bluuebunny/crossref_metadata_2025 huggingface dataset:
Brugada syndrome and syncope: a practical approach for diagnosis and treatment
Authors: Mascia Giuseppe , Bona Roberta Della , Ameri Pietro , Canepa Marco , Porto Italo , Parati Gianfranco , Crotti Lia , Brignole Michele
Published: November 2020

Syncope in patients with Brugada electrocardiogram pattern may represent a conundrum in the decision algorithm because incidental benign forms, especially neurally mediated syncope, are very frequent in this syndrome similarly to the general population. Arrhythmic syncope in Brugada syndrome typically results from a self-terminating sustained ventricular tachycardia or paroxysmal ventricular fibrillation, potentially leading to sudden cardiac death. Distinguishing syncope due to malignant arrhythmias from a benign form is often difficult unless an electrocardiogram is recorded during the episode. We performed a review of the existing literature and propose a practical approach for diagnosis and treatment of the patients with Brugada syndrome and syncope.
Present GPS velocity field along 1999 Izmit rupture zone: evidence for continuing afterslip 20 yr after the earthquake
Authors: Özarpacı Seda , Doğan Uğur , Ergintav Semih , Çakır Ziyadin , Özdemir Alpay , Floyd Michael , Reilinger Robert
Published: November 2020

In order to better assess earthquake hazards, it is vital to have a better understanding of the spatial and temporal characteristics of fault creep that occur on ruptured faults during the period following major earthquakes. Towards this end, we use new far-field GPS velocities from continuous stations (extending ∼50–70 km from the fault) and updated near-fault GPS survey observations, with high temporal and spatial density, to constrain active deformation along the Mw7.4, 1999 Izmit, Turkey Earthquake fault. We interpret and model deformation as resulting from post-seismic afterslip on the coseismic fault. In the broadest sense, our results demonstrate that logarithmically decaying post-seismic afterslip continues at a significant level 20 yr following 1999 Earthquake. Elastic models indicate substantially shallower apparent locking depths at present than prior to the 1999 Earthquake, consistent with continuing afterslip on the coseismic fault at depth. High-density, near-fault GPS observations indicate shallow creep on the upper 1–2 km of the coseismic fault, with variable rates, the highest and most clearly defined of which reach ∼12 mm yr−1 (10–15 mm yr−1, 95 per cent c.i.) near the epicentre between 2014–2016. This amounts to ∼half the long-term slip deficit rate.
Pulmonary glycogen deficiency as a new potential cause of respiratory distress syndrome
Authors: Testoni Giorgia , Olmeda Bárbara , Duran Jordi , López-Rodríguez Elena , Aguilera Mònica , Hernández-Álvarez María Isabel , Prats Neus , Pérez-Gil Jesús , Guinovart Joan J
Published: November 2020

The glycogenin knockout mouse is a model of Glycogen Storage Disease type XV. These animals show high perinatal mortality (90%) due to respiratory failure. The lungs of glycogenin-deficient embryos and P0 mice have a lower glycogen content than that of wild-type counterparts. Embryonic lungs were found to have decreased levels of mature surfactant proteins SP-B and SP-C, together with incomplete processing of precursors. Furthermore, non-surviving pups showed collapsed sacculi, which may be linked to a significantly reduced amount of surfactant proteins. A similar pattern was observed in glycogen synthase1-deficient mice, which are devoid of glycogen in the lungs and are also affected by high perinatal mortality due to atelectasis.

These results indicate that glycogen availability is a key factor for the burst of surfactant production required to ensure correct lung expansion at the establishment of air breathing. Our findings confirm that glycogen deficiency in lungs can cause respiratory distress syndrome and suggest that mutations in glycogenin and glycogen synthase 1 genes may underlie cases of idiopathic neonatal death.
Sharp Hardy Space Estimates for Multipliers
Authors: Grafakos Loukas , Park Bae Jun
Published: November 2020

We provide an improvement of Calderón and Torchinsky’s version [ 5] of the Hörmander multiplier theorem on Hardy spaces $H^p$ ($0
\min (1,p)$.
Practice- and individual-level antibiotic prescribing associated with antibiotic treatment non-response in respiratory tract infections: a national retrospective observational study
Authors: Peng Zhuoxin , Hayen Andrew , Liu Bette
Published: November 2020

Objectives

Antibiotic overuse results in adverse clinical outcomes. This study quantified the independent contributions of practice- and individual patient-level antibiotic prescribing to antibiotic treatment non-response in respiratory tract infections (RTIs) in primary care.

Methods

RTI episodes with antibiotic prescribed in 2018 were extracted from an Australian national general practice database. Practices were classified into tertiles by total antibiotic prescriptions per patient and ratios of broad- to narrow-spectrum antibiotic prescriptions. The association between practice- and individual patient-level antibiotic prescribing in the previous year and antibiotic treatment non-response (defined as prescription of a different antibiotic) ≤30 days after the initial RTI episode was quantified using generalized estimating equations.

Results

Of 84 597 RTI episodes with antibiotics prescribed in 558 practices, 5570 (6.6%) episodes of treatment non-response were identified. Patients with high individual-level antibiotic prescribing (≥4 prescriptions/year) had an increased risk of treatment non-response (versus no prescriptions/year: OR = 1.64, 95% CI = 1.52–1.77). At the practice level, there was no significant association between total antibiotic prescriptions per patient and treatment non-response (high versus low: OR = 0.99, 95% CI = 0.92–1.06). RTI episodes in practices with high broad- to narrow-spectrum antibiotic ratios had an increased risk of treatment non-response (versus low-ratio practices: OR = 1.14, 95% CI = 1.05–1.23); this association was only observed among patients with <4 antibiotic prescriptions/year.

Conclusions

The general practice-level broad- to narrow-spectrum antibiotic ratio was a predictor of RTI antibiotic treatment non-response in patients with lower individual-level antibiotic use. The measure of practice-level antibiotic prescribing could potentially guide the improvement of antibiotic treatment.
Dietary replacement of fish meal by defatted and fermented soybean meals with taurine supplementation for pompano fish: effects on growth performance, nutrient digestibility, and biological parameters in a long-term feeding period
Authors: Nguyen Hung Phuc , Do Thinh Van , Tran Hau Duc
Published: November 2020

A 16-wk growth trial was conducted to examine the effects of dietary replacement of fish meal by defatted soybean meal (SBM) and fermented soybean meal (FSBM) with taurine supplementation on growth performance, nutrient apparent digestibility coefficient (ADC) and biological parameters of pompano fish. The FSBM was produced by fermenting SBM with Lactobacillus spp. Seven isonitrogenous and isoenergetic diets were formulated to replace 35% or 50% of fish meal by SBM or FSBM with taurine supplementation. The diets are denoted as follows: FM, SBM35, SBM35T, FSBM35T, SBM50, SBM50T, and FSBM50T. The FM (the basal diet) contained fish meal as a main source of dietary protein. Taurine was supplemented to SBM35T, FSBM35T, SBM50T, and FSBM50T at the level of 15 g/kg diet. Pompano juveniles with an initial body weight (BW) of 80 g reared in floating net cages were fed the experimental diets twice daily for 16 wk. Results showed that the final BW, weight gain, and feed conversion ratio of fish fed SBM35 and SBM50 were significantly lower than those of fish fed FM (P < 0.05), indicating that the replacement of fish meal by SBM at the rate of 35% in the diet is excessive for pompano. Supplementation of taurine to the SBM-included diets significantly increased growth performance and feed utilization (P < 0.05); however, these diets did not restore the performance back to a level equivalent to that of fish offered the basal diet. Meanwhile, fish fed FSBM35T had comparable growth and feed performances to those fed FM. Hematocrit values, total biliary bile acid levels, whole body lipid contents, and tissue taurine concentrations of fish fed SBM35 and SBM50 were the lowest among the treatments, but these parameters were improved by taurine supplementation and FSBM inclusion in the diet. Taurine supplementation increased lipid ADC, and SBM fermentation slightly enhanced both lipid and protein ADCs of the fish. These findings suggest that the combination of FSBM and taurine supplementation is an effective way to improve growth performance, nutrient digestibility, and biological parameters, and that FSBM with taurine supplementation can replace 35% of fish meal in pompano diets without any negative effects on growth and feed performances in a long-term feeding period.
Effect of wavy wall strut fuel injector on shock wave development and mixing enhancement of fuel and air for a scramjet combustor
Authors: Kummitha Obula Reddy , Pandey K M
Published: November 2020

The shear mixing and streamline vortices are the notable parameters to influence the air–fuel mixing in hypersonic flows. The shock wave development and Mach number significantly influence the shear mixing phenomenon. Hence, this research introduced an unconventional strut and tested its performance for the generation of shock waves at different flow conditions (M = 2,4,6). The Reynolds-averaged Navier–Stokes equations are solved to evaluate the performance of the new strut. Both the DLR scramjet strut injector and wavy wall strut injector are assessed for the shear mixing development. Turbulence for the association of shock waves, mixing layer, and the boundary layer has been modeled with the SST k-ω model. The variation in shock development and its interactions are investigated further with an increase in Mach number. The scramjet flow structure differentiation found the increased number of oblique shock waves with the wavy wall strut fuel injector. It increases the turbulence level with increased streamline vortices, turbulent intensity, and turbulent kinetic energy. The shock wave generation analysis at different Mach numbers (M = 2,4,6) found fewer interactions between the shock wave and shear layer with increased Mach number. From the examination of shock wave generation and its interaction with the shear layer and analysis of turbulent parameters, it is found that the wavy wall strut has an appreciable effect on shock-induced blend augmentation of fuel and air.
Alternative tactics in male African ground squirrels: the impact of variable rainfall on condition and physiology
Authors: O’Brien Kelsey A , Waterman Jane M , Bennett Nigel C
Published: November 2020

Alternative reproductive tactics occur when conspecifics of the same sex use different behavioral processes to maximize reproductive success. Resource availability can have significant impacts on the proximate factors impacting the success and persistence of alternative tactics, such as an individual’s physiology, immunity, and body condition. Male Cape ground squirrels (Xerus inauris) display two alternative tactics, with some mature males dispersing from their natal groups and joining bands of nonrelated males (band males), whereas others do not disperse and remain philopatric in their natal groups past sexual maturation (natal males). Despite differences in metabolism, home ranges, and behavior, there is no difference in reproductive success between the two tactics, allowing us to test if rainfall (as a measure of primary productivity) influences body condition and physiological indices in tactics when fitness is equal. Over a period of 6 years, rainfall was positively related to body condition (mass–spine length residuals) in band males (N = 76), but not in natal males (N = 75). When we followed 18 males prior to and after dispersal, we also found a positive relationship between body condition and age following dispersal, but not prior to dispersal, and natal males maintained a better body condition in low rainfall years. During 2 years of low rainfall, band males (N = 39) had higher total ectoparasite abundance, and white blood cell differentials, implying they are less able to tolerate parasitic infection than natal males (N = 31). We found no difference in bacterial growth inhibition between tactics, suggesting that band and natal males both are equally resistant to parasites. The poorer body condition of band males during lower rainfall suggests they are less tolerant to parasites in these years. Dispersal during years of low rainfall thus may increase the costs to body condition and parasite infection, but the reproductive benefit of overlapping with more females may contribute to maintaining equal fitness between tactics.
Racial Differences in Population Attributable Risk for Epithelial Ovarian Cancer in the OCWAA Consortium
Authors: Peres Lauren C , Bethea Traci N , Camacho Tareq F , Bandera Elisa V , Beeghly-Fadiel Alicia , Chyn Deanna L , Harris Holly R , Joslin Charlotte E , Moorman Patricia G , Myers Evan , Ochs-Balcom Heather M , Rosenow Will , Setiawan V Wendy , Wu Anna H , Rosenberg Lynn , Schildkraut Joellen M
Published: November 2020

Background

The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women.

Methods

We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided.

Results

Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% confidence interval [CI] = 6.5% to 13.7%) compared with White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including body mass index, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04).

Conclusions

Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.
Effects of desiccation of seeds in nine species with morphophysiological dormancy on germination and embryo growth
Authors: Copete Miguel A , Herranz José M , Herranz Raquel , Copete Elena , Ferrandis Pablo
Published: November 2020

Aims

In species with morphophysiological seed dormancy (MPD), little is known about the effects of desiccation of imbibed seeds on embryo growth and germination. We studied seed responses to dehydration in nine species with different levels of MPD.

Methods

For each species, a control test was conducted by keeping seeds permanently hydrated and exposed to the optimal stratification–incubation sequence to promote embryo growth. Simultaneously, tests were run in which seed stratification was interrupted for 1 month by desiccation at room temperature.

Important Findings

In Clematis vitalba and Ribes alpinum, with nondeep simple MPD, desiccation affected neither embryo growth nor seed viability, but the desiccation led to a decrease of germinative ability in R. alpinum by 16%. The seeds of Narcissus pseudonarcissus subsp. munozii-garmendiae, with deep simple epicotyl MPD, tolerated desiccation in different embryo growth stages, but their germinative ability decreased slightly. The response of species with complex levels of MPD to desiccation was more variable: Delphinium fissum subsp. sordidum, with intermediate complex MPD, and Anthriscus sylvestris and Meum athamanticum, both with deep complex MPD, tolerated desiccation. In contrast, Ribes uva-crispa with nondeep complex MPD, Lonicera pyrenaica with intermediate complex MPD and Chaerophyllum aureum with deep complex MPD, had diminished germination ability by desiccation. Although seeds of the species with simple levels of MPD tolerated desiccation, those of some species with complex levels were also highly tolerant. Thus, desiccation did not induce secondary dormancy in late embryo growth stages. The desiccation tolerance of imbibed seeds of most of the nine species may show their adaptability to climate change in the Mediterranean region.
Predicting morbidity in older travellers during a short-term stay in the tropics: the ELDEST study
Authors: Vlot Jessica A , Vive Marissa G D , Brockhoff Henricus J , van Genderen Pieter J J , Trompenaars Marie-Christine E , van Steenbergen James E , Visser Leonardus G
Published: November 2020

Background

Older persons may suffer more from travel-related health problems because of ageing and underlying chronic disorders. Knowledge on who is more likely to have these health problems helps to tailor travel health advice more specifically. This study aimed to determine predictors of travel-related morbidity in older travellers by assessing their pre-travel characteristics and performance using physical and cognitive functioning tests.

Methods

Multicentre prospective cohort study among older travellers (≥60 years) who consulted one of the participating Dutch travel clinics. Handgrip strength and cognitive performance were measured pre-travel. Participants completed questionnaires before departure and 1 and 4 weeks after return. A diary recorded health complaints during travel until 2-week post-travel.

Results

In total, 477 travellers completed the study (follow-up rate of 97%). Participants’ median age was 66 years. The most visited regions were South-East Asia (34%) and South Asia (14%). Median travel duration was 19 days. Polypharmacy (≥5 medications per day) was not uncommon (16%). The median Charlson Comorbidity Index (CCI) score was 0. Self-reported travel-related infectious diseases concerned primarily respiratory tract infections (21%) and gastroenteritis (10%) whereas non-infectious complaints were injuries (13%), peripheral edema (12%) and dehydration (3%). Medical assistance was sought by 18%, mostly post-travel from their general practitioner (87%). Self-reported physical and mental health-related quality of life significantly improved during and after travel. Predictors for an increased risk of travel-related morbidity were higher CCI score, more travel experience, longer travel duration, higher number of daily medications, visiting northern Africa or South-East and East Asia, and phone and social media use.

Conclusion

Older Dutch travellers are generally fit, well-prepared and suffer not only from common infectious health problems, but also from injuries. Travel improved their self-perceived health. The predictors could be used to identify the more at-risk older traveller and to decrease travel-related morbidity by optimizing pre-travel advice.
The Nuremberg Trial in Megillat Esther
Authors: Ron Zvi
Published: November 2020

There is a very popular teaching in Orthodox circles1 that the small letters found in the writing of the names of the sons of Haman in Megillat Esther are a reference to the year of the Nuremberg trials and the ten Nazis hanged at that time. In this article we will explore where this teaching originated, what it is based on, and what its message is understood to be.
The Crab nebula variability at short time-scales with the Cherenkov telescope array
Authors: Mestre E , de Oña Wilhelmi E , Khangulyan D , Zanin R , Acero F , Torres D F
Published: November 2020

Since 2009, several rapid and bright flares have been observed at high energies (>100 MeV) from the direction of the Crab nebula. Several hypotheses have been put forward to explain this phenomenon, but the origin is still unclear. The detection of counterparts at higher energies with the next generation of Cherenkov telescopes will be determinant to constrain the underlying emission mechanisms. We aim at studying the capability of the Cherenkov Telescope Array (CTA) to explore the physics behind the flares, by performing simulations of the Crab nebula spectral energy distribution, both in flaring and steady state, for different parameters related to the physical conditions in the nebula. In particular, we explore the data recorded by Fermi during two particular flares that occurred in 2011 and 2013. The expected GeV and TeV gamma-ray emission is derived using different radiation models. The resulting emission is convoluted with the CTA response and tested for detection, obtaining an exclusion region for the space of parameters that rule the different flare emission models. Our simulations show different scenarios that may be favourable for achieving the detection of the flares in Crab with CTA, in different regimes of energy. In particular, we find that observations with low sub-100 GeV energy threshold telescopes could provide the most model-constraining results.
Simulations of multiple nova eruptions induced by wind accretion in symbiotic systems
Authors: Hillman Yael , Kashi Amit
Published: November 2020

We use a combined binary evolution code including dynamical effects to study nova eruptions in a symbiotic system. Following the evolution, over ∼105 yr, of multiple consecutive nova eruptions on the surface of a $1.25\hbox{-}\rm {M_\odot }$ white dwarf (WD) accretor, we present a comparison between simulations of two types of systems. The first is the common, well-known, cataclysmic variable (CV) system in which a main-sequence donor star transfers mass to its WD companion via Roche lobe overflow. The second is a detached, widely separated, symbiotic system in which an asymptotic giant branch donor star transfers mass to its WD companion via strong winds. For the latter we use the Bondi–Hoyle–Lyttleton prescription along with orbital dynamics to calculate the accretion rate. We use the combined stellar evolution code to follow the nova eruptions of both simulations including changes in mass, accretion rate, and orbital features. We find that while the average accretion rate for the CV remains fairly constant, the symbiotic system experiences distinct epochs of high and low accretion rates. The examination of epochs for which the accretion rates of both simulations are similar shows that the evolutionary behaviors are identical. We obtain that for a given WD mass, the rate that mass is accreted ultimately determines the development, and that the stellar class of the donor is of no significance to the development of novae. We discuss several observed systems and find that our results are consistent with estimated parameters of novae in widely separated symbiotic systems.
fink, a new generation of broker for the LSST community
Authors: Möller Anais , Peloton Julien , Ishida Emille E O , Arnault Chris , Bachelet Etienne , Blaineau Tristan , Boutigny Dominique , Chauhan Abhishek , Gangler Emmanuel , Hernandez Fabio , Hrivnac Julius , Leoni Marco , Leroy Nicolas , Moniez Marc , Pateyron Sacha , Ramparison Adrien , Turpin Damien , Ansari Réza , Allam Jr Tarek , Bajat Armelle , Biswas Biswajit , Boucaud Alexandre , Bregeon Johan , Campagne Jean-Eric , Cohen-Tanugi Johann , Coleiro Alexis , Dornic Damien , Fouchez Dominique , Godet Olivier , Gris Philippe , Karpov Sergey , Nebot Gomez-Moran Ada , Neveu Jérémy , Plaszczynski Stephane , Savchenko Volodymyr , Webb Natalie
Published: November 2020

fink is a broker designed to enable science with large time-domain alert streams such as the one from the upcoming Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). It exhibits traditional astronomy broker features such as automatized ingestion, annotation, selection, and redistribution of promising alerts for transient science. It is also designed to go beyond traditional broker features by providing real-time transient classification that is continuously improved by using state-of-the-art deep learning and adaptive learning techniques. These evolving added values will enable more accurate scientific output from LSST photometric data for diverse science cases while also leading to a higher incidence of new discoveries which shall accompany the evolution of the survey. In this paper, we introduce fink, its science motivation, architecture, and current status including first science verification cases using the Zwicky Transient Facility alert stream.
Reduced Global Genetic Differentiation of Exploited Marine Fish Species
Authors: Gandra Miguel , Assis Jorge , Martins Manuel Ramos , Abecasis David
Published: November 2020

Knowledge on genetic structure is key to understand species connectivity patterns and to define the spatiotemporal scales over which conservation management plans should be designed and implemented. The distribution of genetic diversity (within and among populations) greatly influences species ability to cope and adapt to environmental changes, ultimately determining their long-term resilience to ecological disturbances. Yet, the drivers shaping connectivity and structure in marine fish populations remain elusive, as are the effects of fishing activities on genetic subdivision. To investigate these questions, we conducted a meta-analysis and compiled genetic differentiation data (FST/ΦST estimates) for more than 170 fish species from over 200 published studies globally distributed. We modeled the effects of multiple life-history traits, distance metrics, and methodological factors on observed population differentiation indices and specifically tested whether any signal arising from different exposure to fishing exploitation could be detected. Although the myriad of variables shaping genetic structure makes it challenging to isolate the influence of single drivers, results showed a significant correlation between commercial importance and genetic structure, with widespread lower population differentiation in commercially exploited species. Moreover, models indicate that variables commonly used as proxy for connectivity, such as larval pelagic duration, might be insufficient, and suggest that deep-sea species may disperse further. Overall, these results contribute to the growing body of knowledge on marine genetic connectivity and suggest a potential effect of commercial fisheries on the homogenization of genetic diversity, highlighting the need for additional research focused on dispersal ecology to ensure long-term sustainability of exploited marine species.
Genome-wide investigation of the dynamic changes of epigenome modifications after global DNA methylation editing
Authors: Broche Julian , Kungulovski Goran , Bashtrykov Pavel , Rathert Philipp , Jeltsch Albert
Published: November 2020

Chromatin properties are regulated by complex networks of epigenome modifications. Currently, it is unclear how these modifications interact and if they control downstream effects such as gene expression. We employed promiscuous chromatin binding of a zinc finger fused catalytic domain of DNMT3A to introduce DNA methylation in HEK293 cells at many CpG islands (CGIs) and systematically investigated the dynamics of the introduced DNA methylation and the consequent changes of the epigenome network. We observed efficient methylation at thousands of CGIs, but it was unstable at about 90% of them, highlighting the power of genome-wide molecular processes that protect CGIs against DNA methylation. Partially stable methylation was observed at about 1000 CGIs, which showed enrichment in H3K27me3. Globally, the introduced DNA methylation strongly correlated with a decrease in gene expression indicating a direct effect. Similarly, global but transient reductions in H3K4me3 and H3K27ac were observed after DNA methylation but no changes were found for H3K9me3 and H3K36me3. Our data provide a global and time-resolved view on the network of epigenome modifications, their connections with DNA methylation and the responses triggered by artificial DNA methylation revealing a direct repressive effect of DNA methylation in CGIs on H3K4me3, histone acetylation, and gene expression.
The CONJUDOR pipeline for multiplexed knockdown of gene pairs identifies RBBP-5 as a germ cell reprogramming barrier in C. elegans
Authors: Kazmierczak Marlon , Farré i Díaz Carlota , Ofenbauer Andreas , Herzog Sergej , Tursun Baris
Published: November 2020

Multiple gene activities control complex biological processes such as cell fate specification during development and cellular reprogramming. Investigating the manifold gene functions in biological systems requires also simultaneous depletion of two or more gene activities. RNA interference-mediated knockdown (RNAi) is commonly used in Caenorhabditis elegans to assess essential genes, which otherwise lead to lethality or developmental arrest upon full knockout. RNAi application is straightforward by feeding worms with RNAi plasmid-containing bacteria. However, the general approach of mixing bacterial RNAi clones to deplete two genes simultaneously often yields poor results. To address this issue, we developed a bacterial conjugation-mediated double RNAi technique ‘CONJUDOR’. It allows combining RNAi bacteria for robust double RNAi with high-throughput. To demonstrate the power of CONJUDOR for large scale double RNAi screens we conjugated RNAi against the histone chaperone gene lin-53 with more than 700 other chromatin factor genes. Thereby, we identified the Set1/MLL methyltransferase complex member RBBP-5 as a novel germ cell reprogramming barrier. Our findings demonstrate that CONJUDOR increases efficiency and versatility of RNAi screens to examine interconnected biological processes in C. elegans with high-throughput.
Implementation Intentions to Reduce Smoking: A Systematic Review of the Literature
Authors: Hagerman Charlotte J , Hoffman Rebecca K , Vaylay Sruthi , Dodge Tonya
Published: November 2020

Implementation intentions are a goal-setting technique in which an individual commits to perform a particular behavior when a specific context arises. Recently, researchers have begun studying how implementation intention (II) interventions can facilitate antismoking efforts. The current systematic review synthesized results of experimental studies that tested the effect of an II intervention on smoking cognitions and behavior. Of 29 reviewed articles, 11 studies met inclusion criteria. Nine studies (81.8%) tested an II intervention as a cessation tool for current smokers, whereas two tested II interventions as a tool to prevent smoking among predominantly nonsmoking adolescents. A majority of the studies (66.7%) testing II interventions as a cessation tool reported a positive effect on cessation at long-term follow-up. Of the two studies testing II interventions as a tool for prevention, one study found a positive effect on long-term follow-up. Methodology varied between the studies, highlighting the discrepancies between what researchers consider “implementation intentions” to be. II interventions are a promising tool for antismoking efforts, but more research is necessary to determine the best methodology and the populations for whom this intervention will be most effective.

Implications

Brief, free, and easily scalable, II interventions to prevent smoking are highly attractive for antismoking efforts. This review outlines the circumstances under which II interventions have demonstrated effectiveness in helping people resist smoking cigarettes. We illuminate gaps in the existing literature, limitations, methodological discrepancies between studies, and areas for future study.
Which blood cutoff value should be used for vitamin A deficiency in children aged 3–10 years? A systematic review
Authors: Collese Tatiana S , Norde Marina M , Nascimento-Ferreira Marcus V , Kim Hanseul , Marchioni Dirce M , Carvalho Heráclito B , Giovannucci Edward
Published: November 2020

Context

Blood cutoff values for vitamin A deficiency in children aged 3–10 years have not been addressed in the literature.

Objective

To identify blood retinol concentrations for determining severe vitamin A deficiency in children aged 3–10 years.

Data Sources

The MEDLINE, Web of Science, Embase, and Scopus databases were searched.

Data Extraction

Two reviewers independently extracted article data and assessed quality.

Data Analysis

The hierarchical summary receiver operating characteristic models were applied for the diagnostic accuracy meta-analysis. This review is registered at PROSPERO (identifier: CRD42020149367).

Results

A total of 15 articles met the eligibility criteria, and 9 were included in the diagnostic accuracy meta-analysis. The summary estimates (95%CI) were: Sensitivity, 0.39 (0.20–0.62); specificity, 0.79 (0.65–0.88); positive likelihood ratio, 1.85 (1.33–2.57); and negative likelihood ratio, 0.77 (0.60–0.99). The area under the curve of the overall analysis was 0.68 (95%CI 0.63–0.72).

Conclusions

Blood retinol concentrations have low diagnostic accuracy for severe vitamin A deficiency in children aged 3–10 years. Therefore, there is unclear evidence about the preferable cutoff point for determining severe vitamin A deficiency in children in this age group.
Psb35 Protein Stabilizes the CP47 Assembly Module and Associated High-Light Inducible Proteins during the Biogenesis of Photosystem II in the CyanobacteriumSynechocystissp. PCC6803
Authors: Pascual-Aznar Guillem , Konert Grzegorz , Bečkov� Martina , Kotabov� Eva , Gardian Zdenko , Knoppov� Jana , Bučinsk� Lenka , Kaňa Radek , Sobotka Roman , Komenda Josef
Published: November 2020

Photosystem II (PSII) is a large membrane protein complex performing primary charge separation in oxygenic photosynthesis. The biogenesis of PSII is a complicated process that involves a coordinated linking of assembly modules in a precise order. Each such module consists of one large chlorophyll (Chl)-binding protein, number of small membrane polypeptides, pigments and other cofactors. We isolated the CP47 antenna module from the cyanobacterium Synechocystis sp. PCC 6803 and found that it contains a 11-kDa protein encoded by the ssl2148 gene. This protein was named Psb35 and its presence in the CP47 module was confirmed by the isolation of FLAG-tagged version of Psb35. Using this pulldown assay, we showed that the Psb35 remains attached to CP47 after the integration of CP47 into PSII complexes. However, the isolated Psb35-PSIIs were enriched with auxiliary PSII assembly factors like Psb27, Psb28-1, Psb28-2 and RubA while they lacked the lumenal proteins stabilizing the PSII oxygen-evolving complex. In addition, the Psb35 co-purified with a large unique complex of CP47 and photosystem I trimer. The absence of Psb35 led to a lower accumulation and decreased stability of the CP47 antenna module and associated high-light-inducible proteins but did not change the growth rate of the cyanobacterium under the variety of light regimes. Nevertheless, in comparison with WT, the Psb35-less mutant showed an accelerated pigment bleaching during prolonged dark incubation. The results suggest an involvement of Psb35 in the life cycle of cyanobacterial Chl-binding proteins, especially CP47.
Adaptation or Exploration? Understanding Older Workers’ Plans for Post-Retirement Paid and Volunteer Work
Authors: van Solinge Hanna , Damman Marleen , Hershey Douglas A
Published: November 2020

Numerous investigations have sought to understand the types of individuals who engage in post-retirement work. However, little is known about why older adults are motivated to engage. The aim of the present article is to examine the extent to which two possible mechanisms—adaptation (adjusting to the loss of work role) and exploration (retirement as opportunity to engage in activities in line with personal values)—play a role in explaining planning for paid work or volunteering after retirement. Analyses are based on large-scale survey data collected in 2015 among older workers in the Netherlands (N = 6,278). Results show that the large majority of older Dutch workers have plans for post-retirement paid and/or volunteer work. Moreover, both mechanisms appear to contribute to the understanding of post-retirement work plans, yet in different ways. Specifically, older workers who expect to miss latent work functions are more likely to have plans for post-retirement work, with their general values guiding the type of work they gravitate toward. Having plans for post-retirement paid work was more prevalent among older workers who attached more importance to personal growth, whereas having plans for volunteer work was more prevalent among older workers who had a stronger social orientation. Moreover, results suggest that men, more often than women, translate the anticipated loss of latent work functions into plans for post-retirement paid work. These insights regarding the motivational antecedents of post-retirement work plans are highly relevant in light of policy discussions of active and healthy aging.
Time Management Strategies for New Nurses
Authors: Leis Sheila J. , Anderson Amanda
Published: November 2020

This column is designed to help new nurses in their first year at the bedside—a time of insecurity, growth, and constant challenges—and to offer advice as they learn what it means to be a nurse. This article provides strategies and tips new nurses can use to improve their time management skills.
CNS-Active Medications Widely Prescribed for Adults with Dementia
Authors: Rosenberg Karen
Published: November 2020

According to this study:

Frequent prescribing of opioids and other central nervous system—active medications for community-dwelling Medicare beneficiaries with dementia raises concerns about the risk–benefit balance.
Moderators of the Effect of Spinal Manipulative Therapy on Pain Relief and Function in Patients with Chronic Low Back Pain
Authors: de Zoete Annemarie , de Boer Michiel R. , Rubinstein Sidney M. , van Tulder Maurits W. , Underwood Martin , Hayden Jill A. , Buffart Laurien M. , Ostelo Raymond
Published: November 2020

Study Design.

Individual participant data (IPD) meta-analysis.

Objective.

The aim of this study was to identify which participant characteristics moderate the effect of spinal manipulative therapy (SMT) on pain and functioning in chronic LBP.

Summary of Background.

The effects of SMT are comparable to other interventions recommended in guidelines for chronic low back pain (LBP); however, it is unclear which patients are more likely to benefit from SMT compared to other therapies.

Methods.

IPD were requested from randomized controlled trials (RCTs) examining the effect of SMT in adults with chronic LBP for pain and function compared to various other therapies (stratified by comparison). Potential patient moderators (n = 23) were a priori based on their clinical relevance. We investigated each moderator using a one-stage approach with IPD and investigated this interaction with the intervention for each time point (1, 3, 6, and 12 months).

Results.

We received IPD from 21 of 46 RCTs (n = 4223). The majority (12 RCTs, n = 2249) compared SMT to recommended interventions. The duration of LBP, baseline pain (confirmatory), smoking, and previous exposure to SMT (exploratory) had a small moderating effect across outcomes and follow-up points; these estimates did not represent minimally relevant differences in effects; for example, patients with <1 year of LBP demonstrated more positive point estimates for SMT versus recommended therapy for the outcome pain (mean differences ranged from 4.97 (95% confidence interval, CI: −3.20 to 13.13) at 3 months, 10.76 (95% CI: 1.06 to 20.47) at 6 months to 5.26 (95% CI: –2.92 to 13.44) at 12 months in patients with over a year LBP. No other moderators demonstrated a consistent pattern across time and outcomes. Few moderator analyses were conducted for the other comparisons because of too few data.

Conclusion.

We did not identify any moderators that enable clinicians to identify which patients are likely to benefit more from SMT compared to other treatments.

Level of Evidence: 2
Intravenous Immunoglobulin Plus Methylprednisolone Mitigate Respiratory Morbidity in Coronavirus Disease 2019
Authors: Sakoulas George , Geriak Matthew , Kullar Ravina , Greenwood Kristina L. , Habib MacKenzie , Vyas Anuja , Ghafourian Mitra , Dintyala Venkata Naga Kiran , Haddad Fadi
Published: November 2020

Objectives:

Dysregulated neutrophil and platelet interactions mediate immunothrombosis and cause lung injury in coronavirus disease 2019. IV immunoglobulin modulates neutrophil activation through FcγRIII binding. We hypothesized that early therapy with IV immunoglobulin would abrogate immunothrombosis and improve oxygenation and reduce progression to mechanical ventilation in coronavirus disease 2019 pneumonia.

Design:

Prospective randomized open label.

Setting:

Inpatient hospital.

Patients and Intervention:

Hypoxic subjects with coronavirus disease 2019 pneumonia were randomized 1:1 to receive standard of care plus IV immunoglobulin 0.5 g/kg/d with methylprednisolone 40 mg 30 minutes before infusion for 3 days versus standard of care alone.

Main Results:

Sixteen subjects received IV immunoglobulin and 17 standard of care. Median ages were 51 and 58 years for standard of care and IV immunoglobulin, respectively. Acute Physiology and Chronic Health Evaluation II and Charlson comorbidity scores were similar for IV immunoglobulin and standard of care. Seven standard of care versus two IV immunoglobulin subjects required mechanical ventilation (p = 0.12, Fisher exact test). Among subjects with A-a gradient of greater than 200 mm Hg at enrollment, the IV immunoglobulin group showed: 1) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p = 0.038 Fisher exact test), 2) shorter median hospital length of stay (11 vs 19 d, p = 0.01 Mann Whitney U test), 3) shorter median ICU stay (2.5 vs 12.5 d, p = 0.006 Mann Whitey U test), and 4) greater improvement in Pao
2/Fio
2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [–115 to +157], p = 0.01, Mann Whitney U test) than standard of care. Pao
2/Fio
2 improvement at day 7 was significantly less for the standard of care patients who received glucocorticoid therapy than those in the IV immunoglobulin arm (p = 0.0057, Mann Whiney U test).

Conclusions:

This pilot study showed that IV immunoglobulin significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in coronavirus disease 2019 patients with A-a gradient greater than 200 mm Hg. A phase 3 multicenter randomized double-blinded clinical trial is under way to validate these findings.
Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients*
Authors: Rosano Antonio , Martinelli Enrico , Fusina Federica , Albani Filippo , Caserta Rosalba , Morandi Alessandro , Dell’Agnolo Piera , Dicembrini Alessandra , Mansouri Leila , Marchini Andrea , Schivalocchi Valeria , Natalini Giuseppe
Published: November 2020

Objectives:

Early tracheotomy, defined as a procedure performed within 10 days from intubation, is associated with more ventilator free days, shorter ICU stay, and lower mortality than late tracheotomy. During the coronavirus disease 2019 pandemic, it was especially important to save operating room resources and to have a shorter ICU stay for patients, when ICUs had insufficient beds. In this context of limited resources, early percutaneous tracheostomy could be an effective way to manage mechanically ventilated patients. Nevertheless, current recommendations suggest delaying or avoiding the tracheotomy in coronavirus disease 2019 patients. Aim of the study was to analyze the hospital mortality of coronavirus disease 2019 patients who had received early percutaneous tracheostomy and factors associated with removal of tracheostomy cannula at ICU discharge.

Design:

Cohort study.

Setting:

Coronavirus disease 2019 ICU.

Patients:

Adult patients with coronavirus disease 2019 3 days after ICU admission.

Interventions:

None.

Measurements and Main Results:

Three days after ICU admission, 164 patients were present in ICU and included in the analysis. One-hundred and twenty-one patients (74%) were tracheostomized, whereas the other 43 (26%) were managed with translaryngeal intubation only. In multivariable analysis, early percutaneous tracheostomy was associated with lower hospital mortality. Sixty-six of tracheostomized patients (55%) were discharged alive from the hospital. Age and male sex were the only characteristics that were independently associated with mortality in the tracheostomized patients (45.5% and 62.8% in tracheostomized and nontracheostomized patients, respectively; p = 0.009). Tracheostomy tube was removed in 47 of the tracheostomized patients (71%). The only variable independently associated with weaning from tracheostomy at ICU discharge was a faster start of spontaneous breathing after tracheotomy was performed.

Conclusions:

Early percutaneous tracheostomy was safe and effective in coronavirus disease 2019 patients, giving a good chance of survival and of weaning from tracheostomy cannula at ICU discharge.
An update on adult forms of hereditary pheochromocytomas and paragangliomas
Authors: Dariane Charles , Goncalves Judith , Timsit Marc-Olivier , Favier Judith
Published: November 2020

Purpose of review

Pheochromocytomas and paragangliomas (PPGL) display a strong genetic determinism with 40% of inherited forms. The purpose of this review is to provide an update on current knowledge on adult forms of hereditary PPGL and their management.

Recent findings

PPGL are genetically-driven in 70% of cases, with germline and/or somatic mutations identified in more than 20 genes. Although eight new susceptibility genes have recently emerged, mutations on SDHx genes remain the most frequent. In addition to SDHB, mutations in SLC25A11, FH and MDH2 may predispose to a metastatic disease and somatic alterations including TERT and ATRX mutations, and the differential expression on noncoding RNAs are also associated with the occurrence of metastases.

The biochemical diagnosis remains the mainstay of functional PPGL and does not differ between hereditary PPGL while the choice of the best nuclear imaging approach is dictated by the tumor type and can be influenced by the presence of a germline mutation (18F-DOPA PET/CT for cluster 2 mutation and 68Ga-DOTATATE PET/CT for cluster 1 mutation).

A systematic genetic testing and counselling is recommended for all PPGL patients and should lead to conservative surgery and an adapted follow up, in case of hereditary form.