bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct neural correlates of poor decoding and poor comprehension in children with reading disability
Authors: Feng Guoyan , Yan Xiaohui , Shen Linling , Perkins Kyle , Mao Jiaqi , Wu Yu , Shi Liping , Cao Fan
Published: July 2022

Reading disability (RD) can manifest itself as a word decoding problem or a reading comprehension problem. In the current study, we identified 3 subtypes of RD: poor decoders (PD), poor comprehenders (PC), and poor-in-both (PB). We found that PD had greater deficits in meta-linguistic skills such as phonological awareness, orthographic skills, and morphological skills than PC, whereas PC had greater deficits in listening comprehension than PD. In the brain, we also found different patterns of deficits during an auditory rhyming judgment task using functional magnetic resonance imaging. PD showed less activation than PC and age controls in the left dorsal inferior frontal gyrus (IFG) and pre-supplementary motor area (SMA), brain activation of which was correlated with phonological awareness and working memory. In contrast, PC showed less activation in the left fusiform gyrus than PD and age controls, which was correlated with reading comprehension fluency and morphological skill. Last, PB showed both PD’s and PC’s deficits, as well as additional deficits in the bilateral lingual gyri. Our findings contribute to revealing different neural signatures of poor decoding and poor comprehension, which are distinct disorders but co-occur very often. These findings implicate possibility and necessity of precise diagnosis and individualized intervention.
Estrogens rapidly shape synaptic and intrinsic properties to regulate the temporal precision of songbird auditory neurons
Authors: Scarpa Garrett B , Starrett Joseph R , Li Geng-Lin , Brooks Colin , Morohashi Yuichi , Yazaki-Sugiyama Yoko , Remage-Healey Luke
Published: July 2022

Sensory neurons parse millisecond-variant sound streams like birdsong and speech with exquisite precision. The auditory pallial cortex of vocal learners like humans and songbirds contains an unconventional neuromodulatory system: neuronal expression of the estrogen synthesis enzyme aromatase. Local forebrain neuroestrogens fluctuate when songbirds hear a song, and subsequently modulate bursting, gain, and temporal coding properties of auditory neurons. However, the way neuroestrogens shape intrinsic and synaptic properties of sensory neurons remains unknown. Here, using a combination of whole-cell patch clamp electrophysiology and calcium imaging, we investigate estrogenic neuromodulation of auditory neurons in a region resembling mammalian auditory association cortex. We found that estradiol rapidly enhances the temporal precision of neuronal firing via a membrane-bound G-protein coupled receptor and that estradiol rapidly suppresses inhibitory synaptic currents while sparing excitation. Notably, the rapid suppression of intrinsic excitability by estradiol was predicted by membrane input resistance and was observed in both males and females. These findings were corroborated by analysis of in vivo electrophysiology recordings, in which local estrogen synthesis blockade caused acute disruption of the temporal correlation of song-evoked firing patterns. Therefore, on a modulatory timescale, neuroestrogens alter intrinsic cellular properties and inhibitory neurotransmitter release to regulate the temporal precision of higher-order sensory neurons.
Entanglement: cybercrime connections of a public forum population
Authors: Paquet-Clouston Masarah , Paquette Serge-Olivier , Garcia Sebastian , Erquiaga Maria José
Published: July 2022

Many activities related to cybercrime operations do not require much secrecy, such as developing websites or translating texts. This research provides indications that many users of a popular public internet marketing forum have connections to cybercrime. It does so by investigating the involvement in cybercrime of a population of users interested in internet marketing, both at a micro and macro scale. The research starts with a case study of three users confirmed to be involved in cybercrime and their use of the public forum. It provides a first glimpse that some business with cybercrime connections is being conducted in the clear. The study then pans out to investigate the forum population's ties with cybercrime by finding crossover users, that is, users from the public forum who also comment on cybercrime forums. The cybercrime forums on which they discuss are analyzed and the crossover users’ strength of participation is reported. Also, to assess if they represent a sub-group of the forum population, their posting behavior on the public forum is compared with that of non-crossover users. This blend of analyses shows that (i) a minimum of 7.2% of the public forum population are crossover users that have ties with cybercrime forums; (ii) their participation in cybercrime forums is limited; and (iii) their posting behavior is relatively indistinguishable from that of non-crossover users. This is the first study to formally quantify how users of an internet marketing public forum, a space for informal exchanges, have ties to cybercrime activities. We conclude that crossover users are a substantial part of the population in the public forum, and even though they have thus far been overlooked, their aggregate effect in the ecosystem must be considered. This study opens new research questions on cybercrime participation that should consider online spaces beyond their cybercrime branding.
The vocalization of the red junglefowl is a signal of body size and individual health
Authors: Hao Peipei , Zhao Kai , Huang Xi , Rao Xiaodong , Liang Wei , Zhang Yanyun
Published: July 2022

Bird songs are considered a sexually selected trait that can reflect the individual health of males as well as the vitality of potential mates and their competitors. Vocalization features should, therefore, be related to parasite load and body condition. Here, we performed a thorough acoustic analysis of the display calls of 9-month-old sub-adults and 18-month-old adults of pasture-raised red junglefowls Gallus gallus. We investigated whether the calls of pasture-raised red junglefowls can indicate body size and body condition, in addition to the influence of parasitic infection intensity on the expression of sexual traits. We found that frequency-related syllable parameters were significantly positively correlated with wing length in adults, whereas body weight was independent of both the frequency and temporal parameters of calls. In addition, we correlated parasitic load with the expression of sexually selected traits and discovered a positive association between the intensity of parasite infection and wing length in sub-adults, independent of vocal parameters. Overall, the results suggest that the vocalization of red junglefowls may convey reliable body size information, which will facilitate further studies of different vocal parameters in the transmission of bird vocalizations.
Pulmonary valve preservation during tetralogy of Fallot repair: midterm functional outcomes and risk factors for pulmonary regurgitation
Authors: Guariento Alvise , Schiena Chiara A , Cattapan Claudia , Avesani Martina , Doulamis Ilias P , Padalino Massimo A , Castaldi Biagio , di Salvo Giovanni , Vida Vladimiro
Published: July 2022

OBJECTIVES

Many centres have recently adopted pulmonary valve (PV) preservation (PVP) during tetralogy of Fallot (ToF) repair. We sought to identify the midterm functional outcomes and risk factors for pulmonary regurgitation after this procedure.

METHODS

All patients undergoing PVP during transatrial–transpulmonary repair for ToF with PV stenosis at our institution between January 2007 and December 2020 were reviewed.

RESULTS

Overall, 73 patients were included. At the index surgery, the body surface area was 0.31 ± 0.04 m2, the age was 4.9 ± 2.9 months and the preoperative PV z-score was -3.02 ± 1.11. At a mean follow-up of 5.3 ± 2.7 years, the fractional area change of the right ventricle (RV) was 47.1 ± 5.2%, and the tricuspid annular plane systolic excursion z-score was -3.31 ± 1.89%. The 5-year freedom from moderate/severe PV regurgitation was 61.3% [95% confidence interval (CI): 48, 73%]. There was a significant correlation between RV function and moderate/severe PR at follow-up (R2: 0.08; P = 0.03). A comparison with a group of patients undergoing a transannular patch procedure (N = 33) showed superior outcomes for patients with PVP. The preoperative PV z-score and the degree of PR at discharge were risk factors for the early development of moderate/severe PR at follow-up [hazard ratio (HR): 0.64; 95% CI: 0.48, 0.86, P = 0.01 and HR: 2.31; 95% CI: 1.00, 5.36, P = 0.04, respectively]. A preoperative PV annulus z-score ≤ -2.85 was found to be predictive for moderate/severe PR at 5 years after PVP (HR: 2.56; 95% CI: 1.31, 5.01, P = 0.002).

CONCLUSIONS

A pulmonary valve preservation strategy during tetralogy of Fallot repair should always be attempted. However, a preoperative PV annulus z-score < -2.85 and moderate/severe regurgitation upon discharge are risk factors for midterm pulmonary regurgitation.
How to organize an urban revolt in medieval Northern France: strategies of mobilization and political communication of craftsmen in Saint-Omer, 1305–1306
Authors: Serneels Hannah , Haemers Jelle
Published: July 2022

This article studies the strategies of mobilization and political communication of craftsmen during a revolt in Saint-Omer in 1305–6. An analysis of a written series of testimonies about the revolt shows that it was not a spontaneous happening, but the outcome of a strategically planned and cunningly carried out mobilization of men, money and means. The well-established practices of gathering, the remarkable culture of assembly and the efficiency of the mobilization of craftsmen of Saint-Omer demonstrate that these corporate associations had developed a sophisticated ‘repertoire of contention’ already around 1300. The repertoire was not new or unheard of, but rather strongly rooted in existing structures, corporate practices and venerable communal ideas of protecting the city.
COVID-19-Related Changes in Assistance Networks for U.S. Older Adults with and without Dementia
Authors: Brown Monique J , Wang Haowei , Lin I-Fen , Gan Daniel , Oyeyemi Deborah , Manning Mark , Freedman Vicki A
Published: July 2022

Objectives

Pre-pandemic research suggests assistance networks for older adults grow over time and are larger for those living with dementia. We examined how assistance networks of older adults changed in response to the onset of the COVID-19 pandemic and whether these changes differed for those with and without dementia.

Methods

We used three rounds of the National Health and Aging Trends Study. We estimated multinomial logistic regression models to test whether changes in assistance networks during COVID-19 (2019-2020) - defined as expansion, contraction, and adaptation - differed from changes prior to COVID-19 (2018-2019). We also estimated OLS regression models to test differences in numbers of helpers assisting with one (specialist) vs. multiple (generalist) domains before and during COVID-19. For both sets of outcomes, we investigated whether pandemic-related changes differed for those with and without dementia.

Results

Over all activity domains, a greater proportion of assistance networks adapted during COVID-19 compared to the pre-COVID-19 period (RRR = 1.19, p < .05). Contractions in networks occurred for those without dementia. Transportation assistance contracted for those with and without dementia, and mobility/self-care assistance contracted for those with dementia. The average number of generalist helpers decreased during COVID-19 (β = -0.09, p < .001).

Discussion

Early in the pandemic, assistance networks of older adults adapted by substituting helpers, by contracting to reduce exposures with more intimate tasks for recipients with dementia, and by reducing transportation assistance. Future research should explore the impact of such changes on the well-being of older adults their assistance networks.
Practical rationality as a determinant of formality in communicative situations: toward a procedure for causal interpretation in qualitative communication research
Authors: Shavit Nimrod
Published: July 2022

This article develops an updated version of formality as an analytical framework in the comparative study of communicative situations, and especially of meetings. The discussion remakes Judith Irvine’s formality framework by adding to it the explanatory principle of practical rationality as used within Weber’s Interpretive Sociology. This conceptual move provides an efficient and accurate means by which to infer the final causes, reasons, or ends of communicative situations. To illustrate this analytical approach and how it can contribute to qualitative theorization in general, the article conducts an in-depth ethnographic and comparative examination of civic software production meetings in Israel and the United States. The overall argument of the article is that practical rationality can provide a valuable means for deepening explanations of cultural difference in qualitative communication research.
Dynamics of the most common pathogenic mtDNA variant m.3243A > G demonstrate frequency-dependency in blood and positive selection in the germline
Authors: Franco Melissa , Pickett Sarah J , Fleischmann Zoe , Khrapko Mark , Cote-L’Heureux Auden , Aidlen Dylan , Stein David , Markuzon Natasha , Popadin Konstantin , Braverman Maxim , Woods Dori C , Tilly Jonathan L , Turnbull Doug M , Khrapko Konstantin
Published: July 2022

The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease in blood with age, and an age correction representing ~ 2% annual decline is often applied to account for this change in mutation level. Here we report that recent data indicate that the dynamics of m.3243A > G are more complex and depend on the mutation level in blood in a bi-phasic way. Consequently, the traditional 2% correction, which is adequate ‘on average’, creates opposite predictive biases at high and low mutation levels. Unbiased age correction is needed to circumvent these drawbacks of the standard model. We propose to eliminate both biases by using an approach where age correction depends on mutation level in a biphasic way to account for the dynamics of m.3243A > G in blood. The utility of this approach was further tested in estimating germline selection of m.3243A > G. The biphasic approach permitted us to uncover patterns consistent with the possibility of positive selection for m.3243A > G. Germline selection of m.3243A > G shows an ‘arching’ profile by which selection is positive at intermediate mutant fractions and declines at high and low mutant fractions. We conclude that use of this biphasic approach will greatly improve the accuracy of modelling changes in mtDNA mutation frequencies in the germline and in somatic cells during aging.
Limit Shape of Perfect Matchings on Rail-Yard Graphs
Authors: Li Zhongyang
Published: July 2022

We obtain limit shape of perfect matchings on a large class of rail-yard graphs with right boundary condition given by the empty partition and left boundary condition given by either by a staircase partition with constant density or a piecewise partition with densities either 1 or 0. We prove the parametric equations for the frozen boundary and find conditions under which the frozen boundary is a cloud curve, or a union of disjoint cloud curves.
Consecutive Real Quadratic Fields with Large Class Numbers
Authors: Cherubini Giacomo , Fazzari Alessandro , Granville Andrew , Kala Vítězslav , Yatsyna Pavlo
Published: July 2022

For a given positive integer $k$, we prove that there are at least $x^{1/2-o(1)}$ integers $d\leq x$ such that the real quadratic fields ${\mathbb {Q}}(\sqrt {d+1}),\dots ,{\mathbb {Q}}(\sqrt {d+k})$ have class numbers essentially as large as possible.
Natural History of Malaria Infections During Early Childhood in Twins
Authors: Gonçalves Bronner P , Pérez-Caballero Raúl , Barry Amadou , Gaoussou Santara , Lewin Alexandra , Issiaka Djibrilla , Keita Sekouba , Diarra Bacary S , Mahamar Almahamoudou , Attaher Oumar , Narum David L , Kurtis Jonathan D , Dicko Alassane , Duffy Patrick E , Fried Michal
Published: July 2022

Background

The frequency and clinical presentation of malaria infections show marked heterogeneity in epidemiological studies. However, deeper understanding of this variability is hampered by the difficulty in quantifying all relevant factors. Here, we report the history of malaria infections in twins, who are exposed to the same in utero milieu, share genetic factors, and are similarly exposed to vectors.

Methods

Data were obtained from a Malian longitudinal birth cohort. Samples from 25 twin pairs were examined for malaria infection and antibody responses. Bayesian models were developed for the number of infections during follow-up.

Results

In 16 of 25 pairs, both children were infected and often developed symptoms. In 8 of 25 pairs, only 1 twin was infected, but usually only once or twice. Statistical models suggest that this pattern is not inconsistent with twin siblings having the same underlying infection rate. In a pair with discordant hemoglobin genotype, parasite densities were consistently lower in the child with hemoglobin AS, but antibody levels were similar.

Conclusions

By using a novel design, we describe residual variation in malaria phenotypes in naturally matched children and confirm the important role of environmental factors, as suggested by the between-twin pair heterogeneity in malaria history.
Mechanisms of high-level fosfomycin resistance in Staphylococcus aureus epidemic lineage ST5
Authors: Chen Tianchi , Zhao Lin , Liu Yao , Wang Ya’nan , Jian Ying , Zhao Na , Yang Ziyu , Wang Xi , Liu Qian , Li Min
Published: July 2022

Objectives

Fosfomycin resistance has become a clinical concern. In this study, we analysed the dynamic change of fosfomycin MIC in the epidemic Staphylococcus aureus lineages in a teaching hospital in Shanghai for 12 years and sought to elucidate the major underlying mechanisms.

Methods

MLST was conducted for 4580 S. aureus isolates recovered from 2008 to 2019. Fosfomycin MIC was determined by the agar dilution method. The genome data of 230 S. aureus epidemic lineage isolates were acquired from a next-generation sequencing (NGS) platform. Gene deletion and corresponding complementation mutants were constructed to confirm the mechanism of fosfomycin resistance.

Results

The predominant S. aureus lineages during the past 12 years were ST5 and ST239 (45.6%; 2090/4580). However, ST5 has been spreading clinically, while ST239 has gradually disappeared recently. Consistent with epidemic trends, fosfomycin-resistant ST5 increased from 19.5% to 67.3%. Most fosfomycin-resistant ST5 isolates (92.7%; 647/698) possessed high-level resistance (MIC > 1024 mg/L) with combined mutations mainly in glpT and uhpT. In contrast, fosfomycin-resistant ST239 isolates (76.8%; 149/194) mainly acquired low-level resistance (MIC = 64–128 mg/L) with mutation primarily in hptA. Deletion of a single resistant gene merely resulted in low-level fosfomycin resistance, while double-gene mutants ΔglpTΔuhpT, ΔglpTΔhptA and ΔglpTΔhptR acquired high-level fosfomycin resistance.

Conclusions

The high-level fosfomycin resistance of S. aureus epidemic lineage ST5 is mainly due to the accumulation of mutations in the resistant genes related to membrane transporter systems, and partly contributes to its persistent prevalence under clinical antibiotic pressure.
Identification and validation of a metabolism-related gene signature for the prognosis of colorectal cancer: a multicenter cohort study
Authors: Han Ping , Yang Xiudeng , Li Lina , Bao Jie , Zhang Wenqiong , Zai Shubei , Zhu Zhaoqin , Wu Minle
Published: July 2022

Objective

Cell metabolism plays a vital role in the proliferation, metastasis and sensitivity to chemotherapy drugs of colorectal cancer. The purpose of this multicenter cohort study is to investigate the potential genes indicating clinical outcomes in colorectal cancer patients.

Methods

We analyzed gene expression profiles of colorectal cancer to identify differentially expressed genes then used these differentially expressed genes to construct prognostic signature based on the least absolute shrink-age and selection operator Cox regression model. In addition, the multi-gene signature was validated in independent datasets including our multicenter cohort. Finally, nomograms were set up to evaluate the prognosis of colorectal cancer patients.

Results

Seventeen metabolism-related genes were determined in the least absolute shrink-age and selection operator model to construct signature, with area under receiver operating characteristic curve for relapse-free survival, 0.741, 0.755 and 0.732 at 1, 3 and 5 year, respectively. External validation datasets, GSE14333, GSE37892, GSE17538 and the Cancer Genome Atlas cohorts, were analyzed and stratified, indicating that the metabolism-related signature was reliable in discriminating high- and low-risk colorectal cancer patients. Area under receiver operating characteristic curves for relapse-free survival in our multicenter validation cohort were 0.801, 0.819 and 0.857 at 1, 3 and 5 year, respectively. Nomograms incorporating the genetic biomarkers and clinical pathological features were set up, which yielded good discrimination and calibration in the prediction of prognosis for colorectal cancer patients.

Conclusion

An original metabolism-related signature was developed as a predictive model for the prognosis of colorectal cancer patients. A nomogram based on the signature was advantageous to facilitate personalized counselling and treatment of colorectal cancer patients.
Associates from infancy influence postweaning juvenile associations for common bottlenose dolphins (Tursiops truncatus) in Florida
Authors: Greenfield Michelle R , Durden Wendy N , Jablonski Teresa A , Moreland Lydia D , Fabry Agatha C , Gemma Lisa Y , Clifford Heidy H
Published: July 2022

In many long-lived mammalian species, association patterns between individuals have been found to influence sociality, behavioral traits, survival, and longevity. In common bottlenose dolphins (Tursiops truncatus), the early stages of development are of particular importance as associations experienced as dependent calves may influence future association patterns. While behavioral characteristics associated with the transition from a dependent calf state to an independent juvenile state have been documented, there are limited studies that examine associations between these time periods. This study aims to document association longevity for bottlenose dolphins as they transition from calves to juveniles and determine the extent to which kinship plays a role in the development of these associations. Using social network analysis, a generalized linear mixed model (GLMM), and a tiered association scale, we found 53.7% of associations were retained from the calf to the juvenile phase. GLMM results indicated that preferred associates (half-weight index [HWI] > 0.178) from the calf state were 3.6 times more likely to associate in the juvenile state (0.178 > HWI > 0) and 5.67 times more likely to be preferred associates in the juvenile state compared to nonpreferred calf associates. The majority of juveniles, 76.92%, maintained a low–moderate to moderate level association (0.089–0.54) with their mother, and a few retained their mother as their top associate. Kin were preferred associates in 46.15% of cases and found to be the top juvenile associate in 26.92% of cases. Identifying continuity in associations, particularly from the calving state to the juvenile state, is imperative as mammalian association patterns may influence community structure, disease transmission, reproductive success, and predict survival.
Risk and Protective Factors for Physical Activity Engagement Among Adolescents With Comorbid Asthma and Obesity
Authors: Yourell Jacqlyn , Koskela-Staples Natalie , Doty Jennifer , Fedele David A
Published: July 2022

Objective

The current study identifies levels of physical activity (PA) engagement among adolescents with neither asthma nor overweight/obesity (OW/OB), one, or both conditions. Risk and protective factors are examined across groups.

Methods

Data from 8th, 9th, and 11th graders were obtained from the 2019 Minnesota Student Survey (N = 125,164). One-way analysis of variance was used to assess PA levels across risk groups. Linear regressions were used to examine patterns of risk and protective factors for adolescent PA engagement across four groups (neither asthma nor OW/OB, asthma only, OW/OB only, and comorbid asthma + OW/OB). Results were stratified by race/ethnicity.

Results

Adolescents with OW/OB only or asthma + OW/OB had significantly lower PA levels than youth with asthma only or neither condition (M = 3.65–3.67 days/week, SD = 2.20 vs M = 4.15–4.19 days/week, SD = 2.16–2.17, p < .001). The following variables were associated with adolescent PA (p < .001): Adult community care across all risk groups (β ranges = .13–.16), depressive symptoms among those with neither and both asthma + OW/OB (β’s = –.10), and extracurriculars among those with asthma + OW/OB (β = .10). Extracurriculars and parent connectedness were protective for Hispanic adolescents.

Conclusions

Adolescents with OW/OB had significantly lower levels of PA compared to those without, regardless of asthma status. Individual and relational factors influenced adolescent PA. Future research investigating factors influencing adolescent PA should consider depressive symptoms, connectedness to adults in the community, non-sport-related extracurricular activity involvement, and address disparities among minoritized youth.
Effects on Pediatric Cancer Survivors: The FAMily-Oriented Support (FAMOS) Randomized Controlled Trial
Authors: Bidstrup Pernille E , Salem Hanin , Andersen Elisabeth Wreford , Schmiegelow Kjeld , Rosthøj Steen , Wehner Peder Skov , Hasle Henrik , Dalton Susanne O , Johansen Christoffer , Kazak Anne E
Published: July 2022

Objective

To examine as secondary analyses the effect the FAMily-Oriented Support (FAMOS) family therapy program on reducing parent-reported medical traumatic stress in the sub-sample of pediatric cancer survivors, age 2–5 years.

Methods

The FAMOS study was a national multicenter randomized controlled trial with all four pediatric oncology departments in Denmark (Clinicaltrials.gov [NCT02200731]). Families were randomized in parallel design (1:1) to intervention or usual care. The FAMOS program includes seven home-based psychotherapeutic sessions and is based on family systems therapy to address the individuals in the family system using cognitive behavioral, problem-solving and goal-setting techniques. Questionnaires were completed by parents at baseline, 6, and 12 months. In linear mixed-effects models, the effect of FAMOS on reducing children’s trauma-related behavior after 6 and 12 months was examined in 62 children (31 in the intervention and 29 in the control group, respectively). It was also examined if a trauma-related behavior effect was mediated through reduced symptoms of depression in mothers and fathers, respectively.

Results

On average, children in the intervention group experienced significantly larger decreases in trauma-related behaviors at 6 and 12 months than the control group (predicted mean difference –3.89, p = .02 and –6.24, p = .003, respectively). The effect on trauma-related behavior was partly mediated through reduced symptoms of depression in mothers, but not fathers.

Conclusions

Adding to previously reported positive effects of the FAMOS intervention on parents’ symptoms of post-traumatic stress and depression, significant improvements were found in young children’s trauma related-behavior. Further research is needed to develop therapy for children with cancer.
The small subunit of Rubisco and its potential as an engineering target
Authors: Mao Yuwei , Catherall Ella , Díaz-Ramos Aranzazú , Greiff George R L , Azinas Stavros , Gunn Laura , McCormick Alistair J
Published: July 2022

Rubisco catalyses the first rate-limiting step in CO2 fixation and is responsible for the vast majority of organic carbon present in the biosphere. The function and regulation of Rubisco remain an important research topic and a longstanding engineering target to enhance the efficiency of photosynthesis for agriculture and green biotechnology. The most abundant form of Rubisco (Form I) consists of eight large and eight small subunits, and is found in all plants, algae, cyanobacteria, and most phototrophic and chemolithoautotrophic proteobacteria. Although the active sites of Rubisco are located on the large subunits, expression of the small subunit regulates the size of the Rubisco pool in plants and can influence the overall catalytic efficiency of the Rubisco complex. The small subunit is now receiving increasing attention as a potential engineering target to improve the performance of Rubisco. Here we review our current understanding of the role of the small subunit and our growing capacity to explore its potential to modulate Rubisco catalysis using engineering biology approaches.
The Custodial History of the Sadler Partbooks (Oxford, Bodleian Library MSS Mus. e. 1–5)
Authors: Burke James
Published: July 2022

The Sadler partbooks (Oxford, Bodleian Library, MSS Mus. e. 1–5), one of the most important English polyphonic sources to survive from the sixteenth century, reflect the interventions of several generations of later owners. Today the volumes bear a number of marks that were clearly not coeval with their copying in the sixteenth century; they have also been subjected to at least one rebinding, and some leaves are in a disrupted position, hitherto unobserved (and still misplaced). This article seeks to account for the custodial history of the Sadler partbooks, and to chart the bearing that their later owners have had on the partbooks’ present state. Apart from showing that the books travelled widely—they can be traced in Norwich, London, Bath, Bristol, Manchester, and eventually Oxford—it also shows that the partbooks came to the brink of destruction in the hands of one former owner, surviving fire, flood, and theft.
The very knotty lenser: Exploring the role of regularization in source and potential reconstructions using Gaussian process regression
Authors: Vernardos G , Koopmans L V E
Published: July 2022

Reconstructing lens potentials and lensed sources can easily become an underconstrained problem, even when the degrees of freedom are low, due to degeneracies, particularly when potential perturbations superimposed on a smooth lens are included. Regularization has traditionally been used to constrain the solutions where the data failed to do so, e.g. in unlensed parts of the source. In this exploratory work, we go beyond the usual choices of regularization and adopt observationally motivated priors for the source brightness. We also perform a similar comparison when reconstructing lens potential perturbations, which are assumed to be stationary, i.e. permeate the entire field of view. We find that physically motivated priors lead to lower residuals, avoid overfitting, and are decisively preferred within a Bayesian quantitative framework in all the examples considered. For the perturbations, choosing the wrong regularization can have a detrimental effect that even high-quality data cannot correct for, while using a purely smooth lens model can absorb them to a very high degree and lead to biased solutions. Finally, our new implementation of the semi-linear inversion technique provides the first quantitative framework for measuring degeneracies between the source and the potential perturbations.
Systematic comparison of CRISPR-based transcriptional activators uncovers gene-regulatory features of enhancer–promoter interactions
Authors: Wang Kaiyuan , Escobar Mario , Li Jing , Mahata Barun , Goell Jacob , Shah Spencer , Cluck Madeleine , Hilton Isaac B
Published: July 2022

Nuclease-inactivated CRISPR/Cas-based (dCas-based) systems have emerged as powerful technologies to synthetically reshape the human epigenome and gene expression. Despite the increasing adoption of these platforms, their relative potencies and mechanistic differences are incompletely characterized, particularly at human enhancer–promoter pairs. Here, we systematically compared the most widely adopted dCas9-based transcriptional activators, as well as an activator consisting of dCas9 fused to the catalytic core of the human CBP protein, at human enhancer–promoter pairs. We find that these platforms display variable relative expression levels in different human cell types and that their transactivation efficacies vary based upon the effector domain, effector recruitment architecture, targeted locus and cell type. We also show that each dCas9-based activator can induce the production of enhancer RNAs (eRNAs) and that this eRNA induction is positively correlated with downstream mRNA expression from a cognate promoter. Additionally, we use dCas9-based activators to demonstrate that an intrinsic transcriptional and epigenetic reciprocity can exist between human enhancers and promoters and that enhancer-mediated tracking and engagement of a downstream promoter can be synthetically driven by targeting dCas9-based transcriptional activators to an enhancer. Collectively, our study provides new insights into the enhancer-mediated control of human gene expression and the use of dCas9-based activators.
Elucidation of structure–function relationships in Methanocaldococcus jannaschii RNase P, a multi-subunit catalytic ribonucleoprotein
Authors: Phan Hong-Duc , Norris Andrew S , Du Chen , Stachowski Kye , Khairunisa Bela H , Sidharthan Vaishnavi , Mukhopadhyay Biswarup , Foster Mark P , Wysocki Vicki H , Gopalan Venkat
Published: July 2022

RNase P is a ribonucleoprotein (RNP) that catalyzes removal of the 5′ leader from precursor tRNAs in all domains of life. A recent cryo-EM study of Methanocaldococcus jannaschii (Mja) RNase P produced a model at 4.6-Å resolution in a dimeric configuration, with each holoenzyme monomer containing one RNase P RNA (RPR) and one copy each of five RNase P proteins (RPPs; POP5, RPP30, RPP21, RPP29, L7Ae). Here, we used native mass spectrometry (MS), mass photometry (MP), and biochemical experiments that (i) validate the oligomeric state of the Mja RNase P holoenzyme in vitro, (ii) find a different stoichiometry for each holoenzyme monomer with up to two copies of L7Ae, and (iii) assess whether both L7Ae copies are necessary for optimal cleavage activity. By mutating all kink-turns in the RPR, we made the discovery that abolishing the canonical L7Ae–RPR interactions was not detrimental for RNase P assembly and function due to the redundancy provided by protein–protein interactions between L7Ae and other RPPs. Our results provide new insights into the architecture and evolution of RNase P, and highlight the utility of native MS and MP in integrated structural biology approaches that seek to augment the information obtained from low/medium-resolution cryo-EM models.
Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis
Authors: Mestre-Farràs Neus , Guerrero Santiago , Bley Nadine , Rivero Ezequiel , Coll Olga , Borràs Eva , Sabidó Eduard , Indacochea Alberto , Casillas-Serra Carlos , Järvelin Aino I , Oliva Baldomero , Castello Alfredo , Hüttelmaier Stefan , Gebauer Fátima
Published: July 2022

RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.
Exploration of DNA processing features unravels novel properties of ICE conjugation in Gram-positive bacteria
Authors: Laroussi Haifa , Aoudache Yanis , Robert Emilie , Libante Virginie , Thiriet Louise , Mias-Lucquin Dominique , Douzi Badreddine , Roussel Yvonne , Chauvot de Beauchêne Isaure , Soler Nicolas , Leblond-Bourget Nathalie
Published: July 2022

Integrative and conjugative elements (ICEs) are important drivers of horizontal gene transfer in prokaryotes. They are responsible for antimicrobial resistance spread, a major current health concern. ICEs are initially processed by relaxases that recognize the binding site of oriT sequence and nick at a conserved nic site. The ICESt3/Tn916/ICEBs1 superfamily, which is widespread among Firmicutes, encodes uncanonical relaxases belonging to a recently identified family called MOBT. This family is related to the rolling circle replication initiators of the Rep_trans family. The nic site of these MOBT relaxases is conserved but their DNA binding site is still unknown. Here, we identified the bind site of RelSt3, the MOBT relaxase from ICESt3. Unexpectedly, we found this bind site distantly located from the nic site. We revealed that the binding of the RelSt3 N-terminal HTH domain is required for efficient nicking activity. We also deciphered the role of RelSt3 in the initial and final stages of DNA processing during conjugation. Especially, we demonstrated a strand transfer activity, and the formation of covalent DNA-relaxase intermediate for a MOBT relaxase.
Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology
Authors: Chen Jinfeng , Cheng Jingfei , Chen Xiufei , Inoue Masato , Liu Yibin , Song Chun-Xiao
Published: July 2022

Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.
Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial
Authors: Lassman Andrew B , Pugh Stephanie L , Wang Tony J C , Aldape Kenneth , Gan Hui K , Preusser Matthias , Vogelbaum Michael A , Sulman Erik P , Won Minhee , Zhang Peixin , Moazami Golnaz , Macsai Marian S , Gilbert Mark R , Bain Earle E , Blot Vincent , Ansell Peter J , Samanta Suvajit , Kundu Madan G , Armstrong Terri S , Wefel Jeffrey S , Seidel Clemens , de Vos Filip Y , Hsu Sigmund , Cardona Andrés F , Lombardi Giuseppe , Bentsion Dmitry , Peterson Richard A , Gedye Craig , Bourg Véronique , Wick Antje , Curran Walter J , Mehta Minesh P
Published: July 2022

Background

Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody–drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

Methods

In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5% 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing.

Results

There were 639 randomized patients (median age 60, range 22–84; 62% men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82–1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% confidence interval [CI] 0.70–1.01, p = 0.029), particularly among those with EGFRvIII-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56–0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77, 95% CI 0.61–0.97; 1-sided p = 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m-treated patients (61% grade 3–4), causing 12% to discontinue.

Conclusions

Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.
Implementation of Outpatient Infectious Diseases E-Consults at a Safety Net Healthcare System
Authors: Medford Richard J , Granger Madison , Pickering Madison , Lehmann Christoph U , Mayorga Christian , King Helen
Published: July 2022

Background

Safety net healthcare systems have high patient volumes and significant demands for specialty care including infectious diseases (ID) consultations. Electronic ID consults (E-consults) can lessen this burden by providing an alternative to face-to-face ID referrals and decreasing financial, time, and travel constraints on patients. This system could increase access to ID care for patients in limited-resource settings.

Methods

We described characteristics of all outpatient ID E-consults at Parkland Health in Dallas, Texas, from March 2018 to February 2021. We used modeling to determine which characteristics influenced conversion of E-consults to clinic visits and integrated these data into a predictive model for face-to-face conversion.

Results

For 725 E-consults, common E-consult topics included 118 (16%) latent tuberculosis, 116 (16%) syphilis, and 76 (10%) gastrointestinal infections. Nearly two-thirds of E-consults (456 [63%]) were requested by primary care providers. The majority (78%) were resolved without a face-to-face ID visit. Osteomyelitis, nontuberculous mycobacterial, and gastrointestinal questions frequently required face-to-face visits at rates of 65%, 49%, and 32%, respectively. Our logistic regression model predicted the need for a face-to-face visit with 80% accuracy and an area under the receiver operating characteristic curve of 0.72.

Conclusions

An outpatient ID E-consult program at a safety net healthcare system was an effective tool to provide timely input on common ID topics. E-consults were requested by a range of providers, and most were completed without a face-to-face visit. Predictive modeling identified important characteristics of E-consults and predicted conversion to face-to-face visits with reasonable accuracy.
JOINT SOGC-CPS CLINICAL PRACTICE GUIDELINE
Authors: McDonald Sarah D , Narvey Michael , Ehman William , Jain Venu , Cassell Krista
Published: July 2022

Objective

To assess the impact of deferred (delayed) cord clamping (DCC) and umbilical cord milking in singleton and twin gestations on maternal and infant mortality and morbidity.

Target Population

Women who are pregnant with preterm or term singletons or twins.

Benefits, Harms, and Costs

In preterm singletons, DCC for (ideally) 60 to 120 seconds, but at least for 30 seconds, reduces infant risk of mortality and morbidity. DCC in preterm twins is associated with some benefits. In term singletons, DCC for 60 seconds improves hematological parameters. In very preterm infants, umbilical cord milking increases risk for intraventricular hemorrhage.

Evidence

Searches of Medline, PubMed, Embase, and the Cochrane Library from inception to March 2020 were undertaken using Medical Subject Heading (MeSH) terms and key words related to deferred cord clamping and umbilical cord milking. This document represents an abstraction of the evidence rather than a methodological review.

Validation Methods

The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).
Zircon Reveals Diverse Trends of Magma Crystallization from Two Types of Early Post-Collisional Diorites (Variscan Orogen, NE Bohemian Massif)
Authors: Pietranik Anna , Farina Federico , Derkowska Katarzyna , Schaltegger Urs , Przybyło Arkadiusz , Storey Craig , Lasalle Stephanie , Dhuime Bruno , Pańczyk Magdalena , Zieliński Grzegorz , Nowak Małgorzata , Bulcewicz Kamil , Kierczak Jakub
Published: July 2022

Amphibole- and clinopyroxene-bearing monzodiorites were emplaced at 340 Ma (CA-ID-TIMS zircon age), suggesting the formation of hydrous and dry magmas closely related in space and time in the NE Bohemian Massif. Hafnium and oxygen isotopes of zircon in less evolved rocks (<55 wt% SiO2) are similar between Amp and Cpx monzodiorites (εHf = −3.3 ± 0.5 and − 3.5 ± 0.8; δ18O = 6.4 ± 1.0 and 6.8 ± 0.7, respectively), consistent with a common source—a contaminated mafic magma derived from an enriched mantle. At the same time, the conditions of crystallization are distinct and zircon appears to be an excellent tool for distinguishing between hydrous and anhydrous crystallization conditions, a process that may be more ambiguously recorded by whole rock and major mineral chemistry. In particular, elements fractionated by either amphibole or plagioclase crystallization, such as Hf, Dy, and Eu, differ in zircon from amphibole- and clinopyroxene-bearing rocks, and Zr/Hf, Yb/Dy, and Eu/Dy are therefore useful indices of crystallization conditions. We show that the composition of zircon from hydrous dioritic magmas is not comparable with that of typical zircon from dioritic-granitic suites worldwide, suggesting a specific process involved in their formation. Here, we propose that fluid-present remelting of a mafic underplate is necessary to explain the rock textures as well as the composition of the whole rock, zircon, and other minerals of amphibole-bearing monzodiorites and that a similar process may control the formation of amphibole-rich dioritic rocks worldwide, including appinitic suites. Overall, we show that dioritic rocks represent snapshots of differentiation processes that occur in the early stages of magma evolution before the magma is homogenized into large-scale batholiths.