bluuebunny/crossref_metadata_2025 huggingface dataset:
Front-end Electronics for Timing with pico-second precision using 3D Trench Silicon Sensors
Authors: Cossu Gian Matteo , Lai Adriano
Published: January 2023

The next generation of collider experiments require tracking
detectors with extreme performance capabilities in terms of spatial
resolution (tens of µm), radiation hardness
(1017 1 MeV neq/cm2) and timing resolution (tens of
ps). 3D silicon sensors, recently developed within the TimeSPOT
initiative, offer a viable solution to cope with such demanding
requirements. In order to accurately characterize the timing
performance of these new sensors, several read-out boards, based on
discrete active components, have been designed, assembled, and
tested. The same electronics is also suitable for characterization
of similar pixel sensors whenever timing performance in the order
and below 10 ps is a requirement. This paper describes the general
characteristics needed by front-end electronics to exploit
solid-state sensors with fast timing capabilities and in particular,
showcases the performance of the developed electronics in the
testing and characterization of fast 3D silicon sensors.
First results from a multiplexed and massive instrument with sub-electron noise Skipper-CCDs
Authors: Chierchie F. , Chavez C.R. , Sofo Haro M. , Fernandez Moroni G. , Cervantes-Vergara B.A. , Perez S. , Estrada J. , Tiffenberg J. , Uemura S. , Botti A.
Published: January 2023

We present a new instrument composed of a large number of
sub-electron noise Skipper-CCDs operated with a two stage analog
multiplexed readout scheme suitable for scaling to thousands of
channels. New, thick, 1.35 Mpix sensors, from a new foundry, are
glued into a Multi-Chip Module (MCM) printed circuit board on a
ceramic substrate which has 16 sensors each. The instrument, that
can hold up-to 16 MCMs, a total of 256 Skipper-CCD sensors (called a
Super-Module with ≈ 130 grams of active mass and
346 Mpix), is part of the R&D effort of the OSCURA experiment
which will have ≈ 94 super-modules. Experimental results
with 10 MCMs and 160 Skipper-CCDs sensors are presented in this
paper. This is already the largest ever built instrument with single
electron sensitivity CCDs using nondestructive readout, both, in
terms of active mass and number of channels.
Repopulation of decellularized organ scaffolds with human pluripotent stem cell-derived pancreatic progenitor cells
Authors: Goh Saik-Kia , Bertera Suzanne , Richardson Thomas , Banerjee Ipsita
Published: January 2023

Diabetes is an emerging global epidemic that affects more that 285 million people worldwide. Engineering of endocrine pancreas tissue holds great promise for the future of diabetes therapy. Here we demonstrate the feasibility of re-engineering decellularized organ scaffolds using regenerative cell source. We differentiated human pluripotent stem cells (hPSC) toward pancreatic progenitor (PP) lineage and repopulated decellularized organ scaffolds with these hPSC-PP cells. We observed that hPSCs cultured and differentiated as aggregates are more suitable for organ repopulation than isolated single cell suspension. However, recellularization with hPSC-PP aggregates require a more extensive vascular support, which was found to be superior in decellularized liver over the decellularized pancreas scaffolds. Upon continued culture for nine days with chemical induction in the bioreactor, the seeded hPSC-PP aggregates demonstrated extensive and uniform cellular repopulation and viability throughout the thickness of the liver scaffolds. Furthermore, the decellularized liver scaffolds was supportive of the endocrine cell fate of the engrafted cells. Our novel strategy to engineer endocrine pancreas construct is expected to find potential applications in preclinical testing, drug discovery and diabetes therapy.
Storylines of Maritime Continent dry period precipitation changes under global warming
Authors: Ghosh Rohit , Shepherd Theodore G
Published: January 2023

The dry half of the year from May to October over the Maritime Continent (MC) has experienced unprecedented damages from forest fires in recent decades. The observed interannual rainfall variability during this period is closely tied to sea surface temperature (SST) variability over the equatorial Pacific (EP). Therefore, the future evolution of EP SST can be expected to influence the climatological precipitation over the MC. Whilst multi-model means (MMMs) suggest a future drying trend over the south-western part of the MC, there is considerable model uncertainty. Here, using a storyline approach with the 38 climate models from Coupled Model Intercomparison Project Phase 6, we distinguish the model uncertainty associated with changes in the zonal EP SST gradient from that associated with the basin-wide EP (BEP) warming. We find that an increase in east-to-west EP SST gradient would bring more rainfall over the north-eastern regions including northern Borneo, Sulawesi and New Guinea. In contrast, the intensity of the basin-wide warming of EP SST is directly linked with the drying response seen over the south-western MC in the MMM. This drying affects the highly vulnerable regions of Sumatra and Kalimantan for forest fires. Our results suggest that a storyline under higher BEP warming accompanied by an El-Niño like change in zonal SST gradient would lead to even drier climatic conditions over these key regions. However, the observed record of more than one hundred years favours a storyline of lower BEP warming accompanied by a La-Niña like change in zonal SST gradient, which would lead to minimal drying over the south-western MC and wetter conditions over the north-eastern parts of the MC.
Diagrammatics for the inverse problem in spin systems and simple liquids
Authors: Kühn Tobias , van Wijland Frédéric
Published: January 2023

Modeling complex systems, like neural networks, simple liquids or flocks of birds, often works in reverse to textbook approaches: given data for which averages and correlations are known, we try to find the parameters of a given model consistent with it. In general, no exact calculation directly from the model is available and we are left with expensive numerical approaches. A particular situation is that of a perturbed Gaussian model with polynomial corrections for continuous degrees of freedom. Indeed perturbation expansions for this case have been implemented in the last 60 years. However, there are models for which the exactly solvable part is non-Gaussian, such as independent Ising spins in a field, or an ideal gas of particles. We implement a diagrammatic perturbative scheme in weak correlations around a non-Gaussian yet solvable probability weight. This applies in particular to spin models (Ising, Potts, Heisenberg) with weak couplings, or to a simple liquid with a weak interaction potential. Our method casts systems with discrete degrees of freedom and those with continuous ones within the same theoretical framework. When the core theory is Gaussian it reduces to the well-known Feynman diagrammatics.
Extracellular vesicles-derived miRNAs as mediators of pulmonary exacerbation in pediatric cystic fibrosis
Authors: Stachowiak Zuzanna , Wojsyk-Banaszak Irena , Jończyk-Potoczna Katarzyna , Narożna Beata , Langwiński Wojciech , Szczepankiewicz Aleksandra
Published: January 2023

Children with cystic fibrosis (CF) suffer from chronic inflammation and recurrent pulmonary exacerbations (PEs). We aimed to test whether a specific miRNA could be associated with the occurrence of PE. We sequenced extracellular vesicle (EV)-derived miRNA in sputum (n = 20), exhaled breath condensate (EBC) (n = 11), and serum (n = 8) samples from pediatric patients during PE and the stable stage of CF. Four miRNAs: let-7c, miR-16, miR-25-3p and miR-146a, have been selected for validation in a larger group with reverse transcription quantitative real-time PCR (RT-qPCR) in sputum and serum, or droplet digital PCR (ddPCR) in EBC. Next-generation sequencing (NGS) differential expression analysis was done in Base Space, and the correlation between miRNAs expression and clinical data was calculated with Statistica. Functional annotation of selected miRNAs and their potential target genes was performed with miRDip and DAVID software. There were no differences in miRNA expression between stable and exacerbation in sputum and in serum. Validation of four selected miRNAs showed significant downregulation of miR-146a in serum. A panel of all four miRNAs (peripherally) was the best predictive model of exacerbation (p < 0.001, AUC = 0.96). Expression of airway miR-25-3p improved the diagnostic value of FEV1% pred and FVC% pred, while peripheral miR-146a improved the predictive model of C-reactive protein and neutrophilia. In silico analysis revealed a potential role for selected miRNAs in regulating processes associated with inflammation and tissue remodeling. We demonstrated that EVs contained in peripheral blood as well as local biomaterials can act as carriers for miRNAs with the diagnostic potential of predicting exacerbation in pediatric CF.
Embroidered textile electrodes for long-term ECG monitoring
Authors: Nigusse Abreha Bayrau , Malengier Benny , Mengistie Desalegn Alemu , Maru Ambachew , Tseghai Granch Berhe , Langenhove Lieva Van
Published: January 2023

Electrocardiography (ECG) monitoring is very important for the diagnosis and examination of heart-related diseases. Electrodes are the main components in monitoring and recording ECG signals. In this work, we have developed embroidered electrodes using two types of conductive yarns. ECG detection performance of the electrodes was measured at static and dynamic conditions and results were compared to standard Ag/AgCl electrodes. The electrodes were developed with three different dimensional areas to investigate the effect of the size on ECG acquisition performance. ECG signals collected from both the embroidered and standard Ag/AgCl electrodes have visible P, QRS, and T waveforms. Signals collected using large-size textile electrodes show better signal amplitude, which would reveal that the performance of the electrodes becomes improved with an increase in size. However, signals collect more artifacts dynamic conditions contain motion artifacts, indicating this aspect requires further improvement.
Green and sustainable dyeing of wool with madder plant of the Moroccan flora
Authors: Mesrar F E , Tachallait H , Cherkaoui O , Bougrin K , Benhida R
Published: January 2023

Textile industry is evolving towards limiting the use of synthetic dyes due to their environmental and health concerns. Natural dyes are considered the ultimate alternative as it is green and ecofriendly. However, natural dyeing is limited by the use of metal mordants to enhance the colorimetric and fastness behavior of dyed textiles. In this work, madder roots (Rubia Tinctorum) from Morocco were analyzed by mean of HPLC-PDA and used to dye wool yarns. The effect of pre-mordanting with different metal mordants was assessed. Color properties, exhaustion, and fixation rates of dyed wool was also evaluated depending on the mordants.
Hearing Conservation Programme Costs at Selected South African Companies
Authors: Rikhotso Oscar , Morodi Thabiso John , Masekameni Daniel Masilu
Published: January 2023

The Occupational Health and Safety Act 1993 and its attending Regulations in South Africa, require employers to conduct cost analysis studies to inform decision-making related to exposure control for occupational health hazard such as noise. Cost analysis, as per South African National Standard/ISO 31000 risk assessment guideline, is an important input for the decision-making process of the risk management process. The costs of administrating a hearing conservation programme intended to minimise noise-induced hearing loss is an example of a cost analysis. This study enrolled four companies from the South African manufacturing and utilities sectors with the aim of establishing whether cost analysis is included during the noise risk assessment process; and determining administration costs of HCP administration. A HCP cost questionnaire was completed by each company’s occupational hygiene professionals and risk officers. None of the companies in the study included cost analysis in their respective risk assessment processes. The overall costs, derived from the HCP cost item questionnaire, was much greater for Company A (4 290 014 Rands) than all of the other companies combined (970 685 Rands). Hearing protection device expenditures across the four companies were the greatest expense, while audiometry was the smallest expense owing to service internalisation. The HCP expenditures are incurred on periodic basis, yearly or biennial, and are internalised in companies as direct costs. Cost analysis can enhance the noise risk assessment process by providing additional input to support the decision-making process related to noise control. This challenges the occupational hygiene profession to pursue new frontiers and decision-making models in the scope of noise risk management, beyond noise measurements and hearing protection device use recommendation.
Revisiting primary endocrine therapy versus surgery in older women with breast cancer: meta-analysis
Authors: Chan Kai Siang , Chong Michelle Tian Hui , Chia Clement Luck Khng , Cheung Kwok Leung
Published: January 2023

Background

Old age is associated with increased co-morbidities, resulting in reduced life expectancy. Primary endocrine therapy is an alternative to primary surgical therapy for patients with breast cancer and increased co-morbidities. The aim was to review outcomes of primary endocrine therapy versus primary surgical therapy in older women with breast cancer.

Methods

PubMed, Embase (Ovid), Scopus, and the Cochrane Library were searched systematically from January 2000 to May 2022. Single-arm studies were excluded. Primary outcomes were overall survival and breast cancer-specific survival. Secondary outcomes were local and regional failure of primary endocrine therapy, recurrence after primary surgical therapy, and health-related quality of life.

Results

There were 14 studies including 14 254 patients (primary endocrine therapy 2829, 19.8 per cent; primary surgical therapy 11 425, 80.2 per cent), with the addition of four major studies (9538 patients) compared with the latest review in 2014. Seven studies defined primary surgical therapy as surgery plus adjuvant endocrine therapy, and six studies included patients with oestrogen receptor-positive tumours only. Patients in the primary endocrine therapy group were older than the primary surgical therapy group (mean difference 2.43 (95 per cent c.i. 0.73 to 4.13) years). Primary endocrine therapy led to worse overall survival than primary surgical therapy (HR 1.42, 95 per cent c.i. 1.06 to 1.91). Subgroup analysis of RCTs and prospective studies, however, showed comparable overall survival. Breast cancer-specific survival was also comparable (HR 1.28, 95 per cent c.i. 0.87 to 1.87). At 6 weeks, operated patients had significant arm symptoms and illness burden following major breast surgery compared with patients receiving primary endocrine therapy. Health-related quality of life, measured by the European Organization for Research and Treatment of Cancer QLQ-C30 and EuroQol EQ-5D-5L™, was comparable in the two treatment groups.

Conclusion

Overall survival was worse among older women receiving primary endocrine therapy in an analysis including all studies, but comparable in RCTs and prospective studies. This may be due to confounding by age and co-morbidities in retrospective cohort studies of primary endocrine therapy.
Chromosomal and genomic data in Neotropical Dorstenia species (Moraceae) and their relationships with African species
Authors: Barreto Lucas Mesquita , de Assis Rafael , Vanzela André Luís Laforga
Published: January 2023

Dorstenia spp. are characterized by a herbaceous habit, the presence of rhizomes and inflorescences being coenanthia. They occur in different forest formations, and it is believed that there are two distribution centres for Dorstenia, one Palaeotropical (Africa) and one Neotropical (Central and South America). The present study aimed to undertake a comparative analysis of the karyotype diversity of Dorstenia, based on chromosome data and DNA C values of 13 Neotropical species, and an analysis of low-coverage genomic sequencing of three African and one Neotropical species. The most frequent chromosome number is 2n = 32, with variations for 2n = 28 and 30, suggesting an important role of polyploidy in the karyotype differentiation of Dorstenia. Karyotypes varied in the number of metacentric, submetacentric and acrocentric chromosomes, with evidence of rearrangements. Genome sizes (C values) varied almost two-fold, from 2C = 2.50 to 5.47 pg. There was no clear relationship between DNA C value variations and karyotype features, such as chromosome numbers and distribution of CMA/DAPI bands or rDNA sites. Proximal heterochromatin was most frequent, but CMA+ and DAPI+ bands predominated in relation to DAPI+ bands. 5S and 35S ribosomal DNA (rDNA) sites were also observed in the proximal regions in almost all species. Based on a chromosome modelling approach, our data suggest that dysploidy events may have been responsible for the chromosome number variations, whereas rearrangements involving repetitive fractions may have been associated with changes in genome size. There was great variability in the amount of rDNA between species, including a remarkable 5S rDNA amplification in D. bahiensis, and a diversity of transposable elements in the four genomes with genomic sequence data. The combination of data from karyotypes, genomes and phylogeny suggests that dysploidy has played a predominant role in the evolution of Neotropical Dorstenia spp.
Functional regeneration of dilated cardiomyopathy by transcatheter bilateral pulmonary artery banding: first-in-human case series
Authors: Schranz Dietmar , Krause Ulrich , Kerst Gunter , Esmaeili Anoosh , Paul Thomas
Published: January 2023

Background

Dilated cardiomyopathy (DCM) is a leading cause of heart transplantation (HTx) in children. Surgical pulmonary artery banding (PAB) is used worldwide to achieve functional heart regeneration and remodelling.

Case summary

We report for the first-time successful bilateral transcatheter implantation of bilateral pulmonary artery flow restrictors in a case series of three infants with severe DCM based on left-ventricular non-compaction morphology associated with Barth syndrome in one and a non-classified syndrome in another. Functional cardiac regeneration was observed in two patients after almost 6 months of endoluminal banding, and in the neonate with Barth syndrome already after 6 weeks. Accompanied by an improvement in functional class (Class IV to Class I), the left ventricular end-diastolic dimensions z-score normalized, as did the elevated serum brain natriuretic peptide levels. A listing for HTx could be avoided.

Discussion

Percutaneous bilateral endoluminal PAB is a novel minimally invasive approach that enables functional cardiac regeneration in infants with severe DCM and preserved right ventricular function. Interruption of the ventriculo-ventricular interaction, the key mechanism for recovery, is avoided. Intensive care for these critically ill patients is reduced to a minimum. However, investing in ‘heart regeneration to avoid transplantation’ remains a challenge.
Comparative effect of different physical exercise training on exercise capacity and cardiac function in heart failure with preserved ejection fraction: a network meta-analysis—ExIC-FEp Study
Authors: Cavero-Redondo Iván , Martínez-García Irene , Saz-Lara Alicia , Garcia-Klepzig José Luis , Álvarez-Bueno Celia , Martínez-Vizcaino Vicente
Published: January 2023

Aims

This network meta-analysis aimed to compare the effect of different types of physical exercise [endurance training, endurance/resistance training, and high-intensity interval training (HIIT)] on exercise capacity and cardiac function parameters in patients with heart failure with preserved ejection fraction.

Methods and results

A systematic search of the MEDLINE (via PubMed), Scopus, and Web of Science databases was conducted to identify experimental studies addressing the effect of different physical exercise training programmes on exercise capacity and cardiac function in heart failure with preserved ejection fraction. Comparative evaluation of the effect of exercise training type was performed by conducting a standard pairwise meta-analysis and a network meta-analysis for direct and indirect comparisons between exercise training types and controls/non-interventions. Eleven studies were included in the analysis showing that endurance training improves the main exercise capacity parameters (VO2peak, workload, exercise time, peak heart rate, VO2, and 6 min walk distance). Additionally, endurance/resistance training showed a significant effect on VO2peak, workload, early mitral annulus velocity, and early mitral/mitral annulus velocity ratio. Finally, HIIT showed a significant effect on VO2peak, VO2, and the early mitral/mitral annulus velocity ratio.

Conclusion

Our findings support the effect of three different types of physical exercise on exercise capacity, mainly VO2peak. Additionally, endurance/resistance training and HIIT could reverse left ventricular remodelling in patients with heart failure with preserved ejection fraction.

Registration

PROSPERO: CRD42021276111
A 21-bp InDel in the promoter ofSTP1selected during tomato improvement accounts for soluble solid content in fruits
Authors: Wang Ying , Shi Chunmei , Ge Pingfei , Li Fangman , Zhu Lihui , Wang Yaru , Tao Jinbao , Zhang Xingyu , Dong Haiqiang , Gai Wenxian , Wang Fei , Ye Zhibiao , Grierson Donald , Xu Wei , Zhang Yuyang
Published: January 2023

Domestication and improvement are important processes that generate the variation in genome and phonotypes underlying crop improvement. Unfortunately, during selection for certain attributes, other valuable traits may be inadvertently discarded. One example is the decline in fruit soluble solids content (SSC) during tomato breeding. Several genetic loci for SSC have been identified, but few reports on the underlying mechanisms are available. In this study we performed a genome-wide association study (GWAS) for SSC of the red-ripe fruits in a population consisting of 481 tomato accessions with large natural variations and found a new quantitative trait locus, STP1, encoding a sugar transporter protein. The causal variation of STP1, a 21-bp InDel located in the promoter region 1124 bp upstream of the start codon, alters its expression. STP1Insertion accessions with an 21-bp insertion have higher SSC than STP1Deletion accessions with the 21-bp deletion. Knockout of STP1 in TS-23 with high SSC using CRISPR/Cas9 greatly decreased SSC in fruits. In vivo and in vitro assays demonstrated that ZAT10-LIKE, a zinc finger protein transcription factor (ZFP TF), can specifically bind to the promoter of STP1Insertion to enhance STP1 expression, but not to the promoter of STP1Deletion, leading to lower fruit SSC in modern tomatoes. Diversity analysis revealed that STP1 was selected during tomato improvement. Taking these results together, we identified a naturally occurring causal variation underlying SSC in tomato, and a new role for ZFP TFs in regulating sugar transporters. The findings enrich our understanding of tomato evolution and domestication, and provide a genetic basis for genome design for improving fruit taste.
Joining and exiting the value chain of foreign multinationals and performance of their local suppliers: evidence from interfirm transaction data
Authors: Masso Jaan , Vahter Priit
Published: January 2023

This paper investigates the productivity effects for domestic suppliers from joining and exiting the value chains of foreign-owned multinational enterprises (MNEs). Our econometric analysis is based on firm-to-firm transactions recorded in the value-added tax declarations’ data from Estonia and use of propensity score matching and difference-in-difference regression approach. The treatment analysis based on period 2015–2019 suggests that starting to supply the foreign-owned firms initially boosts the value added per employee of the domestic firms, including the effects on the scale of production and the capital–labor ratio. These first linkages to the foreign-owned MNEs do not affect the total factor productivity (TFP) of domestic firms, suggesting that the TFP effects take time to materialize. We find no significant positive effects on the second-tier suppliers: the positive effects are limited to the first-tier suppliers with direct links to foreign-owned firms. One novel result is the evidence that the productivity of suppliers does not fall, on average, after decreasing or ending supplier relationships with the foreign-owned firms. However, this average effect hides significant heterogeneity. Domestic firms with prior high levels of productivity and those at the time of exit from the MNE relationship start to export, gain in productivity in next periods, whereas the firms with low prior productivity levels lose.
Simultaneous adjustment of uncontrolled confounding, selection bias and misclassification in multiple-bias modelling
Authors: Brendel Paul , Torres Aracelis , Arah Onyebuchi A
Published: January 2023

Background

Adjusting for multiple biases usually involves adjusting for one bias at a time, with careful attention to the order in which these biases are adjusted. A novel, alternative approach to multiple-bias adjustment involves the simultaneous adjustment of all biases via imputation and/or regression weighting. The imputed value or weight corresponds to the probability of the missing data and serves to ‘reconstruct’ the unbiased data that would be observed based on the provided assumptions of the degree of bias.

Methods

We motivate and describe the steps necessary to implement this method. We also demonstrate the validity of this method through a simulation study with an exposure-outcome relationship that is biased by uncontrolled confounding, exposure misclassification, and selection bias.

Results

The study revealed that a non-biased effect estimate can be obtained when correct bias parameters are applied. It also found that incorrect specification of every bias parameter by +/-25% still produced an effect estimate with less bias than the observed, biased effect.

Conclusions

Simultaneous multi-bias analysis is a useful way of investigating and understanding how multiple sources of bias may affect naive effect estimates. This new method can be used to enhance the validity and transparency of real-world evidence obtained from observational, longitudinal studies.
Uncertainty quantification in the Bradley–Terry–Luce model
Authors: Gao Chao , Shen Yandi , Zhang Anderson Y
Published: January 2023

The Bradley–Terry–Luce (BTL) model is a benchmark model for pairwise comparisons between individuals. Despite recent progress on the first-order asymptotics of several popular procedures, the understanding of uncertainty quantification in the BTL model remains largely incomplete, especially when the underlying comparison graph is sparse. In this paper, we fill this gap by focusing on two estimators that have received much recent attention: the maximum likelihood estimator (MLE) and the spectral estimator. Using a unified proof strategy, we derive sharp and uniform non-asymptotic expansions for both estimators in the sparsest possible regime (up to some poly-logarithmic factors) of the underlying comparison graph. These expansions allow us to obtain: (i) finite-dimensional central limit theorems for both estimators; (ii) construction of confidence intervals for individual ranks; (iii) optimal constant of $\ell _2$ estimation, which is achieved by the MLE but not by the spectral estimator. Our proof is based on a self-consistent equation of the second-order remainder vector and a novel leave-two-out analysis.
Imaging of COVID-19 Vaccine–Related Axillary Lymphadenopathy: Initial Outcomes Based on US Features of Axillary Lymph Nodes
Authors: Ahn Richard W , Porembka Jessica H , Mootz Ann R , Goudreau Sally H , Dogan Basak E , Xi Yin , Seiler Stephen J
Published: January 2023

Objective

The purpose of this study is to describe the imaging characteristics and outcomes of COVID-19 vaccine–related axillary adenopathy and subsequent follow-up.

Methods

This was an IRB-approved, retrospective study of patients with imaging evidence of axillary lymphadenopathy who had received at least one dose of a COVID-19 vaccine and presented between January 1, 2021, and February 28, 2021. Sonographic cortical thickness and morphology was evaluated. A mixed effects model was used to model lymph node cortical thickness decrease over time.

Results

A total of 57 women were identified with lymphadenopathy and a COVID vaccination during the study period with 51 (89.5%) women completing imaging surveillance or undergoing tissue sampling of a lymph node. Three women (5.9%) were diagnosed with metastatic breast cancer to an axillary node. There was a statistically significant correlation with cortical thickness at initial US evaluation and malignancy (7.7 mm [SD ± 0.6 mm] for metastatic nodes and 5 mm [SD ± 2 mm] for benign nodes, P = 0.02). Suspicious morphological features (effacement of fatty hilum, P = 0.02) also correlated with malignancy. Time to resolution of lymphadenopathy can be prolonged with estimated half-life of the rate of decrease in cortical thickness modeled at 77 days (95% CI, 59–112 days). Diffuse, smooth cortical thickening over 3 mm was the most common lymph node morphology.

Conclusion

Malignant lymph node morphology and cortical thickness best predicted malignancy. Benign hyperplastic lymph nodes were the most common morphology observed after COVID-19 vaccination. Lymphadenopathy after vaccination is slow to resolve.
Epidemiology of Primary and Recurrent Healthcare-Associated and Community-Associated Pediatric Clostridioides difficile Infection in Canada, 2015–2020
Authors: Silva Anada , Du Tim , Choi Kelly B , Pelude Linda , Golding George R , Hizon Romeo , Lee Bonita E , Chow Blanda , Srigley Jocelyn A , Hota Susy S , Comeau Jeannette L , Thampi Nisha ,   the CNISP C. difficile working group, Davis Ian , Evans Gerald A , Frenette Charles , Johnstone Jennie , Kibsey Pamela , Katz Kevin C , Langley Joanne M , Longtin Yves , Mertz Dominik , Minion Jessica , Stagg Paula , Science Michelle , Suh Kathryn N , Wong Alice
Published: January 2023

Clostridioides difficile infection (CDI) among children remains a concerning cause of morbidity in hospital settings. We present epidemiological and molecular trends in healthcare- and community-associated CDI among children in Canadian inpatient and outpatient settings, including those who experienced recurrent infections.
The simulated catalogue of optical transients and correlated hosts (SCOTCH)
Authors: Lokken Martine , Gagliano Alexander , Narayan Gautham , Hložek Renée , Kessler Richard , Crenshaw John Franklin , Salo Laura , Alves Catarina S , Chatterjee Deep , Vincenzi Maria , Malz Alex I ,   The LSST Dark Energy Science Collaboration
Published: January 2023

As we observe a rapidly growing number of astrophysical transients, we learn more about the diverse host galaxy environments in which they occur. Host galaxy information can be used to purify samples of cosmological Type Ia supernovae, uncover the progenitor systems of individual classes, and facilitate low-latency follow-up of rare and peculiar explosions. In this work, we develop a novel data-driven methodology to simulate the time-domain sky that includes detailed modelling of the probability density function for multiple transient classes conditioned on host galaxy magnitudes, colours, star formation rates, and masses. We have designed these simulations to optimize photometric classification and analysis in upcoming large synoptic surveys. We integrate host galaxy information into the snana simulation framework to construct the simulated catalogue of optical transients and correlated hosts (SCOTCH, a publicly available catalogue of 5-million idealized transient light curves in LSST passbands and their host galaxy properties over the redshift range 0 < z < 3. This catalogue includes supernovae, tidal disruption events, kilonovae, and active galactic nuclei. Each light curve consists of true top-of-the-galaxy magnitudes sampled with high (≲2 d) cadence. In conjunction with SCOTCH, we also release an associated set of tutorials and transient-specific libraries to enable simulations of arbitrary space- and ground-based surveys. Our methodology is being used to test critical science infrastructure in advance of surveys by the Vera C. Rubin Observatory and the Nancy G. Roman Space Telescope.
High-salt transcription from enzymatically gapped promoters nets higher yields and purity of transcribed RNAs
Authors: MalagodaPathiranage Kithmie , Cavac Elvan , Chen Tien-Hao , Roy Bijoyita , Martin Craig T
Published: January 2023

T7 RNA polymerase is commonly used to synthesize large quantities of RNA for a wide variety of applications, from basic science to mRNA therapeutics. This in vitro system, while showing high fidelity in many ways, is also well known for producing longer than encoded RNA products, particularly under high-yield reaction conditions. Specifically, the resulting product pool is contaminated by an often disperse collection of longer cis-primed extension products. In addition to reducing yield via the conversion of correctly encoded RNA to longer products, self-primed extension generates partially double-stranded RNAs that can trigger the innate immune response. Extensive and low-yield purifications are then required to produce therapeutic RNA. Under high-yield conditions, accumulating concentrations of RNA effectively compete with promoter DNA for polymerase binding, driving self-primed extension at the expense of correct initiation. In the current work, we introduce a simple and novel modification in the DNA to strengthen promoter binding, shifting the balance back toward promoter-driven synthesis and so dramatically reducing self-primed extension. The result is higher yield of the encoded RNA at the outset and reduced need for extensive purifications. The approach can readily be applied to the synthesis of mRNA-length products under high-yield conditions.
Identification of RNA helicases with unwinding activity on angiogenin-processed tRNAs
Authors: Drino Aleksej , König Lisa , Capitanchik Charlotte , Sanadgol Nasim , Janisiw Eva , Rappol Tom , Vilardo Elisa , Schaefer Matthias R
Published: January 2023

Stress-induced tRNA fragmentation upon environmental insult is a conserved cellular process catalysed by endonucleolytic activities targeting mature tRNAs. The resulting tRNA-derived small RNAs (tsRNAs) have been implicated in various biological processes that impact cell-to-cell signalling, cell survival as well as gene expression regulation during embryonic development. However, how endonuclease-targeted tRNAs give rise to individual and potentially biologically active tsRNAs remains poorly understood. Here, we report on the in vivo identification of proteins associated with stress-induced tsRNAs-containing protein complexes, which, together with a ‘tracer tRNA’ assay, were used to uncover enzymatic activities that can bind and process specific endonuclease-targeted tRNAs in vitro. Among those, we identified conserved ATP-dependent RNA helicases which can robustly separate tRNAs with endonuclease-mediated ‘nicks’ in their anticodon loops. These findings shed light on the existence of cellular pathways dedicated to producing individual tsRNAs after stress-induced tRNA hydrolysis, which adds to our understanding as to how tRNA fragmentation and the resulting tsRNAs might exert physiological impact.
Distinctly localized lipid phosphate phosphatases mediate endoplasmic reticulum glycerolipid metabolism in Arabidopsis
Authors: Nguyen Van C , Nakamura Yuki
Published: January 2023

Inter-organelle communication is an integral subcellular process in cellular homeostasis. In plants, cellular membrane lipids are synthesized in the plastids and endoplasmic reticulum (ER). However, the crosstalk between these organelles in lipid biosynthesis remains largely unknown. Here, we show that a pair of lipid phosphate phosphatases (LPPs) with differential subcellular localizations is required for ER glycerolipid metabolism in Arabidopsis (Arabidopsis thaliana). LPPα2 and LPPε1, which function as phosphatidic acid phosphatases and thus catalyze the core reaction in glycerolipid metabolism, were differentially localized at ER and chloroplast outer envelopes despite their similar tissue expression pattern. No mutant phenotype was observed in single knockout mutants; however, genetic suppression of these LPPs affected pollen growth and ER phospholipid biosynthesis in mature siliques and seeds with compromised triacylglycerol biosynthesis. Although chloroplast-localized, LPPε1 was localized close to the ER and ER-localized LPPα2. This proximal localization is functionally relevant, because overexpression of chloroplastic LPPε1 enhanced ER phospholipid and triacylglycerol biosynthesis similar to the effect of LPPα2 overexpression in mature siliques and seeds. Thus, ER glycerolipid metabolism requires a chloroplast-localized enzyme in Arabidopsis, representing the importance of inter-organelle communication in membrane lipid homeostasis.
Glutamatergic neurons in the paraventricular hypothalamic nucleus regulate isoflurane anesthesia in mice
Authors: Yin Jianyin , Qin Jie , Lin Zhaojing , Li Aiyuan , Liu Damin , Jiang Yurong , Zhao Qiuni , Chen Liang , Liu Chengxi
Published: January 2023

The glutamatergic–mediated excitatory system in the brain is vital for the regulation of sleep–wake and general anesthesia. Specifically, the paraventricular hypothalamic nucleus (PVH), which contains mainly glutamatergic neurons, has been shown to play a critical role in sleep–wake. Here, we sought to explore whether the PVH glutamatergic neurons have an important effect on the process of general anesthesia. We used c‐fos staining and in vivo calcium signal recording to observe the activity changes of the PVH glutamatergic neurons during isoflurane anesthesia and found that both c‐fos expression in the PVH and the calcium activity of PVH glutamatergic neurons decreased in isoflurane anesthesia and significantly increased during the recovery process. Chemogenetic activation of PVH glutamatergic neurons prolonged induction time and shortened emergence time from anesthesia by decreasing the depth of anesthesia. Using chemogenetic inhibition of PVH glutamatergic neurons under isoflurane anesthesia, we found that inhibition of PVH glutamatergic neurons facilitated the induction process and delayed the emergence accompanied by deepening the depth of anesthesia. Together, these results identify a crucial role for PVH glutamatergic neurons in modulating isoflurane anesthesia.
The Incidence and Disparities in Use of Stigmatizing Language in Clinical Notes for Patients With Substance Use Disorder
Authors: Weiner Scott G. , Lo Ying-Chih , Carroll Aleta D. , Zhou Li , Ngo Ashley , Hathaway David B. , Rodriguez Claudia P. , Wakeman Sarah E.
Published: January 2023

Objective

The language used to describe people with substance use disorder impacts stigma and influences clinical decision making. This study evaluates the presence of stigmatizing language (SL) in clinical notes and detects patient- and provider-level differences.

Methods

All free-text notes generated in a large health system for patients with substance-related diagnoses between December 2020 and November 2021 were included. A natural language processing algorithm using the National Institute on Drug Abuse’s “Words Matter” list was developed to identify use of SL in context.

Results

There were 546,309 notes for 30,391 patients, of which 100,792 (18.4%) contained SL. A total of 18,727 patients (61.6%) had at least one note with SL. The most common SLs used were “abuse” and “substance abuse.” Nurses were least likely to use SL (4.1%) while physician assistants were most likely (46.9%). Male patients were more likely than female patients to have SL in their notes (adjusted odds ratio [aOR], 1.17; 95% confidence internal [CI], 1.11–1.23), younger patients aged 18 to 24 were less likely to have SL than patients 45 to 54 years (aOR, 0.55; 95% CI, 0.50–0.61), Asian patients were less likely to have SL than White patients (aOR, 0.45; 95% CI, 0.36–0.56), and Hispanic patients were less likely to have SL than non-Hispanic patients (aOR, 0.88; 95% CI, 0.80–0.98).

Conclusions

The majority of patients with substance-related diagnoses had at least one note containing SL. There were also several patient characteristic disparities associated with patients having SL in their notes. The work suggests that more clinician interventions about use of SL are needed.
Examining Efficiency in Open-Bay and Single-Family Room NICU Designs
Authors: Fay Lindsey , Real Kevin , Haynes Shannon , Daneshvar Zahra
Published: January 2023

Background:

There is growing awareness of the relationship between physical work environments and efficiency. Two conflicting factors shape efficiency in the neonatal intensive care unit (NICU) environment: the move to single-family rooms (SFRs) and increased demand for care, requiring growth in unit size.

Purpose:

The goal of this research was to understand the impact of SFR NICUs on efficiency factors such as unit design, visibility and proximity, staff time, and workspace usage by various health professionals.

Methods:

A pre-/postoccupancy evaluation assessed a NICU moving from an open-bay to an SFR unit composed of 6 neighborhoods. A NICU patient care manager and researchers in design and communication implemented a multimethodological design using staff surveys, observations, and focus groups.

Results:

Outcomes revealed SFR NICUs contribute to increased efficiency and overall satisfaction with design. Outside of staff time spent in patient rooms, decentralized nurse stations were the most frequented location for staff work, followed by huddle stations, medication and supply rooms, and corridors. Work at the observed locations was largely performed independently. Survey outcomes reported increased feelings of isolation, but focus groups revealed mixed opinions regarding these concerns.

Implications for Practice and Research:

Design solutions found to enhance efficiency include a neighborhood unit design, standardized access to medications and supplies, and proximity of supplies, patient rooms, and nurse workstations. Although feelings of isolation were reported and most staff work was done independently in the patient room, the SFR unit might not be the culprit when considered alongside staff's desire to be closer to the patient room.
Factors Influencing Parents' Perception of Their Infants' Transition From a 6-Bed Pod to Single Family Room in a Mixed-Room Neonatal Intensive Care Unit
Authors: Crump Laura , Gosselin Émilie , D'addona Melissa , Feeley Nancy
Published: January 2023

Background:

While hospitalized in the neonatal intensive care unit (NICU), infants and their families undergo multiple transitions, and these have been found to be a source of stress for families. Although mixed-room NICU designs allow for infants to benefit from different room types as their needs evolve during their stay, these can necessitate a transfer from one room type to another, which represents a transition for families. As some NICUs change to mixed-room designs, there is a need to better understand the factors impacting these particular transitions from the perception of parents.

Purpose:

Examine parent perceptions of factors affecting the transition from a 6-bed pod to single family room in a mixed-room design NICU.

Methods:

Using a qualitative descriptive design, semistructured interviews were conducted with 17 parents whose infant had transitioned from a 6-bed pod to single family room. Interviews were transcribed verbatim and then analyzed using content analysis.

Results:

Four categories of factors were identified: (1) framing, timing, and comprehensiveness of information provided by staff regarding the transition; (2) parents' perception of advantages and disadvantages of the new space; (3) parent's own well-being and quality of support from staff; and (4) parent's previous NICU and parenting experience.

Implications for Practice:

Staff should frame the information they provide about this transition in a positive way to help parents adjust. A family-centered approach should also be used to provide tailored information and support to individual families.

Implications for Research:

Future studies are needed into intraunit transfers including sources of support for parents, as well as staff perceptions of these transitions.
Cancer prevention: innovative strategies in the role of the European Cancer Prevention Organization
Authors: Corso Giovanni , Janssens Jaak Ph. , La Vecchia Carlo
Published: January 2023

Epidemiological studies demonstrate the key role of cancer prevention in reducing global cancer mortality. However, within Europe there are persisting important disparities in incidence and cancer-related mortality. The future strategy of cancer prevention will aim at reducing these disparities through abolition of tobacco educational campaigns to a correct diet and lifestyle through primary prevention, increasing screening (secondary prevention). We also consider focusing on genetics and precision oncology to identify high-risk individuals, and on tertiary prevention to reduce second cancer risk. The application of these approaches could reduce cancer mortality by 35% and increase cancer survival to 70% in 2070. Tobacco control and abolition remain key measures across Europe.
Promoting Reproducibility and Integrity in Observational Research: One Approach of an Epidemiology Research Community
Authors: Stopsack Konrad H. , Mucci Lorelei A. , Tworoger Shelley S. , Kang Jae H. , Eliassen A. Heather , Willett Walter C. , Stampfer Meir J.
Published: January 2023

To increase research reproducibility, sharing of study data, analysis code, and use of standardized reporting are increasingly advocated. However, beyond reproducibility, few initiatives have addressed the integrity of how research is conducted before manuscripts are submitted. We describe a decades-long experience with a comprehensive approach based in an academic research community around prospective cohort studies that is aimed at promoting a culture of integrity in observational research. The approach includes prespecifying hypotheses and analysis plans, which are discussed in the research community and posted; presentation and discussion of analysis results; mandatory analysis code review by a programmer; review of concordance between analysis output and manuscripts by a technical reviewer; and checks of adherence to the process, including compliance with institutional review board requirements and reporting stipulations by the National Institutes of Health. The technical core is based in shared computing and analytic environments with long-term archiving. More than simply a list of rules, our approach promotes research integrity through integrated educational elements, making it part of the “hidden curriculum,” by fostering a sense of belonging, and by providing efficiency gains to the research community. Unlike reproducibility checklists, such long-term investments into research integrity require substantial and sustained funding for research personnel and computing infrastructure. Our experiences suggest avenues for how institutions, research communities, and funders involved in observational research can strengthen integrity within the research process.