bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project
Authors: Ward Mary , Hughes Catherine F. , Strain J. J. , Reilly Rosie , Cunningham Conal , Molloy Anne M. , Horigan Geraldine , Casey Miriam , McCarroll Kevin , O’Kane Maurice , Gibney Michael J. , Flynn Albert , Walton Janette , McNulty Breige A. , McCann Adrian , Kirwan Laura , Scott John M. , McNulty Helene
Published: November 2020

Background

Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension.

Methods

Observational data on 6076 adults of 18–102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008–2012 using standardised methods.

Results

The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34–6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027).

Conclusions

The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.
Salmonella enterica subspecies houtenae as an opportunistic pathogen in a case of meningoencephalomyelitis and bacteriuria in a dog
Authors: Andruzzi Melissa N. , Krath Mary L. , Lawhon Sara D. , Boudreau Beth
Published: November 2020

Background

We report the first case of canine Salmonella meningoencephalomyelitis and second case of canine Salmonella bacteriuria, as well as the first reported case of Salmonella enterica subspecies houtenae in a dog.

Case presentation

Immunosuppressive treatment in a dog for a relapse of steroid-responsive meningitis and arteritis (SRMA) allowed for the opportunistic establishment of a bacteremia with Salmonella enterica subsp. houtenae, ultimately causing meningoencephalomyelitis and subclinical bacteriuria. The bacterial infections were treated with a four-month course of amoxicillin; clinical treatment success was determined by serial negative urine cultures and lack of clinical signs correlated to the meningoencephalomyelitis.

Conclusions

Both the bacteriuria and meningoencephalomyelitis represented opportunistic infections in a dog immunosuppressed for SRMA. The clinical course of this infectious meningoencephalitis emphasizes the importance of differentiating relapse of initial disease from opportunistic infection occurring in a compromised central nervous system. The novel Salmonella species identified in this case acts as a reminder that infectious disease diagnostics should not be curbed by anecdotal prediction of routine pathogenic suspects.
Measuring the contribution of human mobility to malaria persistence
Authors: Gomes Marcelo F. C. , Codeço Cláudia T , Bastos Leonardo S. , Lana Raquel M.
Published: November 2020

Background

To achieve malaria elimination, it is important to determine the role of human mobility in parasite transmission maintenance. The Alto Juruá basin (Brazil) exhibits one of the largest vivax and falciparum malaria prevalence in the Amazon. The goal of this study was to estimate the contribution of human commutes to malaria persistence in this region, using data from an origin-destination survey.

Methods

Data from an origin-destination survey were used to describe the intensity and motivation for commutations between rural and urban areas in two Alto Juruá basin (Brazil) municipalities, Mâncio Lima and Rodrigues Alves. The relative time-person spent in each locality per household was estimated. A logistic model was developed to estimate the effect of commuting on the probability of contracting malaria for a certain residence zone inhabitant commuting to another zone.

Results

The main results suggest that the assessed population is not very mobile. A total of $$96\%$$

96
%

households reported spending over $$90\%$$

90
%

of their annual person-hour in areas within the same residence zone. Study and work were the most prevalent commuting motivations, calculated at $$40.5\%$$

40.5
%

and $$29.5\%$$

29.5
%

respectively. Spending person-hours in urban Rodrigues Alves conferred relative protection to urban Mâncio Lima residents. The opposite effect was observed for those spending time in rural areas of both municipalities.

Conclusion

Residence area is a stronger determinant for contracting malaria than commuting zones in the Alto Juruá region. As these municipalities are a hotspot for Plasmodium transmission, understanding the main local human fluxes is essential for planning control strategies, since the probability of contracting malaria is dependent on the transmission intensity of both the origin and the displacement area. The natural conditions for the circulation of certain pathogens, such as Plasmodium spp., combined with the Amazon human mobility pattern indicate the need for disease control perspective changes. Therefore, intersectoral public policies should become the basis for health mitigation actions.
A microfluidic platform for in situ investigation of biofilm formation and its treatment under controlled conditions
Authors: Straub Hervé , Eberl Leo , Zinn Manfred , Rossi René M. , Maniura-Weber Katharina , Ren Qun
Published: November 2020

Background

Studying bacterial adhesion and early biofilm development is crucial for understanding the physiology of sessile bacteria and forms the basis for the development of novel antimicrobial biomaterials. Microfluidics technologies can be applied in such studies since they permit dynamic real-time analysis and a more precise control of relevant parameters compared to traditional static and flow chamber assays. In this work, we aimed to establish a microfluidic platform that permits real-time observation of bacterial adhesion and biofilm formation under precisely controlled homogeneous laminar flow conditions.

Results

Using Escherichia coli as the model bacterial strain, a microfluidic platform was developed to overcome several limitations of conventional microfluidics such as the lack of spatial control over bacterial colonization and allow label-free observation of bacterial proliferation at single-cell resolution. This platform was applied to demonstrate the influence of culture media on bacterial colonization and the consequent eradication of sessile bacteria by antibiotic. As expected, the nutrient-poor medium (modified M9 minimal medium) was found to promote bacterial adhesion and to enable a higher adhesion rate compared to the nutrient-rich medium (tryptic soy broth rich medium ). However, in rich medium the adhered cells colonized the glass surface faster than those in poor medium under otherwise identical conditions. For the first time, this effect was demonstrated to be caused by a higher retention of newly generated bacteria in the rich medium, rather than faster growth especially during the initial adhesion phase. These results also indicate that higher adhesion rate does not necessarily lead to faster biofilm formation. Antibiotic treatment of sessile bacteria with colistin was further monitored by fluorescence microscopy at single-cell resolution, allowing in situ analysis of killing efficacy of antimicrobials.

Conclusion

The platform established here represents a powerful and versatile tool for studying environmental effects such as medium composition on bacterial adhesion and biofilm formation. Our microfluidic setup shows great potential for the in vitro assessment of new antimicrobials and antifouling agents under flow conditions.
Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea
Authors: Gong Lin-Jing , Wang Xin-Yuan , Gu Wen-Yu , Wu Xu
Published: November 2020

Background

Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic functions under IH condition are still unknown.

Methods

An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay.

Results

In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway.

Conclusions

In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.
Promoting rational antibiotic use in Turkey and among Turkish migrants in Europe – implications of a qualitative study in four countries
Authors: Westerling R. , Daryani A. , Gershuni O. , Czabanowska K. , Brand H. , Erdsiek F. , Aksakal T. , Uner S. , Karadag Caman O. , Ozcebe H. , Brzoska P.
Published: November 2020

Background

Antimicrobial resistance is considered one of the major threats to global health. The emergence of resistant microorganisms is a consequence of irrational use of antibiotics. In Turkey, the consumption of antibiotics is relatively high and antibiotics are among the most commonly used drugs. However, Turkey has adopted new, more restrictive policies and regulations on antibiotics. In addition, Turkish migrants to EU countries, such as Germany, the Netherlands and Sweden, may encounter health systems that promote a more restrictive and rational antibiotic use.

The objective of this paper was to explore the variation in implemented policies related to rational antibiotic use that citizens in Turkey and Turkish migrants in Germany, the Netherlands and Sweden are subjected to and to discuss the implications for the promotion of rational antibiotic use.

Data were collected through focus groups and individual interviews with citizens, physicians and pharmacists in the four countries. In total, 130 respondents were interviewed. Content analysis was used.

Results

Three relevant themes were identified: Implementation of regulations and recommendations, Access to antibiotics and Need for health communication. Irrational use of antibiotics was reported mainly in Turkey. While it had become less likely to get antibiotics without a prescription, non-prescribed antibiotics remained a problem in Turkey. In the three EU countries, there were also alternative ways of getting antibiotics. Low levels of knowledge about the rational antibiotic use were reported in Turkey, while there were several sources of information on this in the EU countries. Communication with and trust in physicians were considered to be important. There were also system barriers, such as lacking opportunities for physicians to manage care in accordance with current evidence in Turkey and factors limiting access to care in EU countries.

Conclusions

Several fields of importance for promoting rational antibiotic use were identified. There is a need for harmonisation of health-related regulations and policy programmes. Antibiotics should only be available with a prescription. Programmes for rational antibiotic use should be implemented on a broad scale, in medical care, at pharmacies and in the population. Methods for health communication and patient-centred care should be further developed and implemented in this field.
The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
Authors: Sánchez-Blázquez Pilar , Cortés-Montero Elsa , Rodríguez-Muñoz María , Merlos Manuel , Garzón-Niño Javier
Published: November 2020

The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout mice. In contrast to σ1R deficient mice, σ2R knockout mice developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the σ1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and β-endorphin increased in σ1R−/− mice and diminished in σ2R−/− mice. The analgesic effect of morphine was increased in σ2R−/− mice by treatment with S1RA. However, σ2R−/− mice and wild-type mice exhibited comparable antinociceptive responses to the delta receptor agonist [D-Pen2,5]-encephalin (DPDPE), the cannabinoid type 1 receptor agonist WIN55,212-2 and the α2-adrenergic receptor agonist clonidine. Therefore, while σR1 inhibits and σ2R facilitates MOR-mediated analgesia these receptors exchange their roles when regulating neuropathic pain perception. Our study may help identify new pharmacological targets for diminishing pain perception and improving opioid detoxification therapies.
CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients
Authors: Kimbung Siker , Inasu Maria , Stålhammar Tor , Nodin Björn , Elebro Karin , Tryggvadottir Helga , Ygland Rödström Maria , Jirström Karin , Isaksson Karolin , Jernström Helena , Borgquist Signe
Published: November 2020

Background

27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear.

Methods

Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis.

Results

CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HRadjusted = 1.93, 95%CI = 1.26–2.97, P = 0.003; breast cancer-specific survival (BCSS), HRadjusted = 2.33, 95%CI = 1.28–4.23, P = 0.006] and among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 1.99, 95%CI = 1.24–3.21, P = 0.004; BCSS, HRadjusted = 2.78, 95%CI = 1.41–5.51, P = 0.003].

Among all patients in cohort 2 (median follow-up of 7.0 years), CYP27A1 expression was significantly associated with shorter OS and RFS in univariable analyses across the full follow-up period. However after adjusting for tumor characteristics and treatments, the association with survival after 5 years from diagnosis was non-significant among all patients [OS, HRadjusted = 1.08, 95%CI = 0.05–2.35, P = 0.83 and RFS, HRadjusted = 1.22, 95%CI = 0.68–2.18, P = 0.50] as well as among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 0.46 95% CI = 0.11–1.98, P = 0.30 and RFS, HRadjusted = 0.97 95% CI = 0.44–2.10, P = 0.93].

Conclusion

CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.
Multiple insecticide resistance target sites in adult field strains of An. gambiae (s.l.) from southeastern Senegal
Authors: Diouf El hadji , Niang El hadji Amadou , Samb Badara , Diagne Cheikh Tidiane , Diouf Mbaye , Konaté Abdoulaye , Dia Ibrahima , Faye Ousmane , Konaté Lassana
Published: November 2020

Background

High coverage of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of vector control strategy in Senegal where insecticide resistance by the target vectors species is a great of concern. This study explores insecticide susceptibility profile and target-site mutations mechanisms within the Anophelesgambiae complex in southeastern Senegal.

Methods

Larvae of Anopheles spp. were collected in two sites from southeastern Senegal Kedougou and Wassadou/Badi in October and November 2014, and reared until adult emergence. Wild F0 adult mosquitoes were morphologically identified to species. Susceptibility of 3–5-day-old An. gambiae (s.l.) samples to 11 insecticides belonging to the four insecticide classes was assessed using the WHO insecticide susceptibility bioassays. Tested samples were identified using molecular techniques and insecticide resistance target-site mutations (kdr, ace-1 and rdl) were determined.

Results

A total of 3742 An.gambiae (s.l.) were exposed to insecticides (2439 from Kedougou and 1303 from Wassadou-Badi). Tests with pyrethroid insecticides and DDT showed high level of resistance in both Kedougou and Wassadou/Badi. Resistance to pirimiphos-methyl and malathion was not detected while resistance to bendoicarb and fenitrothion was confirmed in Kedougou. Of the 745 specimens of An.gambiae (s.l.) genotyped, An.gambiae (s.s.) (71.6%) was the predominant species, followed by An.arabiensis (21.7%), An.coluzzii (6.3%) and hybrids (An. gambiae (s.s.)/An.coluzzii; 0.4%). All target site mutations investigated (Vgsc-1014F, Vgsc-1014S, Ace-1 and Rdl) were found at different frequencies in the species of the Anophelesgambiae complex. Vgsc-1014F mutation was more frequent in An.gambiae (s.s.) and An.coluzzii than An.arabiensis. Vgsc-1014S was present in An.gambiae (s.l.) populations in Wassadou but not in Kedougou. Ace-1 and rdl mutations were more frequent in An.gambiae (s.s.) in comparison to An.arabiensis and An.coluzzii.

Conclusions

Resistance to all the four insecticide classes tested was detected in southeastern Senegal as well as all target site mutations investigated were found. Data will be used by the national Malaria Control Programme.
Human toxoplasmosis in Mozambique: gaps in knowledge and research opportunities
Authors: Manuel Leonardo , Santos-Gomes Gabriela , Noormahomed Emilia V.
Published: November 2020

Toxoplasmosis is a parasitic zoonotic disease caused byToxoplasma gondiithat afflicts humans worldwide and wild and domestic warm-blooded animals. In immunocompetent individuals, the acute phase of infection presents transient low or mild symptoms that remain unnoticed. In immunocompromised patients,T. gondiiis a life-threatening opportunistic infection, which can result from the reactivation of latent infection or primary infection. Moreover, congenital toxoplasmosis, which results from the transplacental passage of tachyzoites into the fetus during a pregnant primary infection, can lead to miscarriage, stillbirth, or ocular and neurologic disease, and neurocognitive deficits in the newborns. Thus, the present review aims to address the current knowledge ofT. gondiiinfection and toxoplasmosis in Africa and especially in Mozambique, stressing the importance of identifying risk factors and promote awareness among the health care providers and population, assessing the gaps in knowledge and define research priorities. In Mozambique, and in general in southern African countries, clinical disease and epidemiological data have not yet been entirely addressed in addition to the implications ofT. gondiiinfection in immunocompetent individuals, in pregnant women, and its relation with neuropsychiatric disorders. The main gaps in knowledge in Mozambique include lack of awareness of the disease, lack of diagnostic methods in health facilities, lack of genetic data, and lack of control strategies.

Graphical Abstract
A spatio-temporal agent-based approach for modeling the spread of zoonotic cutaneous leishmaniasis in northeast Iran
Authors: Tabasi Mohammad , Alesheikh Ali Asghar , Sofizadeh Aioub , Saeidian Bahram , Pradhan Biswajeet , AlAmri Abdullah
Published: November 2020

Background

Zoonotic cutaneous leishmaniasis (ZCL) is a neglected tropical disease worldwide, especially the Middle East. Although previous works attempt to model the ZCL spread using various environmental factors, the interactions between vectors (Phlebotomus papatasi), reservoir hosts, humans, and the environment can affect its spread. Considering all of these aspects is not a trivial task.

Methods

An agent-based model (ABM) is a relatively new approach that provides a framework for analyzing the heterogeneity of the interactions, along with biological and environmental factors in such complex systems. The objective of this research is to design and develop an ABM that uses Geospatial Information System (GIS) capabilities, biological behaviors of vectors and reservoir hosts, and an improved Susceptible-Exposed-Infected-Recovered (SEIR) epidemic model to explore the spread of ZCL. Various scenarios were implemented to analyze the future ZCL spreads in different parts of Maraveh Tappeh County, in the northeast region of Golestan Province in northeastern Iran, with alternative socio-ecological conditions.

Results

The results confirmed that the spread of the disease arises principally in the desert, low altitude areas, and riverside population centers. The outcomes also showed that the restricting movement of humans reduces the severity of the transmission. Moreover, the spread of ZCL has a particular temporal pattern, since the most prevalent cases occurred in the fall. The evaluation test also showed the similarity between the results and the reported spatiotemporal trends.

Conclusions

This study demonstrates the capability and efficiency of ABM to model and predict the spread of ZCL. The results of the presented approach can be considered as a guide for public health management and controlling the vector population.
An integrative knowledge graph for rare diseases, derived from the Genetic and Rare Diseases Information Center (GARD)
Authors: Zhu Qian , Nguyen Dac-Trung , Grishagin Ivan , Southall Noel , Sid Eric , Pariser Anne
Published: November 2020

Background

The Genetic and Rare Diseases (GARD) Information Center was established by the National Institutes of Health (NIH) to provide freely accessible consumer health information on over 6500 genetic and rare diseases. As the cumulative scientific understanding and underlying evidence for these diseases have expanded over time, existing practices to generate knowledge from these publications and resources have not been able to keep pace. Through determining the applicability of computational approaches to enhance or replace manual curation tasks, we aim to both improve the sustainability and relevance of consumer health information, but also to develop a foundational database, from which translational science researchers may start to unravel disease characteristics that are vital to the research process.

Results

We developed a meta-ontology based integrative knowledge graph for rare diseases in Neo4j. This integrative knowledge graph includes a total of 3,819,623 nodes and 84,223,681 relations from 34 different biomedical data resources, including curated drug and rare disease associations. Semi-automatic mappings were generated for 2154 unique FDA orphan designations to 776 unique GARD diseases, and 3322 unique FDA designated drugs to UNII, as well as 180,363 associations between drug and indication from Inxight Drugs, which were integrated into the knowledge graph. We conducted four case studies to demonstrate the capabilities of this integrative knowledge graph in accelerating the curation of scientific understanding on rare diseases through the generation of disease mappings/profiles and pathogenesis associations.

Conclusions

By integrating well-established database resources, we developed an integrative knowledge graph containing a large volume of biomedical and research data. Demonstration of several immediate use cases and limitations of this process reveal both the potential feasibility and barriers of utilizing graph-based resources and approaches to support their use by providers of consumer health information, such as GARD, that may struggle with the needs of maintaining knowledge reliant on an evolving and growing evidence-base. Finally, the successful integration of these datasets into a freely accessible knowledge graph highlights an opportunity to take a translational science view on the field of rare diseases by enabling researchers to identify disease characteristics, which may play a role in the translation of discover across different research domains.
Palladium-catalyzed Decarbonylative Cyanation of Acyl Fluorides and Chlorides
Authors: Sakurai Shun , Tobisu Mamoru
Published: November 2020

Decarbonylative cyanation of acyl fluorides can be catalyzed by a Pd/Xantphos system. This protocol is also applicable to the conversion of acyl chlorides.
Ελλάδα, διακύβευμα μνήμης και λήθης: περηφάνιας, τραύματος και ντροπής
Authors: Μαντόγλου Άννα
Published: November 2020

The present study aims at exploring the role of age, gender, intra-national identification and political positioning in the recollection of the representational voluntary (=memory) and involuntary (=oblivion) historical-national past of Greece in conditions of pride, trauma and shame. In this experimental field study participated 254 men and women of different ages, who, after having read a text of a concise presentation of the Greek past -cutting off events either of pride, or of trauma and shame- noted three events that they wish to remember and three events that they wish to forget for ever from the Greek history. The interesting finding of the present study is associated with the emergence of four voluntary and involuntary organizing principles of thought about the historical past of Greece: a) a powerful and ruling memory, b) a regal memory of pride, c) a traumatical oblivion and, d) ashameful oblivion. The above ways of thinking are consensus and independent of the age, gender, political positioning and participants’ intra-national identification, as well. Any possible differences in perceiving the historical past concern individual variations rather than national collective concepts. This result is in line with the idea of a superior, urgent or regal national identity, which is constructed against other national identities and strategically «select» -institutionally and communicatively- to remember a positive, glorious, ruling and regal past, which makes ingroup members feel proud, while it decides not to communicate its traumatical (remedy oblivion) and, mainly, the shameful past (wormwood oblivion).
Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis
Authors: Mutiawati Endang , Syahrul Syahrul , Fahriani Marhami , Fajar Jonny Karunia , Mamada Sukamto S. , Maliga Helnida Anggun , Samsu Nur , Ilmawan Muhammad , Purnamasari Yeni , Asmiragani Annisa Ayu , Ichsan Ichsan , Emran Talha Bin , Rabaan Ali A. , Masyeni Sri , Nainu Firzan , Harapan Harapan
Published: November 2020

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19.

Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases.

Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04.

Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache  emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms.

PROSPERO registration: CRD42020210332 (28/09/2020)
Histological and clinical evaluation of wound healing in pressure ulcers: a novel animal model
Authors: Sami Diana G , Abdellatif Ahmed
Published: November 2020

Objective:

Pressure ulcers (PUs) are a major healthcare problem, commonly associated with older people, patients who are bedbound and patients with diabetes. The impact of PUs can decrease patients' quality of life, and lead to high morbidity and mortality rates. In this study, we aimed to describe a novel PU model that simulates pressure ulcers in humans to provide a research tool for new drug testing.

Method:

Diabetes was induced using streptozocin in 75 adult Sprague Dawley rats. To create the PU, skin was sandwiched between two magnets, one of them implanted below the panniculus carnosus muscle and the other above the skin. The model was tested on nondiabetic rats and diabetic rats, each with pressure ulcers, compared to nondiabetic rats with excisional wounds.

Results:

Results showed that the PU model in diabetic (p-value<0.000001) and non-diabetic rats (p-value<0.05) exhibited significantly delayed healing (no healing over 21 days) compared with the excisional wound that was completely healed by day 21.

Conclusion:

Diabetic rats showed significant changes in intact skin compared with non-diabetic rats, as well as a significant delay in the healing process compared with the non-diabetic group. By effectively impairing the skin contraction otherwise seen in the rats, and thereby delaying healing and making it similar to that seen in hard-to-heal PUs in humans, this model provides an effective tool for wound healing research.
All-dielectric bulk isotropic double-negative metamaterials
Authors: Zharov Alexander , Fierro Vanessa , Celzard Alain
Published: November 2020

We propose the design of all-dielectric isotropic micro- or nanoparticles which, when used as structural elements of a metamaterial, can simultaneously provide negative effective electric permittivity and negative magnetic permeability. The particles comprise three dielectric layers with specially adjusted parameters that ensure simultaneous excitation of the electric and magnetic Mie dipole modes. The layer parameters were found by Mie scattering analysis and then verified by the simulations, which confirmed the double-negative behavior of the metamaterial at up to visible light frequencies. The isotropy of such particles suggests the possibility of using them in a double-negative liquid metamaterial.
Viscosity imaging using heterodyne holographic spectral analysis of Brownian nanorod rotation
Authors: Gentner Clémence , Kuszelewicz Robert , Berto Pascal , Khelfa Haithem , Tessier Gilles
Published: November 2020

Under polarized illumination, non-spherical objects display anisotropic scattering, and their rotation induces a blinking. We present a method based on heterodyne holography to measure images of the Brownian rotation frequencies of gold nanorods over a broad frequency range (0-10 MHz). Since Brownian rotation often occurs on shorter space and time scales than translation, it can provide local viscosity measurements, and high resolution imaging is possible. Here, we demonstrate that viscosity contrast imaging is revealed by heterodyne imaging at one or several investigation frequencies. After calibration, a frequency scan can give access to quantitative viscosity imaging.
Mode control through anti-Hermitian coupling in regular-polygonal microcavities with non-uniform gain and loss
Authors: Yang Yue-De , Hao You-Zeng , Ma Chun-Guang , Shen Zheng-Zheng , Xiao Jin-Long , Huang Yong-Zhen
Published: November 2020

We theoretically and numerically study optical modes in regular-polygonal microcavities with non-uniform gain and loss, where high quality (Q) whispering-gallery-like modes typically appear as superscar states. High Q superscar modes can be described by the propagating plane waves in an effective rectangle formed by unfolding the periodic orbits and exhibit regular and predictable spatial field distributions and transverse-mode spectra. With non-uniform gain and loss, anti-Hermitian coupling between the transverse modes with close frequencies occurs according to the mode coupling theory, which results in novel mode properties such as modified mode spectra and field patterns, and the appearance of exceptional points. Numerical simulation results are in good agreement with the theoretical analyses, and such analyses are also suitable for other kinds of high Q microcavities with non-uniform gain and loss. These results will be highly useful for studying non-Hermitian physics in optical microcavities and advancing the practical applications of microcavity devices.
Hyperspectral two-photon excitation microscopy using visible wavelength
Authors: Kubo Toshiki , Temma Kenta , Smith Nicholas I. , Lu Kai , Matsuda Tomoki , Nagai Takeharu , Fujita Katsumasa
Published: November 2020

We demonstrate hyperspectral imaging by visible-wavelength two-photon excitation microscopy using line illumination and slit-confocal detection. A femtosecond pulsed laser light at 530 nm was used for the simultaneous excitation of fluorescent proteins with different emission wavelengths. The use of line illumination enabled efficient detection of hyperspectral images and achieved simultaneous detection of three fluorescence spectra in the observation of living HeLa cells with an exposure time of 1 ms per line, which is equivalent to about 2 µs per pixel in point scanning, with 160 data points per spectrum. On combining linear spectral unmixing techniques, localization of fluorescent probes in the cells was achieved. A theoretical investigation of the imaging property revealed high-depth discrimination property attained through the combination of nonlinear excitation and slit detection.
Ten simple rules for writing a paper about scientific software
Authors: Romano Joseph D. , Moore Jason H.
Published: November 2020

Papers describing software are an important part of computational fields of scientific research. These “software papers” are unique in a number of ways, and they require special consideration to improve their impact on the scientific community and their efficacy at conveying important information. Here, we discuss 10 specific rules for writing software papers, covering some of the different scenarios and publication types that might be encountered, and important questions from which all computational researchers would benefit by asking along the way.
Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer
Authors: Dong Zhexu , Dai Lei , Zhang Yong , Fang Chao , Shi Gang , Chen Ye , Li Junshu , Wang Qin , Fu Jiamei , Yu Yan , Wang Wenshuang , Cheng Lin , Liu Yi , Lin Yi , Wang Yuan , Wang Qingnan , Wang Huiling , Zhang Hantao , Zhang Yujing , Su Xiaolan , Zhang Shuang , Wang Feng , Qiu Meng , Zhou Zongguang , Deng Hongxin
Published: November 2020

Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC.
The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition
Authors: Gonzalez Curto Gloria , Der Vartanian Audrey , Frarma Youcef El-Mokhtar , Manceau Line , Baldi Lorenzo , Prisco Selene , Elarouci Nabila , Causeret Frédéric , Korenkov Daniil , Rigolet Muriel , Aurade Frédéric , De Reynies Aurélien , Contremoulins Vincent , Relaix Frédéric , Faklaris Orestis , Briscoe James , Gilardi-Hebenstreit Pascale , Ribes Vanessa
Published: November 2020

The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformationin vivo. The reason for this is unclear. To address this, we developed anin ovomodel to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS.
A haplotype-phased genome of wheat stripe rust pathogen Puccinia striiformis f. sp. tritici, race PST-130 from the Western USA
Authors: Vasquez-Gross Hans , Kaur Sukhwinder , Epstein Lynn , Dubcovsky Jorge
Published: November 2020

More virulent and aggressive races of Puccinia striiformis f. sp. tritici (Pst), the pathogen causing wheat stripe rust, have been spreading around the world since 2000 causing large grain yield losses. A better understanding of the genome and genetic diversity of these new Pst races will be useful to develop new strategies to ameliorate these losses. In this study, we generated an improved genome assembly of a post-2000 virulent race from the Western USA designated as PST-130. We implemented a haplotype phasing strategy using the diploid-aware assembler, Falcon-Unzip and new long-read technology from PacBio to phase the two genomes of this dikaryotic organism. The combination of these new technologies resulted in an improved PST-130 assembly with only 151 contigs (85.4 Mb, N50 of 1.44 Mb), and a complementary assembly (haplotigs) with 458 contigs (65.9 Mb, N50 of 0.235 Mb, PRJNA650506). This new assembly improved gene predictions resulting in 228 more predicted complete genes than in the initial Illumina assembly (29,178 contigs, N50 of 5 kb). The alignment of the non-repetitive primary and haplotig contigs revealed and average of 5.22 SNP/kb, with 39.1% showing <2 SNP/kb and 15.9% >10 SNP/kb. This large divergent regions may represent introgressions of chromosome segments from more divergent Pst races in regions where a complete sexual cycle and recombination are possible. We hypothesize that some of the divergent regions in PST-130 may be related to the European “Warrior” race PST-DK0911 because this genome is more similar to PST-130 (3.18 SNP/kb) than to the older European race PST-104E (3.75 SNP/kb). Complete phasing of additional Pst genomes or sequencing individual nuclei will facilitate the tracing of the haploid genomes introduced by the new Pst races into local populations.
Species-dependent variation of the gut bacterial communities across Trypanosoma cruzi insect vectors
Authors: Arias-Giraldo Luisa M. , Muñoz Marina , Hernández Carolina , Herrera Giovanny , Velásquez-Ortiz Natalia , Cantillo-Barraza Omar , Urbano Plutarco , Ramírez Juan David
Published: November 2020

Triatomines (Hemiptera: Reduviidae) are the insect vectors of Trypanosoma cruzi, the causative agent of Chagas disease. The gut bacterial communities affect the development of T. cruzi inside the vector, making the characterization of its composition important in the understanding of infection development. We collected 54 triatomine bugs corresponding to four genera in different departments of Colombia. DNA extraction and PCR were performed to evaluate T. cruzi presence and to determine the discrete typing unit (DTU) of the parasite. PCR products of the bacterial 16S rRNA gene were pooled and sequenced. Resulting reads were denoised and QIIME 2 was used for the identification of amplicon sequence variants (ASVs). Diversity (alpha and beta diversity) and richness analyses, Circos plots, and principal component analysis (PCA) were also performed. The overall T. cruzi infection frequency was 75.9%, with TcI being the predominant DTU. Approximately 500,000 sequences were analyzed and 27 bacterial phyla were identified. The most abundant phyla were Proteobacteria (33.9%), Actinobacteria (32.4%), Firmicutes (19.6%), and Bacteroidetes (7.6%), which together accounted for over 90% of the gut communities identified in this study. Genera were identified for these main bacterial phyla, revealing the presence of important bacteria such as Rhodococcus, Serratia, and Wolbachia. The composition of bacterial phyla in the gut of the insects was significantly different between triatomine species, whereas no significant difference was seen between the state of T. cruzi infection. We suggest further investigation with the evaluation of additional variables and a larger sample size. To our knowledge, this study is the first characterization of the gut bacterial structure of the main triatomine genera in Colombia.
Bone mineral density in Palestinian patients with end-stage renal disease and the related clinical and biochemical factors: Cross-sectional study
Authors: Nazzal Zaher , Khader Shahd , Zawyani Hiba , Abdallah Mazen , Sawalmeh Osama , Hamdan Zakaria
Published: November 2020

Introduction

End-Stage Renal Disease (ESRD) is the ultimate result of chronic kidney disease (CKD). In Palestine, the prevalence of ESRD was 240.3 PMP which is comparable with the nearby countries. Accelerated bone loss among ESRD patients is attributed to abnormal bone turn over that leads to osteoporosis and osteopenia. The risk of fractures is increased four-fold in men and women on hemodialysis, which explains the importance of assessing the bone mineral density among these population. The goals of this study were to find the prevalence of osteoporosis in ESRD patients as determined by bone mineral density (BMD) at different sites and to determine whether BMD correlates with many other clinical parameters.

Methods

A cross-sectional study of 194 ESRD patients were recruited from the dialysis unit in An-Najah National University Hospital, Nablus, Palestine. The patients were on regular hemodialysis or peritoneal dialysis. BMD was measured at the lumbar spine and the hip using the dual-energy X-Ray absorptiometry (DEXA) and the value is expressed as T-score. The data were analyzed using SPSS, version 26. The relationship between BMD and the clinical and biochemical parameters among the ESRD patients was assessed.

Results

We found that 42.8% of ESRD patient had osteoporosis and 40.2% had osteopenia. There were significantly higher proportions of osteoporosis and osteopenia among patients >60 years of age (p<0.005). Patients with osteoporosis and osteopenia had significantly higher serum levels of PTH (792.9 and 469.7) (p<0.05). BMD decreases as the duration of dialysis (39.0 months Vs. 56.8 months), (p<0.05). We found no significant difference between patients on hemodialysis or peritoneal dialysis.

Conclusion

This study showed that Palestinian patients with ESRD have low BMD at the hip and spine. The observed high serum level of PTH was associated with low BMD. Those patients should be closely monitored especially those with more than one risk factor. Moreover, more attention should be paid for these category of patients to decrease the incidence of falling down and the resulting fractures that might lead to mortality and morbidity.