effective method of feedback and therefore preferable in teaching.
Arterial calcification at multiple sites: sex-specific cardiovascular risk profiles and mortality risk—the Rotterdam Study
Authors: van der Toorn Janine E. , Rueda-Ochoa Oscar L. , van der Schaft Niels , Vernooij Meike W. , Ikram M. Arfan , Bos Daniel , Kavousi Maryam
Published: September 2020

Background

Evidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex. Yet there is a scarcity of population-based data on aggregated sex-specific cardiovascular risk profiles, instead of single risk factors, and mortality risk according to the location of arteriosclerosis. We assessed sex-specific cardiovascular risk profiles and mortality risk associated with arteriosclerosis.

Methods

From the population-based Rotterdam Study, 2357 participants (mean age 69 years, 53% women) underwent non-contrast computed tomography to quantify calcification, as a proxy for arteriosclerosis, in the coronary arteries (CAC), aortic arch (AAC), extracranial (ECAC) and intracranial carotid arteries (ICAC), vertebrobasilar arteries (VBAC), and aortic valve (AVC). Principal component analysis (PCA) of eight distinct cardiovascular risk factors was performed, separately for women and men, to derive risk profiles based on the shared variance between factors. We used sex-stratified multivariable logistic regression to examine the associations between PCA-derived risk profiles and severe calcification at different locations. We investigated the associations of severe calcification with mortality risk using sex-stratified multivariable Cox regression.

Results

PCA identified three cardiovascular risk profiles in both sexes: (1) anthropometry, glucose, and HDL cholesterol; (2) blood pressure; and (3) smoking and total cholesterol. In women, the strongest associations were found for profile 2 with severe ECAC and ICAC (adjusted OR [95% CI] 1.32 [1.14–1.53]) and for profile 3 with severe at all locations, except AVC. In men, the strongest associations were found for profile 2 with VBAC (1.31 [1.12–1.52]) and profile 3 with severe AAC (1.28 [1.09–1.51]). ECAC and AVC in women and CAC in men showed the strongest, independent associations with cardiovascular mortality (HR [95% CI] 2.11 [1.22–3.66], 2.05 [1.21–3.49], 2.24 [1.21–3.78], respectively).

Conclusions

Our findings further underline the existence of sex- and location-specific differences in the etiology and consequences of arteriosclerosis. Future research should unravel which distinct pathological processes underlie differences in risk profiles for arteriosclerosis.
Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and α-SMA genes expression
Authors: Elbialy Zizy I. , Atiba Ayman , Abdelnaby Aml , Al-Hawary Ibrahim I. , Elsheshtawy Ahmed , El-Serehy Hamed A. , Abdel-Daim Mohamed M. , Fadl Sabreen E. , Assar Doaa H.
Published: September 2020

Background

Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR.

Results

The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis.

Conclusions

The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.
Dual-responsive doxorubicin-loaded nanomicelles for enhanced cancer therapy
Authors: Zhang Xinyi , Zhu Tiantian , Miao Yaxin , Zhou Lu , Zhang Weifang
Published: September 2020

Background

The enhancement of tumor retention and cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform, armed with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS)-induced drug release, is constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle.

Results

The surface charge of this system was converted from negative to positive from pH 7.4 to pH 6.8, which facilitated the cellular uptake. In addition, methionine-based system was dissociated in a ROS-rich and acidic intracellular environment, resulting in the release of DOX and α-tocopheryl succinate (TOS). Then, the exposed TOS segments further induced the generation of ROS, leading to self-amplifiable disassembly of the micelles and drug release.

Conclusions

We confirms efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro. The system exhibits outstanding tumor inhibition capability in vivo, indicating that dual stimuli nano-system has great potential to function as an anticancer drug delivery platform.
Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model
Authors: Wang Benfan , Li Qinyan , Wang Jinyan , Zhao Siting , Nashun Bayaer , Qin Li , Chen Xiaoping
Published: September 2020

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of an effective treatment for this disease results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate of these patients remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model.

Methods

This study aimed to investigate the inhibitory effect of Plasmodium infection on hepatocellular carcinoma in mice, and various techniques for gene expression analysis were used to identify possible signal regulation mechanisms.

Results

We found that Plasmodium infection efficiently inhibited tumor progression and prolonged survival in tumor-bearing mice, which served as a murine implanted hepatoma model. The inhibition of tumor progression by Plasmodium infection was related to suppression of tumor angiogenesis within the tumor tissue and decreased infiltration of tumor-associated macrophages (TAMs). Further study demonstrated that matrix metalloprotease 9 (MMP-9) produced by TAMs contributed to tumor angiogenesis in the tumor tissue and that the parasite-induced reduction in MMP-9 expression in TAMs resulted in the suppression of tumor angiogenesis. A mechanistic study revealed that the Plasmodium-derived hemozoin (HZ) that accumulated in TAMs inhibited IGF-1 signaling through the PI3-K and MAPK signaling pathways and thereby decreased the expression of MMP-9 in TAMs.

Conclusions

Our study suggests that this novel approach of inhibiting tumor angiogenesis by Plasmodium infection is of high importance for the development of new therapies for cancer patients.