bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood DNA methylation provides an accurate biomarker ofKMT2B-related dystonia and predicts onset
Authors: Mirza-Schreiber Nazanin , Zech Michael , Wilson Rory , Brunet Theresa , Wagner Matias , Jech Robert , Boesch Sylvia , Škorvánek Matej , Necpál Ján , Weise David , Weber Sandrina , Mollenhauer Brit , Trenkwalder Claudia , Maier Esther M , Borggraefe Ingo , Vill Katharina , Hackenberg Annette , Pilshofer Veronika , Kotzaeridou Urania , Schwaibold Eva Maria Christina , Hoefele Julia , Waldenberger Melanie , Gieger Christian , Peters Annette , Meitinger Thomas , Schormair Barbara , Winkelmann Juliane , Oexle Konrad
Published: September 2021

Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking.

Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia.

Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)—being lower in samples with late or incomplete penetrance—thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation.
Midbrain organoids with anSNCAgene triplication model key features of synucleinopathy
Authors: Mohamed Nguyen-Vi , Sirois Julien , Ramamurthy Janani , Mathur Meghna , Lépine Paula , Deneault Eric , Maussion Gilles , Nicouleau Michael , Chen Carol X -Q , Abdian Narges , Soubannier Vincent , Cai Eddie , Nami Harris , Thomas Rhalena A , Wen Dingke , Tabatabaei Mahdieh , Beitel Lenore K , Singh Dolt Karamjit , Karamchandani Jason , Stratton Jo Anne , Kunath Tilo , Fon Edward A , Durcan Thomas M
Published: September 2021

SNCA, the first gene associated with Parkinson’s disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. The presence of Lewy bodies is one of the classical hallmarks found in the brain of patients with Parkinson’s disease, and Lewy bodies have also been observed in patients with other synucleinopathies. However, the study of α-synuclein pathology in cells has relied largely on two-dimensional culture models, which typically lack the cellular diversity and complex spatial environment found in the brain. Here, to address this gap, we use three-dimensional midbrain organoids, differentiated from human-induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. In particular, we find that SNCA triplication human midbrain organoids express elevated levels of α-synuclein and exhibit an age-dependent increase in α-synuclein aggregation, manifested by the presence of both oligomeric and phosphorylated forms of α-synuclein. These phosphorylated α-synuclein aggregates were found in both neurons and glial cells and their time-dependent accumulation correlated with a selective reduction in dopaminergic neuron numbers. Thus, human midbrain organoids from patients carrying SNCA gene multiplication can reliably model key pathological features of Parkinson’s disease and provide a powerful system to study the pathogenesis of synucleinopathies.
Circulating Omentin-1 levels and altered iron balance in chronic haemodialysis patients
Authors: Bolignano Davide , Dounousi Evangelia , Presta Pierangela , Greco Marta , Duni Anila , Crugliano Giuseppina , Pappas Charalambos , Pappas Ethymios , Dragone Francesco , Lakkas Lampros , Foti Daniela Patrizia , Andreucci Michele , Coppolino Giuseppe
Published: September 2021

Background

Iron deficiency is highly prevalent among patients undergoing chronic haemodialysis (HD) but its correct identification is often problematic as common biomarkers of iron status, such as transferrin saturation (TSAT) and ferritin, can be altered by inflammation or malnutrition.

Methods

In this pilot multicentre study, we aimed at evaluating circulating levels of Omentin-1, a novel fat depot-specific adipokine that is also involved in iron regulation, in a cohort of 85 chronic HD patients with relation to their iron status.

Results

Omentin-1 levels in HD were statistically higher than in healthy controls (P = 0.03) and there was a significant, growing trend in all iron parameters across Omentin-1 tertiles (P < 0.001). Compared with patients with optimal iron status, Omentin-1 levels were lower in subjects categorized according to TSAT ≤20% or serum ferritin ≤200 μg/L (both P < 0.001) and even more reduced in 19 patients (22%) simultaneously displaying low levels of both markers (P < 0.001). In this latter group, Omentin-1 levels increased in parallel to all other iron markers after iron correction by i.v. supplementation. At multivariate regression analyses, ferritin (β = 0.71; P < 0.001) and TSAT (β = 0.32; P = 0.03) remained the sole independent predictors of Omentin-1 levels. This biomarker also showed a remarkable diagnostic capacity at receiver operating characteristic analyses in identifying iron-depleted HD patients according to a criterion of TSAT ≤20% [area under the curve (AUC) 0.827], ferritin ≤200 μg/L (AUC 0.863) or low levels of both parameters (AUC 0.907).

Conclusions

Findings obtained indicate that Omentin-1 is somewhat involved in iron balance regulation and might be a candidate biomarker for diagnosing and managing altered iron conditions in HD patients.
PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm
Authors: Whooley J , Alazzawi M , Donlon N E , Bolger J C , Robb W B
Published: September 2021

Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.
Automated left atrial volume measurement by two-dimensional speckle-tracking echocardiography: feasibility, accuracy, and reproducibility
Authors: Florescu Diana R , Badano Luigi P , Tomaselli Michele , Torlasco Camilla , Târtea Georgică C , Bălșeanu Tudor A , Volpato Valentina , Parati Gianfranco , Muraru Denisa
Published: September 2021

Aims

A byproduct of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Accordingly, we sought to (i) assess the feasibility of automated LAVmax measurement by 2DSTE; (ii) compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and (iii) evaluate the accuracy and reproducibility of the three echocardiography techniques.

Methods and results

LAVmax (34–197 mL) were obtained from 198/210 (feasibility 94%) consecutive patients (median age 67 years, 126 men) by 2DSTE, 2DE, and 3DE. 2DE and 2DSTE measurements resulted in similar LAVmax values [bias = 1.5 mL, limits of agreement (LOA) ± 7.5 mL], and slightly underestimated 3DE LAVmax (biases = −5 mL, LOA ± 17 mL and −6 mL, LOA ± 16 mL, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r = 0.946 and r = 0.935, respectively; P < 0.001). However, LAVmax obtained by 2DSTE (bias = −9.5 mL, LOA ± 16 mL) and 2DE (bias = −8 mL, LOA ± 17 mL) were significantly smaller than those measured by CMR. Conversely, 3DE LAVmax were similar to CMR (bias = −2 mL, LOA ± 10 mL). Excellent intra- and inter-observer intraclass correlations were found for 3DE (0.995 and 0.995), 2DE (0.990 and 0.988), and 2DSTE (0.990 and 0.989).

Conclusion

Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax.
Causal relation of tricuspid regurgitation for heart failure outcomes: a mediation analysis of echocardiographic predictors
Authors: Hakuno Daihiko , Fukae Tomoaki , Takahashi Masashi , Sueyoshi Koichiro
Published: September 2021

Aims

Although significant tricuspid regurgitation (TR) is critically associated with heart failure (HF) prognosis, the predictors for large TR impact on HF outcomes remain unknown. This study aimed to identify echocardiographic predictors for a causal relation of TR to HF outcomes.

Methods and results

In a retrospective, acute HF cohort of 462 patients, multivariate logistic regression analysis was performed to determine subgroups with strong association of greater-than-moderate TR with HF readmission or cardiovascular death in a year. We then conducted causal mediation analysis according to persistent atrial fibrillation (Af) or mitral regurgitation (MR) to identify the echocardiographic predictors. The association of TR with HF outcomes was prominent in subgroups of females, with Af, the enlarged indexed tricuspid annular diameter (TADi) or right atrial area, or within certain ranges of the left ventricular ejection fraction, indexed right ventricular end-systolic area, or fractional area change (FAC). Causal mediation analysis found that the TR impact was significant in patients with Af. Furthermore, combination of TADi ≥2.1 cm/m2 and FAC ≥30%, which accounted for half of TR patients, predicted a much larger TR impact irrespective of Af and MR. Its prediction ability was superior to that of the modified Model for End-stage Liver Disease score.

Conclusion

The causal impact and burden of TR on HF outcomes was significant in patients with Af, and combining TADi ≥2.1 cm/m2 with FAC ≥30% could provide superior echocardiographic prediction of larger TR impact in HF patients.
Comparative analysis ofMalassezia furfurmitogenomes and the development of a mitochondria-based typing approach
Authors: Theelen Bart , Christinaki Anastasia C , Dawson Thomas L , Boekhout Teun , Kouvelis Vassili N
Published: September 2021

Malassezia furfur is a yeast species belonging to Malasseziomycetes, Ustilaginomycotina and Basidiomycota that is found on healthy warm-blooded animal skin, but also involved in various skin disorders like seborrheic dermatitis/dandruff and pityriasis versicolor. Moreover, Malassezia are associated with bloodstream infections, Crohn's disease and pancreatic carcinoma. Recent advances in Malassezia genomics and genetics have focused on the nuclear genome. In this work, we present the M. furfur mitochondrial (mt) genetic heterogenicity with full analysis of 14 novel and six available M. furfur mt genomes. The mitogenome analysis reveals a mt gene content typical for fungi, including identification of variable mt regions suitable for intra-species discrimination. Three of them, namely the trnK–atp6 and cox3–nad3 intergenic regions and intron 2 of the cob gene, were selected for primer design to identify strain differences. Malassezia furfur strains belonging to known genetic variable clusters, based on AFLP and nuclear loci, were assessed for their mt variation using PCR amplification and sequencing. The results suggest that these mt regions are excellent molecular markers for the typing of M. furfur strains and may provide added value to nuclear regions when assessing evolutionary relationships at the intraspecies level.
Thermal expansivity, heat capacity and bulk modulus of the mantle
Authors: Stixrude Lars , Lithgow-Bertelloni Carolina
Published: September 2021

We derive exact expressions for the thermal expansivity, heat capacity and bulk modulus for assemblages with arbitrarily large numbers of components and phases, including the influence of phase transformations and chemical exchange. We illustrate results in simple two-component, two-phase systems, including Mg–Fe olivine-wadsleyite and Ca–Mg clinopyroxene-orthopyroxene and for a multicompontent model of mantle composition in the form of pyrolite. For the latter we show results for the thermal expansivity and heat capacity over the entire mantle pressure–temperature regime to 40 GPa, or a depth of 1000 km. From the thermal expansivity, we derive a new expression for the phase buoyancy parameter that is valid for arbitrarily large numbers of phases and components and which is defined at every point in pressure–temperature space. Results reveal regions of the mantle where the magnitude of the phase buoyancy parameter is larger in magnitude than for those phase transitions that are most commonly included in mantle convection simulations. These regions include the wadsleyite to garnet and ferropericlase transition, which is encountered along hot isentropes (e.g. 2000 K potential temperature) in the transition zone, and the ferropericlase and stishovite to bridgmanite transition, which is encountered along cold isentropes (e.g. 1000 K potential temperature) in the shallow lower mantle. We also show the bulk modulus along a typical mantle isentrope and relate it to the Bullen inhomogeneity parameter. All results are computed with our code HeFESTo, updates and improvements to which we discuss, including the implementation of the exact expressions for the thermal expansivity, heat capacity and bulk modulus, generalization to allow for pressure dependence of non-ideal solution parameters and an improved numerical scheme for minimizing the Gibbs free energy. Finally, we present the results of a new global inversion of parameters updated to incorporate more recent results from experiment and first principles theory, as well as a new phase (nal phase), and new species: Na-majorite and the NaAlO2 end-member of ferropericlase.
Relationship between glucose homeostasis and obesity in early life—a study of Italian children and adolescents
Authors: Balkhiyarova Zhanna , Luciano Rosa , Kaakinen Marika , Ulrich Anna , Shmeliov Aleksey , Bianchi Marzia , Chioma Laura , Dallapiccola Bruno , Prokopenko Inga , Manco Melania
Published: September 2021

Epidemic obesity is the most important risk factor for prediabetes and type 2 diabetes (T2D) in youth as it is in adults. Obesity shares pathophysiological mechanisms with T2D and is likely to share part of the genetic background. We aimed to test if weighted genetic risk scores (GRSs) for T2D, fasting glucose (FG) and fasting insulin (FI) predict glycaemic traits and if there is a causal relationship between obesity and impaired glucose metabolism in children and adolescents. Genotyping of 42 SNPs established by genome-wide association studies for T2D, FG and FI was performed in 1660 Italian youths aged between 2 and 19 years. We defined GRS for T2D, FG and FI and tested their effects on glycaemic traits, including FG, FI, indices of insulin resistance/beta cell function and body mass index (BMI). We evaluated causal relationships between obesity and FG/FI using one-sample Mendelian randomization analyses in both directions. GRS-FG was associated with FG (beta = 0.075 mmol/l, SE = 0.011, P = 1.58 × 10−11) and beta cell function (beta = −0.041, SE = 0.0090 P = 5.13 × 10−6). GRS-T2D also demonstrated an association with beta cell function (beta = −0.020, SE = 0.021 P = 0.030). We detected a causal effect of increased BMI on levels of FI in Italian youths (beta = 0.31 ln (pmol/l), 95%CI [0.078, 0.54], P = 0.0085), while there was no effect of FG/FI levels on BMI. Our results demonstrate that the glycaemic and T2D risk genetic variants contribute to higher FG and FI levels and decreased beta cell function in children and adolescents. The causal effects of adiposity on increased insulin resistance are detectable from childhood age.
The interspecific competition presents greater nutrient facilitation compared with intraspecific competition through AM fungi interacting with litter for two host plants in karst soil
Authors: Guo Yun , He Yuejun , Wu Pan , Wu Bangli , Lin Yan , He Minhong , Han Xu , Xia Tingting , Shen Kaiping , Kang Liling , Tan Qiyu , Ren Wenda , Sun Yan , Li Qing
Published: September 2021

Litter is the crucial carrier of soil nutrition transformation. The influence of arbuscular mycorrhizal (AM) fungi on nutrient acquisition in plants has been widely recognized. However, in nutrient-deficient karst habitat, how competitive plants utilize nutrients regulated by AM fungi via litter remain largely unknown. The experimental treatments included the inoculation with or without Glomus etunicatum, the litter addition by the mixed leaves of Broussonetia papyrifera and Carpinus pubescens or no addition, and the competition through the intraspecific competition of B. papyrifera and C. pubescens, respectively, and the interspecific competition mixed both plants. AM fungi differently affected plant on nutrient acquisition, increasing nutrients acquisitions of B. papyrifera in intra- and interspecific competitions while decreasing for C. pubescens. Litter presented opposite influences on N acquisitions of both plants in interspecific competition with AM fungi, being positive for C. pubescens and negative for B. papyrifera, respectively. Under the interaction of AM fungi and litter, nitrogen (N), phosphorus (P) and potassium (K) acquisitions by B. papyrifera and N acquisition by C. pubescens in interspecific competition were all greater than intraspecific competition. In the interspecific competition, the competitive ability of plants on nutrient absorption presented significant species difference, which of B. papyrifera on P and K was significantly increased, while was converse for C. pubescens on K. In conclusion, these results suggest that the interspecific competition presents greater nutrient facilitation compared with intraspecific competition through AM fungi interacting with litter for plants in karst soil.
Intramuscular desmoplastic fibroblastoma: a case report of extreme rarities in extremities
Authors: Onghena Louis , Verniers Lucas , Woussen Sofie , Van den Broecke Caroline , Fierens Kjell , Van Kerschaver Olivier
Published: September 2021

Soft tissue tumors are part of a wide and sometimes rare differential diagnostic landscape. Case description of these rare soft tissue masses helps the future differentiation and aids in preoperative multidisciplinary approach. Interpretation and staging, with the help of imaging, is key.
The Effects of a Targeted “Early Bird” Incentive Strategy on Response Rates, Fieldwork Effort, and Costs in a National Panel Study
Authors: McGonagle Katherine A , Sastry Narayan , Freedman Vicki A
Published: September 2021

Adaptive survey designs are increasingly used by survey practitioners to counteract ongoing declines in household survey response rates and manage rising fieldwork costs. This paper reports findings from an evaluation of an early-bird incentive (EBI) experiment targeting high-effort respondents who participate in the 2019 wave of the US Panel Study of Income Dynamics. We identified a subgroup of high-effort respondents at risk of nonresponse based on their prior wave fieldwork effort and randomized them to a treatment offering an extra time-delimited monetary incentive for completing their interview within the first month of data collection (treatment group; N = 800) or the standard study incentive (control group; N = 400). In recent waves, we have found that the costs of the protracted fieldwork needed to complete interviews with high-effort cases in the form of interviewer contact attempts plus an increased incentive near the close of data collection are extremely high. By incentivizing early participation and reducing the number of interviewer contact attempts and fieldwork days to complete the interview, our goal was to manage both nonresponse and survey costs. We found that the EBI treatment increased response rates and reduced fieldwork effort and costs compared to a control group. We review several key findings and limitations, discuss their implications, and identify the next steps for future research.
Rice β-glucosidase Os12BGlu38 is required for synthesis of intine cell wall and pollen fertility
Authors: Shim Su-Hyeon , Mahong Bancha , Lee Sang-Kyu , Kongdin Manatchanok , Lee Chanhui , Kim Yu-Jin , Qu Guorun , Zhang Dabing , Ketudat Cairns James R , Jeon Jong-Seong
Published: September 2021

Glycoside hydrolase family1 β-glucosidases play a variety of roles in plants, but their in planta functions are largely unknown in rice (Oryza sativa). In this study, the biological function of Os12BGlu38, a rice β-glucosidase, expressed in bicellular to mature pollen, was examined. Genotype analysis of progeny of the self-fertilized heterozygous Os12BGlu38 T-DNA mutant, os12bglu38-1, found no homozygotes and a 1:1 ratio of wild type to heterozygotes. Reciprocal cross analysis demonstrated that Os12BGlu38 deficiency cannot be inherited through the male gamete. In cytological analysis, the mature mutant pollen appeared shrunken and empty. Histochemical staining and TEM showed that mutant pollen lacked intine cell wall, which was rescued by introduction of wild-type Os12BGlu38 genomic DNA. Metabolite profiling analysis revealed that cutin monomers and waxes, the components of the pollen exine layer, were increased in anthers carrying pollen of os12bglu38-1 compared with wild type and complemented lines. Os12BGlu38 fused with green fluorescent protein was localized to the plasma membrane in rice and tobacco. Recombinant Os12BGlu38 exhibited β-glucosidase activity on the universal substrate p-nitrophenyl β-d-glucoside and some oligosaccharides and glycosides. These findings provide evidence that function of a plasma membrane-associated β-glucosidase is necessary for proper intine development.
ATOMS: ALMA Three-millimeter Observations of Massive Star-forming regions – IV. Radio recombination lines and evolution of star formation efficiencies
Authors: Zhang C , Evans Neal J , Liu T , Wu J-W , Wang Ke , Liu H-L , Zhu F-Y , Ren Z-Y , Dewangan L K , Lee Chang Won , Li Shanghuo , Bronfman L , Tej A , Li D
Published: September 2021

We report the detection of radio recombination line (RRL) H40α towards 75 sources, with data obtained from ACA (Atacama Compact 7 m Array) observations in the ATOMS (ALMA Three-millimeter Observations of Massive Star-forming regions) survey of 146 active Galactic star-forming regions. We calculated ionized gas mass and star formation rate (SFR) with H40α line emission. The mass of ionized gas is significantly smaller than molecular gas mass, indicating that ionized gas is negligible in the star-forming clumps of the ATOMS sample. The SFR estimated with RRL H40α agrees well with that calculated with the total bolometric luminosity (Lbol) when SFR ≥ 5 M⊙ Myr−1, suggesting that millimetre RRLs could well sample the upper part of the initial mass function and thus be good tracers of SFR. We also study the relationships between Lbol and the molecular line luminosities (L$^{^{\prime }}_{\rm mol}$) of CS J = 2–1 and HC3N J = 11–10 for all the 146 ATOMS sources. The $L_{\rm bol} \!-\! L^{\prime }_{\rm mol}$ correlations of both the CS J = 2–1 and HC3N J = 11–10 lines appear approximately linear and these transitions have success in predicting Lbol similar to that of more commonly used transitions. The Lbol-to-$L^{\prime }_{\rm mol}$ ratios or SFR-to-mass ratios (star formation efficiency) do not change with galactocentric distances (RGC). Sources with H40α emission (or H ii regions) show higher Lbol-to-$L^{\prime }_{\rm mol}$ ratios than those without H40α emission, which may be an evolutionary effect.
Pair-regulated Klein–Nishina relativistic magnetic reconnection with applications to blazars and accreting black holes
Authors: Mehlhaff J M , Werner G R , Uzdensky D A , Begelman M C
Published: September 2021

Relativistic magnetic reconnection is a powerful agent through which magnetic energy can be tapped in astrophysics, energizing particles that then produce observed radiation. In some systems, the highest energy photons come from particles Comptonizing an ambient radiation bath supplied by an external source. If the emitting particle energies are high enough, this inverse Compton (IC) scattering enters the Klein–Nishina regime, which differs from the low-energy Thomson IC limit in two significant ways. First, radiative losses become inherently discrete, with particles delivering an order-unity fraction of their energies to single photons. Secondly, Comptonized photons may pair produce with the ambient radiation, opening up another channel for radiative feedback on magnetic reconnection. We analytically study externally illuminated highly magnetized reconnecting systems for which both of these effects are important. We identify a universal (initial magnetization-independent) quasi-steady state in which gamma-rays emitted from the reconnection layer are absorbed in the upstream region, and the resulting hot pairs dominate the energy density of the inflow plasma. However, a true pair cascade is unlikely, and the number density of created pairs remains subdominant to that of the original plasma for a wide parameter range. Future particle-in-cell simulation studies may test various aspects. Pair-regulated Klein–Nishina reconnection may explain steep spectra (quiescent and flaring) from flat-spectrum radio quasars and black hole accretion disc coronae.
Multiresolution angular momentum measurements of z ∼ 1.5−2 star-forming galaxies
Authors: Espejo Salcedo Juan M , Glazebrook Karl , Fisher Deanne B , Sweet Sarah M , Obreschkow Danail , Swinbank A M , Gillman Steven , Tiley Alfred L
Published: September 2021

We present detailed stellar specific angular momentum (j*) measurements of 10 star-forming galaxies at z ∼ 1.5−2, using both high and low spatial resolution integral field spectroscopic data. We developed a code that simultaneously models the adaptive optics (AO) assisted observations from OSIRIS/SINFONI along with their natural seeing (NS) counterparts from KMOS at spatial resolutions of [0.1−0.4] arcsec and [0.6−1.0] arcsec, respectively. The AO data reveal 2/10 systems to be mergers and for the remaining eight the mean uncertainties $\bar{\Delta }j_*$ decrease from 49 per cent (NS), and 26.5 per cent (AO), to 16 per cent in the combined analysis. These j* measurements agree within 20 per cent with simple estimates ($\tilde{j_*}$) calculated from Hubble Space Telescope photometry and NS kinematics; however, higher resolution kinematics are required to first identify these discs. We find that the choice of surface mass density model and the measurement of effective radius from photometry are the key sources of systematic effects in the measurement of j* between different analyses. Fitting the j* versus M* relations (Fall 1983) with a fixed power-law slope of β = 2/3, we find a zero-point consistent with prior NS results at z ≥ 1 within ∼0.3 dex. Finally, we find a ∼0.38 dex scatter about that relation that remains high despite the AO data so we conclude it is intrinsic to galaxies at z > 1. This compares to a scatter of ≤0.2 dex for discs at z ≃ 0 pointing to a settling of the Fall relation with cosmic time.
ATOMS: ALMA Three-millimeter Observations of Massive Star-forming regions – V. Hierarchical fragmentation and gas dynamics in IRDC G034.43+00.24
Authors: Liu Hong-Li , Tej Anandmayee , Liu Tie , Issac Namitha , Saha Anindya , Goldsmith Paul F , Wang Jun-Zhi , Zhang Qizhou , Qin Sheng-Li , Wang Ke , Li Shanghuo , Soam Archana , Dewangan Lokesh , Lee Chang Won , Li Pak-Shing , Liu Xun-Chuan , Zhang Yong , Ren Zhiyuan , Juvela Mika , Bronfman Leonardo , Wu Yue-Fang , Tatematsu Ken’ichi , Chen Xi , Li Di , Stutz Amelia , Zhang Siju , Viktor Toth L , Luo Qiu-Yi , Xu Feng-Wei , Li Jinzeng , Liu Rong , Zhou Jianwen , Zhang Chao , Tang Mengyao , Zhang Chao , Baug Tapas , Mannfors E , Chakali Eswaraiah , Dutta Somnath
Published: September 2021

We present new 3-mm continuum and molecular lines observations from the ATOMS survey towards the massive protostellar clump, MM1, located in the filamentary infrared dark cloud (IRDC), G034.43+00.24 (G34). The lines observed are the tracers of either dense gas (e.g. HCO+/H13CO+ J= 1–0) or outflows (e.g. CS J= 2–1). The most complete picture to date of seven cores in MM1 is revealed by dust continuum emission. These cores are found to be gravitationally bound, with virial parameter, αvir < 2. At least four outflows are identified in MM1 with a total outflowing mass of ∼45 M⊙, and a total energy of 1 × 1047 erg, typical of outflows from a B0-type star. Evidence of hierarchical fragmentation, where turbulence dominates over thermal pressure, is observed at both the cloud and the clump scales. This could be linked to the scale-dependent, dynamical mass inflow/accretion on clump and core scales. We therefore suggest that the G34 cloud could be undergoing a dynamical mass inflow/accretion process linked to the multiscale fragmentation, which leads to the sequential formation of fragments of the initial cloud, clumps, and ultimately dense cores, the sites of star formation.
A differential RR Lyrae line-of-sight distance between M31 and M33
Authors: Sarajedini Ata
Published: September 2021

We present a purely differential line-of-sight distance between M31 and M33 using ab-type RR Lyrae variables observed in each galaxy by the Hubble Space Telescope Advanced Camera for Surveys in the F606W filter. Using 1481 RR Lyraes in 13 M31 fields and 181 RR Lyraes in 6 M33 fields, and placing all of these stars on a uniform photometric scale with internally consistent corrections for metal abundance and extinction, we find a relative absolute distance modulus of Δ(m − M)o = –0.298 ± 0.016 in the sense of (m − M)o, M31 – (m − M)o, M33. Adopting an absolute distance modulus of (m− M)o = 24.46 ± 0.10 for M31 places M33 115 kpc beyond M31 in line-of-sight distance.
The human sperm basal body is a complex centrosome important for embryo preimplantation development
Authors: Amargant Farners , Pujol Aïda , Ferrer-Vaquer Anna , Durban Mercè , Martínez Meritxell , Vassena Rita , Vernos Isabelle
Published: September 2021

The mechanism of conversion of the human sperm basal body to a centrosome after fertilization, and its role in supporting human early embryogenesis, has not been directly addressed so far. Using proteomics and immunofluorescence studies, we show here that the human zygote inherits a basal body enriched with centrosomal proteins from the sperm, establishing the first functional centrosome of the new organism. Injection of human sperm tails containing the basal body into human oocytes followed by parthenogenetic activation, showed that the centrosome contributes to the robustness of the early cell divisions, increasing the probability of parthenotes reaching the compaction stage. In the absence of the sperm-derived centrosome, pericentriolar material (PCM) components stored in the oocyte can form de novo structures after genome activation, suggesting a tight PCM expression control in zygotes. Our results reveal that the sperm basal body is a complex organelle which converts to a centrosome after fertilization, ensuring the early steps of embryogenesis and successful compaction. However, more experiments are needed to elucidate the exact molecular mechanisms of centrosome inheritance in humans.
Fukomys mechowii(Rodentia: Bathyergidae)
Authors: Caspar Kai R , Burda Hynek , Begall Sabine
Published: September 2021

Fukomys mechowii (Peters, 1881), the giant mole-rat or Mechow’s mole-rat, is a cooperatively breeding, tooth-digging, subterranean rodent. It is the largest representative of the genus Fukomys, which is part of the African mole-rat family Bathyergidae. It is found in mesic shrubland, savannah habitats, and agricultural lands in central Africa, its range extending through Angola, the Democratic Republic of Congo, and Zambia. Fukomys mechowii is hunted for its meat in rural areas but its population is considered to be stable. It is rarely housed in captivity and is listed as “Least Concern” (LC) on the International Union for Conservation of Nature Red List of Threatened Species.
Inciting Military Disaffection in Interwar Britain and Fascist Italy: Security, Crime and Authoritarian Law
Authors: Skinner Stephen
Published: September 2021

During the interwar period, two apparently different states, liberal democratic Britain and Fascist Italy, passed similar legislation establishing inchoate offences against military loyalty and obedience. These laws, the Incitement to Disaffection Act 1934 and article 266 of the 1930 Italian Penal Code, were intended to protect state security and the monopoly of force against political threats. This article compares these laws’ scope, rationales and purposes, and traces their longer-term origins in the consolidation of the modern state. It argues that this comparative historical analysis evidences important intersections in these systems’ uses of criminal law, and provides insights into the forms and extent of authoritarian tendencies and techniques in states’ legal practices, specifically in the security context and more generally within criminal law as a vector of state power across the political spectrum.
Imaging the living plant cell: From probes to quantification
Authors: Colin Leia , Martin-Arevalillo Raquel , Bovio Simone , Bauer Amélie , Vernoux Teva , Caillaud Marie-Cecile , Landrein Benoit , Jaillais Yvon
Published: September 2021

At the center of cell biology is our ability to image the cell and its various components, either in isolation or within an organism. Given its importance, biological imaging has emerged as a field of its own, which is inherently highly interdisciplinary. Indeed, biologists rely on physicists and engineers to build new microscopes and imaging techniques, chemists to develop better imaging probes, and mathematicians and computer scientists for image analysis and quantification. Live imaging collectively involves all the techniques aimed at imaging live samples. It is a rapidly evolving field, with countless new techniques, probes, and dyes being continuously developed. Some of these new methods or reagents are readily amenable to image plant samples, while others are not and require specific modifications for the plant field. Here, we review some recent advances in live imaging of plant cells. In particular, we discuss the solutions that plant biologists use to live image membrane-bound organelles, cytoskeleton components, hormones, and the mechanical properties of cells or tissues. We not only consider the imaging techniques per se, but also how the construction of new fluorescent probes and analysis pipelines are driving the field of plant cell biology.
MODELLING AUTOMATIC EXPOSURE CONTROL RESPONSE TO THE PRESENCE OF THE PATIENT SCANNING BED IN A HYBRID PET/CT SCANNER
Authors: Cournane Seán , Reade Matthew , McCavana Jackie , Lucey Julie
Published: September 2021

Automatic Exposure Control (AEC) systems optimise radiation dose to the patient while providing adequate image quality. This study examined the effect that the increased localiser region of interest of a hybrid PET/CT has on the CTDIvol, focussing on the role of extraneous objects and patient attenuation profiles. A Siemens Biograph™ 16 Horizon PET/CT system and a Siemens Somatom Sensation 64, both employing the Siemens CAREDose 4D AEC system, were used for acquisition of a range of phantoms.

The effect of patient miscentring and effect of the patient bed impinging on the localiser was established and modelled. For PA localiser scans, a non-linear relationship between miscentring and CTDIvol was observed, attributable to the presence of the patient bed being misinterpreted as the patient width.

The model identified how the presence of the patient bed led to an increase in the CTDIvol significantly larger than expected (~12%, or 1 mSv), particularly prevalent for smaller patients.
Cluster Analysis of Clozapine Consumer Perspectives and Comparison to Consumers on Other Antipsychotics
Authors: Sharma Sumeet , Kopelovich Sarah L , Janjua A Umair , Pritchett Cristina , Broussard Beth , Dhir Meena , Wilson Joseph G , Goldsmith David R , Cotes Robert O
Published: September 2021

Despite its unique efficacy, clozapine remains underutilized in the United States. Perceptions about clozapine and barriers to its use have been examined among prescribers, but insufficiently studied among consumers. We surveyed 211 antipsychotic consumers (86 on clozapine and 125 on other antipsychotics) on their medication-related perspectives in a public hospital system in Atlanta, Georgia, USA. In contrast to their previous regimen, 72% of clozapine consumers reported they were more satisfied with clozapine. When compared with consumers taking other antipsychotics, clozapine consumers reported more side effects but did not differ on other measures of satisfaction or efficacy. We found Caucasians to be overrepresented among clozapine, as compared to other antipsychotic consumers. Side effects most strongly associated with poor safety ratings were sedation, limb jerking, and dizziness when standing. However, clozapine was only rated less safe by consumers who experienced more than one of these side effects. We used an unsupervised clustering approach to identify three major groups of clozapine consumers. Cluster A (19%) had the lowest safety ratings, aversion to blood work, and a high rate of side effects that associate with lower safety ratings. Cluster B (25%) experienced more hospitalizations and reported satisfaction with clozapine that correlated with efficacy ratings, irrespective of safety ratings. Cluster C (56%) experienced fewer hospitalizations, fewer previous drug trials, greater educational attainment, lower rates of smoking, and rated clozapine more highly. This work identifies common side effects that influence the subjective safety of clozapine and suggests that attitudes toward clozapine depend on context-specific factors.
Effects of eye patches on corneal ulcer healing and weight gain in stocker steers on pasture: a randomized controlled trial
Authors: Maier Gabriele U , Davy Josh S , Forero Larry C , Bang Heejung , Clothier Kristin , Angelos John A
Published: September 2021

Infectious bovine keratoconjunctivitis (IBK) is a painful ocular disease in cattle that is characterized by the presence of a corneal ulcer and production losses. A common industry practice is to cover an affected eye with a piece of cloth to reduce exposure to face flies and ultraviolet light with the goal of alleviating pain, accelerating healing, and reducing spread. To study the efficacy of eye patches in the treatment of IBK, a group of 216 clinically normal Angus crossbred steers were followed between April and August 2019 and evaluated weekly for the development of IBK. Eyes of cattle that developed IBK were enrolled with a blocked randomization scheme based on ulcer severity score to receive either an eye patch (treatment group) or no eye patch (control group). All treatment and control group animals received parenteral antimicrobial and nonsteroidal anti-inflammatory treatments and were housed in a pasture separated from the rest of the cohort for a maximum of 28 d or until clinical cure. Corneal ulcer areas were measured, and body weights were recorded twice weekly for steers in the treatment and control groups. Weights of all steers in the cohort were recorded three times during the trial period. The primary outcome, rate of corneal ulcer healing, was higher (P = 0.001) for lesions in eyes receiving an eye patch as determined by a linear mixed model that controlled for ulcer severity score at enrollment and previous IBK in the opposite eye. Median corneal ulcer healing time was 10 (IQR [Interquartile range] 7–17) d for patched eyes vs. 14 (IQR 7–21) d for unpatched eyes. In a Cox proportional hazards model adjusted for severity score at diagnosis, the hazard ratio for ulcer healing was 1.62 (95% CI: 1.02–2.56, P = 0.042) for eyes that received a patch compared to eyes that did not. Among all 216 steers in the cohort, those that were diagnosed with IBK had a numerically higher average daily gain (ADG) (0.45 [±SE 0.01] kg) vs. those that were not (0.42 [±SE 0.12] kg; P = 0.06). In enrolled steers that received a patch, the secondary outcome ADG was 0.47 (±SE 0.02) kg compared to 0.43 (±SE 0.02) kg in controls (P = 0.22). Weight gain may have been confounded by pasture during the treatment period. Results of this trial support the use of this low-cost intervention; further investigation into possible reasons for observed differences in weight gain may be warranted.
Intravenous Cetirizine vs Intravenous Diphenhydramine for the Prevention of Hypersensitivity Infusion Reactions: Results of an Exploratory Phase 2 Study
Authors: Holmes Jarrod P. , Peguero Julio A. , Garland R. Campbell , North Janine , Young Stacia , Brent Lonnie D. , Joseph-Ridge Nancy
Published: September 2021

Pretreatment with antihistamines for the prevention of hypersensitivity infusion reactions is recommended for certain biologics and chemotherapies. Cetirizine is the first injectable second-generation antihistamine recently approved for acute urticaria. A randomized, exploratory phase 2 study evaluated intravenous (IV) cetirizine 10 mg versus IV diphenhydramine 50 mg as pretreatment in patients receiving an anti-CD20 agent or paclitaxel. In the overall population (N = 34) and an elderly subgroup (n = 21), IV cetirizine was as effective as IV diphenhydramine in preventing infusion reactions (primary outcome) and associated with less sedation at all time points, a shorter infusion center stay, and fewer treatment-related adverse events.
A Quality Initiative to Decrease Time Until Analgesic for Fracture-associated Pain in the Pediatric Emergency Department
Authors: Davis Justin , Kappler Kristin , Stoker Skye
Published: September 2021

Introduction:

Long bone fractures are a common cause of pain in the pediatric emergency department (PED), and ensuring timely delivery of analgesic medications is essential for these children. We aimed to decrease the median time to the first dose of analgesic for long bone fracture–associated pain in our PED to 36 minutes or less by July 1, 2015.

Methods:

A series of 4 initiatives were implemented in successive “plan, do, study, act” rapid cycles. Initiatives consisted of educational interventions for staff regarding Emergency Severity Index procedures for triaging pain, transition to in-room triage, enhanced communication about quality goals using a “quality board,” and ongoing staff educational sessions on outlier cases as well as biases and barriers to quality.

Results:

We implemented the initiatives from April through July of 2015. The monthly median time to analgesic delivery for long bone fracture–associated pain in the PED decreased from 72 minutes in April to 33.5 minutes in July of 2015. For 12 months following the first intervention, the average monthly median time to the first analgesic dose was 48.5 versus 66.3 minutes for the prior 12 months.

Conclusions:

A series of 4 interventions led to a decrease in the median time to the first dose of analgesic for long bone fracture–associated pain in the PED.
Improving Physical Abuse Documentation and Photography through a Remote Peer Review Intervention
Authors: Moles Rebecca L. , Melville John , Martinez Kim , Palusci Vincent
Published: September 2021

Introduction:

Child Abuse Pediatrics is a small and geographically dispersed specialty. This article reports on an intervention to improve written and photodocumentation quality and uniformity in suspected child physical abuse cases, using a remote, de-identified case review system.

Methods:

In each cycle, participants submitted de-identified medical reports and photographs for review by a child abuse pediatrics expert. Experts evaluated 3 cycles of 5 cases using a novel rubric and assigned quality interventions for the participants based on their scores.

Results:

15 of 16 participants improved scores between cycles 1 and 3 (78% versus 89%, P < 0.001). All participants rated the program as helpful and would recommend it to a colleague.

Conclusion:

A quality improvement project administered via the internet improves the quality and uniformity of written and photographic documentation in child physical abuse evaluations.