bluuebunny/crossref_metadata_2025 huggingface dataset:
Obtaining district-level health estimates using geographically masked location from Demographic and Health Survey data
Authors: Wilson Emily , Hazel Elizabeth , Park Lois , Carter Emily , Moulton Lawrence H. , Heidkamp Rebecca , Perin Jamie
Published: February 2020

Background

Demographic and Health Survey (DHS) data are an important source of maternal, newborn, and child health as well as nutrition information for low- and middle-income countries. However, DHSs are often unavailable at the administrative unit that is most interesting or useful for program planning. In addition, the location of DHS survey clusters are geomasked within 10 km, and prior to 2009, may have crossed district boundaries. We aim to use DHS surveyed information with these geomasked coordinates to estimate district assignments for use in health program planning and evaluation.

Methods

We developed three methods to assign a district to a geomasked survey cluster in two DHS surveys from Malawi: 2000 and 2004. Method A assigns districts of origin in proportion to the likelihood that results from repeated simulated geomasking, allowing more than one possible district of origin. Method B assigns a single district of origin which contains the greatest proportion of simulated geomasked survey clusters. Method C maps the geomasked survey cluster’s location to a district polygon. We used these method assignments to estimate a selection of commonly used coverage indicators for each district. We compared the district coverage estimates, confidence intervals, and concordance correlation coefficients, by each of the methods, to those which used validated district assignments in 2004, and we looked at coverage change from 2000 to 2004.

Results

The methods we tested each approximated the validated estimates in 2004 by confidence interval comparison and concordance correlation coefficient. Estimated agreement for method A was between .14 and .98, for method B the estimated agreement was between .97 and .99, and for method C the agreement ranged from .93 to .99 when compared with the validated district assignments. Therefore, we recommend the protocol which is the simplest to implement—method C—overlaying geomasked survey cluster within district polygon.

Conclusions

Using geomasked survey clusters from DHSs to assign districts provided district level coverage rates similar to those using the validated surveyed locations. This method may be applied to data sources where survey cluster centroids are available and where district level estimates are needed for program implementation and evaluation in low- and middle-income settings. This method is of special interest to those using DHSs to study spatiotemporal trends as it allows for the utilization of historic DHS data where geomasking hinders the generation of reliable subnational estimates of health in areas smaller than the first-order administrative unit (ADM1).
DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma
Authors: Lu Chenfei , Wei Yutian , Wang Xiefeng , Zhang Zhuoran , Yin Jianxing , Li Wentao , Chen Lijiu , Lyu Xiao , Shi Zhumei , Yan Wei , You Yongping
Published: February 2020

Background

Accumulating evidence shows that long noncoding RNAs (lncRNAs) are important regulator molecules involved in diverse biological processes. Acquired drug resistance is a major challenge in the clinical treatment of glioblastoma (GBM), and lncRNAs have been shown to play a role in chemotherapy resistance. However, the underlying mechanisms by which lncRNA mediates TMZ resistance in GBM remain poorly characterized.

Methods

Quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization assays were used to detect small nucleolar RNA host gene 12 (SNHG12) levels in TMZ-sensitive and TMZ-resistant GBM cells and tissues. The effects of SNHG12 on TMZ resistance were investigated through in vitro assays (western blots, colony formation assays, flow cytometry assays, and TUNEL assays). The mechanism mediating the high expression of SNHG12 in TMZ-resistant cells and its relationships with miR-129-5p, mitogen-activated protein kinase 1 (MAPK1), and E2F transcription factor 7 (E2F7) were determined by bioinformatic analysis, bisulfite amplicon sequencing, methylation-specific PCR, dual luciferase reporter assays, chromatin immunoprecipitation assays, RNA immunoprecipitation assays, immunofluorescence, qRT-PCR, and western blot. For in vivo experiments, an intracranial xenograft tumor mouse model was used to investigate SNHG12 function.

Results

SNHG12 was upregulated in TMZ-resistant cells and tissues. Overexpression of SNHG12 led to the development of acquired TMZ resistance, while knockdown of SNHG12 restored TMZ sensitivity. An abnormally low level of DNA methylation was detected within the promoter region of SNHG12, and loss of DNA methylation made this region more accessible to the Sp1 transcription factor (SP1); this indicated that methylation and SP1 work together to regulate SNHG12 expression. In the cytoplasm, SNHG12 served as a sponge for miR-129-5p, leading to upregulation of MAPK1 and E2F7 and endowing the GBM cells with TMZ resistance. Disinhibition of MAPK1 regulated TMZ-induced cell apoptosis and the G1/S cell cycle transition by activating the MAPK/ERK pathway, while E2F7 dysregulation was primarily associated with G1/S cell cycle transition. Clinically, SNHG12 overexpression was associated with poor survival of GBM patients undergoing TMZ treatment.

Conclusion

Our results suggest that SNHG12 could serve as a promising therapeutic target to surmount TMZ resistance, thereby improving the clinical efficacy of TMZ chemotherapy.
Review of published evidence on knowledge translation capacity, practice and support among researchers and research institutions in low- and middle-income countries
Authors: Murunga Violet Ibukayo , Oronje Rose Ndakala , Bates Imelda , Tagoe Nadia , Pulford Justin
Published: February 2020

Background

Knowledge translation (KT) is a dynamic and iterative process that includes synthesis, dissemination, exchange and ethically sound application of knowledge to yield beneficial outcomes for society. Effective KT requires researchers to play an active role in promoting evidence uptake. This paper presents a systematised review of evidence on low- and middle-income country (LMIC) researchers’ KT capacity, practice and interventions for enhancing their KT practice (support) with the aim of identifying gaps and informing future research and interventions.

Methods

An electronic search for peer-reviewed publications focusing on LMIC researchers’ KT capacity, practice and support across all academic fields, authored in English and from the earliest records available to February 2019, was conducted using PubMed and Scopus. Selected studies were appraised using the Mixed Methods Appraisal Tool, data pertaining to publication characteristics and study design extracted, and an a priori thematic analysis of reported research findings completed.

Results

The search resulted in 334 screened articles, of which 66 met the inclusion criteria. Most (n = 43) of the articles presented original research findings, 22 were commentaries and 1 was a structured review; 47 articles reported on researchers’ KT practice, 12 assessed the KT capacity of researchers or academic/research institutions and 9 reported on KT support for researchers. More than half (59%) of the articles focused on sub-Saharan Africa and the majority (91%) on health research. Most of the primary studies used the case study design (41%). The findings suggest that LMIC researchers rarely conduct KT and face a range of barriers at individual and institutional levels that limit their KT practice, including inadequate KT knowledge and skills, particularly for communicating research and interacting with research end-users, insufficient funding, and inadequate institutional guidelines, structures and incentives promoting KT practice. Furthermore, the evidence-base on effective interventions for enhancing LMIC researchers' KT practice is insufficient and largely of weak quality.

Conclusions

More high-quality research on researchers’ KT capacity, practice and effective KT capacity strengthening interventions is needed. Study designs that extend beyond case studies and descriptive studies are recommended, including better designed evaluation studies, e.g. use of realist approaches, pragmatic trials, impact evaluations, implementation research and participatory action research.
Inflammation, infection, and allergy of upper airways: new insights from national and real-world studies
Authors: Varricchio Attilio , La Mantia Ignazio , Brunese Francesco Paolo , Ciprandi Giorgio
Published: February 2020

The upper airways (UA) should be considered as a functional unit. Current functional anatomy divides URT in three, mutually dependent, “junction boxes”: i) the ostio-meatal complex (OMC), ii) the spheno-ethmoidal recess (SER), and iii) the rhinopharynx (RP). Correct ventilation and effective mucociliary clearance of these sites significantly affect the healthy physiology of the entire respiratory system. The OMC, SER, and RP obstruction is the first pathogenic step in the inflammatory/infectious cascade of UA disorders. The inflammation of the respiratory mucosa is the main pathogenic factor for airway obstruction. Moreover, bacterial biofilm (a strategy modality of bacterial survival) is an important local cause of systemic antibiotic ineffectiveness, recurrent infections, and antibiotic resistance. Health microbiota guarantees UA wellness; on the contrary, dysbiosis promotes and worsens UA infections. Allergy, namely type 2 inflammation, is a common cause of UA obstruction such as promoting in turn infections. Fiberoptic endoscopy is a mandatory diagnostic tool in clinical practice. Nasal cytology, mainly concerning flow cytometry, allows defining rhinitis phenotypes so allowing a precision medicine approach. Several conventional therapeutic approaches are available, but efficacy and safety should be ever properly considered before the prescription. Also, complementary medicine plays a fruitful role in the management of UA diseases. National and real-world studies are reported and discussed as they may be useful in daily clinical practice.
Direct-to-Implant Extracellular Matrix Hammock-based Breast Reconstruction; Prepectoral or Subpectoral?
Authors: Dyrberg Diana L. , Gunnarsson Gudjon L. , Bille Camilla , Sørensen Jens A. , Thomsen Jørn B.
Published: February 2020

Background

Skin-sparing mastectomy followed by immediate implant-based breast reconstruction is a commonly used treatment for breast cancer. However, when placing the implant in a subpectoral pocket, a high incidence of breast animation deformity (BAD) has been reported. Besides the nuisance that BAD can cause, lifting of the pectoralis major muscle (PMM) can result in a more extended postoperative recovery period. When placing the implant solely prepectorally leaving the PMM undisturbed, the incidence and severity of BAD might be mitigated. However, new challenges may occur because of thinner skin cover.

Methods/design

A prospective, multi-centre, randomised controlled trial will be carried out with the primary aim of assessing and comparing the incidence and degree of BAD in women having a direct-to-implant breast reconstruction with either a prepectorally or a subpectorally placed implant. The secondary outcomes are shoulder and arm function, quality of life, aesthetic evaluation, length of stay, complications, need for surgical corrections, and development of capsular contracture. A total of 70 included patients will be followed under admittance and at clinical check-ups 3 months and 1 year after surgery.

Discussion

To our knowledge, this trial is the first randomised controlled trial evaluating and comparing subpectoral and prepectoral implant placement when performing direct-to-implant breast reconstruction following skin-sparing mastectomy. The results will hopefully provide us with a broader knowledge of the outcomes of immediate breast reconstruction, making better preoperative planning possible in the future by providing our patients with a more objective information.

Trial registration

ClinicalTrials.gov, ID: NCT03143335. Prospectively registered on 8 May 2017.
Night shift work, short sleep and obesity
Authors: Brum Maria Carlota Borba , Dantas Filho Fábio Fernandes , Schnorr Claúdia Carolina , Bertoletti Otávio Azevedo , Bottega Gustavo Borchardt , da Costa Rodrigues Ticiana
Published: February 2020

Background

Obesity is associated with increased general mortality and comorbidities, it is multifactorial and some evidence has shown that sleep duration and shift work may be implicated in its pathogenesis.

Objectives

The aim of this study was to evaluate the association between shift work, quality of life and obesity among healthcare workers of a Brazilian University Hospital.

Methods

A cross-sectional study was performed from April 2013 to December 2014 with 200 workers of a University Hospital. Sociodemographic data were evaluated and BREF WHOQOL was used for quality of life. The physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ), Chronotypes and daily sleep preference were investigated using Munich Chronotype Questionnaire (MCTQ). Venous blood was collected after 12-h of fasting for laboratory tests.

Results

In this sample, the night shift workers had higher income and were older compared to day shift workers. Night shift workers sleep less hours, had higher weight, body mass index and abdominal circumference when compared to the day shift workers. Night shift workers had almost 3 times higher association with abdominal obesity independent of age and gender, than day shift workers. MCTQ parameters showed that night shift workers had lower sleep duration during working days and also during free days, associated with a higher level of social jetlag. Social jetlag had an association with obesity. We found no difference for quality of life between shifts.

Conclusions

Night work was a risk factor for abdominal obesity, social jetlag was higher in night shift workers and it was associated with presence of obesity.
Oropouche infection a neglected arbovirus in patients with acute febrile illness from the Peruvian coast
Authors: Martins-Luna Johanna , del Valle-Mendoza Juana , Silva-Caso Wilmer , Sandoval Isabel , del Valle Luis J. , Palomares-Reyes Carlos , Carrillo-Ng Hugo , Peña-Tuesta Isaac , Aguilar-Luis Miguel Angel
Published: February 2020

Objective

To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016.

Results

OROV was detected in 26.4% (131/496) of serum samples from patients with AFI. Co-infections with Dengue virus (7.3%), Zika virus (1.8%) and Chikungunya (0.2%) were observed. The most common clinical symptoms reported among the patients with OROV infections were headache 85.5% (112/131), myalgia 80.9% (106/131), arthralgia 72.5% (95/131) and loss of appetite 67.9% (89/131). Headache and myalgia were predominant in all age groups. Both OROV infections and co-infections were more frequent in May, June and July corresponding to the dry season of the region.
Links between self-injury and suicidality in autism
Authors: Moseley R. L. , Gregory N. J. , Smith P. , Allison C. , Baron-Cohen S.
Published: February 2020

Background

Autistic individuals without intellectual disability are at heightened risk of self-injury, and appear to engage in it for similar reasons as non-autistic people. A wide divergence of autistic perspectives on self-injury, including those who frame it as a helpful coping mechanism, motivate investigating the link between self-injury, suicide ideation, and attempts which has been reported in typically developing individuals.

Method

One hundred three autistic participants completed the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), the Suicide Behaviors Questionnaire (SBQ-R), and the Interpersonal Social Evaluation List (ISEL-12) across two online studies. Logistic regression was conducted to predict self-harming status via responses to questions on suicidality, and to predict whether certain self-injurious behaviors, including cutting, were especially associated with suicide ideation and attempts. Non-parametric correlation analysis examined relationships between suicide ideation/attempts and other variables that might characterize self-harmers especially at risk of suicidality. These included perceived access to social support, purposes or reasons for self-injury, the number of different self-injurious behaviors engaged in, the duration and lifetime incidence of self-injury, and the individual’s feelings about their self-injury.

Results

While self-injuring status was significantly predicted by responses to a question on suicide ideation and attempts, there was no relationship between suicide ideation/attempts and a participant’s personal feelings about their self-injury. The method of cutting was also predicted by suicide ideation and attempts, though other methods common in autistic people were at borderline significance. Use of self-injury for the regulation of low-energy emotional states like depression, for self-punishment or deterrence from suicide, and for sensory stimulation, was associated with suicide ideation and attempts, as was the number of self-injurious behaviors engaged in. There was no significant relationship between suicide ideation/attempts and the duration and lifetime incidence of self-injury or social support.

Conclusions

These preliminary data suggest that while individuals might frame their self-injury as a positive or neutral thing, there remains a concerning relationship between self-injury and suicidality which exists regardless of individual feelings on self-injury. This is consistent with the theoretical perspective that self-injury can be a “gateway” through which individuals acquire capability for lethal suicidal behaviors. The data highlight that particular methods (cutting) and reasons for self-injury may be of significant concern, but this information, which might be of extreme value for clinicians, requires further investigation and validation.
PEDV enters cells through clathrin-, caveolae-, and lipid raft-mediated endocytosis and traffics via the endo-/lysosome pathway
Authors: Wei Xiaona , She Gaoli , Wu Tingting , Xue Chunyi , Cao Yongchang
Published: February 2020

With the emergence of highly pathogenic variant strains, porcine epidemic diarrhea virus (PEDV) has led to significant economic loss in the global swine industry. Many studies have described how coronaviruses enter cells, but information on PEDV invasion strategies remains insufficient. Given that the differences in gene sequences and pathogenicity between classical and mutant strains of PEDV may lead to diverse invasion mechanisms, this study focused on the cellular entry pathways and cellular transport of the PEDV GI and GII subtype strains in Vero cells and IPEC-J2 cells. We first characterized the kinetics of PEDV entry into cells and found that the highest invasion rate of PEDV was approximately 33% in the IPEC-J2 cells and approximately 100% in the Vero cells. To clarify the specific endocytic pathways, systematic research methods were used and showed that PEDV enters cells via the clathrin- and caveolae-mediated endocytosis pathways, in which dynamin II, clathrin heavy chain, Eps15, cholesterol, and caveolin-1 were indispensably involved. In addition, lipid raft extraction assay showed that PEDV can also enter cells through lipid raft-mediated endocytosis. To investigate the trafficking of internalized PEDV, we found that PEDV entry into cells relied on low pH and internalized virions reached lysosomes through the early endosome–late endosome–lysosome pathway. The results concretely revealed the entry mechanisms of PEDV and provided an insightful theoretical basis for the further understanding of PEDV pathogenesis and guidance for new targets of antiviral drugs.
Approximate controllability of a semilinear impulsive stochastic system with nonlocal conditions and Poisson jumps
Authors: Anguraj A. , Ravikumar K. , Baleanu Dumitru
Published: February 2020

The objective of this paper is to investigate the approximate controllability of a semilinear impulsive stochastic system with nonlocal conditions and Poisson jumps in a Hilbert space. Nonlocal initial condition is a generalization of the classical initial condition and is motivated by physical phenomena. The results are obtained by using Sadovskii’s fixed point theorem. Finally, an example is provided to illustrate the effectiveness of the obtained result.
Do fluorescent agents alter the mechanical strength of orthodontic adhesives? An in vitro and clinical study
Authors: Rossato Paulo Henrique , Kaneshima Edmilson Nobumito , Domingues Fábio , Fernandes Thais Maria Freire , Berger Sandrine Bittencourt , Oltramari Paula Vanessa Pedron
Published: February 2020

Background

Fluorescent agents are added to orthodontic adhesives with the aim of making them visible under ultraviolet (UV) light, which ensures the complete, safe removal of remnants after orthodontic treatment. However, it is necessary to evaluate if the mechanical strength of these materials is maintained. Therefore, this study evaluated whether the addition of fluorescent agents influences the shear bond strength and clinical performance of a UV light-sensitive adhesive system.

Methods

This study consisted of two stages: (1) In vitro phase: 40 human teeth were selected, divided at random into 2 groups (n = 20), according to the adhesive system used: UV group—adhesive with fluorescent agent, and control group—conventional adhesive. A shear bond strength test was performed using a DL 2000 universal testing machine, at a speed of 0.5 mm/min. The accessories were removed and an evaluation of the Adhesive Remnant Index (ARI) was carried out. (2) Clinical phase: 8 patients were selected and had their appliances bonded using the split-mouth design (160 teeth) with the same tested adhesive systems (UV, n = 80; control, n = 80). The patients were monitored for bonding failure for a period of 24 months. Statistical analysis was performed using the Independent t test, chi-squared tests, and Mann-Whitney test, at a level of significance of 5% and confidence interval of 95%.

Results

Regarding the in vitro phase, the shear bond strength test yielded similar results in the two groups (p > 0.05) and the ARI showed statistically significant differences between the groups with a score of 1 being the most frequent ARI for both groups (70%). In addition, there was no clinical difference in terms of bonding failure between the groups (p > 0.05).

Conclusion

The addition of fluorescent elements does not alter the mechanical strength and performance of the orthodontic adhesive and represents a viable alternative for clinical application.
Recycling performance of graphene oxide-chitosan hybrid hydrogels for removal of cationic and anionic dyes
Authors: Vo Thi Sinh , Vo Tran Thi Bich Chau , Suk Ji Won , Kim Kyunghoon
Published: February 2020

Water is one of the most important resources for human survival and development. Efficient wastewater treatment techniques such as coagulation, filtration, ozonation, and reverse osmosis have been studied to remove toxic materials from water. Implementation of adsorption columns has been proven to be an efficient wastewater treatment method, particularly for the removal of organic contaminants. In this study, we present the preparation of an eco-friendly graphene oxide–chitosan (GC) composite hydrogel column (GCCHC) and its application as a broad-spectrum adsorbent for wastewater treatment. The GCCHC shows a high removal capacity towards different contaminants including both cationic dyes [methylene blue (MB) and rhodamine B (RhB)] and anionic dyes [methylene orange (MO) and congo red (CR)]. Moreover, the samples can be regenerated and recycled without loss of contaminant removal capacity over successive adsorption and washing cycles.
Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity
Authors: Tamborino Giulia , De Saint-Hubert Marijke , Struelens Lara , Seoane Dayana C. , Ruigrok Eline A. M. , Aerts An , van Cappellen Wiggert A. , de Jong Marion , Konijnenberg Mark W. , Nonnekens Julie
Published: February 2020

Background

Survival and linear-quadratic model fitting parameters implemented in treatment planning for targeted radionuclide therapy depend on accurate cellular dosimetry. Therefore, we have built a refined cellular dosimetry model for [177Lu]Lu-DOTA-[Tyr3]octreotate (177Lu-DOTATATE) in vitro experiments, accounting for specific cell morphologies and sub-cellular radioactivity distributions.

Methods

Time activity curves were measured and modeled for medium, membrane-bound, and internalized activity fractions over 6 days. Clonogenic survival assays were performed at various added activities (0.1–2.5 MBq/ml). 3D microscopy images (stained for cytoplasm, nucleus, and Golgi) were used as reference for developing polygonal meshes (PM) in 3DsMax to accurately render the cellular and organelle geometry. Absorbed doses to the nucleus per decay (S values) were calculated for 3 cellular morphologies: spheres (MIRDcell), truncated cone-shaped constructive solid geometry (CSG within MCNP6.1), and realistic PM models, using Geant4-10.03. The geometrical set-up of the clonogenic survival assays was modeled, including dynamic changes in proliferation, proximity variations, and cell death. The absorbed dose to the nucleus by the radioactive source cell (self-dose) and surrounding source cells (cross-dose) was calculated applying the MIRD formalism. Finally, the correlation between absorbed dose and survival fraction was fitted using a linear dose-response curve (high α/β or fast sub-lethal damage repair half-life) for different assumptions, related to cellular shape and localization of the internalized fraction of activity.

Results

The cross-dose, depending on cell proximity and colony formation, is a minor (15%) contributor to the total absorbed dose. Cellular volume (inverse exponential trend), shape modeling (up to 65%), and internalized source localization (up to + 149% comparing cytoplasm to Golgi) significantly influence the self-dose to nucleus. The absorbed dose delivered to the nucleus during a clonogenic survival assay is 3-fold higher with MIRDcell compared to the polygonal mesh structures. Our cellular dosimetry model indicates that 177Lu-DOTATATE treatment might be more effective than suggested by average spherical cell dosimetry, predicting a lower absorbed dose for the same cellular survival. Dose-rate effects and heterogeneous dose delivery might account for differences in dose-response compared to x-ray irradiation.

Conclusion

Our results demonstrate that modeling of cellular and organelle geometry is crucial to perform accurate in vitro dosimetry.
The effect of educational intervention on healthcare providers’ knowledge, attitude, & practice towards antimicrobial stewardship program at, National Liver Institute, Egypt
Authors: Tahoon Marwa Ali , Khalil Magdy Mohammed , Hammad Essam , Morad Wesam Saber , awad Samah Mohammed , Ezzat Sameera
Published: February 2020

Background

Inappropriate use of antimicrobials results in rapid emergence of resistance, selection pressure on resistant microorganisms, adverse reactions, and treatment failures. An effective approach to improving antimicrobial use in healthcare settings is a structured antimicrobial management program known as antimicrobial stewardship (AMS). Education and training is considered a backbone element of AMS program .This study aimed to evaluate the impact of educational program on the knowledge, attitude, and practice (KAP) of healthcare providers (HCPs) towards antimicrobial stewardship before and after the educational program at the surgery department and surgical ICU, National Liver Institute hospital (NLI), Egypt.

Results

Among the 69 invited HCPs, 48 attended the educational program sessions with attendance response rate about 70%. Regarding pre-educational KAP score of the respondents’ physicians and pharmacists, 39.3% of them had good knowledge score, 85.7% of them had positive attitude, &and 31.8% of physicians had good practice score; however, 100% of the pharmacists had poor practice. Regarding the respondents’ nurse, the pre-education mean score of knowledge was 13.3/20, attitude 14.8/16, and practice 9.3/14. Following educational program, there was a significant improvement in knowledge, attitude, and practice of the respondents’ health care providers (P < 0.001); on the contrary, there was no significant improvement in the practice of pharmacists (P > 0.05).

Conclusion

The implemented educational program was successful in improving the knowledge, attitude, and practice of HCPs; therefore, continuous efforts are needed to implement more educational programs to increase awareness towards AMS among HCPs.
A viscoplastic model of creep in shale
Authors: Haghighat Ehsan , Rassouli Fatemeh S. , Zoback Mark D. , Juanes Ruben
Published: February 2020

We have developed a viscoplastic model that reproduces creep behavior and inelastic deformation of rock during loading-unloading cycles. We use a Perzyna-type description of viscous deformation that derives from a maximization of dissipated energy during plastic flow, in combination with a modified Cam-clay model of plastic deformation. The plastic flow model is of the associative type, and the viscous deformation is proportional to the ratio of driving stress and a material viscosity. Our model does not rely on any explicit time parameters; therefore, it is well-suited for standard and cyclic loading of materials. We validate the model with recent triaxial experiments of time-dependent deformation in clay-rich (Haynesville Formation) and carbonate-rich (Eagle Ford Formation) shale samples, and we find that the deformation during complex, multiscale loading-unloading paths can be reproduced accurately. We elucidate the role and physical meaning of each model parameter, and we infer their value from a gradient-descent minimization of the error between simulation and experimental data. This inference points to the large, and often unrecognized, uncertainty in the preconsolidation stress, which is key to reproducing the observed hysteresis in material deformation.
The structure of mania: An overview of factorial analysis studies
Authors: Martino Diego J. , Valerio Marina P. , Parker Gordon
Published: February 2020

Background.

Operational definitions of mania are based on expert consensus rather than empirical data. The aim of this study is to identify the key domains of mania, as well as the relevance of the different signs and symptoms of this clinical construct.

Methods.

A review of latent factor models studies in manic patients was performed. Before extraction, a harmonization of signs and symptoms of mania and depression was performed in order to reduce the variability between individual studies.

Results.

We identified 12 studies fulfilling the inclusion criteria and comprising 3039 subjects. Hyperactivity was the clinical item that most likely appeared in the first factor, usually covariating with other core features of mania, such as increased speech, thought disorder, and elevated mood. Depressive–anxious features and irritability–aggressive behavior constituted two other salient dimensions of mania. Altered sleep was frequently an isolated factor, while psychosis appeared related to grandiosity, lack of insight and poor judgment.

Conclusions.

Our results confirm the multidimensional nature of mania. Hyperactivity, increased speech, and thought disorder appear as core features of the clinical construct. The mood experience could be heterogeneous, depending on the co-occurrence of euphoric (elevated mood) and dysphoric (irritability and depressive mood) emotions of varying intensity. Results are also discussed regarding their relationship with other constitutive elements of bipolar disorder, such as mixed and depressive states.
“Not a Figure in the Past”
Authors: May Chelsie
Published: February 2020

This article uses the racial divisions encouraged by European Zionism in early-state Israel among European and Middle Eastern Jews as a point of departure to explore racialization and gendering among Iraqi Jewish women during the years 1941–51 from a sociopolitical standpoint. Restricting itself to politics given this standpoint, a study of Jewish women’s participation in the illegal Zionist and Communist movements of Iraq reveals that racializations, rather than a single racialization, occurred—a racial reality no other scholarship provides for Iraq’s Jewish community. Because Jewish women participating in these movements contended with patriarchal organizing structures, it is necessary to set apart the racial logics palpable in their articulations. This argument rests on primary sources in the form of three memoirs from the Iraqi Jewish women Tikva Agassi, Shoshana Levy, and Shoshana Almoslino, as well as Zionist women’s letters, a biographical dictionary of Communist participation, and British Foreign Office documents.
Sexual cell cycle initiation is regulated by CDK19 and CYC9 in Tetrahymena thermophila
Authors: Ma Yang , Yan Guanxiong , Han Xiaojie , Zhang Jing , Xiong Jie , Miao Wei
Published: February 2020

To investigate the mechanisms underlying initiation of the sexual cell cycle in eukaryotes, we have focused on cyclins and cyclin-dependent kinases (CDKs) in the well-studied model ciliate, Tetrahymena thermophila. We identified two genes, CDK19 and CYC9, which are highly co-expressed with the mating-associated factors MTA, MTB and HAP2. Both CDK19 and CYC9 were found to be essential for mating in T. thermophila. Subcellular localization experiments suggested that these proteins are located at the oral area, including the conjugation junction area, and that CDK19 or CYC9 knockout prevents mating. We found that CDK19 and CYC9 form a complex, and also identified several additional subunits, which may have regulatory or constitutive functions. RNA sequencing analyses and cytological experiments showed that mating is abnormal in both ΔCDK19 and ΔCYC9, mainly at the entry to the co-stimulation stage. These results indicate that the CDK19–CYC9 complex initiates the sexual cell cycle in T. thermophila.
The Sts1 nuclear import adapter uses a non-canonical bipartite nuclear localization signal and is directly degraded by the proteasome
Authors: Budenholzer Lauren , Breckel Carolyn , Hickey Christopher M. , Hochstrasser Mark
Published: February 2020

The proteasome is an essential regulator of protein homeostasis. In yeast and many mammalian cells, proteasomes strongly concentrate in the nucleus. Sts1 from the yeast Saccharomyces cerevisiae is an essential protein linked to proteasome nuclear localization. Here, we show that Sts1 contains a non-canonical bipartite nuclear localization signal (NLS) important for both nuclear localization of Sts1 itself and the proteasome. Sts1 binds the karyopherin-α import receptor (Srp1) stoichiometrically, and this requires the NLS. The NLS is essential for viability, and over-expressed Sts1 with an inactive NLS interferes with 26S proteasome import. The Sts1–Srp1 complex binds preferentially to fully assembled 26S proteasomes in vitro. Sts1 is itself a rapidly degraded 26S proteasome substrate; notably, this degradation is ubiquitin independent in cells and in vitro and is inhibited by Srp1 binding. Mutants of Sts1 are stabilized, suggesting that its degradation is tightly linked to its role in localizing proteasomes to the nucleus. We propose that Sts1 normally promotes nuclear import of fully assembled proteasomes and is directly degraded by proteasomes without prior ubiquitylation following karyopherin-α release in the nucleus.
ORP3 phosphorylation regulates phosphatidylinositol 4-phosphate and Ca2+ dynamics at plasma membrane–ER contact sites
Authors: Gulyás Gergő , Sohn Mira , Kim Yeun Ju , Várnai Péter , Balla Tamas
Published: February 2020

Oxysterol-binding protein (OSBP)-related proteins (ORPs) mediate non-vesicular lipid transfer between intracellular membranes. Phosphoinositide (PI) gradients play important roles in the ability of OSBP and some ORPs to transfer cholesterol and phosphatidylserine between the endoplasmic reticulum (ER) and other organelle membranes. Here, we show that plasma membrane (PM) association of ORP3 (also known as OSBPL3), a poorly characterized ORP family member, is triggered by protein kinase C (PKC) activation, especially when combined with Ca2+ increases, and is determined by both PI(4,5)P2 and PI4P. After activation, ORP3 efficiently extracts PI4P and to a lesser extent phosphatidic acid from the PM, and slightly increases PM cholesterol levels. Full activation of ORP3 resulted in decreased PM PI4P levels and inhibited Ca2+ entry via the store-operated Ca2+ entry pathway. The C-terminal region of ORP3 that follows the strictly defined lipid transfer domain was found to be critical for the proper localization and function of the protein.
Pumping the brakes on RAS – negative regulators and death effectors of RAS
Authors: Harrell Stewart Desmond R. , Clark Geoffrey J.
Published: February 2020

Mutations that activate the RAS oncoproteins are common in cancer. However, aberrant upregulation of RAS activity often occurs in the absence of activating mutations in the RAS genes due to defects in RAS regulators. It is now clear that loss of function of Ras GTPase-activating proteins (RasGAPs) is common in tumors, and germline mutations in certain RasGAP genes are responsible for some clinical syndromes. Although regulation of RAS is central to their activity, RasGAPs exhibit great diversity in their binding partners and therefore affect signaling by multiple mechanisms that are independent of RAS. The RASSF family of tumor suppressors are essential to RAS-induced apoptosis and senescence, and constitute a barrier to RAS-mediated transformation. Suppression of RASSF protein expression can also promote the development of excessive RAS signaling by uncoupling RAS from growth inhibitory pathways. Here, we will examine how these effectors of RAS contribute to tumor suppression, through both RAS-dependent and RAS-independent mechanisms.
Swimming in unsteady water flows: is turning in a changing flow an energetically expensive endeavor for fish?
Authors: Soerensen Mathias S. , Steffensen John F. , Bushnell Peter G. , Korsmeyer Keith E.
Published: February 2020

Unsteady, dynamic flow regimes commonly found in shallow marine ecosystems such as coral reefs pose an energetic challenge for mobile organisms that typically depend on station holding for fitness-related activities. The majority of experimental studies, however, have measured energetic costs of locomotion at steady speeds, with only a few studies measuring the effects of oscillatory flows. In this study, we used a bidirectional swimming respirometer to create six oscillatory water flow regimes consisting of three frequency and amplitude combinations for both unidirectional and bidirectional oscillatory flows. Using the goldring surgeonfish, Ctenochaetus strigosus, a pectoral-fin (labriform) swimmer, we quantified the net cost of swimming (swimming metabolic rate minus standard metabolic rate) associated with station-holding under these various conditions. We determined that the swimming costs of station-holding in the bidirectional flow regime increased by 2-fold compared with costs based on swimming over the same range velocities at steady speeds. Furthermore, as we found minimal differences in energetic costs associated with station-holding in the unidirectional, oscillating-flow compared with that predicted from steady swimming costs, we conclude that the added acceleration costs are minimal, while the act of turning is an energetically expensive endeavor for this reef fish species.
Dynamic changes in cytoskeleton proteins of olfactory ensheathing cells induced by radiofrequency electromagnetic fields
Authors: Grasso Rosaria , Pellitteri Rosalia , Caravella Santi A. , Musumeci Francesco , Raciti Giuseppina , Scordino Agata , Sposito Giovanni , Triglia Antonio , Campisi Agata
Published: February 2020

Several evidences have suggested the ability of radio frequency electromagnetic fields to influence biological systems, even if the action mechanisms are not well understood. Only few data have reported about the effect of radio frequency electromagnetic fields on self-renewal of neural progenitor cells. A particular glial type, which shows characteristics of stem cells, are Olfactory Ensheathing Cells (OECs). Herein, we assessed the non-thermal effects induced on Olfactory Ensheathing Cells through radio frequency electromagnetic fields changing the envelope of the electromagnetic wave. Primary OEC cultures were exposed to continuous or amplitude modulated 900 MHz electromagnetic fields, in far field condition and at different exposition times (10, 15, 20 min). The expression of Olfactory Ensheathing Cells markers (S-100 and Nestin), cytoskeletal proteins (GFAP and Vimentin), apoptotic pathway activation by Caspase-3 cleavage and cell viability were evaluated.

Our results highlight that 20 min of exposure to continuous or amplitude modulated 900 MHz electromagnetic fields induced a different and significant decrease in cell viability. In addition, according to the electromagnetic fields waveform, diverse dynamic changes in the expression of the analysed markers in Olfactory Ensheathing Cells and activation of apoptotic pathway were observed. The data suggest that radio frequency electromagnetic fields might play different and important role in the self-renewal of OEC stem cells, which are involved in nervous system repair.
Dynamism of Supramolecular DNA/RNA Nanoarchitectonics: From Interlocked Structures to Molecular Machines
Authors: Liang Xingguo , Li Lin , Tang Jiaxuan , Komiyama Makoto , Ariga Katsuhiko
Published: February 2020

In order to fabricate highly sophisticated nanostructures, various research fields must be fused into one unified concept. In recently emerging nanoarchitectonics, nanotechnology is combined with materials science, supramolecular self-assembly, and biological science to construct functional materials from nanoscale units. This review article focuses on dynamic features of nanoarchitectonics. In terms of this concept, molecular machines as one of the forefront research targets are produced from DNA and RNA. Fundamental designs of DNA/RNA molecular machines are first described with an emphasis on the significant roles of interlocked structures such as rings, catenanes, rotaxanes, and connectors of these parts. In the latter part, DNA/RNA molecular machines including shuttles, molecular transporters, walkers, nano pumps, robots, amplifiers, and logic gates are presented, together with related functions such as sensitive sensing and catalysis regulation. The exemplified strategy should be universally useful to fabricate various functional materials which fulfill social demands at the present as well as in the future.
DOMENICO TREZZINI E ALTRI MAESTRI TICINESI A PIETROBURGO E TALLINN ALL’INIZIO DEL SETTECENTO
Authors: Androsov Sergey
Published: February 2020

The activities and work of architect Domenico Trezzini (1670–1734),and the masters that arrived in Russia with him, have been researchedfor a long time, and many contentions have been concretised ordisproven at various times. This article focuses on the issue of howmasters from a single area – Ticino, Switzerland – ended up creatingimportant fortifications, palaces and churches in the Russian Empireduring the reign of Peter the Great at the beginning of 18th century.The author describes the movement of Trezzini and the Ticino mastersfrom Copenhagen to Moscow as reported in various historical sourcesand the works of Danish and Russian researchers.
The mystery of the Votic inessive
Authors: Markus Elena , Rozhanskiy Fedor
Published: February 2020

This paper analyzes the morphophonological structure of the inessive singular forms in Liivtšülä-Luuditsa Votic. There are no fluent speakers of this variety; the research is based on the materials recorded in 2003–2016. The inessive singular forms demonstrate variation of the weak and strong grade stems, which is very untypical for a case form. In all other morphological cases, the distribution of weak and strong stems is very stable. The variation in the inessive stem is observed both in the examples from published sources on the Votic language, and in our field materials. The acoustic research has confirmed the variation. Additionally, in the strong grade stem we find a shorter geminate stop or affricate compared to other strong grade forms (in the paper, the inessive singular is compared to the inessive plural and partitive singular). We consider several hypotheses that could explain the variation and the shorter geminate. The conducted experiments do not confirm the role of the word structure as the primary factor defining the geminate length. We suggest that both the variation of stems and the shorter geminate might result from language contact. In the neighbouring Ingrian varieties, the inessive is built from the weak grade stem. Since all the last fluent speakers of Votic knew Ingrian to some extent, the Votic and Ingrian patterns might have mixed. It is probable that originally the variation was triggered by some other factors, and the increasing role of the language contact turned it into a dominant factor in the course of the 20th century.

Kokkuvõte. Elena Markus ja Fedor Rozhanskiy: Vadja inessiivi mõistatus. Artiklis analüüsitakse ainsuse inessiivi morfofonoloogilist struktuuri Liivtšülä- Luuditsa vadja keeles. Selle keele soravaid kõnelejaid enam pole; uurimus põhineb 2003–2016 lindistatud materjalidel. Ainsuse inessiivi vormid näitavad nõrga- ja tugevaastmeliste tüvede varieerumist, mis on ühe käändevormi kohta väga ebatüüpiline. Kõikide teiste morfoloogiliste käänete puhul on nõrkade ja tugevate tüvede jaotus korrapärane. Inessiivi tüve varieerumist vaadeldakse nii varem avaldatud vadja keele allikates kui ka meie välitööde materjalides. Akustiline analüüs kinnitab tüvede varieerumist. Lisaks esineb tugevas astmes inessiivis lühem geminaatkonsonant või afrikaat kui teistes tugeva astme vormides (artiklis võrreldakse ainsuse inessiivi mitmuse inessiivi ja ainsuse partitiiviga). Me esitame mõned hüpoteesid, mis võiksid sellist varieerumist ja lühemat geminaati selgitada. Tehtud eksperimendid ei kinnita sõnastruktuuri rolli esmase faktorina geminaadi pikkuse defineerimisel. Me arvame, et nii tüvede varieerumine kui ka lühike geminaat võivad olla tingitud keelekontaktist. Naabruses olevates isuri murretes moodustatakse inessiiv nõrgaastmelisest tüvest. Kuna kõik viimased head vadja keele kõnelejad oskasid mingil määral isuri keelt, võisid vadja ja isuri keel olla segunenud. On tõenäoline, et algselt oli varieerumine tingitud teistest faktoritest, kuid keelekontakti suurenenud roll kujunes 20. sajandi jooksul domineerivaks.
Novel origin of cerebral phaeohyphomycosis: A case report
Authors: Daniele Christopher , Ferguson Miriam , Phillips Cooper , Lachmansingh Jinesh , Nichols Jacob , Fisher John , Holstead Brady , Opoku Akwasi
Published: February 2020

Cerebral phaeohyphomycosis is infection of the central nervous system (CNS) caused by dematiaceous fungi. The most common mechanisms of infection are by direct extension from the paranasal sinuses or by hematogenous spread. The mortality rate is high and ranges from 50%–79% in the limited studies on this infection. Our case describes a young man without any preexisting disease who acquired cerebral phaeohyphomycosis following nasal inhalation of garden mushrooms. Despite aggressive treatment, he ultimately died due to this severe infection. Our case report discusses our treatment approach and reviews the literature on this deadly infection.
Keywords: fungal infection, cerebral abscess, Bipolaris, phaeohyphomycosis