bluuebunny/crossref_metadata_2025 huggingface dataset:
A fractional vertical derivative technique for regional-residual separation
Authors: Florio G , Fedi M , Cella F
Published: September 2022

The separation of the effects of deep-seated sources of potential fields from those of shallower ones is a frequent requirement when interpreting magnetic or gravity fields. A common procedure is estimating the regional, long wavelength, component of the field by analysing the data over an area larger than that of the local feature of interest. The local components are found by subtracting the estimated regional from the observed data. These approaches may have difficulties in their application, as the dataset over large areas may not be available and other local anomalies, in the enlarged area, may prevent a reliable estimate of the regional field. We present an alternative and simple approach to the regional-residual separation problem not requiring the analysis over large areas and aiming at estimating the local, rather than the regional, component. Our method exploits the natural enhancement of short wavelengths obtainable by computing vertical derivatives of potential fields. An equivalent layer source is computed from the vertical derivative and is used to estimate the local field. The optimal differentiation order can be determined by inspecting the obtained results. This parameter may assume even fractional values, so that the method results a very versatile tool. The application to a complex synthetic case and two real data examples demonstrates the utility of this approach. In summary, our method has some peculiar characteristics making it an interesting alternative to currently used approaches to regional-residual separation: (i) it is a local method, so it can work well even when processing datasets relative to areas of limited extension; (ii) unlike most current methods, estimating a smooth regional component, our method directly produces an estimate of the local field and (iii) it is highly versatile, as the key parameter, that is the fractional differentiation order, can be finely adjusted up to obtain an optimal local field.
Prdx5 regulates DNA damage response through autophagy-dependent Sirt2-p53 axis
Authors: Agborbesong Ewud , Zhou Julie X , Li Linda X , Harris Peter C , Calvet James P , Li Xiaogang
Published: September 2022

DNA damage response (DDR) is an important signaling-transduction network that promotes the repair of DNA lesions which can induce and/or support diseases. However, the mechanisms involved in its regulation are not fully understood. Recent studies suggest that the peroxiredoxin 5 (Prdx5) enzyme, which detoxifies reactive oxygen species, is associated to genomic instability and signal transduction. Its role in the regulation of DDR, however, is not well characterized. In this study, we demonstrate a role of Prdx5 in the regulation of the DDR signaling pathway. Knockdown of Prdx5 resulted in DNA damage manifested by the induction of phosphorylated histone H2AX (γ-H2AX) and p53-binding protein 1 (53BP1). We show that Prdx5 regulates DDR through (1) polo-like kinase 1 (Plk1) mediated phosphorylation of ataxia telangiectasia mutated (ATM) kinase to further trigger downstream mediators Chek1 and Chek2; (2) the increase of the acetylation of p53 at lysine 382, stabilizing p53 in the nucleus and enhancing transcription and (3) the induction of autophagy, which regulates the recycling of molecules involved in DDR. We identified Sirt2 as a novel deacetylase of p53 at lysine 382, and Sirt2 regulated the acetylation status of p53 at lysine 382 in a Prdx5-dependent manner. Furthermore, we found that exogenous expression of Prdx5 decreased DNA damage and the activation of ATM in Pkd1 mutant renal epithelial cells, suggesting that Prdx5 may play a protective role from DNA damage in cystic renal epithelial cells. This study identified a novel mechanism of Prdx5 in the regulation of DDR through the ATM/p53/Sirt2 signaling cascade.
Deficit of PKHD1L1 in the dentate gyrus increases seizure susceptibility in mice
Authors: Yu Jiangning , Wang Guoxiang , Chen Zhiyun , Wan Li , Zhou Jing , Cai Jingyi , Liu Xu , Wang Yun
Published: September 2022

Epilepsy is a chronic neurological disorder featuring recurrent, unprovoked seizures, which affect more than 65 million people worldwide. Here, we discover that the PKHD1L1, which is encoded by polycystic kidney and hepatic disease1-like 1 (Pkhd1l1), wildly distributes in neurons in the central nervous system (CNS) of mice. Disruption of PKHD1L1 in the dentate gyrus region of the hippocampus leads to increased susceptibility to pentylenetetrazol-induced seizures in mice. The disturbance of PKHD1L1 leads to the overactivation of the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK)-Calpain pathway, which is accompanied by remarkable degradation of cytoplasmic potassium chloride co-transporter 2 (KCC2) level together with the impaired expression and function of membrane KCC2. However, the reduction of membrane KCC2 is associated with the damaged inhibitory ability of the vital GABA receptors, which ultimately leads to the significantly increased susceptibility to epileptic seizures. Our data, thus, indicate for the first time that Pkhd1l1, a newly discovered polycystic kidney disease (PKD) association gene, is required in neurons to maintain neuronal excitability by regulation of KCC2 expression in CNS. A new mechanism of the clinical association between genetic PKD and seizures has been built, which could be a potential therapeutic target for treating PKD-related seizures.
Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria
Authors: Ververi Athina , Zagaglia Sara , Menzies Lara , Baptista Julia , Caswell Richard , Baulac Stephanie , Ellard Sian , Lynch Sally ,   Genomics England Research Consortium, Jacques Thomas S , Chawla Maninder Singh , Heier Martin , Kulseth Mari Ann , Mero Inger-Lise , Våtevik Anne Katrine , Kraoua Ichraf , Ben Rhouma Hanene , Ben Younes Thouraya , Miladi Zouhour , Ben Youssef Turki Ilhem , Jones Wendy D , Clement Emma , Eltze Christin , Mankad Kshitij , Merve Ashirwad , Parker Jennifer , Hoskins Bethan , Pressler Ronit , Sudhakar Sniya , DeVile Catherine , Homfray Tessa , Kaliakatsos Marios ,   Ponnudas (Prab) Prabhakar, Robinson Robert , Keim Sara Margrete Bøen , Habibi Imen , Reymond Alexandre , Sisodiya Sanjay M , Hurst Jane A
Published: September 2022

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5. Cases were identified clinically. Available records, including magnetic resonance imaging and electroencephalography, were reviewed. Genetic testing was performed by whole exome and whole-genome sequencing and cascade screening. In addition, immunohistochemistry was performed on skin biopsy. The phenotype was identified in nine children, eight of which are described in detail herein. Six of the children were of Irish Traveller, two of Tunisian and one of Lebanese origin. The Irish Traveller children shared the same DEPDC5 germline homozygous missense variant (p.Thr337Arg), whereas the Lebanese and Tunisian children shared a different germline homozygous variant (p.Arg806Cys). Consistent phenotypic features included extensive bilateral polymicrogyria, congenital macrocephaly and early-onset refractory epilepsy, in keeping with other mTOR-opathies. Eye and cardiac involvement and severe neutropenia were also observed in one or more patients. Five of the children died in infancy or childhood; the other four are currently aged between 5 months and 6 years. Skin biopsy immunohistochemistry was supportive of hyperactivation of the mTOR pathway. The clinical, histopathological and genetic evidence supports a causal role for the homozygous DEPDC5 variants, expanding our understanding of the biology of this gene.
Boucksom–Zariski and Weyl Chambers on Irreducible Holomorphic Symplectic Manifolds
Authors: Denisi Francesco Antonio
Published: September 2022

Inspired by the work of Bauer, Küronya, and Szemberg, we provide for the big cone of a projective irreducible holomorphic symplectic (IHS) manifold a decomposition into chambers (which we describe in detail), in each of which the support of the negative part of the divisorial Zariski decomposition is constant. We see how the obtained decomposition of the big cone allows to describe the volume function. Moreover, similarly to the case of surfaces, we see that the big cone of a projective IHS manifold admits a decomposition into simple Weyl chambers, which we compare to that induced by the divisorial Zariski decomposition. To conclude, we determine the structure of the pseudo-effective cone.
Potential of Drosophila melanogaster (fruit fly) as a dietary protein source for broilers
Authors: Yuan Chaohai , Cai Yafei , Niu Zikang , Hu Lanxin , Kuang Ershuai , Zhang Wei
Published: September 2022

This study was conducted to systematically assess and compare the fluctuations in crude protein (CP), crude fat (CF), and mineral content of staged (larva to adult) Drosophila (fruit fly) to that of a market-purchased black soldier fly larvae (BSFL) product. Results suggested that the relative CP content by dry matter ranged from 40.11% to 53.73% during Drosophila development, significantly higher (P < 0.001) than the 36.90% in BSFL. The relative CF was higher in BSFL (39.14%) compared to that of Drosophila (27.03–30.10%, P < 0.001). Although both insects contained sufficient levels of minerals to meet the dietary requirements of most animals, Drosophila overall possessed a lower content of iron, sodium, and calcium (P < 0.001) with a higher gross energy than the BSFL (P < 0.01). Comparative studies of amino acid (AA) and fatty acid (FA) profiles were further carried out among Drosophila larva (DL), pupa, and BSFL for their economic effectiveness. The AA spectra of insect larvae generally were similar except that the DL was higher in certain AA such as lysine (P < 0.01), which is an essential AA often critical for chicken growth. In contrast, the BSFL included more essential FA such as linoleic (C18:2, ω-6) and linolenic (C18:3, ω-3) acids (P < 0.01). To follow up, a husbandry trial was performed by allotting 120, 1-d-old, weight-matched, Arbor Acres broilers at random into treatment groups consisting of a low-protein diet background that contained ~20% CP supplemented with 4% BSFL and 4% or 8% DL. The average daily growth (ADG) and average daily feed intake (ADFI) of broilers, compared to the control low-protein diet, were significantly improved by feeding DL diets (P < 0.01), with better live and carcass weight and higher muscle pH (P < 0.001), which were positively correlated with the inclusion level of DL (P < 0.001). However, no differences between the control and 4% BSFL diet were observed for the performance parameters mentioned above. Moreover, all birds under our experimental setting exhibited a comparable feed conversion ratio (FCR) and were in a healthy status as indicated by the meat traits and hematological indexes within normal physiological ranges. Collectively, the findings in this study provide a theoretical basis for the further exploitation of Drosophila as potential dietary ingredients for feed production in order to meet the food challenge in the future.
The regulation mechanism of different hair types in inner Mongolia cashmere goat based on PI3K-AKT pathway and FGF21
Authors: Gong Gao , Fan Yixing , Zhang Yan , Yan Xiaochun , Li Wenze , Yan Xiaomin , He Libing , Wang Na , Chen Oljibilig , He Dong , Jiang Wei , Li Jinquan , Wang Zhiying , Lv Qi , Su Rui
Published: September 2022

There is genetic diversity of hair types in the Inner Mongolia cashmere goat population. Previous studies have found that fibroblast growth factor 21 (FGF21) and PI3K-AKT signal pathways may be related to different hair types in Inner Mongolia cashmere goats. Therefore, the purpose of this study was to explore the effects of the PI3K-AKT signal pathway on different hair types, the expression of mRNA and protein expression sites of FGF21 in the hair follicles of cashmere goats with different hair types, so as to lay a foundation for understanding the molecular mechanism of different hair types and the role of skin hair follicle development. In this experiment, the skin tissues of long hair type (LHG) and short hair type (SHG) of Inner Mongolia cashmere goat were collected in three key periods of secondary hair follicle growth, namely, anagen (September), catagen (December), and telogen (March). The relative expression of FGF21 and PI3K-AKT signal pathway candidate gene mRNA in different periods and different hair types was detected by real-time fluorescence quantitative technique (qRT-PCR), and the expression site of FGF21 protein was located by immunohistochemical technique. Through qRT-PCR, it was found that the relative expression of FGF21, FGFR1, AKT3, BRCA1, PKN3, SPP1, and GNG4 was significantly different between LHG and SHG. The expression of FGF21 in the skin of LHG was significantly higher than that of SHG in the three periods. Through immunohistochemical test, it was found that FGF21 protein was mainly expressed in primary hair follicle connective tissue sheath, primary hair follicle outer root sheath, secondary hair follicle outer root sheath, and sebaceous glands. It was also found that the expression of LHG skin tissue in the outer root sheath of primary hair follicles was higher than that of SHG in three periods. In summary, it is suggested that the PI3K-AKT signal pathway may play an important role in the formation of different hair types in Inner Mongolia cashmere goats.
Evidence of High Frequencies of Insecticide Resistance Mutations in Aedes aegypti (Culicidae) Mosquitoes in Urban Accra, Ghana: Implications for Insecticide-based Vector Control of Aedes-borne Arboviral Diseases
Authors: Kwame Amlalo Godwin , Akorli Jewelna , Etornam Akyea-Bobi Nukunu , Sowa Akporh Samuel , Aqua-Baidoo Dominic , Opoku Millicent , Frempong Kwadwo , Pi-Bansa Sellase , Boakye Helena A , Joannides Joannitta , Nyarko Osei Joseph Harold , Pwalia Rebecca , Abla Akorli Esinam , Manu Alexander , Dadzie Samuel K
Published: September 2022

The most widespread arboviral diseases such as Dengue, Chikungunya, and Zika are transmitted mainly by Aedes mosquitoes. Due to the lack of effective therapeutics for most of these diseases, vector control remains the most effective preventative and control measure. This study investigated and compared the species composition, insecticide susceptibility, and resistance mechanisms in Aedes mosquito populations from a forest reserve converted to an eco-park and a peri-domestic sites in urban Accra, Ghana. Immature Aedes were sampled from the study sites, raised to adults, and exposed to deltamethrin, permethrin, DDT, fenitrothion, bendiocarb, permethrin + PBO, and deltamethrin + PBO using WHO tube assays. Melting curve analyses were performed for F1536C, V1016I, and V410L genetic mutations in surviving and dead mosquitoes following exposure to deltamethrin and permethrin. Microplate assay was used to access enzyme activity levels in adult mosquitoes from both populations. Aedes aegypti was found to be the dominant species from both study populations. The susceptibility test results revealed a high frequency of resistance to all the insecticides except fenitrothion. F1534C mutations were observed in 100% and 97% of mosquitoes from the peri-domestic and forest population, respectively but were associated with pyrethroid resistance only in the forest population (P < 0.0001). For the first time in Aedes mosquitoes in Ghana, we report the existence V410L mutations, mostly under selection only in the forest population (HWE P < 0.0001) and conclude that Aedes vectors in urban Accra have developed resistance to many commonly used insecticides. This information is important for the formulation of vector control strategies for Aedes control in Ghana.
Haploid induction by nanobody-targeted ubiquitin-proteasome-based degradation of EYFP-tagged CENH3 in Arabidopsis thaliana
Authors: Demidov Dmitri , Lermontova Inna , Moebes Michael , Kochevenko Andriy , Fuchs Jörg , Weiss Oda , Rutten Twan , Sorge Eberhard , Zuljan Erika , Giehl Ricardo Fabiano Hettwer , Mascher Martin , Somasundaram Saravanakumar , Conrad Udo , Houben Andreas
Published: September 2022

The generation of haploid plants accelerates the crop breeding process. One of the haploidization strategies is based on the genetic manipulation of endogenous centromere-specific histone 3 (CENH3). To extend the haploidization toolbox, we tested whether targeted in vivo degradation of CENH3 protein can be harnessed to generate haploids in Arabidopsis thaliana. We show that a recombinant anti-GFP nanobody fused to either heterologous F-box (NSlmb) or SPOP/BTB ligase proteins can recognize maternally derived enhanced yellow fluorescent protein (EYFP)-tagged CENH3 in planta and make it accessible for the ubiquitin-proteasome pathway. Outcrossing of the genomic CENH3-EYFP-complemented cenh3.1 mother with plants expressing the GFP-nanobody-targeted E3 ubiquitin ligase resulted in a haploid frequency of up to 7.6% in pooled F1 seeds. EYFP-CENH3 degradation occurred independently in embryo and endosperm cells. In reciprocal crosses, no haploid induction occurred. We propose that the uniparental degradation of EYFP-fused genomic CENH3 during early embryogenesis leads to a decrease in its level at centromeres and subsequently weakens the centromeres. The male-derived wild type CENH3 containing centromere outcompetes the CENH3-EYFP depleted centromere. Consequently, maternal chromosomes undergo elimination, resulting in haploids.
Forward-modelling the luminosity, distance, and size distributions of the Milky Way satellites
Authors: Manwadkar Viraj , Kravtsov Andrey V
Published: September 2022

We use GRUMPY, a simple regulator-type model for dwarf galaxy formation and evolution, to forward model the dwarf galaxy satellite population of the Milky Way (MW) using the Caterpillar zoom-in simulation suite. We show that luminosity and distance distributions of the model satellites are consistent with the distributions measured in the DES, PS1, and SDSS surveys, even without including a model for the orphan galaxies. We also show that our model for dwarf galaxy sizes can simultaneously reproduce the observed distribution of stellar half-mass radii, r1/2, of the MW satellites and the overall r1/2–M⋆ relation exhibited by observed dwarf galaxies. The model predicts that some of the observed faint stellar systems with r1/2 < 10 pc are ultra-faint dwarf galaxies. Scaling of the stellar mass M⋆ and peak halo mass Mpeak for the model satellites is not described by a power law, but has a clear flattening of M⋆–Mpeak scaling at $M_{\rm peak}\lt 10^8\, \, M_{\odot }$ imprinted by reionization. As a result, the fraction of low mass haloes ($M_{\rm peak}\lt 10^8 \, M_{\odot }$) hosting galaxies with MV < 0 is predicted to be 50 per cent at $M_{\rm peak}\sim 3.6 \times 10^7\, \, M_{\odot }$. We find that such high fraction at that halo mass helps to reproduce the number of dwarf galaxies discovered recently in the HSC-SSP survey. Using the model we forecast that there should be the total of $440^{+201}_{-147}$ (68 per cent confidence interval) MW satellites with MV < 0 and r1/2 > 10 pc within 300 kpc and make specific predictions for the HSC-SSP, DELVE-WIDE, and LSST surveys.
Global structure and dynamics of slowly rotating accretion flows
Authors: Ranjbar Razieh , Mosallanezhad Amin , Abbassi Shahram
Published: September 2022

We study the global solutions of slowly rotating accretion flows around the supermassive black hole in the nucleus of an elliptical galaxy. The velocity of accreted gas surrounding the black hole is initially subsonic and then falls on to the black hole supersonically, so accretion flow must be transonic. We numerically solve equations from the Bondi radius to near the black hole. The focus of our discussion will be on the properties of slightly rotating accretion flows in which radiative losses have been ignored. This study discusses how outer boundary conditions (the temperature and specific angular momentum at the outer boundary) influence accretion flow dynamics. We investigate two physically discontinuous regimes: the Bondi-like type accretion and the disc-like type accretion. A Bondi-like accretion occurs when the specific angular momentum at the Bondi radius ℓB is smaller than the specific angular momentum at the marginally stable orbit ℓms. In comparison, a disc-like accretion occurs when the specific angular momentum at the Bondi radius ℓB is larger than the specific angular momentum of the marginally stable orbit ℓms. We also keep the assumption of hydrostatic equilibrium and compare our results with the case in which it is not considered. According to this study, considering the assumption of hydrostatic equilibrium reduces the mass accretion rate. Additionally, we find our solution for different ranges of the viscosity parameter α. Finally, we study the effect of galaxy potential on slowly rotating accretion flows.
Switchback deflections beyond the early parker solar probe encounters
Authors: Laker R , Horbury T S , Matteini L , Bale S D , Stawarz J E , Woodham L D , Woolley T
Published: September 2022

Switchbacks are Aflvénic fluctuations in the solar wind, which exhibit large rotations in the magnetic field direction. Observations from Parker Solar Probe’s (PSP’s) first two solar encounters have formed the basis for many of the described switchback properties and generation mechanisms. However, this early data may not be representative of the typical near-Sun solar wind, biasing our current understanding of these phenomena. One defining switchback property is the magnetic deflection direction. During the first solar encounter, this was primarily in the tangential direction for the longest switchbacks, which has since been discussed as evidence, and a testable prediction, of several switchback generation methods. In this study, we re-examine the deflection direction of switchbacks during the first eight PSP encounters to confirm the existence of a systematic deflection direction. We first identify switchbacks exceeding a threshold deflection in the magnetic field and confirm a previous finding that they are arc-polarized. In agreement with earlier results from PSP’s first encounter, we find that groups of longer switchbacks tend to deflect in the same direction for several hours. However, in contrast to earlier studies, we find that there is no unique direction for these deflections, although several solar encounters showed a non-uniform distribution in deflection direction with a slight preference for the tangential direction. This result suggests a systematic magnetic configuration for switchback generation, which is consistent with interchange reconnection as a source mechanism, although this new evidence does not rule out other mechanisms, such as the expansion of wave modes.
Efficacy and safety of methylprednisolone pulse followed by oral prednisone vs. oral prednisone alone in sarcoidosis tubulointerstitial nephritis: a randomized, open-label, controlled clinical trial
Authors: Mahevas Matthieu , Audard Vincent , Rousseau Alexandra , Cez Alexandre , Guerrot Dominique , Verhelst David , Delahousse Michel , Hanrotel Catherine , Pillebout Evangeline , Daugas Eric , Krastinova Evguenia , Valeyre Dominique , Boffa Jean-Jacques ,    for the GSF French Sarcoidosis Group, Thomas Papo , Vincent Cottin , Arnaud Lionet , Dominique Chauveau , Jean-Marc Naccache , Sandrine Hirschi , Gabriel Choukroun , Tabassome Simon , Hakeem Admane , Laurence Berard , Aurélie Hummel , Laurence Vrigneaud , Bertrand Godeau , Laurent Juillard , Bertrand Dussol , Bruno Moulin
Published: September 2022

Background

We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis.

Methods

We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization.

Results

We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16–44} and before MP was 25 mL/min/1.73m2 (IQR, 22–36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34–74) and 46 (IQR, 39–65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P < .0001). The two groups did not differ in severe adverse events.

Conclusion

Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis.

Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012–000149-11
Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study
Authors: Greenhall George H B , Robb Matthew , Johnson Rachel J , Ibrahim Maria , Hilton Rachel , Tomlinson Laurie A , Callaghan Chris J , Watson Christopher J E
Published: September 2022

Background

Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function.

Methods

We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR).

Results

Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years.

Conclusions

Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.
Coronary and extra-coronary artery calcium scores as predictors of cardiovascular events and mortality in chronic kidney disease stages 1–5: a prospective cohort study
Authors: Sørensen Ida M H , Bjergfelt Sasha S , Hjortkjær Henrik Ø , Kofoed Klaus F , Lange Theis , Feldt-Rasmussen Bo , Christoffersen Christina , Bro Susanne
Published: September 2022

Background

Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites.

Methods

This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1–100, 101–400 and >400.

Results

During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%–0.26%, P < .001], 0.26 (95% CI 0.22%–0.3%, P < .001) and 0.20 (95% CI 0.16%–0.24%, P < .001), respectively. This trend also applied to all-cause mortality.

Conclusions

The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.
CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018
Authors: Ostrom Quinn T , Price Mackenzie , Ryan Katherine , Edelson Jacob , Neff Corey , Cioffi Gino , Waite Kristin A , Kruchko Carol , Barnholtz-Sloan Jill S
Published: September 2022

The CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and other CNS tumors in children and adolescents ages 0–19 years, collected and reported by central cancer registries covering approximately 100% of the United States population. Overall, brain and other CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in children and adolescents ages 0–19 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.
Canfar an Dán
Authors: Ó Bróithe Éamonn
Published: September 2022

This chapter explores the work of the eighteenth-century Gaelic poets of Ireland from the perspective of their musical performance. The lyrics of several songs from the Gaelic literary tradition are combined with the melodies associated with them and re-animated as songs within the discipline and aesthetic of the living, Irish-language singing tradition. The premise is that a true appraisal of these compositions requires an understanding of the interplay between metre and melody and the impact intended by the poet on their audiences by the oral delivery of their work as songs. Further insight is gained into the eighteenth-century literary song as an artform, the tradition from which it was derived and the interrelationship of that tradition with the popular song culture in Irish-speaking Ireland.
BREEDIT: a multiplex genome editing strategy to improve complex quantitative traits in maize
Authors: Lorenzo Christian Damian , Debray Kevin , Herwegh Denia , Develtere Ward , Impens Lennert , Schaumont Dries , Vandeputte Wout , Aesaert Stijn , Coussens Griet , De Boe Yara , Demuynck Kirin , Van Hautegem Tom , Pauwels Laurens , Jacobs Thomas B , Ruttink Tom , Nelissen Hilde , Inzé Dirk
Published: September 2022

Ensuring food security for an ever-growing global population while adapting to climate change is the main challenge for agriculture in the 21st century. Although new technologies are being applied to tackle this problem, we are approaching a plateau in crop improvement using conventional breeding. Recent advances in CRISPR/Cas9-mediated gene engineering have paved the way to accelerate plant breeding to meet this increasing demand. However, many traits are governed by multiple small-effect genes operating in complex interactive networks. Here, we present the gene discovery pipeline BREEDIT, which combines multiplex genome editing of whole gene families with crossing schemes to improve complex traits such as yield and drought tolerance. We induced gene knockouts in 48 growth-related genes into maize (Zea mays) using CRISPR/Cas9 and generated a collection of over 1,000 gene-edited plants. The edited populations displayed (on average) 5%–10% increases in leaf length and up to 20% increases in leaf width compared with the controls. For each gene family, edits in subsets of genes could be associated with enhanced traits, allowing us to reduce the gene space to be considered for trait improvement. BREEDIT could be rapidly applied to generate a diverse collection of mutants to identify promising gene modifications for later use in breeding programs.
Gene expression and genetic divergence in oak species highlight adaptive genes to soil water constraints
Authors: Le Provost Grégoire , Brachi Benjamin , Lesur Isabelle , Lalanne Céline , Labadie Karine , Aury Jean-Marc , Da Silva Corinne , Postolache Dragos , Leroy Thibault , Plomion Christophe
Published: September 2022

Drought and waterlogging impede tree growth and may even lead to tree death. Oaks, an emblematic group of tree species, have evolved a range of adaptations to cope with these constraints. The two most widely distributed European species, pedunculate (PO; Quercus robur L.) and sessile oak (SO; Quercus petraea Matt. Lieb), have overlapping ranges, but their respective distribution are highly constrained by local soil conditions. These contrasting ecological preferences between two closely related and frequently hybridizing species constitute a powerful model to explore the functional bases of the adaptive responses in oak. We exposed oak seedlings to waterlogging and drought, conditions typically encountered by the two species in their respective habitats, and studied changes in gene expression in roots using RNA-seq. We identified genes that change in expression between treatments differentially depending on species. These “species × environment”-responsive genes revealed adaptive molecular strategies involving adventitious and lateral root formation, aerenchyma formation in PO, and osmoregulation and ABA regulation in SO. With this experimental design, we also identified genes with different expression between species independently of water conditions imposed. Surprisingly, this category included genes with functions consistent with a role in intrinsic reproductive barriers. Finally, we compared our findings with those for a genome scan of species divergence and found that the expressional candidate genes included numerous highly differentiated genetic markers between the two species. By combining transcriptomic analysis, gene annotation, pathway analyses, as well as genome scan for genetic differentiation among species, we were able to highlight loci likely involved in adaptation of the two species to their respective ecological niches.
Factual Corrections Eliminate False Beliefs About COVID-19 Vaccines
Authors: Porter Ethan , Velez Yamil , Wood Thomas J
Published: September 2022

The spread of misinformation about COVID-19 vaccines threatens to prolong the pandemic, with prior evidence indicating that exposure to misinformation has negative effects on intent to be vaccinated. We describe results from randomized experiments in the United States (n = 5,075) that allow us to measure the effects of factual corrections on false beliefs about the vaccine and vaccination intent. Our evidence makes clear that corrections eliminate the effects of misinformation on beliefs about the vaccine, but that neither misinformation nor corrections affect vaccination intention. These effects are robust to formatting changes in the presentation of the corrections. Indeed, corrections without any formatting modifications whatsoever prove effective at reducing false beliefs, with formatting variations playing a very minor role. Despite the politicization of the pandemic, misperceptions about COVID-19 vaccines can be consistently rebutted across party lines.
Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis
Authors: Choreño-Parra José Alberto , Cervantes-Rosete Diana , Jiménez-Álvarez Luis Armando , Ramírez-Martínez Gustavo , Márquez-García José Eduardo , Cruz-Lagunas Alfredo , Magaña-Sánchez Ana Yelli , Lima Guadalupe , López-Maldonado Humberto , Gaytán-Guzmán Emanuel , Caballero Adrian , Fernández-Plata Rosario , Furuzawa-Carballeda Janette , Mendoza-Milla Criselda , Navarro-González Maria del Carmen , Llorente Luis , Zúñiga Joaquín , Rodríguez-Reyna Tatiana Sofía
Published: September 2022

Objectives

SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc.

Material and methods

Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs.

Results

In general, we observed an increased production of Th17-related cytokines like IL-1β, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2–Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup.

Conclusions

Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.
Lens Equivalent dose of Staff During Endoscopic Retrograde Cholangiopancreatography: Dose Comparison Using Two Types of Dosemeters
Authors: Morishima Yoshiaki , Chida Koichi , Meguro Takayoshi , Hirota Morihisa , Chiba Hiroo , Fukuda Hiroshi
Published: September 2022

This study aimed to compare the lens equivalent dose (LED) measured during endoscopic retrograde cholangiopancreatography (ERCP) using DOSIRIS™ as a dedicated dosemeter to that measured using glass badges to determine if glass badges can be alternative tools for LED measurement.

LEDs for physicians during ERCP were measured using the DOSIRIS™ [3-mm dose equivalent] worn on the outer edge of the eyes and personal dosemeters (glass badges) [0.07-mm dose equivalent] worn on the right and left sides of the neck.

The cumulated doses over 6 months for the left eye using DOSIRIS™ were 9.5 and 11.8 mSv for physicians A and B, whereas doses measured using glass badges were 7.5 and 11.6 mSv, respectively. The LEDs of the physicians at the left eye and left neck side showed almost similar values and were significantly correlated (r = 0.95; p < 0.01).

For an accurate LED measurement during ERCP, using a dosemeter such as DOSIRIS™ is recommended, although similar LED estimation values were reported using glass badges on the left neck side.
Negotiating space for knowledge co-production
Authors: Verwoerd Lisa , Brouwers Hilde , Kunseler Eva , Regeer Barbara , de Hoop Evelien
Published: September 2022

Despite increased popularity of knowledge co-production as a research approach to address contemporary environmental issues, its implementation in science–policy contexts is not self-evident. In this paper, we illustrate how researchers at the PBL Netherlands Environmental Assessment Agency (in Dutch: Planbureau voor de Leefomgeving (PBL)) ensured a fit between key features of knowledge co-production and conventional norms and customs for knowledge production processes at the science–policy interface while simultaneously challenging those norms to create space for knowledge co-production. Drawing on implementation science, we analyzed two types of alignment activities: negotiation of normative and relational norms and modification of co-production features. Based on three policy evaluation cases, we show that PBL researchers developed co-production capacity over time. They became more skilled at recognizing (un)conducive structures to knowledge co-production, negotiating such structures, and modifying co-production features without compromising co-production integrity. We argue that investment in these skills is required to negotiate space for knowledge co-production in science–policy settings.
Policy seduction and governance resistance? Examining public funding agencies and academic institutions on decarbonisation research
Authors: AbdulRafiu Abbas
Published: September 2022

Public research funding is a critical instrument in technology and social innovation. This paper explores the emerging themes and topical trends that commonly influence interdisciplinary research within a sample of global research projects, including reviewing a recent study of 1,000 projects used in the selection of expert interview participants (n = 15). It examines the extent to which research funding agencies and academic institutions are shifting research priorities in the energy and climate change domain. It asks: What challenges does interdisciplinary research raise? The study reveals how cross-disciplinary research funding focuses on or fails to address the themes of sustainable development goals. In addition, it emphasises policy seduction and difficulty (resistance) in understanding cross-disciplinary methods in research and how research collaborations promote (or fail to promote) global South institutions and topics. Finally, the paper recommends that research funding needs involve a broader array of stakeholders in industrial decarbonisation research, including policymakers, industries, and citizens.
Prediction of Inhospital Mortality in Critically Ill Patients With Sepsis: Confirmation of the Added Value of 24-Hour Lactate to Acute Physiology and Chronic Health Evaluation IV
Authors: Baysan Meryem , Arbous Mendi S. , Steyerberg Ewout W. , van der Bom Johanna G.
Published: September 2022

BACKGROUND:

We previously reported the added value of 24-hour lactate concentration alone and in combination with 24-hour lactate clearance and lactate concentration at admission for the prediction of inhospital mortality in critically ill patients with sepsis. We aimed to validate this finding.

DERIVATION COHORT:

The derivation cohort from Leiden, The Netherlands, consisted of 451 critically ill patients with sepsis.

VALIDATION COHORT:

The validation cohort consisted of 4,440 critically ill adult patients with sepsis from the Medical Information Mart for Intensive Care cohort admitted to the ICU of Beth Israel Deaconness Medical Center, Boston, MA, between January 2006 and 2018.

PREDICTION MODEL:

Predictors of mortality were: age, chronic comorbidities, length of stay pre-ICU, Glasgow Coma Scale, and Acute Physiology Score. Lactate concentration at 24-hour alone, in combination with 24-hour lactate clearance and in combination with lactate concentration at admission, was added to assess improvement of the prediction model. The outcome was inhospital mortality.

RESULTS:

Inhospital mortality occurred in 160 patients (36%) in the derivation cohort and in 2,347 patients (53%) in the validation cohort. The Acute Physiology and Chronic Health Evaluation (APACHE) IV model had a moderate discriminative performance (recalibrated C-statistic, 0.62; 95% CI, 0.60–0.63). Addition of 24-hour lactate concentration increased the recalibrated C-statistic to 0.64 (95% CI, 0.62–0.66). The model with 24-hour lactate concentration and lactate concentration at admission showed the best fit as depicted by the smallest Akaike Information Criterion in both the derivation and validation data.

CONCLUSION:

The 24-hour lactate concentration and lactate concentration at admission contribute modestly to prediction of inhospital mortality in critically ill patients with sepsis. Future updates and possible modification of APACHE IV should consider the incorporation of lactate concentration at baseline and at 24 hours.
Association of lifetime lactation and age at natural menopause: a prospective cohort study
Authors: Scime Natalie V. , Shea Alison K. , Faris Peter D. , Brennand Erin A.
Published: September 2022

Objective

The aim of this study was to examine the association between duration of lifetime lactation and age at natural menopause.

Methods

In this prospective cohort study, we analyzed parous premenopausal women in the multiethnic Study of Women's Health Across the Nation who were followed approximately annually for 10 years (1995-2008). Lifetime lactation was defined as the duration of breastfeeding across all births in months. Age at natural menopause was defined as age in years after 12 consecutive months of amenorrhea after the final menstrual period for no other reported cause. We used Cox proportional hazard models to analyze time to natural menopause with age as the underlying time scale. Multivariable models controlled for education, race/ethnicity, parity, smoking, body mass index, and oral contraceptive use.

Results

Among 2,377 women, 52.6% experienced natural menopause during follow-up and reported a valid final menstrual period date. The small, crude association between lifetime lactation up to 24 months and later age at natural menopause attenuated to nonsignificance in adjusted models (6 months: adjusted hazard ratio [AHR], 0.96; 95% confidence interval (CI), 0.87-1.06; 12 months: AHR, 0.95; 95% CI, 0.82-1.11; 18 months: AHR, 0.96; 95% CI, 0.82-1.13; 24 months: AHR, 0.99; 95% CI, 0.84-1.16).

Conclusions

Duration of lifetime lactation was not associated with age at natural menopause after controlling for sociodemographic characteristics.