bluuebunny/crossref_metadata_2025 huggingface dataset:
ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ
Authors: Rayner Stephanie L , Cheng Flora , Hogan Alison L , Grima Natalie , Yang Shu , Ke Yazi D , Au Carol G , Morsch Marco , De Luca Alana , Davidson Jennilee M , Molloy Mark P , Shi Bingyang , Ittner Lars M , Blair Ian , Chung Roger S , Lee Albert
Published: March 2021

Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD. CCNF encodes for the protein cyclin F, a substrate recognition component of an E3 ubiquitin ligase. We have previously shown that ALS/FTD-linked mutations in CCNF cause disruptions to overall protein homeostasis that leads to a build-up of K48-linked ubiquitylated proteins as well as defects in autophagic machinery. To investigate further processes that may be affected by cyclin F, we used a protein-proximity ligation method, known as Biotin Identification (BioID), standard immunoprecipitations and mass spectrometry to identify novel interaction partners of cyclin F and infer further process that may be affected by the ALS/FTD-causing mutation. Results demonstrate that cyclin F closely associates with proteins involved with RNA metabolism as well as a number of RNA-binding proteins previously linked to ALS/FTD, including SFPQ. Notably, the overexpression of cyclin F(S621G) led to the aggregation and altered subcellular distribution of SFPQ in human embryonic kidney (HEK293) cells, while leading to altered degradation in primary neurons. Overall, our data links ALS/FTD-causing mutations in CCNF to converging pathological features of ALS/FTD and provides a link between defective protein degradation systems and the pathological accumulation of a protein involved in RNA processing and metabolism.
Downregulation of TOP2 modulates neurodegeneration caused by GGGGCC expanded repeats
Authors: Jiao Bin , Wang Mengli , Feng Hao , Bao Han , Zhang Feiran , Wu Hao , Wang Junling , Tang Beisha , Jin Peng , Shen Lu
Published: March 2021

GGGGCC repeats in a non-coding region of the C9orf72 gene have been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We previously showed that the GGGGCC expanded repeats alone were sufficient to cause neurodegeneration in Drosophila. Recent evidence indicates that GGGGCC expanded repeats can modify various gene transcriptomes. To determine the role of these genes in GGGGCC-mediated neurotoxicity, we screened an established Drosophila model expressing GGGGCC expanded repeats in this study. Our results showed that knockdown of the DNA topoisomerase II (Top2) gene can specifically modulate GGGGCC-associated neurodegeneration of the eye. Furthermore, chemical inhibition of Top2 or siRNA-induced Top2 downregulation could alleviate the GGGGCC-mediated neurotoxicity in Drosophila assessed by eye neurodegeneration and locomotion impairment. By contrast, upregulated Top2 levels were detected in Drosophila strains, and moreover, TOP2A level was also upregulated in Neuro-2a cells expressing GGGGCC expanded repeats, as well as in the brains of Sod1G93A model mice. This indicated that elevated levels of TOP2A may be involved in a pathway common to the pathophysiology of distinct ALS forms. Moreover, through RNA-sequencing, a total of 67 genes, involved in the pathways of intracellular signaling cascades, peripheral nervous system development, and others, were identified as potential targets of TOP2A to modulate GGGGCC-mediated neurodegeneration.
A global approach to addressing the policy, research and social challenges of male reproductive health
Authors: Barratt Christopher L R , De Jonge Christopher J , Anderson Richard A , Eisenberg Michael L , Garrido Nicolás , Rautakallio Hokkanen Satu , Krausz Csilla , Kimmins Sarah , O’Bryan Moira K , Pacey Allan A , Tüttelmann Frank , Veltman Joris A
Published: March 2021

Male infertility is a global health issue; yet to a large extent, our knowledge of its causes, impact and consequence is largely unknown. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger compared to fertile men. Moreover, several studies point to a significant adverse effect on the health of the offspring. From the startling lack of progress in male contraception combined with the paucity of improvements in the diagnosis of male infertility, we conclude there is a crisis in male reproductive health. The Male Reproductive Health Initiative has been organized to directly address these issues (www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI). The Working Group will formulate an evidence-based strategic road map outlining the ways forward. This is an open consortium desiring to engage with all stakeholders and governments.
New insight into trophic niche partitioning and diet of mackerel (Scomber scombrus) and herring (Clupea harengus) in Icelandic waters
Authors: Kvaavik Cecilia , Óskarsson Gudmundur J , Pétursdóttir Hildur , Marteinsdóttir Gudrun , Daníelsdóttir Anna Kristín
Published: March 2021

Understanding the competitive interactions of ecological similar species is essential to determine their role and niche in the ecosystem. Using both conventional dietary methods and stable isotope analysis, we examined the feeding ecology, trophic position and possible niche partitioning of Northeast Atlantic mackerel (Scomber scombrus), Icelandic summer spawning (ISS) herring (Clupea harengus), and Norwegian spring spawning (NSS) herring from Icelandic waters during the spring and summer 2012 and 2014. The stomach analysis showed differences in prey preferences among the species during summer, where mackerel diets were almost exclusively calanoid copepods, while herring ate larger zooplankton, i.e. euphausiids and amphipods. Analysis of isotopic diet contribution of mackerel and herring using Bayesian mixing models, representing mainly the spring consumption, revealed that euphausiids were the main dietary contributor of both mackerel and herring. Fish prey were also an important dietary source for ISS herring, and amphipods were important to the diet of NSS herring. In addition, mackerel encompassed a broad isotopic niche, whereas the two herring stocks had narrower and separated niches from each other. The results from this analysis reveal new and holistic information into the diet of these species, which have various ecological implications.
Grandmothers’ endocrine disruption during pregnancy, low birth weight, and preterm birth in third generation
Authors: Yim Gyeyoon , Roberts Andrea , Wypij David , Kioumourtzoglou Marianthi-Anna , Weisskopf Marc G
Published: March 2021

Background

Diethylstilbestrol (DES) is an endocrine-disrupting pharmaceutical prescribed to pregnant women to prevent pregnancy complications between the 1940s and 1970s. Although DES has been shown in animal studies to have multigenerational effects, only two studies have investigated potential multigenerational effects in humans on preterm birth (PTB), and none on low birthweight (LBW)—major determinants of later life health.

Methods

Nurses’ Health Study (NHS) II participants (G1; born 1946–64) reported their mothers’ (G0) use of DES while pregnant with them. We used cluster-weighted generalized estimating equations to estimate odds ratios (OR) and 95% confidence intervals (CI) for risk of LBW and PTB among the grandchildren by grandmother use of DES. G1 birthweight and gestational age were considered to explore confounding by indication.

Results

Among 54 334 G0-G1/grandmother-mother pairs, 973 (1.8%) G0 used DES during pregnancy with G1. Of the 128 275 G2 children, 4369 (3.4%) were LBW and 7976 (6.2%) premature. Grandmother (G0) use of DES during pregnancy was associated with an increased risk of G2 LBW [adjusted OR (aOR) = 3.09; 95% CI: 2.57, 3.72], that was reduced when restricted to term births (aOR = 1.59; 95% CI: 1.08, 2.36). The aOR for PTB was 2.88 (95% CI: 2.46, 3.37). Results were essentially unchanged when G1 birthweight and gestational age were included in the model, as well as after adjusting for other potential intermediate variables, such as G2 pregnancy-related factors.

Conclusions

Grandmother use of DES during pregnancy is associated with an increased risk of LBW, predominantly through an increased risk of PTB. Results when considering G1 birth outcomes suggest this does not result from confounding by indication.
Biological Control ofAphis spiraecola(Hemiptera: Aphididae) Using Three Different Flowering Plants in Apple Orchards
Authors: Cai Zhiping , Ouyang Fang , Zhang Xingrui , Chen Jing , Xiao Yunli , Ge Feng , Zhang Jianping
Published: March 2021

Increasing the biodiversity of agroecosystems can increase populations of natural enemies that are useful for pest control. Orchards often have a low diversity of plant species, which is not conducive to maintaining ecosystem functions and services. However, additional flowering plants could provide natural enemies with beneficial resources. To assess the ability of flowering plants to attract predators and increase the biological control of Aphis spiraecola Patch, we established individual plots of three different flowering plant species with sequential bloom periods between the rows of apple orchard. These plants attracted predators such as Coccinellidae, Syrphidae, and Chrysopidae when flowering. The density of predators on trees in the three flowering plant plots was significantly higher than that in the control, whereas the density of aphids on trees in Orychophragmus violaceus (L.) O. E. Schulz (Rhoeadales: Brassicaceae) and Cnidium monnieri (Linn.) Cuss. (Apiales: Apiaceae) plots were significantly lower than that in control. The density of aphids on trees in Calendula officinalis L. (Asterales: Asteraceae) plots was significantly lower than in other plots at second peak period. There was a significant negative correlation between the population of aphids and predators on trees at peak of aphids. Cage exclusion tests showed that the biocontrol services index (BSI) of O. violaceus was highest (32.7%) on 24 May, and the BSI of C. monnieri was highest (47.6%) on 7 June. Our results suggest that the temporal combination of different flowering plants could provide useful effective biocontrol to management pest in orchard.
Long-Term Colorectal Cancer Incidence and Mortality After Colonoscopy Screening According to Individuals’ Risk Profiles
Authors: Wang Kai , Ma Wenjie , Wu Kana , Ogino Shuji , Giovannucci Edward L , Chan Andrew T , Song Mingyang
Published: March 2021

Background

It remains unknown whether the benefit of colonoscopy screening against colorectal cancer (CRC) and the optimal age to start screening differ by CRC risk profile.

Methods

Among 75 873 women and 42 875 men, we defined a CRC risk score (0-8) based on family history, aspirin, height, body mass index, smoking, physical activity, alcohol, and diet. We calculated colonoscopy screening-associated hazard ratios and absolute risk reductions (ARRs) for CRC incidence and mortality and age-specific CRC cumulative incidence according to risk score. All statistical tests were 2-sided.

Results

During a median of 26 years of follow-up, we documented 2407 CRC cases and 874 CRC deaths. Although the screening-associated hazard ratio did not vary by risk score, the ARRs in multivariable-adjusted 10-year CRC incidence more than doubled for individuals with scores 6-8 (ARR = 0.34%, 95% confidence interval [CI] = 0.26% to 0.42%) compared with 0-2 (ARR = 0.15%, 95% CI = 0.12% to 0.18%, Ptrend < .001). Similar results were found for CRC mortality (ARR = 0.22%, 95% CI = 0.21% to 0.24% vs 0.08%, 95% CI = 0.07% to 0.08%, Ptrend < .001). The ARR in mortality of distal colon and rectal cancers was fourfold higher for scores 6-8 than 0-2 (distal colon cancer: ARR = 0.08%, 95% CI = 0.07% to 0.08% vs 0.02%, 95% CI = 0.02% to 0.02%, Ptrend < .001; rectal cancer: ARR = 0.08%, 95% CI = 0.08% to 0.09% vs 0.02%, 95% CI = 0.02% to 0.03%, Ptrend < .001). When using age 45 years as the benchmark to start screening, individuals with risk scores of 0-2, 3, 4, 5, and 6-8 attained the threshold CRC risk level (10-year cumulative risk of 0.47%) at age 51 years, 48 years, 45 years, 42 years, and 38 years, respectively.

Conclusions

The absolute benefit of colonoscopy screening is more than twice higher for individuals with the highest than lowest CRC risk profile. Individuals with a high- and low-risk profile may start screening up to 6-7 years earlier and later, respectively, than the recommended age of 45 years.
Feasibility of Medical Student Mentors to Improve Transition in Sickle Cell Disease
Authors: Viola Adrienne S , Drachtman Richard , Kaveney Amanda , Sridharan Ashwin , Savage Beth , Delnevo Cristine D , Coups Elliot J , Porter Jerlym S , Devine Katie A
Published: March 2021

Objective

Advances in medical care have resulted in nearly 95% of all children with sickle cell disease (SCD) living to adulthood. There is a lack of effective transition programming, contributing to high rates of mortality and morbidity among adolescents and young adults (AYAs) during the transition from pediatric to adult healthcare. This nonrandomized study evaluated the feasibility, acceptability, and preliminary outcomes of a novel medical student mentor intervention to improve transition outcomes for AYA with SCD.

Methods

Eligible participants were ages 18–25 years, either preparing for transition or had transferred to adult care within the past year. Twenty-four AYA with SCD (Mage = 20.3, SD = 2.6) enrolled in the program and were matched with a medical student mentor. Feasibility and acceptability of the intervention was assessed through enrollment rates, reasons for refusal, retention rates, engagement with the intervention, satisfaction, and reasons for drop-out. Dependent t-tests were used to evaluate the preliminary effects of the intervention on patient transition readiness, health-related quality of life, self-efficacy, SCD knowledge, medication adherence, and health literacy.

Results

Participants (N = 24) demonstrated adequate retention (75.0%), adherence to the intervention (M = 5.3 of 6 sessions), and satisfaction with the intervention components. Participants demonstrated significant improvements in transition readiness (p = .001), self-efficacy (p = .002), medication adherence (p = .02), and health literacy (p = .05).

Conclusions

A medical student mentor intervention to facilitate transition from pediatric to adult care for AYA with SCD is both feasible and acceptable to patients and medical students. Preliminary results suggest benefits for patients, warranting a larger efficacy study.
Sclerosing angiomatoid nodular transformation (SANT) of the spleen: a rare cause of acute abdomen
Authors: Ojeda Rommel , Molina Gabriel A , Jiménez Galo E , González Hernán , Pinto Johanna C , Jiménez Andres , Leon Flor M
Published: March 2021

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is an extremely rare benign lesion. It originates from the spleen's red pulp; however, its pathogenesis is not clearly defined. These tumors are usually asymptomatic or cause nonspecific abdominal symptoms. Most SANTs are found incidentally on radiographic examination or during surgery for an unrelated condition. The differential diagnosis from other splenic tumors or malignant lesions can be challenging due to the risk for a possible malignancy of the suspicious lesion. As more SANTs are being discovered and treated, they should always be considered in the differential.

We present the case of an otherwise healthy 30-year-old female; she presented with abdominal pain and a mass in her spleen. Surgery was performed, and an SANT was discovered. The patient underwent full recovery, and on follow-up is doing well.
Negation as a modality in a quantified setting
Authors: Speranski Stanislav O
Published: March 2021

The idea of treating negation as a modality manifests itself in various logical systems, especially in Došen’s propositional logic $\textsf {N}$, whose negation is weaker than that of Johansson’s minimal logic. Among the interesting extensions of $\textsf {N}$ are the propositional logics $\textsf {N}^{\ast }$ and $\textsf {Hype}$; the former was proposed in Cabalar et al. (2006, Proceedings of the 10th International Conference on Principles of Knowledge Representation and Reasoning, 25–36), while the latter has recently been advocated in Leitgeb (2019, J. Philos. Logic, 48, 305–405), but was first introduced in Moisil (1942, Disquisitiones Math. et Phys., 2, 3–98). I shall develop predicate versions of $\textsf {N}$ and $\textsf {N}^{\ast }$ and provide a simple Routley-style semantics for the predicate version of $\textsf {Hype}$. The corresponding strong completeness results will be proved by means of a useful general technique. It should be remarked that this work can also be seen as a starting point for the investigation of intuitionistic predicate modal logics.
The morphology of the X-ray afterglows and of the jetted GeV emission in long GRBs
Authors: Ruffini R , Moradi R , Rueda J A , Li L , Sahakyan N , Chen Y-C , Wang Y , Aimuratov Y , Becerra L , Bianco C L , Cherubini C , Filippi S , Karlica M , Mathews G J , Muccino M , Pisani G B , Xue S S
Published: March 2021

We recall evidence that long gamma-ray bursts (GRBs) have binary progenitors and give new examples. Binary-driven hypernovae (BdHNe) consist of a carbon–oxygen core (COcore) and a neutron star (NS) companion. For binary periods ∼5 min, the COcore collapse originates the subclass BdHN I characterized by (1) an outstanding supernova (SN; the ‘SN-rise’); (2) a black hole (BH), born from the NS collapse by SN matter accretion, leading to a GeV emission with luminosity $L_{\rm GeV} = A_{\rm GeV}\, t^{-\alpha _{\rm GeV}}$, observed only in some cases; and (3) a new NS (νNS), born from the SN, originating from the X-ray afterglow with $L_\mathrm{ X} = A_{\rm X}\, t^{-\alpha _{\rm X}}$, observed in all BdHN I. We record 378 sources and present for four prototype GRBs 130427A, 160509A, 180720B, and 190114C: (1) spectra, luminosities, SN-rise duration; (2) AX, αX = 1.48 ± 0.32, and (3) the νNS spin time evolution. We infer (i) AGeV, αGeV = 1.19 ± 0.04 and (ii) the BdHN I morphology from time-resolved spectral analysis, three-dimensional simulations, and the GeV emission presence/absence in 54 sources within the Fermi-Large Area Telescope boresight angle. For 25 sources, we give the integrated and time-varying GeV emission, 29 sources have no GeV emission detected and show X/gamma-ray flares previously inferred as observed along the binary plane. The 25/54 ratio implies the GeV radiation is emitted within a cone of half-opening angle ≈60° from the normal to the orbital plane. We deduce BH masses of 2.3–8.9 M⊙ and spin of 0.27–0.87 by explaining the GeV emission from the BH rotational energy extraction, while their time evolution validates the BH mass–energy formula.
Particle acceleration in radio galaxies with flickering jets: GeV electrons to ultrahigh energy cosmic rays
Authors: Matthews James H , Taylor Andrew M
Published: March 2021

Variability is a general property of accretion discs and their associated jets. We introduce a semi-analytical model for particle acceleration and radio jet/lobe evolution and explore the effect of Myr time-scale jet variability on the particles accelerated by an active galactic nucleus (AGN) jet. Our work is motivated by the need for local powerful ultrahigh energy cosmic ray (UHECR) sources and evidence for variability in AGN and radio galaxies. Our main results are (i) UHECR and non-thermal radiative luminosities track the jet power but with a response set by the escape and cooling times, respectively; (ii) jet variability produces structure in the electron, synchrotron, and UHECR spectra that deviates from that produced for a constant jet power – in particular, spectral hardening features may be signatures of variability; (iii) the cutoff in the integrated cosmic ray (CR) spectrum is stretched out due to the variation in jet power (and, consequently, maximum CR energy). The resulting spectrum is the convolution of the jet power distribution and the source term. We derive an approximate form for a lognormal distribution of powers; and (iv) we introduce the idea of ${\sim}10\,$ GeV ‘proxy electrons’ that are cooling at the same rate that UHECRs of rigidity $10\,$ EV are escaping from the source, and determine the corresponding photon frequencies that probe escaping UHECRs. Our results demonstrate the link between the history of an astrophysical particle accelerator and its particle contents, non-thermal emission, and UHECR spectrum, with consequences for observations of radio galaxies and UHECR source models.
Radiative parameters of high-lying levels in neutral rhodium
Authors: Li Yongfan , Geng Yidan , Liu Meina , Ma Huiting , Wu Yaxin , Zhang Lijun , Gamrath Sébastien , Quinet Pascal , Dai Zhenwen
Published: March 2021

Radiative lifetimes of 20 high-lying excited levels in neutral rhodium (Rh i) were measured using time-resolved laser-induced fluorescence technique, 17 of which are reported for the first time to our knowledge. These lifetimes were combined with theoretical branching fractions obtained from pseudo-relativistic Hartree–Fock calculations to deduce semi-empirical transition probabilities and oscillator strengths for 63 Rh i spectral lines.
Updated parameters of 1743 open clusters based on Gaia DR2
Authors: Dias W S , Monteiro H , Moitinho A , Lépine J R D , Carraro G , Paunzen E , Alessi B , Villela L
Published: March 2021

In this study, we follow up our recent paper (Monteiro et al. 2020) and present a homogeneous sample of fundamental parameters of open clusters in our Galaxy, entirely based on Gaia DR2 data. We used published membership probability of the stars derived from Gaia DR2 data and applied our isochrone fitting code, updated as in Monteiro et al. (2020), to GBP and GRPGaia DR2 data for member stars. In doing this, we take into account the nominal errors in the data and derive distance, age, and extinction of each cluster. This work therefore provides parameters for 1743 open clusters and, as a by-product, a list of likely not physical or dubious open clusters is provided as well for future investigations. Furthermore, it was possible to estimate the mean radial velocity of 831 clusters (198 of which are new and unpublished so far), using stellar radial velocities from Gaia DR2 catalogue. By comparing the open cluster distances obtained from isochrone fitting with those obtained from a maximum likelihood estimate of individual member parallaxes, we found a systematic offset of (−0.05 ± 0.04) mas.
Constraining planetesimal stirring: how sharp are debris disc edges?
Authors: Marino Sebastian
Published: March 2021

The dust production in debris discs by grinding collisions of planetesimals requires their orbits to be stirred. However, stirring levels remain largely unconstrained, and consequently the stirring mechanisms as well. This work shows how the sharpness of the outer edge of discs can be used to constrain the stirring levels. Namely, the sharper the edge the lower the eccentricity dispersion must be. For a Rayleigh distribution of eccentricities (e), I find that the disc surface density near the outer edge can be parametrized as tanh [(rmax  − r)/lout], where rmax  approximates the maximum semimajor axis and lout defines the edge smoothness. If the semimajor axis distribution has sharp edges erms is roughly 1.2lout/rmax  or erms = 0.77lout/rmax  if semimajor axes have diffused due to self-stirring. This model is fitted to Atacama Large Millimeter/submillimeter Array data of five wide discs: HD 107146, HD 92945, HD 206893, AU Mic, and HR 8799. The results show that HD 107146, HD 92945, and AU Mic have the sharpest outer edges, corresponding to erms values of 0.121 ± 0.05, $0.15^{+0.07}_{-0.05}$, and 0.10 ± 0.02 if their discs are self-stirred, suggesting the presence of Pluto-sized objects embedded in the disc. Although these stirring values are larger than typically assumed, the radial stirring of HD 92945 is in good agreement with its vertical stirring constrained by the disc height. HD 206893 and HR 8799, on the other hand, have smooth outer edges that are indicative of scattered discs since both systems have massive inner companions.
Constraining the state of the intergalactic medium during the Epoch of Reionization using MWA 21-cm signal observations
Authors: Ghara Raghunath , Giri Sambit K , Ciardi Benedetta , Mellema Garrelt , Zaroubi Saleem
Published: March 2021

The Murchison Widefield Array (MWA) team has derived new upper limits on the spherically averaged power spectrum of the 21-cm signal at six redshifts in the range z ≈ 6.5–8.7. We use these upper limits and a Bayesian inference framework to derive constraints on the ionization and thermal state of the intergalactic medium (IGM) as well as on the strength of a possible additional radio background. We do not find any constraints on the state of the IGM for z ≳ 7.8 if no additional radio background is present. In the presence of such a radio background, the 95 per cent credible intervals of the disfavoured models at redshift ≳ 6.5 correspond to an IGM with a volume-averaged fraction of ionized regions below 0.6 and an average gas temperature ≲ 103 K. In these models, the heated regions are characterized by a temperature larger than that of the radio background, and by a distribution with characteristic size $\lesssim 10\, h^{-1}$ Mpc and a full width at half maximum (FWHM) of $\lesssim 30\, h^{-1}$ Mpc. Within the same credible interval limits, we exclude an additional radio background of at least $0.008{{\ \rm per\ cent}}$ of the CMB at 1.42 GHz.
Correlations between H α equivalent width and galaxy properties at z = 0.47: Physical or selection-driven?
Authors: Khostovan A A , Malhotra S , Rhoads J E , Harish S , Jiang C , Wang J , Wold I , Zheng Z-Y , Barrientos L F , Coughlin A , Hu W , Infante L , Perez L A , Pharo J , Valdes F , Walker A R
Published: March 2021

The H α equivalent width (EW) is an observational proxy for specific star formation rate (sSFR) and a tracer of episodic, bursty star-formation activity. Previous assessments show that the H α EW strongly anticorrelates with stellar mass as M−0.25 similar to the sSFR – stellar mass relation. However, such a correlation could be driven or even formed by selection effects. In this study, we investigate how H α EW distributions correlate with physical properties of galaxies and how selection biases could alter such correlations using a z = 0.47 narrow-band-selected sample of 1572 H α emitters from the Ly α Galaxies in the Epoch of Reionization (LAGER) survey as our observational case study. The sample covers a 3 deg2 area of COSMOS with a survey comoving volume of 1.1 × 105 Mpc3. We assume an intrinsic EW distribution to form mock samples of H α emitters and propagate the selection criteria to match observations, giving us control on how selection biases can affect the underlying results. We find that H α EW intrinsically correlates with stellar mass as W0∝M−0.16 ± 0.03 and decreases by a factor of ∼3 from 107 M⊙ to 1010 M⊙, while not correcting for selection effects steepens the correlation as M−0.25 ± 0.04. We find low-mass H α emitters to be ∼320 times more likely to have rest-frame EW>200 Å compared to high-mass H α emitters. Combining the intrinsic W0–stellar mass correlation with an observed stellar mass function correctly reproduces the observed H α luminosity function, while not correcting for selection effects underestimates the number of bright emitters. This suggests that the W0–stellar mass correlation when corrected for selection effects is physically significant and reproduces three statistical distributions of galaxy populations (line luminosity function, stellar mass function, EW distribution). At lower stellar masses, we find there are more high-EW outliers compared to high stellar masses, even after we take into account selection effects. Our results suggest that high sSFR outliers indicative of bursty star formation activity are intrinsically more prevalent in low-mass H α emitters and not a byproduct of selection effects.
Crucial role ofSalmonellagenomic island 1 master activator in the parasitism of IncC plasmids
Authors: Durand Romain , Huguet Kévin T , Rivard Nicolas , Carraro Nicolas , Rodrigue Sébastien , Burrus Vincent
Published: March 2021

IncC conjugative plasmids and the multiple variants of Salmonella Genomic Island 1 (SGI1) are two functionally interacting families of mobile genetic elements commonly associated with multidrug resistance in the Gammaproteobacteria. SGI1 and its siblings are specifically mobilised in trans by IncC conjugative plasmids. Conjugative transfer of IncC plasmids is activated by the plasmid-encoded master activator AcaCD. SGI1 carries five AcaCD-responsive promoters that drive the expression of genes involved in its excision, replication, and mobilisation. SGI1 encodes an AcaCD homologue, the transcriptional activator complex SgaCD (also known as FlhDCSGI1) that seems to recognise and activate the same SGI1 promoters. Here, we investigated the relevance of SgaCD in SGI1′s lifecycle. Mating assays revealed the requirement for SgaCD and its IncC-encoded counterpart AcaCD in the mobilisation of SGI1. An integrative approach combining ChIP-exo, Cappable-seq, and RNA-seq confirmed that SgaCD activates each of the 18 AcaCD-responsive promoters driving the expression of the plasmid transfer functions. A comprehensive analysis of the activity of the complete set of AcaCD-responsive promoters of SGI1 and the helper IncC plasmid was performed through reporter assays. qPCR and flow cytometry assays revealed that SgaCD is essential to elicit the excision and replication of SGI1 and destabilise the helper IncC plasmid.
Long-Term Mortality and Active Tuberculosis Disease Among Patients Who Were Lost to Follow-Up During Second-Line Tuberculosis Treatment in 2011–2014: Population-Based Study in the Country of Georgia
Authors: Kuchukhidze Giorgi , Baliashvili Davit , Adamashvili Natalia , Kasradze Ana , Kempker Russell R , Magee Matthew J
Published: March 2021

Background

High rates of loss to follow-up (LFU) exist among patients with multidrug and extensively drug-resistant tuberculosis (M/XDR TB). We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment.

Methods

We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011–2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire, and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture.

Results

Follow-up information was obtained for 461 patients. Among these patients, 107 (23%) died and 177 (38%) were contacted. Of those contacted, 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time period for transmitting drug-resistant TB in the community of 480 days (interquartile range = 803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio = 13.3; 95% confidence interval, 4.2–42.2)

Conclusions

Approximately one quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, 1 in 7 remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.
The Dynamics of Infectious Diseases Associated With Injection Drug Use in Lawrence and Lowell, Massachusetts
Authors: Gonsalves Gregg S , David Paltiel A , Thornhill Thomas , Iloglu Suzan , DeMaria Alfred , Cranston Kevin , Monina Klevens R , Walensky Rochelle P , Warren Joshua L
Published: March 2021

Background

There are a wide variety of infectious complications of injection drug use. Understanding the trajectory of these complications might inform the development of an early warning system for human immunodeficiency virus (HIV) outbreaks that occur regularly among people who inject drugs (PWID).

Methods

A distributed lag Poisson regression model in the Bayesian setting was used to examine temporal patterns in the incidence of injection-associated infectious diseases and their association with HIV cases in Lawrence and Lowell, Massachusetts between 2005 and 2018.

Results

Current-month HIV counts are associated with fatal overdoses approximately 8 months prior, cases of infective endocarditis 10 months prior, and cases of skin and soft tissue infections and incision and drainage procedures associated with these infections 12 months prior.

Conclusions

Collecting data on these other complications associated with injection drug use by public health departments may be important to consider because these complications may serve as input to a sentinel system to trigger early intervention and avert potential outbreaks of HIV.
The Law of Monetary Finance under Unconventional Monetary Policy
Authors: Bateman Will
Published: March 2021

Monetary finance (money creation by central banks to fund public expenditure) is a high-profile part of economic, political and policy debates concerning the legitimacy of central banks in liberal economies and democracies. This article makes a distinctively legal contribution to those debates by analysing the legal frameworks governing monetary finance in three prominent central banking systems between 2008 and 2020: the Federal Reserve System, the Eurosystem and the Bank of England. It begins by explaining the law governing central bank and national treasury relations in the United States, the EU and the UK. It then examines how that law operated under the unconventional monetary policies adopted by central banks in response to the financial crisis and the COVID-19 pandemic. The article concludes by reflecting on the challenges monetary finance presents to the sui generis position of central banks in the liberal constitutional order.
Restless legs syndrome and periodic limb movements in 86 patients with multiple sclerosis
Authors: Sparasci Davide , Ferri Raffaele , Castelnovo Anna , Miano Silvia , Tanioka Kosuke , Tachibana Naoko , Carelli Chiara , Riccitelli Gianna , Disanto Giulio , Zecca Chiara , Gobbi Claudio , Manconi Mauro
Published: March 2021

Study Objectives

To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS−/PLMS− (patients without RLS and PLMS), RLS+/PLMS− (patients with RLS and without PLMS), RLS−/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS).

Methods

In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent polysomnography (PSG) and maintenance of wakefulness test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI).

Results

RLS and PLMS (PLMSI ≥15/h) frequency in patients with MS were of 31.4% and 31.6%, respectively. Among patients with RLS, 37.5% had a PLMSI of at least 15/h. RLS−/PLMS+ group showed higher wake after sleep onset (p = 0.01), stage shifts per hour (p = 0.03), increased stage N1 (p = 0.03), and reduction in stage N3 (p = 0.01) compared to RLS−/PLMS−. RLS had no influence on clinical and PSG parameters (p = 0.45).

Conclusions

RLS is highly frequent in patients with MS. The frequency of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, supports the existence of a distinct symptomatic form of RLS in MS.
Gamification in the study of anatomy: The use of artificial intelligence to improve learning
Authors: Bracaccio Rafael , Hojaij Flavio , Notargiacomo Pollyana
Published: March 2021

In medicine, the study of anatomy is of utmost importance since this fundamental course is relevant to all medical careers. Every single medical student must learn anatomy regardless of which specialization they choose to follow. Technology‐assisted learning is a growing topic not only in medicine, but in each and every area of study. There is a large number of possible approaches to teach/learn assisted by technology such as educative and serious games, the use of virtual and augmented reality, hardware and software created specifically for training a certain skill and many more. Based on this approach, in this research we developed a gamified mobile application to help both the students and the professor at anatomy classes to understand and develop knowledge in this field based on different kinds of media such as videos, texts, images, audios, quizzes and so on. Gamification consists in the use of game elements in different contexts outside games. This involves presenting aspects such as ranking, badges, quests, etc. to promote engagement and institutes an immersion and flow in faculty education. In order to do that, it was applied the Marczewski's Gamification Design Framework, which involves the definition of the problem, users, success to project and building the user journey to attain some specific behaviours, actions and emotion which can be refined to complete the process and promote learning. This framework was combined with Artificial Intelligence techniques to recognize the difficulties of each individual student and is then able to provide targeted content based on the student performance.

Support or Funding Information

The authors thank Mackpesquisa for the financial support.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in the therapeutic landscape of oesophago-gastric cancers
Authors: Fokter Dovnik Nina , Smyth Elizabeth C.
Published: March 2021

Purpose of review

This article reviews recent randomised clinical trials on systemic treatment of oesophago-gastric cancers in the perioperative and metastatic setting.

Recent findings

Adding nivolumab to first-line chemotherapy improved survival in patients with metastatic gastric/gastro-oesophageal junction/oesophageal adenocarcinoma with PD-L1 combined positive score (CPS) ≥ five in a global trial and progression-free survival in metastatic gastric/gastro-oesophageal junction cancers in an Asian trial. The addition of pembrolizumab to first-line chemotherapy improved survival in metastatic oesophageal cancer patients, with the most benefit in oesophageal squamous cancer and tumours with high PD-L1 expression (CPS ≥ 10). Adjuvant nivolumab improved disease-free survival (DFS) in resectable oesophageal cancer patients with residual pathologic disease after neoadjuvant chemoradiation. In human epidermal growth factor receptor 2 (HER2)-positive oesophago-gastric adenocarcinoma, a phase II trial showed improved DFS when pertuzumab and trastuzumab were added to perioperative FLOT (5-fluorouracil/leucovorin, oxaliplatin, docetaxel). Another phase II trial showed improved response rates and survival in pretreated metastatic HER2-positive gastric and gastrooesophageal junction cancer patients who received the antibody-drug conjugate trastuzumab deruxtecan compared to physician's choice of chemotherapy.

Chemo-immunotherapy combinations will become the new standard of care for some patients with metastatic oesophago-gastric cancers. Adjuvant nivolumab is a new option for oesophageal cancer patients with poor response after neoadjuvant chemoradiation.
The role of the tumor matrix environment in progression of head and neck cancer
Authors: Saint Angélique , Van Obberghen-Schilling Ellen
Published: March 2021

Purpose of review

Head and neck squamous cell carcinoma (HNSCC) tissue is composed of multiple cell types embedded in an extracellular matrix (ECM) that actively participates in disease progression, spread and treatment response. In this review, we provide an update of our current knowledge about the ECM landscape of HNSCC, its functions, methods of analysis, and nonimmunological stromal targeting strategies that modify the tumor ECM to improve conventional and emerging therapies.

Recent findings

The tumor ECM differs significantly from that of normal tissue in abundance, composition, organization and mechanical properties. In HNSCC, signaling between malignant epithelial cells and stromal cells prompts the upregulation of a set of ECM components that serve as substrates for carcinoma cell migration, modulate the cytokine environment and promote immune evasion in these tumors. Advanced imaging techniques and molecular profiling at the single-cell level have provided valuable insights into our understanding of the tumor ECM and its role in malignancy, and opened new avenues for predictive and potentially actionable biomarker discovery for more effective management of the disease.

ECM components upregulated in HNSCC can impact several cancer hallmarks by sustaining proliferative signaling, promoting angiogenesis, facilitating invasion and metastasis, modulating growth suppressor activity, and suppressing antitumoral immunity. The tumor ECM is also involved in treatment resistance, making it a potential therapeutic target.
Are the current evaluation tools for advanced therapies biased?
Authors: Givens Raymond C.
Published: March 2021

Purpose of review

Despite attention to racial disparities in outcomes for heart failure (HF) and other chronic diseases, progress against these inequities has been gradual at best. The disparities of COVID-19 and police brutality have highlighted the pervasiveness of systemic racism in health outcomes. Whether racial bias impacts patient access to advanced HF therapies is unclear.

Recent findings

As documented in other settings, racial bias appears to operate in HF providers’ consideration of patients for advanced therapy. Multiple medical and psychosocial elements of the evaluation process are particularly vulnerable to bias.

Reducing gaps in access to advanced therapies will require commitments at multiple levels to reduce barriers to healthcare access, standardize clinical operations, research the determinants of patient success and increase diversity among providers and researchers. Progress is achievable but likely requires as disruptive and investment of immense resources as in the battle against COVID-19.
Patient-Reported Efficacy of the University of California, San Francisco, Custom Pectus Carinatum Orthosis
Authors: Stauffer Samantha , Shirley Corin , Fortson Benjamin , Henry Nicole , Irolla Chrysta , Padilla Benjamin
Published: March 2021

Introduction

Pectus carinatum is a bony deformity of the anterior chest wall and has a strong negative impact on patient self-esteem and quality of life. During adolescence, the deformity is often flexible and can be treated with a compressive orthosis. Compliance with orthoses yields deformity correction and self-esteem improvement (J Pediatr Surg. 2013;48:1055-1059). The purpose of this study is to evaluate the compliance to and patient satisfaction with the custom University of California, San Francisco (UCSF), Pectus Carinatum Orthosis (PCO) design.

Materials and Methods

This was a cross-sectional survey of the patients who received orthotic treatment for pectus carinatum at UCSF between August 2012 and June 2018. Potential subjects were contacted and asked to complete the Pectus Carinatum Evaluation Questionnaire (PCEQ), which was administered online via Research Electronic Data Capture. The PCEQ measures compliance as well as the physical and psychosocial impact of orthotic treatment for pectus carinatum. Results were compiled and summarized using nonparametric descriptive statistics.

Results

Of the 35 consented subjects, 12 (11 male patients and 1 female patient aged 12–17 years) completed the survey. Subjects reported an average wear time of 12.7 hours per day, 5 days a week. Seven reported no symptoms, three experienced chest pain, two reported difficulty breathing, and one had back pain. Eight reported happiness with the results of their orthotic treatment.

Conclusion

Wear times reported by the subjects were comparable with those reported in other studies looking at prefabricated pectus orthoses. However, there were lower reports of pain associated with the UCSF treatment than in other studies. Further research is necessary to determine the benefit of custom fabricated versus prefabricated PCOs.
The Influence of Load Carriage on Knee Joint Loading and Metabolic Cost on Walking with Lower-Limb Amputation: A Preliminary Modeling Study
Authors: Templin Tylan N. , Klute Glenn K. , Neptune Richard R.
Published: March 2021

Introduction

For able-bodied individuals, the mechanical output from the ankle muscles is modulated to meet the altered demands of load carriage. However, for individuals with a lower-limb amputation, the stiffness properties of standard-of-care prosthetic feet do not change with varying load conditions. Thus, individuals with amputation often develop gait asymmetries during load carriage that increase their risk for developing overuse injuries such as in the intact knee and increase the metabolic cost of walking relative to able-bodied individuals. The purpose of this preliminary study was to assess the influence of load carriage technique on knee joint loading and metabolic cost during gait of an individual with a below-knee amputation using a forward dynamics simulation framework.

Methods

Simulations were generated to track the experimental walking data of individuals with amputation for 3 loading conditions (unloaded, front load, and back load).

Results

These simulations showed that individuals with amputation rely on their intact limb as a compensatory strategy to meet the increased demands of carrying a load. Carrying a back load was found to increase intact knee joint loading relative to carrying a front load but reduced metabolic cost.

Conclusion

The tradeoff between joint loading and metabolic cost should be considered when determining the appropriate load carriage technique. Future work should focus on improving prosthetic foot designs to help reduce joint loading asymmetry and elevated metabolic cost during different loading conditions for individuals with lower-limb amputation.