bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubble distancing: focusing on distance measurements in cosmology
Authors: Greene Kylar L. , Cyr-Racine Francis-Yan
Published: June 2022

The Hubble-Lemaître tension is currently one of the most important questions in cosmology. Most of the focus so far has been on reconciling the Hubble constant value inferred from detailed cosmic microwave background measurement with that from the local distance ladder. This emphasis on one number — namely H
0 — misses the fact that the tension fundamentally arises from disagreements of distance measurements. To be successful, a proposed cosmological model must accurately fit these distances rather than simply infer a given value of H
0.
Using the newly developed likelihood package `distanceladder', which integrates the local distance ladder into MontePython, we show that focusing on H
0 at the expense of distances can lead to the spurious detection of new physics in models which change late-time cosmology. As such, we encourage the observational cosmology community to make their actual distance measurements broadly available to model builders instead of simply quoting their derived Hubble constant values.
Theoretical model of external spinal cord stimulation
Authors: Shneider Mikhail N , Pekker Mikhail
Published: June 2022

In this paper, a simple theoretical model of the excitation of action potentials of multiple motor pools by stimulating current pulses over the lumbosacral regions of the spinal cord is presented. The present model is consistent with known experimental data.
Nonlinear waveguides by femtosecond laser writing of lithium triborate crystals
Authors: Zhang Bin , Li Ziqi , Li Lingqi , Lu Qingming , Wang Lei , Chen Feng
Published: June 2022

Nonlinear optical waveguides play a crucial role in the wavelength/frequency conversion of light. Femtosecond laser direct writing is an efficient and flexible technique to produce waveguides in dielectrics. We report on the nonlinear waveguides in LiB3O5 crystals by femtosecond laser writing. The double-line and depressed-cladding structures inscribed by femtosecond laser pulses show excellent guiding properties at 405 nm or 810 nm for both TE and TM polarized light. The investigations of the confocal micro-Raman spectroscopy have indicated that lattice structures in waveguide cores remain almost unchanged compared with those of the bulk. Based on type-I phase matching condition, both second harmonic generation of 810 nm and spontaneous parametric down conversion of 405 nm have been obtained in the laser-written lithium triborate waveguides, suggesting potential applications in integrated nonlinear optics and quantum photonics.
Effect of overdispersion of lethal lesions on cell survival curves
Authors: Loan M , Bhat A
Published: June 2022

The linear-quadratic (LQ) model is the most commonly used mechanism to predict radiobiological outcomes. It has been used extensively to describe dose-response in vitro and in vivo. There are, however, some questions about its applicability in terms of its capacity to represent some profound mechanistic behaviour. Specifically, empirical evidence suggests that the LQ model underestimates the survival of cells at low doses while overestimating cell death at higher doses. It is believed to be driven from the usual LQ model assumption that radiogenic lesions are Poisson distributed. In this context, we use a negative binomial (NB) distribution to study the effect of overdispersion on the shapes and the possibility of reducing dose-response curvature at higher doses. We develop an overdispersion model for cell survival using the non-homologous end-joining (NHEJ) pathway double-strand break (DSB) repair mechanism to investigate the effects of the overdispersion on probabilities of repair of DSBs. The error distribution is customised to ensure that the refined overdispersion parameter depends on the mean of the distribution. The predicted cell survival responses for V79, AG and HSG cells exposed to protons, helium and carbon ions are compared with the experimental data in low and high dose regions at various linear energy transfer (LET) values. The results indicate straightening of dose-response and approaching a log-linear behaviour at higher doses. The model predictions with the measured data show that the NB modelled survival curves agree with the data following medium and high doses. Model predictions are not validated at very tiny and very high doses; the approach presented provides an analysis of mechanisms at the microscopic level. This may help improve the understanding of radiobiological responses of survival curves and resolve discrepancies between experimental and theoretical predictions of cell survival models.
Establishment of leakage detection model for oil and gas pipeline based on VMD-MD-1DCNN
Authors: Yang Dandi , Lu Jingyi , Zhou Yina , Dong Hongli
Published: June 2022

In order to solve the problem of recognition error caused by noise interference in oil and gas pipeline signal and traditional pipeline leakage detection relies on expert experience to extract features manually, an oil and gas pipeline leakage detection model based on deep learning is proposed in this paper. The model consists of data preprocessing part and pattern recognition part. Firstly, a signal denoising algorithm based on variational mode decomposition (VMD) and Manhattan distance (MD) is proposed to reduce the error caused by data quality in the subsequent pattern recognition process. Secondly, combined with the one-dimensional and temporal characteristics of pipeline signal, the signal denoised by VMD-MD algorithm is used as the input of one-dimensional convolution neural network (1DCNN) in deep learning, then the data features are learned independently through the characteristics of network structure. Finally, the network structure and parameters are optimized and analyzed to build the optimal pipeline leakage detection model according to the experiment. The experimental results show that, compared with other existing models, the ensemble VMD-MD-1DCNN model has a better improvement in each evaluation index, which verifies the effectiveness of its application in pipeline leakage detection.
Which will be your firm’s next technology? Comparison between machine learning and network-based algorithms
Authors: Straccamore Matteo , Pietronero Luciano , Zaccaria Andrea
Published: June 2022

We reconstruct the innovation dynamics of about two hundred thousand companies by following their patenting activity for about ten years. We define the technology portfolios of these companies as the set of the technological sectors present in the patents they submit. By assuming that companies move more frequently towards related sectors, we leverage their past activity to build network-based and machine learning algorithms to forecast the future submissions of patents in new sectors. We compare different prediction methodologies using suitable evaluation metrics, showing that tree-based machine learning algorithms outperform the standard methods based on networks of co-occurrences. This methodology can be applied by firms and policymakers to disentangle, given the present innovation activity, the feasible technological sectors from those that are out of reach.
Comparative Analysis of Cognitive, Motor, and Visual-Motor Functions in Pediatric Acute Lymphoblastic Leukemia Survivors With and Without Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Dreneva A A , Devyaterikova A A
Published: June 2022

Objective

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for pediatric high-risk acute lymphoblastic leukemia (ALL) survivors. Still, both the disease and treatment often impair cognitive and motor functions, and HSCT is a risk factor for long-term deficits. The study aimed at investigating the effect of HSCT on cognitive, motor, and visual-motor functions. Two groups were enrolled: The first group received HSCT treatment, and the second group did not.

Method

Sixty-five ALL survivors participated in the study (ages: 7–17). Twenty-one of participants who underwent HSCT comprised the first group. We implemented tests from Cambridge Neuropsychological Test Automated Battery, Wechsler Intelligence Scale for Children, and Test of Memory and Learning to estimate cognitive functions, Bruininks-Oseretsky Test of Motor Proficiency to estimate motor functions, and Beery-Buktenica Developmental Test to estimate visual perceptual and visual motor functions. As independent variables for analysis we chose group (HSCT+/−), age at diagnosis, and current age.

Results

MANCOVA test demonstrated significant effect of current age on cognitive functions (partial η2 = 0.55) and significant effect of HSCT treatment on motor functions (partial η2 = 0.19). Current age also had moderate effect on visual-motor functions (partial η2 = 0.11). Significant differences were found in most cognitive, motor, and visual-motor tests’ results between the two groups, with HSCT+ group demonstrating poorer performance.

Conclusions

This study has several limitations, including small sample size, potentially mismatched groups, imbalanced gender ratio. Still, the findings underline the importance of considering late effects of HSCT, and age when designing rehabilitation programs.
Sensory modality and spoken language shape reading network in blind readers of Braille
Authors: Tian Mengyu , Saccone Elizabeth J , Kim Judy S , Kanjlia Shipra , Bedny Marina
Published: June 2022

The neural basis of reading is highly consistent across many languages and scripts. Are there alternative neural routes to reading? How does the sensory modality of symbols (tactile vs. visual) influence their neural representations? We examined these questions by comparing reading of visual print (sighted group, n = 19) and tactile Braille (congenitally blind group, n = 19). Blind and sighted readers were presented with written (words, consonant strings, non-letter shapes) and spoken stimuli (words, backward speech) that varied in word-likeness. Consistent with prior work, the ventral occipitotemporal cortex (vOTC) was active during Braille and visual reading. A posterior/anterior vOTC word-form gradient was observed only in sighted readers with more anterior regions preferring larger orthographic units (words). No such gradient was observed in blind readers. Consistent with connectivity predictions, in blind compared to sighted readers, posterior parietal cortices were recruited to a greater degree and contained word-preferring patches. Lateralization of Braille in blind readers was predicted by laterality of spoken language and reading hand. The effect of spoken language increased along a cortical hierarchy, whereas effect of reading hand waned. These results suggested that the neural basis of reading is influenced by symbol modality and spoken language and support connectivity-based views of cortical function.
Families’ expectations of an eHealth family-based cardiovascular disease-risk reduction programme
Authors: Kemp Bridie J , Thompson David R , McGuigan Karen , Watson Chris J , Heron Neil , Woodside Jayne V , Devaney Francis K , Harrison Nick , Neill Danielle T , Cutting David , Ski Chantal F
Published: June 2022

Aim

Research has shown that families’ participation in a cardiovascular disease (CVD) prevention programme could boost early adoption of healthy lifestyle behaviours in families. Behaviour-based, eHealth interventions are a potential means of achieving this. This study aimed to explore expectations of families—parents and children—at risk of CVD towards the design and functionality of an eHealth family-based CVD-risk reduction programme ‘Health-e-Hearts’.

Methods and results

Three online focus groups were conducted with six families comprising at least one parent at risk of CVD and at least one child aged 5–17 years. The focus groups were video and audio recorded and transcribed. Content analysis was used to synthesize and identify key categories and subcategories regarding development of and engagement with an eHealth programme. Three categories emerged: experiences of health apps and devices; eHealth application needs of family members; and motivators for using an eHealth programme. Experiences included using health apps individually and inconsistently. Needs included personalization, free and easy-to-use, time efficient, and multiple content formats. Motivators for engaging with the programme included goal setting, rewards, and competition.

Conclusion

Families’ expectations of an eHealth family-based CVD-risk reduction programme include the incorporation of personalized, easy-to-use design features and motivators for engaging with the programme. Family involvement in the development of an eHealth programme such as ‘Health-e-Hearts’ has the potential to boost early adoption of healthy lifestyle behaviours among all family members.
Temporal trends in abdominal aortic aneurysmal disease: a nationwide cohort study on cardiovascular morbidity and medical cardioprotective therapy
Authors: Nicolajsen Chalotte W , Søgaard Mette , Eldrup Nikolaj , Jensen Martin , Larsen Torben B , Goldhaber Samuel Z , Nielsen Peter B
Published: June 2022

Aims

Abdominal aortic aneurysmal disease is associated with increased risk of cardiovascular morbidity and death, which potentially can be reduced with cardioprotective medical therapy. The aim of this study was to observe temporal trends in prevalence and incidence of cardiovascular comorbidity as well as use of medical cardioprotective treatment in patients diagnosed with abdominal aortic aneurysmal disease.

Methods and results

This was a population-based cohort study based on data from national health registries, including all patients diagnosed with abdominal aortic aneurysms between 1998 and 2018. Data were stratified into four time periods (1999–2003, 2004–2008, 2009–2013, and 2014–2018) to illustrate trends over time. Outcome measures were (i) cardiovascular comorbidity and medical cardioprotective therapy at time of diagnosis, (ii) new admissions for atherosclerotic cardiovascular disease, and (iii) all-cause mortality after 2-year follow-up. The study cohort included 33 296 individuals. Mean age was 74 years. Prevalence of atherosclerotic cardiovascular comorbidity at diagnosis decreased from 41.5 to 32.6%. Use of statins increased from 17.9 to 66.9%, antiplatelets from 45.6 to 63.3%, and combined therapy with both antiplatelets and statins from 11.3 to 44.8%, and from 12.1 to 50.7% when anticoagulant therapy was included. Developments in medication use plateaued after 2013. Prevalence and incidence of atherosclerotic cardiovascular disease decreased through all four time periods. The same applied to all-cause mortality, which decreased from 24.3 to 12.4 deaths (per 100 person-years).

Conclusion

In patients diagnosed with abdominal aortic aneurysm, cardiovascular comorbidity at diagnosis, risk of future cardiovascular events, and all-cause mortality is decreasing. Nevertheless, cardiovascular burden and mortality rates remain substantial, and medical cardioprotective therapy can be further improved.
Walking for Cognitive Health: Previous Parity Moderates the Relationship Between Self-Reported Walking and Cognition
Authors: Barha Cindy K , Best John R , Rosano Caterina , Yaffe Kristine , Catov Janet M , Liu-Ambrose Teresa
Published: June 2022

Background

Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health.

Methods

To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates.

Results

Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group.

Conclusion

The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.
Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings
Authors: Langley Joanne M , Bianco Veronique , Domachowske Joseph B , Madhi Shabir A , Stoszek Sonia K , Zaman Khalequ , Bueso Agustin , Ceballos Ana , Cousin Luis , D’Andrea Ulises , Dieussaert Ilse , Englund Janet A , Gandhi Sanjay , Gruselle Olivier , Haars Gerco , Jose Lisa , Klein Nicola P , Leach Amanda , Maleux Koen , Nguyen Thi Lien Anh , Puthanakit Thanyawee , Silas Peter , Tangsathapornpong Auchara , Teeratakulpisarn Jamaree , Vesikari Timo , Cohen Rachel A
Published: June 2022

Background

The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life.

Methods

This prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods.

Results

Of 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88–9.08), 5.50 (95% CI, 4.21–7.07), and 2.87 (95% CI, 2.18–3.70) cases/100 person-years in children aged 0–5, 6–11, and 12–23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0–5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0–2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs.

Conclusions

A substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most.

Clinical Trials Registration. NCT01995175.
People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses
Authors: Lapointe Hope R , Mwimanzi Francis , Cheung Peter K , Sang Yurou , Yaseen Fatima , Umviligihozo Gisele , Kalikawe Rebecca , Speckmaier Sarah , Moran-Garcia Nadia , Datwani Sneha , Duncan Maggie C , Agafitei Olga , Ennis Siobhan , Young Landon , Ali Hesham , Ganase Bruce , Omondi F Harrison , Dong Winnie , Toy Junine , Sereda Paul , Burns Laura , Costiniuk Cecilia T , Cooper Curtis , Anis Aslam H , Leung Victor , Holmes Daniel T , DeMarco Mari L , Simons Janet , Hedgcock Malcolm , Prystajecky Natalie , Lowe Christopher F , Pantophlet Ralph , Romney Marc G , Barrios Rolando , Guillemi Silvia , Brumme Chanson J , Montaner Julio S G , Hull Mark , Harris Marianne , Niikura Masahiro , Brockman Mark A , Brumme Zabrina L
Published: June 2022

Background

Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose.

Methods

We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls.

Results

Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post–third-dose humoral responses substantially exceeded post–second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post–third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post–third-dose responses.

Conclusion

PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.
The Influence of Budgets on Consumer Spending
Authors: Lukas Marcel F , Howard Ray Charles “Chuck”
Published: June 2022

Foundational research in marketing and behavioral economics has revealed a great deal about the psychology of budgeting. However, little is known about the extent to which budgets do (or do not) influence consumers’ real-world spending. The present research addresses this gap in the literature using naturally occurring budgeting and spending data provided by a popular personal finance app in the UK, a field experiment conducted with members of a Canadian credit union, and a financial diary study conducted with consumers in the US. Budget compliance is generally weak because budgets are wildly optimistic. However, optimistic budgets do help consumers reduce their spending. Moreover, the influence of budgets on spending is surprisingly sticky: consumers continue to reduce their spending six months after setting a budget, even though spending remains over-budget. Impulsive consumers exhibit worse budget compliance than less-impulsive consumers. However, counterintuitively, this is predominately because more impulsive consumers set lower budgets than less-impulsive consumers, not because they spend more. Finally, we provide evidence that budgets influence spending across several theory-informing psychographic variables. Taken together, these findings show that budgets can be both wildly optimistic and highly influential and that beliefs about the nature of consumers’ budgets require updating.
Gender Differences in Tournament Choices: Risk Preferences, Overconfidence, or Competitiveness?
Authors: van Veldhuizen Roel
Published: June 2022

A long line of laboratory experiments has found that women are less likely to sort into competitive environments. Although part of this effect may be explained by gender differences in risk attitudes and self-confidence, previous studies have attributed the majority of the gender gap to gender differences in a competitiveness trait. I re-examine this result using a novel experiment that allows me to separate competitiveness from alternative explanations using causal treatments. In contradiction to the main conclusion drawn in a long literature, my results imply that the entire gender gap is driven by gender differences in risk attitudes and self-confidence, which has implications for policy and research.
Time Variation in Cash Flows and Discount Rates
Authors: Cenesizoglu Tolga , Ibrushi Denada
Published: June 2022

We analyze the decomposition of the conditional, rather than the unconditional, variance of market returns based on an extension of the standard Campbell–Shiller approach. The relative importance of cash flow and discount rate news in determining the conditional variance of market returns exhibits significant variation over time and relates to economic conditions. The components of the conditional market variance outperform several benchmark variables, including the conditional market variance itself, in forecasting future market returns and realized variance across different horizons. The forecasts based on the conditional market variance components also provide sizable economic benefits compared with benchmark forecasts in an out-of-sample portfolio exercise where a myopic investor allocates her wealth between the market portfolio and a risk-free asset across different holding periods.
The size–luminosity relation of lensed galaxies at z ∼ 6–9 in the Hubble Frontier Fields
Authors: Yang Lilan , Leethochawalit Nicha , Treu Tommaso , Roberts-Borsani Guido , Bradač Maruša , Birrer Simon , Castellano Marco , Merlin Emiliano , Fontana Adriano , Amorin Ricardo , Trenti Michele
Published: June 2022

We measure the size–luminosity relation of photometrically selected galaxies within the redshift range z ∼ 6–9, using galaxies lensed by six foreground Hubble Frontier Fields (HFF) clusters. The power afforded by strong gravitational lensing allows us to observe fainter and smaller galaxies than in blank fields. We select our sample of galaxies and obtain their properties, e.g. redshift, magnitude, from the photometrically derived ASTRODEEP catalogues. The intrinsic size is measured with the Lenstruction software, and completeness maps are created as a function of size and luminosity via the GLACiAR2 software. We perform a Bayesian analysis to estimate the intrinsic and incompleteness-corrected size–luminosity distribution, with parametrization re ∝ Lβ. We find slopes of $\beta =0.50^{+0.07}_{-0.07}$ at z ∼ 6 − 7 and $\beta =0.67^{+0.14}_{-0.15}$ at z ∼ 8.5, adopting the Bradac lens model. Our inferred slopes are consistent with other independent determinations of the size–luminosity relation from the HFF data set and steeper than that obtained from the bright galaxies in blank fields. We also investigate the systematic uncertainties associated with the choice of lens models, finding that the slopes of size–luminosity relations derived from different models are mutually consistent, i.e. modelling errors are not a significant source of discrepancy between the size–luminosity relation of blank and lensed fields.
Phosphorylation-dependent association of human chromatin protein PC4 to linker histone H1 regulates genome organization and transcription
Authors: Mustafi Pallabi , Hu Mingli , Kumari Sujata , Das Chandrima , Li Guohong , Kundu Tapas K
Published: June 2022

Human Positive Coactivator 4 (PC4) is a multifaceted chromatin protein involved in diverse cellular processes including genome organization, transcription regulation, replication, DNA repair and autophagy. PC4 exists as a phospho-protein in cells which impinges on its acetylation by p300 and thereby affects its transcriptional co-activator functions via double-stranded DNA binding. Despite the inhibitory effects, the abundance of phosphorylated PC4 in cells intrigued us to investigate its role in chromatin functions in a basal state of the cell. We found that casein kinase-II (CKII)-mediated phosphorylation of PC4 is critical for its interaction with linker histone H1. By employing analytical ultracentrifugation and electron microscopy imaging of in vitro reconstituted nucleosomal array, we observed that phospho-mimic (PM) PC4 displays a superior chromatin condensation potential in conjunction with linker histone H1. ATAC-sequencing further unveiled the role of PC4 phosphorylation to be critical in inducing chromatin compaction of a wide array of coding and non-coding genes in vivo. Concordantly, phospho-PC4 mediated changes in chromatin accessibility led to gene repression and affected global histone modifications. We propose that the abundance of PC4 in its phosphorylated state contributes to genome compaction contrary to its co-activator function in driving several cellular processes like gene transcription and autophagy.
Binding of the transcription activator-like effector augments transcriptional regulation by another transcription factor
Authors: Leben Katja , Strmšek Žiga , Lebar Tina , Verbič Anže , Dragovan Matej , Omersa Neža , Anderluh Gregor , Jerala Roman
Published: June 2022

DNA transcription is regulated by a range of diverse mechanisms and primarily by transcription factors that recruit the RNA polymerase complex to the promoter region on the DNA. Protein binding to DNA at nearby or distant sites can synergistically affect this process in a variety of ways, but mainly through direct interactions between DNA-binding proteins. Here we show that a Transcription Activator-Like Effector (TALE), which lacks an activation domain, can enhance transcription in mammalian cells when it binds in the vicinity of and without direct interaction with several different dimeric or monomeric transcription factors. This effect was observed for several TALEs regardless of the recognition sequences and their DNA-bound orientation. TALEs can exert an effect over the distance of tens of nucleotides and it also potentiated KRAB-mediated repression. The augmentation of transcriptional regulation of another transcription factor is characteristic of TALEs, as it was not observed for dCas9/gRNA, zinc finger, or Gal4 DNA-binding domains. We propose that this mechanism involves an allosteric effect exerted on DNA structure or dynamics. This mechanism could be used to modulate transcription but may also play a role in the natural context of TALEs.
Single seeds exhibit transcriptional heterogeneity during secondary dormancy induction
Authors: Krzyszton Michal , Yatusevich Ruslan , Wrona Magdalena , Sacharowski Sebastian P , Adamska Dorota , Swiezewski Szymon
Published: June 2022

Seeds are highly resilient to the external environment, which allows plants to persist in unpredictable and unfavorable conditions. Some plant species have adopted a bet-hedging strategy to germinate a variable fraction of seeds in any given condition, and this could be explained by population-based threshold models. Here, in the model plant Arabidopsis (Arabidopsis thaliana), we induced secondary dormancy (SD) to address the transcriptional heterogeneity among seeds that leads to binary germination/nongermination outcomes. We developed a single-seed RNA-seq strategy that allowed us to observe a reduction in seed transcriptional heterogeneity as seeds enter stress conditions, followed by an increase during recovery. We identified groups of genes whose expression showed a specific pattern through a time course and used these groups to position the individual seeds along the transcriptional gradient of germination competence. In agreement, transcriptomes of dormancy-deficient seeds (mutant of DELAY OF GERMINATION 1) showed a shift toward higher values of the germination competence index. Interestingly, a significant fraction of genes with variable expression encoded translation-related factors. In summary, interrogating hundreds of single-seed transcriptomes during SD-inducing treatment revealed variability among the transcriptomes that could result from the distribution of population-based sensitivity thresholds. Our results also showed that single-seed RNA-seq is the method of choice for analyzing seed bet-hedging-related phenomena.
Genome diploidization associates with cladogenesis, trait disparity, and plastid gene evolution
Authors: Zuo (左胜) Sheng , Guo (郭新异) Xinyi , Mandáková Terezie , Edginton Mark , Al-Shehbaz Ihsan A , Lysak Martin A
Published: June 2022

Angiosperm genome evolution was marked by many clade-specific whole-genome duplication events. The Microlepidieae is one of the monophyletic clades in the mustard family (Brassicaceae) formed after an ancient allotetraploidization. Postpolyploid cladogenesis has resulted in the extant c. 17 genera and 60 species endemic to Australia and New Zealand (10 species). As postpolyploid genome diploidization is a trial-and-error process under natural selection, it may proceed with different intensity and be associated with speciation events. In Microlepidieae, different extents of homoeologous recombination between the two parental subgenomes generated clades marked by slow (“cold”) versus fast (“hot”) genome diploidization. To gain a deeper understanding of postpolyploid genome evolution in Microlepidieae, we analyzed phylogenetic relationships in this tribe using complete chloroplast sequences, entire 35S rDNA units, and abundant repetitive sequences. The four recovered intra-tribal clades mirror the varied diploidization of Microlepidieae genomes, suggesting that the intrinsic genomic features underlying the extent of diploidization are shared among genera and species within one clade. Nevertheless, even congeneric species may exert considerable morphological disparity (e.g. in fruit shape), whereas some species within different clades experience extensive morphological convergence despite the different pace of their genome diploidization. We showed that faster genome diploidization is positively associated with mean morphological disparity and evolution of chloroplast genes (plastid–nuclear genome coevolution). Higher speciation rates in perennials than in annual species were observed. Altogether, our results confirm the potential of Microlepidieae as a promising subject for the analysis of postpolyploid genome diploidization in Brassicaceae.
HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes
Authors: Tu Yi-Tsung , Chen Chia-Yang , Huang Yi-Sui , Chang Chung-Han , Yen Ming-Ren , Hsieh Jo-Wei Allison , Chen Pao-Yang , Wu Keqiang
Published: June 2022

Histone deacetylases (HDAs) play an important role in transcriptional regulation of multiple biological processes. In this study, we investigated the function of HDA15 in abscisic acid (ABA) responses. We used immunopurification coupled with mass spectrometry-based proteomics to identify proteins interacting with HDA15 in Arabidopsis (Arabidopsis thaliana). HDA15 interacted with the core subunits of the MOS4-associated complex (MAC), MAC3A and MAC3B, with interaction between HDA15 and MAC3B enhanced by ABA. hda15 and mac3a/mac3b mutants were ABA-insensitive during seed germination and hyposensitive to salinity. RNA sequencing analysis demonstrated that HDA15 and MAC3A/MAC3B co-regulate ABA-responsive intron retention (IR). Furthermore, HDA15 reduced the histone acetylation level of genomic regions near ABA-responsive IR sites and the association of MAC3B with ABA-responsive pre-mRNA was dependent on HDA15. Our results indicate that HDA15 is involved in ABA responses by interacting with MAC3A/MAC3B to mediate splicing of introns.
Differential roles for lysyl oxidase (like), family members in chronic obstructive pulmonary disease; from gene and protein expression to function
Authors: Migulina Nataliya , Tjin Gavin , Faiz Alen , Borghuis Theo , Zhao Fenghua , Kaper Hans J. , Metzlar Marit , van Dijk Eline , Sharma Prashant K. , Timens Wim , Gosens Reinoud , Brandsma Corry‐Anke , Burgess Janette K.
Published: June 2022

Chronic obstructive pulmonary disease (COPD) is characterized by long‐term airflow obstruction with cigarette smoke as a key risk factor. Extracellular matrix (ECM) alterations in COPD may lead to small airway wall fibrosis. Altered collagen cross‐linking, potentially mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1‐4), orchestrates disturbed ECM homeostasis. In this study, we investigated the effects of smoking status and presence and severity of COPD on LOs gene and protein expression in the airways and the impact of LOs inhibition on airway contraction in an ex vivo mouse model. We used gene expression data from bronchial brushings, airway smooth muscle (ASM) cells in vitro and immunohistochemistry in lung tissue to assess smoke‐ and COPD‐associated differences in LOs gene and protein expression in the small airways. We found higher LOX expression in current‐ compared to ex‐smokers and higher LOXL1 expression in COPD compared to non‐COPD patients. LOX and LOXL2 expression were upregulated in COPD ASM cells treated with cigarette smoke extract. LOXL1 and LOXL2 protein levels were higher in small airways from current‐ compared to non‐smokers. In COPD patients, higher LOXL1 and lower LOX protein levels were observed, but no differences for LOXL2, LOXL3, and LOXL4 protein were detected in small airways. Inhibiting LOs activity increased airway contraction in murine lung slices. COPD‐associated changes in LOs, in particular LOX and LOXL1, may be related to smoking and contribute to impaired airway function, providing potential novel targets for preventing or treating small airways changes in COPD.
Apneic oxygenation in pediatric anesthesia
Authors: Kleine-Brueggeney Maren , Grosshauser Mareike , Greif Robert
Published: June 2022

Purpose of review

Apneic oxygenation is increasingly used in pediatric anesthesia. Its benefit for specific applications depends on the effect of apneic oxygenation on safe apnea time and carbon dioxide (CO2) elimination, on differences between low and high flow oxygen delivery, and on possible adverse effects. The present review summarizes current evidence on these pathophysiological aspects of apneic oxygenation as well as its applications in pediatric anesthesia.

Recent findings

Apneic oxygenation with both low flow and high flow nasal oxygen increases the safe apnea time, but does not lead to increased CO2 elimination. Airway pressures and adverse effects like atelectasis formation, oxidative stress and aerosol generation under apneic oxygenation are not well studied in pediatric anesthesia. Data from adults suggest no important effect on airway pressures when the mouth is open, and no significant formation of atelectasis, oxidative stress or aerosol generation with high flow nasal oxygen.

Apneic oxygenation in pediatric anesthesia is mainly used during standard and difficult airway management. It is sometimes used for airway interventions, but CO2 accumulation remains a major limiting factor in this setting. Reports highlight the use of high flow nasal oxygen in spontaneously breathing rather than in apneic children for airway interventions.
Safe in the first attempt: teaching neonatal airway management
Authors: Garcia-Marcinkiewicz Annery G. , Matava Clyde T.
Published: June 2022

Purpose of review

Quick and precise facemask ventilation and tracheal intubation are critical clinical skills in neonatal airway management. In addition, this vulnerable population requires a thorough understanding of developmental airway anatomy and respiratory physiology to manage and anticipate potential airway mishaps. Neonates have greater oxygen consumption, increased minute ventilation relative to functional residual capacity, and increased closing volumes compared to older children and adults. After a missed airway attempt, this combination can quickly lead to dire consequences, such as cardiac arrest. Keeping neonates safe throughout the first attempt of airway management is key.

Recent findings

Several techniques and practices have evolved to improve neonatal airway management, including improvement in neonatal airway equipment, provision of passive oxygenation, and closer attention to the management of anesthetic depth. The role of nontechnical skills during airway management is receiving more recognition.

Every neonatal intubation should be considered a critical event. Below we discuss some of the challenges in neonatal airway management, including anatomical and physiological principles which must be understood to approach the airway. We then follow with a description of current evidence for best practices and training.
Health equity research in obstetric anesthesia
Authors: Toyobo Olubukola , Guglielminotti Jean , Andreae Doerthe Adriana , Andreae Michael H.
Published: June 2022

Purpose of review

Health equity is an important priority for obstetric anesthesia, but describing disparities in perinatal care process and health outcome is insufficient to achieve this goal. Conceptualizing and framing disparity is a prerequisite to pose meaningful research questions. We emphasize the need to hypothesize and test which mechanisms and drivers are instrumental for disparities in perinatal processes and outcomes, in order to target, test and refine effective countermeasures.

Recent findings

With an emphasis on methodology and measurement, we sketch how health systems and disparity research may advance maternal health equity by narrating, conceptualizing, and investigating social determinants of health as key drivers of perinatal disparity, by identifying the granular mechanism of this disparity, by making the economic case to address them, and by testing specific interventions to advance obstetric health equity.

Measuring social determinants of health and meaningful perinatal processes and outcomes precisely and accurately at the individual, family, community/neighborhood level is a prerequisite for healthcare disparity research. A focus on elucidating the precise mechanism driving disparity in processes of obstetric care would inform a more rational effort to promote health equity. Implementation scientists should rigorously investigate in prospective trials, which countermeasures are most efficient and effective in mitigating perinatal outcome disparities.
Do racial and ethnic disparities lead to the undertreatment of pain? Are there solutions?
Authors: Goree Johnathan H. , Jackson Jaleesa
Published: June 2022

Purpose of review

The current review aims to empower anesthesiologists, specifically pain medicine specialists, to become leaders in ensuring equitable care.

Recent findings

Disparities in both acute and chronic pain medicine lead to increased morbidity for patients of color. Gaps in care include misdiagnosis or under diagnosis of chronic pain disease states, undertreatment of sickle cell disease and other conditions that are common in minorities, under prescription of opioids, and lack of access to novel opioid sparing treatments. While the causes of these disparities are multifactorial, care team implicit bias and lack of representation are two of the major factors. Solutions are challenging, but the authors suggest an inside out solution. We believe that this practice will have far-reaching downstream effects, including improving diversity in our field and quality of care for our patients.

The current article reviews disparities in both acute and chronic pain treatment for underrepresented racial and ethnic minorities in the United States. The authors examine whether implicit bias and lack of representation are a contributing factor for these disparities. Lastly, we will discuss potential solutions.
Individualized multidisciplinary analgesia to prevent persistent postsurgical pain
Authors: Lukas Anne , Buhre Wolfgang
Published: June 2022

Purpose of review

Persistent postsurgical pain as outcome of surgery has reached more attention in the past years. In the first place because of related disability, long-term use of (opioid)analgesics and impact on the quality of life of individual patients. In addition, the individual and societal socio-economic burden of PPSP is high and increasing in the light of increasing numbers of surgery world-wide.

Recent findings

Actual studies identified risk factors for persistent postsurgical pain in relevant patient populations. Astonishingly, most of predicting factors seem unrelated to surgery.

Future perioperative practice will have to focus on identifying patients at risk for PPSP before surgery and develop/offer suitable individually tailored preventive interventions.
Perinatal quality collaboratives and birth equity
Authors: Mason Chawla LaToya , Collier Charlene H. , Penny Stacey C.
Published: June 2022

Purpose of review

The purpose of this review is to discuss how state perinatal quality collaboratives are addressing birth equity to reduce disparities in maternal morbidity and mortality.

Recent finding

Perinatal quality collaboratives are adopting core practices to advance birth equity, reduce disparities and confront racism and bias in obstetric care including securing leadership commitments to equity, providing education on the causes of inequities and mitigation strategies, collecting accurate race/ethnicity data, addressing social determinants of health, and integrating patient and community knowledge, experiences, and narratives in the quality improvement work.

Inequities in maternal morbidity and mortality particularly affecting Black birthing people are driven by racism, inequities in the social determinants of health, and variations in care practices and quality. Perinatal quality collaboratives are an important resource for driving improvement changes to mitigate these factors and improve outcomes.

Video Abstract

Mason CL, Collier CH, Penny SC. Perinatal Quality Collaboratives and Birth Equity. Produced by CLMB Productions for use in this publication. January 10, 2022, http://links.lww.com/COAN/A86.
A pragmatic approach to quality improvement in pediatric anesthesia
Authors: Clausen Nicola G.
Published: June 2022

Purpose of review

The concept of quality improvement (QI) is well implemented in pediatric anesthesia. Conductance, reporting and publishing of QI projects and -results is well described and promoted. However, the perception of quality might differ between stakeholders and beneficiaries. Based on measures of quality as perceived by healthcare professionals and pediatric patients, a pragmatic approach to choosing the relevant quality measure is suggested.

Recent findings

Design of QI projects is often motivated by an incentive to avoid errors and adverse events, and with an overall aim to reduce morbidity and mortality. From a patient- and parent point of view, avoidance of perioperative stress and anxiety might be a priority measure of quality.

In an attempt to embrace both perspectives of quality in pediatric anesthesia care, it is suggested to choose quality items for improvement based on patient safety, professional excellency and benignancy. By following this approach, QI is expected to remain relevant to both healthcare professionals and patients.
MGMT in glial carcinogenesis. Roles from prevention to treatment
Authors: Elmaci İlhan , Altinoz Meric A. , Kahraman Ozlu Eylem Burcu , Sari Ramazan , Er Ozlem , Gokhan Ekmekci Cumhur , Turkgenc Burcu , Ozpinar Alp , Hacker Emily , Ozpinar Aysel
Published: June 2022

Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O6-methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.