bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of premature death and seizures in a Depdc5 mouse epilepsy model through inhibition of mTORC1
Authors: Klofas Lindsay K , Short Brittany P , Zhou Chengwen , Carson Robert P
Published: April 2020

Mutations in DEP domain containing 5 (DEPDC5) are increasingly appreciated as one of the most common causes of inherited focal epilepsy. Epilepsies due to DEPDC5 mutations are often associated with brain malformations, tend to be drug-resistant, and have been linked to an increased risk of sudden unexplained death in epilepsy (SUDEP). Generation of epilepsy models to define mechanisms of epileptogenesis remains vital for future therapies. Here, we describe a novel mouse model of Depdc5 deficiency with a severe epilepsy phenotype, generated by conditional deletion of Depdc5 in dorsal telencephalic neuroprogenitor cells. In contrast to control and heterozygous mice, Depdc5-Emx1-Cre conditional knockout (CKO) mice demonstrated macrocephaly, spontaneous seizures and premature death. Consistent with increased mTORC1 activation, targeted neurons were enlarged and both neurons and astrocytes demonstrated increased S6 phosphorylation. Electrophysiologic characterization of miniature inhibitory post-synaptic currents in excitatory neurons was consistent with impaired post-synaptic response to GABAergic input, suggesting a potential mechanism for neuronal hyperexcitability. mTORC1 inhibition with rapamycin significantly improved survival of CKO animals and prevented observed seizures, including for up to 40 days following rapamycin withdrawal. These data not only support a primary role for mTORC1 hyperactivation in epilepsy following homozygous loss of Depdc5, but also suggest a developmental window for treatment which may have a durable benefit for some time even after withdrawal.
Experimental and numerical investigation of a novel photovoltaic/thermal system using micro-channel flat loop heat pipe (PV/T-MCFLHP)
Authors: Chen Fucheng , Hu Menglong , Badiei Ali , Yu Min , Huang Zicong , Wang Zhangyuan , Zhao Xudong
Published: April 2020

In this paper, a novel photovoltaic/thermal system using micro-channel flat loop heat pipe (PV/T-MCFLHP) is proposed, and the thermal and electrical performance of the system is investigated theoretically and experimentally. The variations of temperatures were analysed, and the efficiency of the system was calculated under different conditions, i.e. simulated solar radiation, water flow rate and refrigerant filling ratio. The maximum overall efficiency of the system was found to be 51.3%, the thermal efficiency 43.8% and the electrical efficiency 7.5% with the refrigerant filling ratio of 25%, simulated solar radiation of 800 W/m2 and water flow rate of 400 L/h. Test results were compared with simulation results, and the recorded average error was 10.2%.
What antimicrobial stewardship strategies do NHS commissioning organizations implement in primary care in England?
Authors: Allison Rosalie , Lecky Donna M , Beech Elizabeth , Costelloe Céire , Ashiru-Oredope Diane , Owens Rebecca , McNulty Cliodna A M
Published: April 2020

Objectives

To identify and explore strategies that English NHS commissioning organizations implemented to improve antimicrobial stewardship (AMS) within primary care.

Methods

Questionnaire sent to the medicines management teams (MMTs) of all 209 clinical commissioning groups (CCGs) in England, in 2017.

Results

A total of 89% (187/209) of all English CCGs responded to the questionnaire; 74% of responding CCGs (123/167) had a prescribing incentive/engagement scheme, with MMTs representing 88% (90/102) considering incentive schemes successful or very successful for prioritizing AMS in primary care, especially when linked to prescribing NHS Quality Premium indicators. AMS audits were considered successful or very successful by 91% (126/138) of responding CCGs, as they identify reasons for inappropriate prescribing and opportunities for future improvement. All responding MMTs (169/169 CCGs) reported feeding back local/national antimicrobial prescribing data to the general practices they commission, 85% (142/168) to their CCG/Commissioning Support Unit (CSU) board and only 33% (56/169) to out-of-hours services. Benchmarking prescribing data was reported as a powerful tool to engage practices, facilitating an element of competition and peer pressure.

Conclusions

National antimicrobial resistance improvement schemes, in particular the NHS England Quality Premium, have influenced CCG improvement priorities. Most CCGs now report successful improvement strategies including the use of both local and national antibiotic prescribing data to motivate improvements; these should be continued and extended to out-of-hours providers. As local audit data have helped to identify reasons for inappropriate prescribing and inform improvement planning, all organizations should adopt this strategy and include it in local quality improvement schemes, ensuring performance reporting to organizational board level.
Application of solid-phase DNA probe method with cleavage by deoxyribozyme for analysis of long non-coding RNAs
Authors: Arakawa Shizuka , Kamizaki Kohsuke , Kuwana Yusuke , Kataoka Naruki , Naoe Chieko , Takemoto Chie , Yokogawa Takashi , Hori Hiroyuki
Published: April 2020

The solid-phase DNA probe method is a well-established technique for tRNA purification. We have applied this method for purification and analysis of other non-coding RNAs. Three columns for purification of tRNAPhe, transfer-messenger RNA (tmRNA) and 16S rRNA from Thermus thermophilus were connected in tandem and purifications were performed. From each column, tRNAPhe, tmRNA and 16S rRNA could be purified in a single step. This is the first report of purification of native tmRNA from T. thermophilus and the purification demonstrates that the solid-phase DNA probe method is applicable to non-coding RNA, which is present in lower amounts than tRNA. Furthermore, if a long non-coding RNA is cleaved site-specifically and the fragment can be purified by the solid-phase DNA probe method, modified nucleosides in the long non-coding RNA can be analysed. Therefore, we designed a deoxyribozyme (DNAzyme) to perform site-specific cleavage of 16S rRNA, examined optimum conditions and purified the resulting RNA fragment. Sequencing of complimentary DNA and mass spectrometric analysis revealed that the purified RNA corresponded to the targeted fragment of 16S rRNA. Thus, the combination of DNAzyme cleavage and purification using solid-phase DNA probe methodology can be a useful technique for analysis of modified nucleosides in long non-coding RNAs.
Failure to Launch: Competing Institutional Logics, Intrapreneurship, and the Case of Chatbots
Authors: Belair-Gagnon Valerie , Lewis Seth C , Agur Colin
Published: April 2020

This article explores the institutional logics of intrapreneurial units, or groups within organizations that are designated to foster organizational innovation. Drawing on interviews with news intrapreneurs developing chatbots in news media organizations, this study shows that innovation can be stymied because of conflicting institutional logics. News intrapreneurs adopt a logic of experimentation, audience orientation, and efficiency-seeking, but that approach clashes with a journalistic logic prioritizing news workflows, formats, and associated autonomy for newsworkers. These clashing logics limit the adoption and influence of chatbots. This study illustrates the shaping influence of competing institutional logics and their negotiation in the development, deployment, and success or failure of intrapreneurial activities within organizations. The lesson is not that the existence of competing logics is, by default, a defeating proposition for innovation. Rather, this study advances scholarly understanding of the role of institutional logics in frustrating or facilitating technological adoption in organizations.
The British Army’s Training in International Humanitarian Law
Authors: Bates Elizabeth Stubbins
Published: April 2020

States must disseminate international humanitarian law (IHL) and integrate it into military instruction. Implementation of the IHL training obligation was delayed in the UK; when the government asserted that IHL was inapplicable to colonial warfare, resisted the development of the IHL of non-international armed conflict, and was keen to maintain the nuclear deterrent. Absent or perfunctory IHL training correlated with recurrent violations of the prohibitions of torture and inhuman treatment, from the 1950s to the 2000s. Despite official assertions that the British Army’s training in IHL was being reformed following the death of Baha Mousa in British military custody in 2003, there were gradual changes from 2004 to 2011, and more thorough improvements from 2012 to 2017. Training materials for soldiers and officers now offer breadth and detail on IHL, with elements of international human rights law. They implement the 71 recommendations in the Baha Mousa Public Inquiry Report which the Ministry of Defence accepted, and are supplemented by practical training. Yet these are reactive reforms, which still lack norm-by-norm evaluation of soldiers’ understanding. Prohibitions on humiliating or degrading treatment of a sexual nature, and on the intentional infliction of severe mental pain and suffering are (respectively) under-emphasised and absent. References to the necessity of restraint positions (as opposed to the prohibited stress positions) may cause confusion. There is a simplistic suggestion that reprisals are lawful if they are politically authorised. Training reforms have been cited as one reason to close criminal investigations into alleged war crimes: a response which neglects coexistent investigatory obligations.
Chronic Illness and Internalizing Symptomatology in a Transdiagnostic Clinical Sample of Youth
Authors: Wolock Elizabeth R , Queen Alexander H , Rodríguez Gabriela M , Weisz John R
Published: April 2020

Objective

In research with community samples, children with chronic physical illnesses have shown elevated anxiety and depressive symptoms, compared to healthy peers. Less is known about whether physical illnesses are associated with elevated internalizing symptoms even among children referred for mental health treatment—a pattern that would indicate distinctive treatment needs among physically ill children receiving mental health care. We investigated the relationship between chronic physical illness and internalizing symptomatology among children enrolling in outpatient mental health treatment.

Method

A total of 262 treatment-seeking children ages 7–15 and their caregivers completed a demographic questionnaire, Child Behavior Checklist, and Youth Self-Report during a pre-treatment assessment. Physical illnesses were identified through caregiver report.

Results

There was no overall association between the presence/absence of chronic physical illness and parent- or child-reported symptoms. However, number of chronic physical illnesses was related to parent- and child-reported affective symptoms. Children with two or more chronic physical illnesses had more severe depressive symptoms than those with fewer physical illnesses.

Conclusion

Having multiple chronic illnesses may elevate children’s risk of depression symptomatology, even in comparison to other children seeking mental health care. This suggests a need to identify factors that may exacerbate depression symptoms in physically ill children who are initiating therapy and to determine whether different or more intensive services may be helpful for this group. The findings suggest the potential utility of screening for depression in youth with chronic physical illnesses, as well as addressing mental and physical health concerns during treatment.
Biological nitrogen fixation in maize: optimizing nitrogenase expression in a root-associated diazotroph
Authors: Bloch Sarah E , Clark Rosemary , Gottlieb Shayin S , Wood L Kent , Shah Neal , Mak San-Ming , Lorigan James G , Johnson Jenny , Davis-Richardson Austin G , Williams Lorena , McKellar Megan , Soriano Dominic , Petersen Max , Horton Alana , Smith Olivia , Wu Leslie , Tung Emily , Broglie Richard , Tamsir Alvin , Temme Karsten
Published: April 2020

Plants depend upon beneficial interactions between roots and root-associated microorganisms for growth promotion, disease suppression, and nutrient availability. This includes the ability of free-living diazotrophic bacteria to supply nitrogen, an ecological role that has been long underappreciated in modern agriculture for efficient crop production systems. Long-term ecological studies in legume–rhizobia interactions have shown that elevated nitrogen inputs can lead to the evolution of less cooperative nitrogen-fixing mutualists. Here we describe how reprogramming the genetic regulation of nitrogen fixation and assimilation in a novel root-associated diazotroph can restore ammonium production in the presence of exogenous nitrogen inputs. We isolated a strain of the plant-associated proteobacterium Kosakonia sacchari from corn roots, characterized its nitrogen regulatory network, and targeted key nodes for gene editing to optimize nitrogen fixation in corn. While the wild-type strain exhibits repression of nitrogen fixation in conditions replete with bioavailable nitrogen, such as fertilized greenhouse and field experiments, remodeled strains show elevated levels in the rhizosphere of corn in the greenhouse and field even in the presence of exogenous nitrogen. Such strains could be used in commercial applications to supply fixed nitrogen to cereal crops.
Fighter Pilots With Nasopharyngeal Carcinoma Successfully Returning to Flight After Radiotherapy: A Case Series
Authors: Chen Shih-Ming , Lin Kuen-Tze , Dai Yang-Hong , Chiang Kwo-Tsao , Lee Shih-Yu
Published: April 2020

For nasopharyngeal carcinoma (NPC), radiotherapy is the primary treatment. However, complications occur after radiation to the nasopharynx, which could potentially affect the flying safety. Four fighter pilots with NPC were reported. With early to locally advanced NPC, they received radiotherapy with or without concurrent chemotherapy. The prescribed radiation dose was 70 Gy to the primary tumor over the nasopharynx. Before treatment, all patients presented with various degrees of hearing loss on pure tone audiometry (main frequencies of 20–45 dB at 3–4.5 kHz for affected ears). After the full course of radiotherapy, tumor regression was noticed during months to years of follow-ups. The follow-up audiometry evaluation showed gradually recovered hearing function (average improvement of 5 dB at pretreatment frequencies) in all pilots. They then returned back to the flight line on annual waiver points. Here, we conclude that fighter pilots with NPC could successfully return to the flight line after radiotherapy. However, detailed physical examinations and confirmation of adaptation to flying condition are warranted.
Magnetar birth: rotation rates and gravitational-wave emission
Authors: Lander S K , Jones D I
Published: April 2020

Understanding the evolution of the angle χ between a magnetar’s rotation and magnetic axes sheds light on the star’s birth properties. This evolution is coupled with that of the stellar rotation Ω, and depends on the competing effects of internal viscous dissipation and external torques. We study this coupled evolution for a model magnetar with a strong internal toroidal field, extending previous work by modelling – for the first time in this context – the strong protomagnetar wind acting shortly after birth. We also account for the effect of buoyancy forces on viscous dissipation at late times. Typically, we find that χ → 90° shortly after birth, then decreases towards 0° over hundreds of years. From observational indications that magnetars typically have small χ, we infer that these stars are subject to a stronger average exterior torque than radio pulsars, and that they were born spinning faster than ∼100–300 Hz. Our results allow us to make quantitative predictions for the gravitational and electromagnetic signals from a newborn rotating magnetar. We also comment briefly on the possible connection with periodic fast radio burst sources.
GASP XXV: neutral hydrogen gas in the striking jellyfish galaxy JO204
Authors: Deb Tirna , Verheijen Marc A W , Gullieuszik Marco , Poggianti Bianca M , van Gorkom Jacqueline H , Ramatsoku Mpati , Serra Paolo , Moretti Alessia , Vulcani Benedetta , Bettoni Daniela , Jaffé L Yara , Tonnesen Stephanie , Fritz Jacopo
Published: April 2020

We present JVLA-C observations of the H i gas in JO204, one of the most striking jellyfish galaxies from the GASP survey. JO204 is a massive galaxy in the low-mass cluster A957 at z = 0.04243. The H i map reveals an extended 90 kpc long ram-pressure stripped tail of neutral gas, stretching beyond the 30 kpc long ionized gas tail and pointing away from the cluster centre. The H i mass seen in emission is $(1.32\pm 0.13) \times 10^{9} \, \rm M_{\odot }$, mostly located in the tail. The northern part of the galaxy disc has retained some H i gas, while the southern part has already been completely stripped and displaced into an extended unilateral tail. Comparing the distribution and kinematics of the neutral and ionized gas in the tail indicates a highly turbulent medium. Moreover, we observe associated H i absorption against the 11 mJy central radio continuum source with an estimated H i absorption column density of 3.2 × 1020 cm−2. The absorption profile is significantly asymmetric with a wing towards higher velocities. We modelled the H i absorption by assuming that the H i and ionized gas discs have the same kinematics in front of the central continuum source, and deduced a wider absorption profile than observed. The observed asymmetric absorption profile can therefore be explained by a clumpy, rotating H i gas disc seen partially in front of the central continuum source, or by ram pressure pushing the neutral gas towards the centre of the continuum source, triggering the AGN activity.
New insight into the stellar mass function of Galactic globular clusters
Authors: Ebrahimi H , Sollima A , Haghi H , Baumgardt H , Hilker M
Published: April 2020

We present the results of the analysis of deep photometric data of 32 Galactic globular clusters. We analysed 69 parallel field images observed with the Wide Field Channel of the Advanced Camera for Surveys of the Hubble Space Telescope which complemented the already available photometry from the globular cluster treasury project covering the central regions of these clusters. This unprecedented data set has been used to calculate the relative fraction of stars at different masses (i.e. the present-day mass function) in these clusters by comparing the observed distribution of stars along the cluster main sequence and across the analysed field of view with the prediction of multimass dynamical models. For a subsample of 31 clusters, we were able to obtain also the half-mass radii, mass-to-light ratios, and the mass fraction of dark remnants using available radial velocity information. We found that the majority of globular clusters have single power-law mass functions F(m) ∝ mα with slopes α > −1 in the mass range 0.2 < m/M⊙ < 0.8. By exploring the correlations between the structural/dynamical and orbital parameters, we confirm the tight anticorrelation between the mass function slopes and the half-mass relaxation times already reported in previous works, and possible second-order dependence on the cluster metallicity. This might indicate the relative importance of both initial conditions and evolutionary effects on the present-day shape of the mass function.
Modelling thermochemical processes in protoplanetary discs I: numerical methods
Authors: Grassi T , Ercolano B , Szűcs L , Jennings J , Picogna G
Published: April 2020

The dispersal phase of planet-forming discs via winds driven by irradiation from the central star and/or magnetic fields in the disc itself is likely to play an important role in the formation and evolution of planetary systems. Current theoretical models lack predictive power to adequately constrain observations. We present prizmo, a code for evolving thermochemistry in protoplanetary discs capable of being coupled with hydrodynamical and multifrequency radiative transfer codes. We describe the main features of the code, including gas and surface chemistry, photochemistry, microphysics, and the main cooling and heating processes. The results of a suite of benchmarks, which include photon-dominated regions, slabs illuminated by radiation spectra that include X-ray, and well-established cooling functions evaluated at different temperatures, show good agreement both in terms of chemical and thermal structures. The development of this code is an important step to perform quantitative spectroscopy of disc winds, and ultimately the calculation of line profiles, which is urgently needed to shed light on the nature of observed disc winds.
Characterization of optical light curves of extreme variability quasars over a ∼16-yr baseline
Authors: Luo Yuanze , Shen Yue , Yang Qian
Published: April 2020

We study the optical light curves – primarily probing the variable emission from the accretion disc – of ∼900 extreme variability quasars (EVQs, with maximum flux variations more than 1 mag) over an observed-frame baseline of ∼16 yr using public data from the SDSS Stripe 82, PanSTARRS-1 and the Dark Energy Survey. We classify the multiyear long-term light curves of EVQs into three categories roughly in the order of decreasing smoothness: monotonic decreasing or increasing (3.7 per cent), single broad peak and dip (56.8 per cent), and more complex patterns (39.5 per cent). The rareness of monotonic cases suggests that the major mechanisms driving the extreme optical variability do not operate over time-scales much longer than a few years. Simulated light curves with a damped random walk model generally under-predict the first two categories with smoother long-term trends. Despite the different long-term behaviours of these EVQs, there is little dependence of the long-term trend on the physical properties of quasars, such as their luminosity, BH mass, and Eddington ratio. The large dynamic range of optical flux variability over multiyear time-scales of these EVQs allows us to explore the ensemble correlation between the short-term (≲6 months) variability and the seasonal-average flux across the decade-long baseline (the rms-mean flux relation). We find that unlike the results for X-ray variability studies, the linear short-term flux variations do not scale with the seasonal-average flux, indicating different mechanisms that drive the short-term flickering and long-term extreme variability of accretion disc emission. Finally, we present a sample of 16 EVQs, where the approximately bell-shaped large amplitude variation in the light curve can be reasonably well fit by a simple microlensing model.
Advanced glycation end-products accelerate telomere attrition and increase pro-inflammatory mediators in human WIL2-NS cells
Authors: Deo Permal , Dhillon Varinderpal S , Lim Wai Mun , Jaunay Emma L , Donnellan Leigh , Peake Brock , McCullough Caitlin , Fenech Michael
Published: April 2020

This study investigated the effect of dietary sugars and advanced glycation end-products (AGE) on telomere dynamics in WIL2-NS cells. Dietary sugars [glucose (Glu) and fructose (Fru); 0.1 M each] were incubated with bovine serum albumin (BSA) (10 mg/ml) at 60 ± 1°C for 6 weeks to generate AGE-BSA. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed total AGE levels as 87.74 ± 4.46 nmol/mg and 84.94 ± 4.28 nmol/mg respectively in Glu-BSA and Fru-BSA model. Cell treatment studies using WIL2-NS cells were based on either glucose, fructose (each 2.5–40 mM) or AGE-BSA (200–600 µg/ml) in a dose-dependent manner for 9 days. Telomere length (TL) was measured using qPCR. Nitric oxide (NO) production and tumour necrosis factor-α (TNF-α) levels were measured in WIL2-NS culture medium. An increasing trend for TNF-α and NO production was observed with higher concentration of glucose (R2 = 0.358; P = 0.019; R2 = 0.307; P = 0.027) and fructose (R2 = 0.669; P = 0.001; R2 = 0.339; P = 0.006). A decreasing trend for TL (R2 = 0.828; P = 0.000), and an increasing trend for NO production (R2 = 0.352; P = 0.031) were observed with increasing Glu-BSA concentrations. Fru-BSA treatment did not show significant trend on TL (R2 = 0.135; P = 0.352) with increasing concentration, however, a significant reduction was observed at 600 µg/ml (P < 0.01) when compared to BSA treatment. No trends for TNF-α levels and a decreasing trend on NO production (R2 = 0.5201; P = 0.019) was observed with increasing Fru-BSA treatment. In conclusion, this study demonstrates a potential relationship between dietary sugars, AGEs and telomere attrition. AGEs may also exert telomere shortening through the production of pro-inflammatory metabolites, which ultimately increase the risk of diabetes complications and age-related disease throughout lifespan.
Characterization of Cas12a nucleases reveals diverse PAM profiles between closely-related orthologs
Authors: Jacobsen Thomas , Ttofali Fani , Liao Chunyu , Manchalu Srinivas , Gray Benjamin N , Beisel Chase L
Published: April 2020

CRISPR-Cas systems comprise diverse adaptive immune systems in prokaryotes whose RNA-directed nucleases have been co-opted for various technologies. Recent efforts have focused on expanding the number of known CRISPR-Cas subtypes to identify nucleases with novel properties. However, the functional diversity of nucleases within each subtype remains poorly explored. Here, we used cell-free transcription-translation systems and human cells to characterize six Cas12a single-effector nucleases from the V-A subtype, including nucleases sharing high sequence identity. While these nucleases readily utilized each other's guide RNAs, they exhibited distinct PAM profiles and apparent targeting activities that did not track based on phylogeny. In particular, two Cas12a nucleases encoded by Prevotella ihumii (PiCas12a) and Prevotella disiens (PdCas12a) shared over 95% amino-acid identity yet recognized distinct PAM profiles, with PiCas12a but not PdCas12a accommodating multiple G’s in PAM positions -2 through -4 and T in position -1. Mutational analyses transitioning PiCas12a to PdCas12a resulted in PAM profiles distinct from either nuclease, allowing more flexible editing in human cells. Cas12a nucleases therefore can exhibit widely varying properties between otherwise related orthologs, suggesting selective pressure to diversify PAM recognition and supporting expansion of the CRISPR toolbox through ortholog mining and PAM engineering.
The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression
Authors: Peruzzi Licia , Coppo Rosanna , Cocchi Enrico , Loiacono Elisa , Bergallo Massimilano , Bodria Monica , Vergano Luca , Krutova Alexandra , Russo Maria Luisa , Amore Alessandro , Lundberg Sigrid , Maixerova Dita , Tesar Vladimir , Perkowska-Ptasińska Agnieszka , Durlik Magdalena , Goumenos Dimitris , Papasotiriou Marios , Galesic Kresimir , Toric Luka , Papagianni Aikaterini , Stangou Maria , Mizerska-Wasiak Malgorzata , Gesualdo Loreto , Montemurno Eustacchio , Benozzi Luisa , Cusinato Stefano , Hryszko Tomasz , Klinger Marian , Kamińska Dorota , Krajewska Magdalena ,   the VALIGA study group of the ERA-EDTA Immunonephrology Working Group
Published: April 2020

The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/β5 and LMP2/β1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/β5 (P < 0.0001). The LMP7/β5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. −1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/β5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/β5 and low CD46 expression.
Early Multicenter Experience With the Neuroform Atlas Stent: Feasibility, Safety, and Efficacy
Authors: Sweid Ahmad , Herial Nabeel , Sajja Kalyan , Chalouhi Nohra , Velagapudi Lohit , Doermann Allison , Kardon Adam , Tjoumakaris Stavropoula , Zarzour Hekmat , Smith Michelle J , Choe Hana , Shah Qaisar , Mackenzie Larami , Kozak Osman , Rosenwasser Robert H , Jabbour Pascal , Gooch M Reid
Published: April 2020

BACKGROUND

The Neuroform Atlas stent™ (by Stryker, Fremont, California) represents the most recent widely available upgrade to intracranial stenting, providing a laser cut open cell stent with a diameter of 3.0 to 4.5 mm that is delivered through an 0.017-inch microcatheter.

OBJECTIVE

To report our initial multicenter experience of the safety, efficacy, and feasibility of the Atlas stent used for treating aneurysms, as well as one case of intracranial stenosis and one carotid artery dissection as well as other pathologies.

METHODS

A retrospective multicenter study of subjects treated with Atlas stent during the period 2018 to 2019.

RESULTS

The total number of patients included in our analysis was 71 patients. The stent was utilized to treat 69 aneurysm cases. Of the aneurysms, 36% presented with acute rupture and 56% of the ruptured aneurysms were high grade. Mean aneurysm dimension was 7 mm with an average neck width of 4.1 mm. Around 30% had received prior treatment. Telescoping or Y-stent was used in 16% of cases. We did not observe any symptomatic major complications in our series. Asymptomatic major complications were seen in 7 patients (10.1%); technical complications occurred in 4.3%. Immediate modified Raymond-Roy-occlusion-outcome class I/II was observed in 87%, and this increased to 97.7% at latest follow-up, which was at 4 mo; 91.8% of patients achieved favorable clinical outcome, and mortality rate was 1.4%.

CONCLUSION

Our series demonstrates the safety, feasibility, and efficacy of the Atlas stent. The low complication rate and the high obliteration rate managing complex aneurysms, even in an acute ruptured setting, are notable.
Intrinsic Cortico-Subcortical Functional Connectivity in Developmental Dyslexia and Developmental Coordination Disorder
Authors: Cignetti Fabien , Nemmi Federico , Vaugoyeau Marianne , Girard Nadine , Albaret Jean-Michel , Chaix Yves , Péran Patrice , Assaiante Christine
Published: April 2020

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are distinct diagnostic disorders. However, they also frequently co-occur and may share a common etiology. It was proposed conceptually a neural network framework that explains differences and commonalities between DD and DCD through impairments of distinct or intertwined cortico-subcortical connectivity pathways. The present study addressed this issue by exploring intrinsic cortico-striatal and cortico-cerebellar functional connectivity in a large (n = 136) resting-state fMRI cohort study of 8–12-year-old children with typical development and with DD and/or DCD. We delineated a set of cortico-subcortical functional circuits believed to be associated with the brain’s main functions (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal control, and default-mode). Next, we assessed, using general linear and multiple kernel models, whether and which circuits distinguished between the groups. Findings revealed that somatomotor cortico-cerebellar and frontoparietal cortico-striatal circuits are affected in the presence of DCD, including abnormalities in cortico-cerebellar connections targeting motor-related regions and cortico-striatal connections mapping onto posterior parietal cortex. Thus, DCD but not DD may be considered as an impairment of cortico-subcortical functional circuits.
Photoperiod and CO2 elevation influence morphological and physiological responses to drought in trembling aspen: implications for climate change-induced migration
Authors: Inoue Sahari , Dang Qing-Lai , Man Rongzhou , Tedla Binyam
Published: April 2020

Past research suggests climate change will cause the climate envelopes of various tree species to shift to higher latitudes and can lead to a northward migration of trees. However, the success and scope of the migration are likely affected by factors that are not contained in the climate envelope, such as photoperiod and interactive effects of multiple environmental factors, and these effects are currently not well understood. In this study, we investigated the interactive effects of CO2 concentrations ([CO2]), photoperiod and soil moisture on the morphological and physiological traits of Populus tremuloides Michx. We grew seedlings under two levels of [CO2] (ambient [CO2] (AC) 400 vs elevated [CO2] (EC) 1000 μmol mol−1), four photoperiod regimes (growing season photoperiods at 48 (seed origin), 52, 55 and 58°N latitude) and two soil moisture regimes (high soil moisture (HSM) vs low soil moisture (LSM), −2 MPa) for two growing seasons in greenhouses. Both morphological and physiological responses were observed. Low soil moisture reduced leaf size, total leaf area and height growth by 33, 46 and 12%, respectively, and increased root/shoot ratio by 20%. The smaller leaf area and increased root/shoot ratio allowed the seedlings in LSM to maintain higher the maximum rate of Rubisco carboxylation (Vcmax) and the maximum rate of electron transport for RuBP regeneration (Jmax) than control seedlings (55 and 83% higher in July, 52 and 70% in August, respectively). Photoperiod and [CO2] modified responses to LSM and LSM altered responses to photoperiod and [CO2], e.g., the August photosynthetic rate was 44% higher in LSM than in HSM under EC but no such a difference existed under AC. The increase in Vcmax and Jmax in response to LSM varied with photoperiod (Vcmax: 36% at 52°N, 22% at 55°N, 47% at 58°N; Jmax: 29% at 52°N, 21% at 55°N, 45% at 58°N). Stomatal conductance and its reduction in response to LSM declined with increasing photoperiod, which can have significant implications for soil moisture effect on northward migration. This study highlights the need to consider the complex interactions of [CO2], photoperiod and soil moisture when planning assisted migration or predicting the natural migration of boreal forests in the future.
Activity of the Succinate Dehydrogenase Inhibitor Fungicide Penthiopyrad Against Sclerotinia sclerotiorum
Authors: Mao Xuewei , Wang Yingfan , Hou Yiping , Zhou Mingguo
Published: April 2020

In present study, the morphological and physiological characteristics of Sclerotinia sclerotiorum (Lib.) de Bary to a novel succinate dehydrogenase inhibitor (SDHI) fungicide penthiopyrad has been reported. The baseline sensitivity of S. sclerotiorum to penthiopyrad was determined using 119 strains by inhibition of mycelial growth. The median effective concentration (EC50) values for penthiopyrad ranged from 0.0096 to 0.2606 μg/ml, and the mean value was 0.0578 (±0.0626) μg/ml. After 1 μg/ml penthiopyrad treatment, mycelia of S. sclerotiorum strains showed increased apical branching and were denser compared with control, and cell membrane permeability significantly increased. In addition, glycerol content, oxalic acid (OA), and exopolysaccharide (EPS) content decreased markedly and mycelial respiration was distinctly inhibited. The number and dry weight of sclerotia significantly decreased after being treated with 2 μg/ml penthiopyrad. Penthiopyrad exhibited both protective and curative activity on the detached rapeseed leaves. Importantly, the above results will provide us more information on penthiopyrad for management of diseases caused by S. sclerotiorum and increase our understanding of action of penthiopyrad against S. sclerotiorum.
What Explains Poor Health-related Quality of Life Associated With Opioid Use Among Adults With Chronic Noncancer Pain Conditions? A Blinder-Oaxaca Decomposition
Authors: Patel Jayeshkumar , Alhussain Khalid , Sambamoorthi Usha
Published: April 2020

Objectives:

The objective of this study was to estimate the extent to which differences in person-level characteristics between opioid users and nonusers contribute to poor health-related quality of life (HRQoL) of long-term opioid users with chronic noncancer pain condition (CNCP).

Materials and Methods:

We conducted a retrospective cohort study of adults (n=5917) using longitudinal data from multiple years of Medical Expenditure Panel Survey. Adults with CNCP were classified into short-term, long-term, and opioid nonusers. We measured HRQoL with physical component summary (PCS) and mental component summary (MCS) scores from the Short-Form 12 Questionnaire. A regression decomposition analysis of results from linear regression was performed.

Results:

Among adults with CNCP, 17.8% and 17.2% reported long-term and short-term opioid use, respectively. Long-term opioid users had lower PCS scores (β=−4.48; P<0.001) as compared with nonusers, even after adjusting for other independent variables. There were no statistically significant associations of long-term opioid use to MCS and short-term opioid use to both PCS and MCS scores. Postlinear regression decomposition analyses revealed that 44.8% of the difference in PCS scores (−3.76 of −8.41) was explained by differences in employment, physical activity, number of CNCP, and other chronic conditions, and use of nonopioid pain medications between long-term opioid users and nonusers.

Conclusions:

Long-term opioid use was associated with lower HRQoL. The difference in HRQoL between long-term opioid users and nonusers was explained by both modifiable and nonmodifiable patient characteristics. Our findings suggest that improving HRQoL among long-term opioid users may require interventions and policies both within and beyond health care.
Ulysses Coercion Through Psychiatric Advanced Directives in Homeless People With Substance Use Disorder: A Qualitative Study of the Colombian Perspective
Authors: Borda Juan P. , Zuleta Pablo
Published: April 2020

Homeless substance users (HSUs) represent a public health challenge given their high social impact and the numerous barriers they have to overcome to receive mental health treatment. Recent public debate in Colombia is concerned with how to approach HSUs within the health system. The aim of this publication was to explore the possibility of implementing Psychiatric Advance Directives (PADs) in HSUs as an alternative to coercive treatment, to favor substance abuse treatment adherence and service retention in this population. For this purpose, the authors conducted 3 in-depth interviews of individuals who previously experienced homelessness and were voluntarily admitted to an inpatient substance abuse treatment ward at the moment of the interview. This research indicates that substance abuse in homeless individuals does not imply an impairment of their mental or legal capacity. Moreover, restraining HSUs during intense craving episodes within inpatient settings by implementation of PAD does not seem to be a viable option given the multiple risks and challenges it poses to mental health care providers. Finally, the use of any coercive measure toward HSUs, and this type of PADs in particular, could potentially be associated with violent episodes or human rights violations within mental health institutions.
The Negative Impact of Cannabis Use on School Grades and Intelligence Among Adolescents
Authors: Bassiony Medhat M. , Fawzi Mohab , Ammar Haidy K. , Khalil Yomna
Published: April 2020

Purpose:

Cannabis use among adolescents is a public health problem, one associated with intellectual and cognitive impairment. This study investigated the negative impact of cannabis use on adolescents’ school grades and intelligence.

Methods:

The study screened 1682 students during their university preadmission medical examination. Thirty-six students tested positive for cannabis, and 36 controls who tested negative for drugs were also included in the study. Sociodemographic and clinical data, school grades, and IQ (Wechsler Adult Intelligence Scale) scores were collected from cases and controls.

Results:

Cases were more likely to have lower final exam grades than controls in secondary and preparatory school, although they had higher grades than controls in primary school before starting cannabis use. Cases were more likely to have lower scores in verbal comprehension, perceptual reasoning, and total IQ than controls. However, the working memory and processing speed scores of both groups were equivalent. Students who started cannabis use at an earlier age (<15 y old) were more likely to have lower scores in total and all domains of IQ except verbal comprehension than students who started at a later age (>15 y old). There was an association between frequent use of cannabis and lower IQ scores (total and all domains).

Conclusions:

Cannabis use is associated with lower school grades and intelligence scores among adolescents, especially those who used cannabis frequently and at a young age.
Spirometric Abnormalities and Lung Function Decline in Current and Former Microwave Popcorn and Current Flavoring Manufacturing Workers
Authors: Cox-Ganser Jean M. , White Sandra K. , Fedan Kathleen B. , Bailey Rachel L. , Fechter-Leggett Ethan , Cummings Kristin J.
Published: April 2020

Objective:

The aim of this study was to compare spirometry results in microwave popcorn and flavoring manufacturing workers.

Methods:

We used NIOSH data on current and former microwave popcorn workers (MPWs) and surveillance data on flavoring manufacturing workers (FMWs).

Results:

Former MPW had higher prevalence of mixed and high severity abnormalities, some had excessive lung function drops. Current MPW had lowest occurrence of excessive lung function drops. FMW with excessive drops and spirometric abnormalities at last test had developed a restrictive pattern. Spirometric abnormalities and excessive drops were associated with work-related factors.

Conclusion:

There was evidence of a healthy worker survivor effect in MPW. Importantly, removal from exposure did not always stabilize lung function decline indicating a need for continued monitoring. The development of a restrictive pattern should raise the level of suspicion for possible work-related disease in flavoring-exposed workers.
Physical Fitness Evaluation of Career Urban and Wildland Firefighters
Authors: Houck Jonathan M. , Mermier Christine M. , Beltz Nicholas M. , Johnson Kelly E. , VanDusseldorp Trisha A. , Escobar Kurt A. , Gibson Ann L.
Published: April 2020

Objective:

Examine the physical fitness of career firefighters and compare their results to normative data and suggested standards for their profession.

Methods:

Eighty firefighters completed a body composition analysis, maximal aerobic capacity (VO2max) test, and fitness testing battery, with results compared with normative value tables. Maximal aerobic capacity was correlated to fitness measures and differences between VO2max quartiles were examined.

Results:

Twenty-two firefighters met the suggested standard for VO2max. Seventy percent of participants were classified as overweight or obese based on body mass index, while 25% were classified as having either “poor” or “very poor” body fat levels. Firefighters were above average for muscular strength.

Conclusion:

The firefighters had low aerobic fitness and higher than optimal body fat levels. Training programs may be necessary to assist firefighters in achieving optimal fitness levels.
Automated Analyzers Are Suited for Diagnosing Celiac Disease Without a Biopsy
Authors: Rozenberg Orit , Rinawi Firas , Haritan Yifat , Yerushalmi Baruch , Kori Michal , Morgenstern Sara , Peleg Sarit , Osyntsov Lidia , Colodner Raul , Shamir Raanan
Published: April 2020

Objectives:

The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue‐transglutaminase (tTg) IgA assays of 4 random‐access analyzers and examine their accuracy in diagnosing CD without a biopsy.

Methods:

We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover.

Results:

In our cohort, all tested tTg IgA‐automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive‐predictive values (PPV) were all >0.99 and negative‐predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93.

Conclusion:

CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high‐volume random‐access analyzers used in our study.