bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature is a common climatic descriptor of lachryphagous activity period in Phortica variegata (Diptera: Drosophilidae) from multiple geographical locations
Authors: Pombi Marco , Marino Valentina , Jaenike John , Graham-Brown John , Bernardini Ilaria , Lia Riccardo P. , Beugnet Fred , Miro Guadalupe , Otranto Domenico
Published: February 2020

Background

The drosophilidPhortica variegatais known as vector ofThelazia callipaeda, the oriental eyeworm native to Asia that has become an emergent zoonotic agent in several European regions. Unlike almost all other arthropod vectors of pathogens, onlyP. variegatamales feed of lachrymal secretions of animals, ingesting first-stage larvae (L1) of the worm living in the orbital cavities of the host, and allowing with the same behaviour the introduction of infective L3. Despite the increased detection ofT. callipaedain many European countries, information about the length of the lachryphagous activity period ofP. variegataand a deep knowledge of the environmental and climatic variables involved are still limited.

Methods

We herein present the results of a multicentre study involving five sites from four different countries (Italy, Spain, UK and USA) where canine thelaziosis is endemic and/or where it has already been ascertained the presence ofP. variegata. Field data have been obtained on a fortnightly basis from mid-April to the end of November 2018 from a contemporary standardized sampling (same sampling effort and time of collection in all sites) of lachryphagous flies collected around the eyes of a human bait using an entomological net. These data have been associated to data collection of local climatic variables (day length, temperature, wind speed, barometric pressure and relative humidity).

Results

Overall, a total of 4862P. variegataflies (4637 males and 224 females) were collected, with high differences in densities among the different sampling sites. Significant positive correlations were found betweenP. variegatamale density and temperature and wind speed, while negative correlations were observed for barometric pressure and relative humidity. However, the above significant differences are confirmed in each sampling site separately only for the temperature.

Conclusions

This multicentre study highlights that temperature is the major common environmental driver in describing the lachryphagous activity ofP. variegatain Europe and USA and, therefore, the transmission risk of thelaziosis.
First report on aberrant Ascaris suum infection in a dog, China
Authors: Xie Yue , Liu Yunjian , Gu Xiaobin , Zhou Xuan , Peng Xuerong , He Ran , Guo Hongrui , Zuo Zhicai , Yang Guangyou
Published: February 2020

An aberrantAscaris suuminfection in a domestic dog in China in 2019 is described for the first time. This pathogen is a common roundworm of pigs with few reported cases in domestic animals. Our findings suggest a wider infection range with a possible transmission ofA. suumto domestic animals that interact with humans.
Plasma concentrations of vitamin A and E and risk of dysglycemia in first-trimester pregnant Saudi women
Authors: Kutbi Hebah Alawi , Hammouda Sahar Ali
Published: February 2020

Background

Existing evidence suggest that low concentrations of vitamin A and E may have a contribution to the development of diabetes complications; however, data regarding the status of vitamin A and E among individuals with prediabetes are lacking. This study aimed to examine the association of plasma concentrations of vitamin A and E with the glycemic control status among first trimester pregnant Saudi women.

Methods

In this cross-sectional study, 1102 first trimester pregnant Saudi women were recruited from antenatal clinics. Sociodemographic and anthropometric information were collected, and laboratory analyses of blood glycated hemoglobin (A1C) and plasma vitamins A and E were performed. Subjects were classified as normoglycemic, prediabetic, or undiagnosed diabetic. Multinomial regression models adjusted for age estimated the adjusted odds ratios (aORs) and [95% confidence intervals (CIs)].

Results

Among the sample, 78.8% (n = 868) had normal glycemic control, while 19.1% (n = 211) had prediabetes and 2.1% (n = 23) had undiagnosed diabetes. Plasma concentrations of vitamin A and E of prediabetic participants were at a level midway between that of normoglycemic and diabetic participants (p < 0.01). Compared to subjects with normoglycemic status, those with higher concentrations of vitamin A and E had lower odds of being prediabetic (aOR = 0.27 [0.21–0.35] and aOR = 0.95 [0.94–0.96], respectively) or diabetic (aOR = 0.18 [0.13–0.24] and aOR = 0.93 [0.92–0.94], respectively).

Conclusions

Our findings indicate a possible contribution of vitamins A and E to the progression of prediabetes to diabetes. Future longitudinal studies are needed to elucidate the association between the antioxidant status and dysglycemia. Clinicians should monitor the glycemic and the antioxidant status closely and provide dietary guidance where needed.
Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis
Authors: Morata-Tarifa Cynthia , Macías-Sánchez María del Mar , Gutiérrez-Pizarraya Antonio , Sanchez-Pernaute Rosario
Published: February 2020

Background

Graft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed for the prevention and the treatment of GvHD in patients undergoing HSCT. Unfortunately, previous studies reported conflicting results regarding the prophylactic and therapeutic effects of MSC for GvHD. Consequently, we carried out a meta-analysis to clarify whether MSC administration can improve the dismal outcome of these patients.

Methods

We carried out a systematic review and selected studies (2004–2019) reporting data about the administration of allogeneic MSC for the prevention (n = 654 patients) or treatment of acute (n = 943 patients) or chronic (n = 76 patients) GvHD after HSCT. Our primary outcome was overall survival at the last follow-up. The secondary outcomes were the response and development of GvHD. Subgroup analyses included age, MSC dose, first infusion day after HSCT, number of organs and organ-specific involvement, acute GvHD grade (I–IV), and chronic GvHD grade (limited or extensive).

Results

Patients infused with MSC for GvHD prophylaxis showed a 17% increased overall survival (95% CI, 1.02–1.33) and a reduced incidence of acute GvHD grade IV (RR = 0.22; 95% CI, 0.06–0.81) and chronic GvHD (RR = 0.64; 95% CI, 0.47–0.88) compared with controls. Overall survival of acute GvHD patients (0.50; 95% CI, 0.41–0.59) was positively correlated with MSC dose (P = 0.0214). The overall response was achieved in 67% (95% CI, 0.61–0.74) and was complete in 39% (95% CI, 0.31–0.48) of acute patients. Organ-specific response was higher for the skin. Twenty-two percent (95% CI, 0.16–0.29) of acute patients infused with MSC developed chronic GvHD. Sixty-four percent (95% CI, 0.47–0.80) of chronic patients infused with MSC survived; the overall response was 66% (95% CI, 0.55–0.76) and was complete in 23% (95% CI 0.12–0.34) of patients.

Conclusions

Our meta-analysis indicates that allogeneic MSC could be instrumental for the prophylaxis and treatment of GvHD. Future trials should investigate the effect of the administration of MSC as an adjuvant therapy for the treatment of patients with GvHD from the onset of the disease.
Multiobjective de novo drug design with recurrent neural networks and nondominated sorting
Authors: Yasonik Jacob
Published: February 2020

Research productivity in the pharmaceutical industry has declined significantly in recent decades, with higher costs, longer timelines, and lower success rates of drug candidates in clinical trials. This has prioritized the scalability and multiobjectivity of drug discovery and design. De novo drug design has emerged as a promising approach; molecules are generated from scratch, thus reducing the reliance on trial and error and premade molecular repositories. However, optimizing for molecular traits remains challenging, impeding the implementation of de novo methods. In this work, we propose a de novo approach capable of optimizing multiple traits collectively. A recurrent neural network was used to generate molecules which were then ranked based on multiple properties by a nondominated sorting algorithm. The best of the molecules generated were selected and used to fine-tune the recurrent neural network through transfer learning, creating a cycle that mimics the traditional design–synthesis–test cycle. We demonstrate the efficacy of this approach through a proof of concept, optimizing for constraints on molecular weight, octanol-water partition coefficient, the number of rotatable bonds, hydrogen bond donors, and hydrogen bond acceptors simultaneously. Analysis of the molecules generated after five iterations of the cycle revealed a 14-fold improvement in the quality of generated molecules, along with improvements to the accuracy of the recurrent neural network and the structural diversity of the molecules generated. This cycle notably does not require large amounts of training data nor any handwritten scoring functions. Altogether, this approach uniquely combines scalable generation with multiobjective optimization of molecules.
Root tracking using time-varying autoregressive moving average models and sigma-point Kalman filters
Authors: Kostoglou Kyriaki , Lunglmayr Michael
Published: February 2020

Root tracking is a powerful technique that provides insight into the mechanisms of various time-varying processes. The poles and the zeros of a signal-generating system determine the spectral characteristics of the signal under consideration. In this work, time-frequency analysis is achieved by tracking the roots of time-varying processes using autoregressive moving average (ARMA) models in cascade form. A cascade ARMA model is essentially a high-order infinite impulse response (IIR) filter decomposed into a series of first- and second-order sections. Each section is characterized by real or conjugate pole/zero pairs. This filter topology allows individual root tracking as well as immediate stability monitoring and correction. Also, it does not suffer from high round-off error sensitivity, as is the case with the filter coefficients of the direct-form ARMA structure. Instead of using conventional gradient-based recursive methods, we investigate the performance of derivative-free sigma-point Kalman filters for root trajectory tracking over time. Based on simulations, the sigma-point estimators provide more accurate estimates, especially in the case of tightly clustered poles and zeros. The proposed framework is applied to real data, and more specifically, it is used to examine the time-frequency characteristics of raw ultrasonic signals from medical ultrasound images.
Bone mineral density is negatively correlated with ulcerative colitis: a systematic review and meta‐analysis
Authors: Zhou Tianyu , Pan Jiaqi , Lai Bin , Cen Li , Jiang Wenxi , Yu Chaohui , Shen Zhe
Published: February 2020

Background

Newer epidemiological studies suggest that the incidence of ulcerative colitis might be increasing rapidly. Furthermore, osteoporosis in ulcerative colitis patients has gained great attention, but the epidemiologic evidence remains controversial. Therefore, a meta‐analysis was performed to explore the association between bone density and ulcerative colitis.

Methods

Two investigators used PubMed, EMBASE and the Cochrane Library databases to identify all studies published before August 2019. Depending on the outcomes, investigators divided these studies into four groups (OR, SMD [BMD], SMD [z‐score] and SMD [t‐score]). To address the use of steroids, which is a major confounding factor in this analysis, another subgroup analysis of studies of steroid‐free patients was conducted. Additionally, heterogeneity, sensitivity and stratified analyses were also performed.

Results

A total of 13 cross‐sectional studies that involved 1154 participants were included in the present meta‐analysis, and three of them were included in the steroid‐free subgroup analysis. The pooled OR was 6.41 (95% CI 2.59–15.87) and the pooled SMD (BMD), SMD (t‐score) and SMD (z‐score) were − 0.24 (95% CI − 0.44 to − 0.04), − 0.55 (95% CI − 0.72 to − 0.37), and − 0.38 (95% CI − 0.56 and − 0.19), respectively. Since steroids are a significant confounder, the pooled SMD of the steroid‐free subgroup was − 0.55 (− 0.85 to − 0.25), which revealed a strong negative relationship between bone density and ulcerative colitis in steroid‐free patients. Additionally, other subgroup analyses also revealed a strong relationship.

Conclusions

This meta‐analysis provides evidence for the potential association between ulcerative colitis and decreased bone density. It is essential for clinicians to consider bone mineral density in ulcerative colitis patients regardless of steroid‐therapy.
The “wing-heeled” traveler
Authors: Kain Taylor , Weinstein Jordan , Thompson Aaron , Boggild Andrea K.
Published: February 2020

Intoxication syndromes may be travel acquired, and are related to intentional or accidental inhalational or percutaneous exposures or ingestions. Due to their myriad clinical presentations, initial differential diagnosis of such intoxications in returned travelers is broad, and typically requires detailed history and laboratory investigations to disentangle. We herein use a case-based clinical problem solving approach to illumination of a mercury intoxication syndrome, which presented in a 48-year-old VFR traveler to Guyana. Common clinical presentations, differential diagnoses, laboratory investigations, and therapeutic interventions are discussed.
Typing methods based on whole genome sequencing data
Authors: Uelze Laura , Grützke Josephine , Borowiak Maria , Hammerl Jens Andre , Juraschek Katharina , Deneke Carlus , Tausch Simon H. , Malorny Burkhard
Published: February 2020

Whole genome sequencing (WGS) of foodborne pathogens has become an effective method for investigating the information contained in the genome sequence of bacterial pathogens. In addition, its highly discriminative power enables the comparison of genetic relatedness between bacteria even on a sub-species level. For this reason, WGS is being implemented worldwide and across sectors (human, veterinary, food, and environment) for the investigation of disease outbreaks, source attribution, and improved risk characterization models. In order to extract relevant information from the large quantity and complex data produced by WGS, a host of bioinformatics tools has been developed, allowing users to analyze and interpret sequencing data, starting from simple gene-searches to complex phylogenetic studies. Depending on the research question, the complexity of the dataset and their bioinformatics skill set, users can choose between a great variety of tools for the analysis of WGS data. In this review, we describe the relevant approaches for phylogenomic studies for outbreak studies and give an overview of selected tools for the characterization of foodborne pathogens based on WGS data. Despite the efforts of the last years, harmonization and standardization of typing tools are still urgently needed to allow for an easy comparison of data between laboratories, moving towards a one health worldwide surveillance system for foodborne pathogens.
Parameterization analysis and field validation of VTI-elastic full-waveform inversion in a walk-away vertical seismic profile configuration
Authors: Pan Wenyong , Innanen Kristopher A. , Wang Yanfei
Published: February 2020

Elastic full-waveform inversion (FWI) in transversely isotropic media with a vertical symmetry axis (VTI) is applied to field walk-away vertical seismic profile (W-VSP) data acquired in Western Canada. The performance of VTI-elastic FWI is significantly influenced by the model parameterization choice. Synthetic analysis based on specific field survey configuration is carried out to evaluate three different VTI-elastic model parameterizations. Interparameter trade-offs are quantified using the recently introduced interparameter contamination sensitivity kernel approach. Synthetic results suggest that neglecting anisotropy leads to inaccurate velocity estimations. For the conventional vertical velocity-Thomsen’s parameter parameterization (i.e., vertical P-wave velocity, vertical S-wave velocity, Thomsen’s parameters [Formula: see text] and [Formula: see text]), a sequential inversion strategy is designed to reduce strong natural interparameter trade-offs. The model parameterizations of elastic-constant ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) and velocity-based (vertical, horizontal, and normal move-out P-wave velocities and vertical S-wave velocity) models appear to suffer from fewer interparameter trade-offs, providing more reliable velocity and anisotropy models. Results derived from application of VTI-elastic FWI to the field W-VSP data set tend to support the synthetic conclusions. Multiparameter point spread functions are calculated to quantify the local interparameter trade-offs of the inverted models. The output inversion results are interpreted to provide valuable references regarding the target hydrocarbon reservoir.
Coupled magnetic resonance and electrical resistivity tomography: An open-source toolbox for surface nuclear-magnetic resonance
Authors: Skibbe Nico , Rochlitz Raphael , Günther Thomas , Müller-Petke Mike
Published: February 2020

Nuclear-magnetic resonance (NMR) is a powerful tool for groundwater system imaging. Ongoing developments in surface NMR, for example, multichannel devices, allow for investigations of increasingly complex subsurface structures. However, with the growing complexity of field cases, the availability of appropriate software to accomplish the in-depth data analysis becomes limited. The open-source Python toolbox coupled magnetic resonance and electrical resistivity tomography (COMET) provides the community with a software for modeling and inversion of complex surface NMR data. COMET allows the NMR parameters’ water content and relaxation time to vary in one dimension or two dimensions and accounts for arbitrary electrical resistivity distributions. It offers a wide range of classes and functions to use the software via scripts without in-depth programming knowledge. We validated COMET to existing software for a simple 1D example. We discovered the potential of COMET by a complex 2D case, showing 2D inversions using different approximations for the resistivity, including a smooth distribution from electrical resistivity tomography (ERT). The use of ERT-based resistivity results in similar water content and relaxation time images compared with using the original synthetic block resistivity. We find that complex inversion may indicate incorrect resistivity by non-Gaussian data misfits, whereas amplitude inversion shows well-fitted data, but leading to erroneous NMR models.
Opportunities for Maintenance of Certification to Better Reflect Scope of Practice Among Medical Oncologists
Authors: Vandergrift Jonathan L. , Gray Bradley M. , Barnhart Brendan J. , Lynn Lorna A. , Lipner Rebecca S.
Published: February 2020

PURPOSE:

Critics argue that the American Board of Internal Medicine’s medical oncology Maintenance of Certification examination requires medical oncologists with a narrow scope of practice to spend time studying material that is no longer relevant to their practice. However, no data are available describing the scope of practice for medical oncologists.

METHODS:

Using Medicare claims, we examined the scope of practice for 9,985 medical oncologists who saw 8.6 million oncology conditions in 2016, each of which was assigned to 1 of 23 different condition groups. Scope of practice was then measured as the percentage of oncology conditions within each of the 23 groups. We grouped physicians with similar scopes of practice by applying K-means clustering to the percentage of conditions seen. The scope of practice for each physician cluster was determined from the cancers that encompassed the majority of average oncology conditions seen among physicians composing the cluster.

RESULTS:

We found 20 distinct scope-of-practice clusters. The largest (n = 6,479 [65.5%]) had a general oncology scope of practice. The remaining physicians focused on a narrow scope of cancers, including 22.6% focused on ≥ 1 solid tumors and 11.9% focused on hematologic malignancies. The largest focused cluster accounted for 7.7% of physicians focused on breast cancer.

CONCLUSION:

A single American Board of Internal Medicine Maintenance of Certification assessment in medical oncology is most appropriate for approximately 65% of certified medical oncologists’ practices. However, the addition of assessments focused on breast cancer and hematologic malignancies could increase this figure to upwards of 85% of certified medical oncologists.
Efficacy of Temozolomide Therapy in Patients With Aggressive Pituitary Adenomas and Carcinomas—A German Survey
Authors: Elbelt Ulf , Schlaffer Sven M , Buchfelder Michael , Knappe Ulrich J , Vila Greisa , Micko Alexander , Deutschbein Timo , Unger Nicole , Lammert Alexander , Topuzoglu-Müller Tengü , Bojunga Jörg , Droste Michael , Johanssen Sarah , Kolenda Herbert , Ritzel Katrin , Buslei Rolf , Strasburger Christian J , Petersenn Stephan , Honegger Jürgen
Published: February 2020

Context

Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging.

Objective

We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness.

Design and subjects

Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients.

Results

Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated.

Conclusion

We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.
Evidence that Nitric Oxide Is Critical for LH Surge Generation in Female Sheep
Authors: McCosh Richard B , Lopez Justin A , Szeligo Brett M , Bedenbaugh Michelle N , Hileman Stanley M , Coolen Lique M , Lehman Michael N , Goodman Robert L
Published: February 2020

Elevated and sustained estradiol concentrations cause a gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) surge that is necessary for ovulation. In sheep, several different neural systems have been implicated in this stimulatory action of estradiol and this study focused on somatostatin (SST) neurons in the ventral lateral region of the ventral medial nucleus (vlVMN) which express c-Fos during the surge. First, we determined if increased activity of SST neurons could be related to elevated GnRH secretion by assessing SST synapses onto GnRH neurons and neurons coexpressing kisspeptin, neurokinin B, dynorphin (KNDy). We found that the percentage of preoptic area GnRH neurons that receive SST input increased during the surge compared with other phases of the cycle. However, since SST is generally inhibitory, and pharmacological manipulation of SST signaling did not alter the LH surge in sheep, we hypothesized that nitric oxide (NO) was also produced by these neurons to account for their activation during the surge. In support of this hypothesis we found that (1) the majority of SST cells in the vlVMN (>80%) contained neuronal nitric oxide synthase (nNOS); (2) the expression of c-Fos in dual-labeled SST-nNOS cells, but not in single-labeled cells, increased during the surge compared with other phases of the cycle; and (3) intracerebroventricular (ICV) infusion of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, completely blocked the estrogen-induced LH surge. These data support the hypothesis that the population of SST-nNOS cells in the vlVMN are a source of NO that is critical for the LH surge, and we propose that they are an important site of estradiol positive feedback in sheep.
Environmental Obesogens and Their Impact on Susceptibility to Obesity: New Mechanisms and Chemicals
Authors: Egusquiza Riann Jenay , Blumberg Bruce
Published: February 2020

The incidence of obesity has reached an all-time high, and this increase is observed worldwide. There is a growing need to understand all the factors that contribute to obesity to effectively treat and prevent it and associated comorbidities. The obesogen hypothesis proposes that there are chemicals in our environment termed obesogens that can affect individual susceptibility to obesity and thus help explain the recent large increases in obesity. This review discusses current advances in our understanding of how obesogens act to affect health and obesity susceptibility. Newly discovered obesogens and potential obesogens are discussed, together with future directions for research that may help to reduce the impact of these pervasive chemicals.
Presenting Features in 269 Patients With Clinically Nonfunctioning Pituitary Adenomas Enrolled in a Prospective Study
Authors: Freda Pamela U , Bruce Jeffrey N , Khandji Alexander G , Jin Zhezhen , Hickman Richard A , Frey Emily , Reyes-Vidal Carlos , Otten Marc , Wardlaw Sharon L , Post Kalmon D
Published: February 2020

Context

Clinically nonfunctioning pituitary adenomas (CNFPAs) typically remain undetected until mass effect symptoms develop. However, currently, head imaging is performed commonly for many other indications, which may increase incidental discovery of CNFPAs. Since current presentation and outcome data are based on older, retrospective series, a prospective characterization of a contemporary CNFPA cohort was needed.

Objective

To determine the prevalence of incidental presentation and hypopituitarism and its predictors in a CNFPA cohort that spanned 6 to 9 mm micro- to macroadenoma included observational and surgical therapy.

Methods

At enrollment in a prospective, observational study, 269 patients with CNFPAs were studied by history, examination, blood sampling, and pituitary imaging analysis and categorized into incidental or symptoms presentation groups that were compared.

Results

Presentation was incidental in 48.7% of patients and due to tumor symptoms in 51.3%. In the symptoms and incidental groups, 58.7% and 27.4% of patients had hypopituitarism, respectively, and 25% of patients with microadenomas had hypopituitarism. Many had unappreciated signs and symptoms of pituitary disease. Most tumors were macroadenomas (87%) and were larger in the symptoms than incidental and hypopituitary groups than in the eupituitary groups. The patients in the incidental group were older, and males were older and had larger tumors in both the incidental and symptoms groups.

Conclusions

Patients with CNFPAs commonly present incidentally and with previously unrecognized hypopituitarism and symptoms that could have prompted earlier diagnosis. Our data support screening all large micro and macro-CNFPAs for hypopituitarism. Most patients with CNFPAs still have mass effect signs at presentation, suggesting the need for more awareness of pituitary disease. Our ongoing, prospective observation of this cohort will assess outcomes of these CNFPA groups.
AstroDot – a new method for studying the spatial distribution of mRNA in astrocytes
Authors: Oudart Marc , Tortuyaux Romain , Mailly Philippe , Mazaré Noémie , Boulay Anne-Cécile , Cohen-Salmon Martine
Published: February 2020

Astrocytes are morphologically complex and use local translation to regulate distal functions. To study the distribution of mRNA in astrocytes, we combined mRNA detection via in situ hybridization with immunostaining of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). mRNAs at the level of GFAP-immunolabelled astrocyte somata, and large and fine processes were analysed using AstroDot, an ImageJ plug-in and the R package AstroStat. Taking the characterization of mRNAs encoding GFAP-α and GFAP-δ isoforms as a proof of concept, we showed that they mainly localized on GFAP processes. In the APPswe/PS1dE9 mouse model of Alzheimer's disease, the density and distribution of both α and δ forms of Gfap mRNA changed as a function of the region of the hippocampus and the astrocyte's proximity to amyloid plaques. To validate our method, we confirmed that the ubiquitous Rpl4 (large subunit ribosomal protein 4) mRNA was present in astrocyte processes as well as in microglia processes immunolabelled for ionized calcium binding adaptor molecule 1 (Iba1; also known as IAF1). In summary, this novel set of tools allows the characterization of mRNA distribution in astrocytes and microglia in physiological or pathological settings.
Increased host ATP efflux and its conversion to extracellular adenosine is crucial for establishing Leishmania infection
Authors: Basu Moumita , Gupta Purnima , Dutta Ananya , Jana Kuladip , Ukil Anindita
Published: February 2020

Intracellular survival of Leishmania donovani demands rapid production of host ATP for its sustenance. However, a gradual decrease in intracellular ATP in spite of increased glycolysis suggests ATP efflux during infection. Accordingly, upon infection, we show here that ATP is exported and the major exporter was pannexin-1, leading to raised extracellular ATP levels. Extracellular ATP shows a gradual decrease after the initial increase, and analysis of cell surface ATP-degrading enzymes revealed induction of the ectonucleotidases CD39 and CD73. Ectonucleotidase-mediated ATP degradation leads to increased extracellular adenosine (eADO), and inhibition of CD39 and CD73 in infected cells decreased adenosine concentration and parasite survival, documenting the importance of adenosine in infection. Inhibiting adenosine uptake by cells did not affect parasite survival, suggesting that eADO exerts its effect through receptor-mediated signalling. We also show that Leishmania induces the expression of adenosine receptors A2AR and A2BR, both of which are important for anti-inflammatory responses. Treating infected BALB/c mice with CD39 and CD73 inhibitors resulted in decreased parasite burden and increased host-favourable cytokine production. Collectively, these observations indicate that infection-induced ATP is exported, and after conversion into adenosine, propagates infection via receptor-mediated signalling.
Dispersion is essential in crop residue application
Authors: Oda Masato
Published: February 2020

Background: Crop residue application can maintain soil fertility and sustain agriculture. However, the effects of residue application are unstable because of variable weather conditions and the residual effects of crop residue application. Furthermore, residue application often reduces crop yields. Therefore, I tried to clarify effective residue application factors in an environment which was has stable weather conditions and low residual effects.

Methods: Majuro atoll, a coral sand atoll near the equator, was selected for the experiment site because of its stable weather and low residual effect of coral sand. A factorial design experiment using sweet corn was conducted based on the following four factors: fungi propagation before application, cutting residue into pieces, dispersion (or accumulation) of applied residue, and placement (on the surface or incorporation) with an equal amount of crop residue. The effects of each factors on the corn yields were evaluated using Cohen’s power analysis.

Results: The dispersion showed the largest effect (1.2 in Cohen’s), which exceeded the effect of incorporation (0.7). The interaction of dispersion and incorporation showed a huge effect (4.9) on corn yield.

Discussion: The effect of dispersion was not positive but it avoided the negative effects of residue clustering. Because, the toxicity of the plant residue and generation of toxic substances by anaerobic decomposition are widely known. Anaerobic decomposition occurs inside the residue clusters. However, dispersion reduced the toxicity by adsorption in soil and avoiding anaerobic decomposition. Furthermore, incorporation showed an interaction effect, but surface placement did not.

Conclusion: The dispersion of crop residue enhanced the positive effect of crop residue incorporation by avoiding the toxicity from crop residue. This finding adds a new viewpoint for the controversy between conventional and conservation agriculture
The effects of interventions preventing self-harm and suicide in children and adolescents: an overview of systematic reviews
Authors: Morken Ida Sund , Dahlgren Astrid , Lunde Ingeborg , Toven Siri
Published: February 2020

Background: Self-harm and suicide in children and adolescents are of serious consequence and increase during the adolescent years. Consequently, there is need for interventions that prevent such behaviour. The objective of this paper: to evaluate the effects of interventions preventing self-harm and suicide in children and adolescents in an overview of systematic reviews.

Methods: We conducted an overview of systematic reviews (OoO). We included reviews evaluating any preventive or therapeutic intervention. The methodological quality of the included reviews was assessed independently, and data was extracted by two reviewers. We report the review findings descriptively. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: Moderate certainty evidence suggests that school-based interventions prevent suicidal ideation and attempts short term, and possibly suicide attempts long term. The effects of community-based interventions following suicide clusters and local suicide plans are unknown, as are the benefits and harms of screening young people for suicide risk.

The effects of most interventions targeting children and adolescents with known self-harm are unknown. However, low certainty evidence suggests that dialectical behavioural therapy and developmental group therapy are equally as effective on repetition of self-harm as enhanced treatment as usual.

Conclusions: Research on several recommended practices, such as local suicide plans, prevention of suicide clusters and approaches to risk assessment, is lacking. When such interventions are implemented, the effects should be closely evaluated. There is also need for more research on treatment of repeated self-harm. Further research should include long term follow-up, and investigate possible adverse effects.

In prevention of self-harm and suicide in children and adolescents, policy makers and health providers should consider evidence from population-based studies with mixed-age samples, adult samples, and studies on conditions associated with self-harm and/or suicidality, such as depression and psychosis.

PROSPERO registration: CRD42019117942 08/02/19
Recent advances in endovascular treatment of peripheral arterial disease
Authors: Lazar Andrew , Morrissey Nicholas
Published: February 2020

As associated co-morbidities have transformed over time, the evaluation and management of peripheral arterial disease have evolved as well. New classification systems have been created to better understand the severity of a patient’s condition and the risk of amputation. These classifications include the Wound, Ischemia, and Foot Infection (WIfI) and Global Anatomic Staging System (GLASS) classification systems. Through the utility of these systems, a patient’s disease can be appropriately staged and managed with medical, endovascular, or surgical therapies or a combination of these. Endovascular therapies specifically have grown with the explosion of new technologies. There are numerous options for patients with disease amenable to endovascular therapy. In this review article, we discuss a number of these different endovascular therapies as well as the new classification systems.
Recent advances toward understanding the role of transplanted stem cells in tissue-engineered regeneration of musculoskeletal tissues
Authors: Altamirano Dallas E. , Noller Kathleen , Mihaly Eszter , Grayson Warren L.
Published: February 2020

Stem cell–based tissue engineering is poised to revolutionize the treatment of musculoskeletal injuries. However, in order to overcome scientific, practical, and regulatory obstacles and optimize therapeutic strategies, it is essential to better understand the mechanisms underlying the pro-regenerative effects of stem cells. There has been an attempted paradigm shift within the last decade to think of transplanted stem cells as “medicinal” therapies that orchestrate healing on the basis of their secretome and immunomodulatory profiles rather than acting as bona fide stem cells that proliferate, differentiate, and directly produce matrix to form de novo tissues. Yet the majority of current bone and skeletal muscle tissue engineering strategies are still premised on a direct contribution of stem cells as building blocks to tissue regeneration. Our review of the recent literature finds that researchers continue to focus on the quantification of de novo bone/skeletal muscle tissue following treatment and few studies aim to address this mechanistic conundrum directly. The dichotomy of thought is reflected in the diversity of new advances ranging from in situ three-dimensional bioprinting to a focus on exosomes and extracellular vesicles. However, recent findings elucidating the role of the immune system in tissue regeneration combined with novel imaging platform technologies will have a profound impact on our future understanding of how stem cells promote healing following biomaterial-mediated delivery to defect sites.
Genomic and protein structure modelling analysis depicts the origin and pathogenicity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China
Authors: Dong Ning , Yang Xuemei , Ye Lianwei , Chen Kaichao , Chan Edward Wai-Chi , Yang Mengsu , Chen Sheng
Published: February 2020

Background: A pandemic outbreak caused by a novel coronavirus, 2019-nCoV, has originated from Wuhan, China and spread to many countries around the world. The outbreak has led to around 45 thousand cases and over one thousand death so far.

Methods: Phylogenetic analysis and sequence alignment were used to align the whole genome sequence of 2019-nCoV with other over 200 sequences of coronaviruses to predict the origin of this novel virus. In addition, protein modeling and analysis were performed to access the potential binding of the spike protein of 2019-nCoV with human cell receptor, angiotensin-converting enzyme 2 (ACE2).

Results: Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds much weaker to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor.

Conclusions: These findings suggest that the new virus should theoretically not be able to cause very serious human infection when compared to human SARS virus. However, the lower pathogenicity of this new virus may lead to longer incubation time and better adaption to human, which may favor its efficient transmission in human. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov. Most importantly, using the analysis platform that we have developed, we should be able to predict whether the new mutations could lead to the increase of infectivity of the mutated virus in a very short time.
A protocol for an observational cohort study of heat strain and its effect on fetal wellbeing in pregnant farmers in The Gambia
Authors: Bonell Ana , Hirst Jane , Vicedo-Cabrera Ana M. , Haines Andy , Prentice Andrew M. , Maxwell Neil S.
Published: February 2020

Introduction: Climate change predictions indicate that global temperatures are likely to exceed those seen in the last 200,000 years, rising by around 4°C above pre-industrial levels by 2100 (without effective mitigation of current emission rates). In regions of the world set to experience extreme temperatures, women often work outside in agriculture even during pregnancy. The implications of heat strain in pregnancy on maternal health and pregnancy outcome are not well understood. This protocol describes a study to assess the physiological response of pregnant women to environmental heat stress and the immediate effect this has on fetal wellbeing.

Methods and analysis: The study will be performed in West Kiang district, The Gambia; a semi-arid zone in West Africa with daily maximum temperatures ranging from approximately 32 to 40°C. We will recruit 125 pregnant women of all ages who perform agricultural work during their pregnancy. Participants will be followed every two months until delivery. At each study visit fetal growth will be measured by ultrasound scan. During the course of their working day we will take the following measurements: continuous maternal physiological measurements (heart rate, respiratory rate, chest skin temperature and tri-axis accelerometer data); intermittent maternal tympanic core temperature, four point skin temperature, blood pressure; intermittent fetal heart rate and, if eligible, umbilical artery doppler; intermittent environmental measurements of air temperature, humidity, solar radiation and wind speed. Venous blood and urine will be collected at beginning and end of day for biomarkers of heat strain or fetal distress and hydration status.
Absolute Value of Number in Mathematical Olympiads Tasks
Authors: Sopuev Ulanbek , Keldibekova Aida
Published: February 2020

The article focuses on the application of tasks containing a variable under the sign of the module in problems of mathematical olympiads. The results are obtained: the topics of the section are determined, on the basis of which the conditions for the olympiad problems of the republican olympiad are compiled, the goals and requirements for studying the absolute value in the olympiad program are determined, 5 main methods for solving equations with a module are identified: methods for sequentially opening modules, intervals, graphical, determining the dependencies between numbers a and b, their modules and squares, geometric interpretation of the module. In the course of the study, conclusions were drawn: due to the increasing complexity of the olympiad problems, there is a need to familiarize students with different methods for solving the olympiad tasks with a module in the system of additional education.
A DIMENSÃO ESPACIAL DA REDE DE FLORES E PLANTAS ORNAMENTAIS DO ESTADO DO RIO DE JANEIRO: UMA ANÁLISE A PARTIR DO MUNICÍPIO DE NOVA FRIBURGO, ENTRE OS ANOS DE 2002 E 2018
Authors: Reis Jorge Luiz Costa da Silva , Marafon Glaucio José
Published: February 2020

Dados globais sobre o comércio mundial de flores e plantas ornamentais mostram o crescimento da produção e consumo desse segmento nas últimas décadas, inclusive no Brasil. Este artigo mostra como o comércio de flores e plantas ornamentais está organizado em forma de redes geográficas, na medida em que tanto a produção quanto o consumo articulam diferentes espaços. Na constituição da rede de flores e plantas ornamentais, torna-se imprescindível a identificação dos seus agentes ou elementos espaciais e das interações estabelecidas entre eles. Tais interações ocorrem em diferentes escalas (local, regional, nacional ou global). Tanto a conexão quanto a escala – marcas da dimensão espacial – são amplamente influenciadas pela dimensão temporal, que, por sua vez, é influenciada pela intensidade dos fluxos, duração e frequência. Essas considerações são importantes para a identificação das diferentes redes de flores e plantas ornamentais tratadas ao longo da pesquisa: a global, liderada pelas relações estabelecidas pela Holanda; a nacional, a partir da atuação das cooperativas de São Paulo, e a regional, por meio da rede de flores e plantas ornamentais encontrada no território fluminense. Nesse território, a formação da rede de flores e plantas ornamentais é analisada a partir das interações espaciais estabelecidas pelo espaço rural de Nova Friburgo, município que apresenta o maior número de produtores do estado e que se destaca no cultivo de flores de corte. O recorte temporal tem início em 2002 e se estende até o ano de 2018, quando foram realizadas as últimas pesquisas de campo. O caminho metodológico tem como referência a abordagem qualitativa, tanto na seleção dos referenciais teóricos quanto na análise dos dados coletados em campo por meio de observações, imagens, diagnósticos do segmento e entrevistas com os agentes espaciais da rede. Espera-se que esta pesquisa sirva como mais um instrumento de reflexão para a tomada de decisão de ações que possam contribuir para o desenvolvimento de um segmento tão relevante para o estado do Rio de Janeiro.
PADRÕES DE FINANCIAMENTO DOS MUNICÍPIOS: UMA AVALIAÇÃO PELA ÓTICA DA HIERARQUIA DOS CENTROS URBANOS
Authors: De Castro Kleber Pacheco
Published: February 2020

Buscando captar padrões de financiamento dos municípios brasileiros, classificados segundo a lógica da hierarquia dos centros urbanos do IBGE, esse artigo apresentou uma análise intertemporal do financiamento local a partir da construção de indicadores fiscais propostos por Cialdini e Afonso (2014). Os resultados corroboram percepções consolidadas sobre o tema, como a alta dependência de transferências intergovernamentais pelos municípios de pequeno porte e o maior esforço fiscal dos municípios de maior porte, mas também trazem informações novas relativas ao uso de instrumentos de empréstimo (operações de crédito) e do nível de liquidez dos governos locais. Apesar do exercício ter sido aplicado para um período no qual o país vivenciou uma crise econômica, não foi possível observar um impacto desse evento nos indicadores, sugerindo que esse padrão de financiamento captado pelo estudo tem um elemento estrutural muito forte, que é pouco sensível ao ciclo econômico ou mesmo político (eleitoral).