bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanosensitive Ion Channel PIEZO1 in Intestinal Epithelial Cells Mediates Inflammation through the NOD-Like Receptor 3 Pathway in Crohn’s Disease
Authors: Liu Qiuyuan , Wang Didi , Yang Xiaodong , Ma Fang , Han Wei , Hu Jing , Mei Qiao
Published: July 2022

Background

Crohn’s disease (CD) is an incurable chronic intestinal inflammatory disease with no recognized cause. It has been reported that the mechanosensitive ion channel PIEZO1 initiates proinflammatory responses. However, little is known about the role of PIEZO1 in CD.

Methods

Ileum biopsies were obtained from 30 patients with CD and 15 healthy volunteers. Clinical data were collected to determine the relationship between CD and PIEZO1. First, HT29 cells were incubated with Yoda1 and GsMTx4 (Grammostola spatulata mechanotoxin 4) to activate and inhibit PIEZO1, respectively. Second, PIEZO1 knockdown was performed using small interfering RNA. Third, calcium imaging, flow cytometry, and immunofluorescence were used to detect intracellular calcium and mitochondrial function. Last, real-time quantitative polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to quantify PIEZO1, proinflammatory cytokines, and NLRP3 (NOD-like receptor 3)–related compounds.

Results

PIEZO1 was highly expressed in the ileum of patients with CD and correlated positively with the Crohn’s Disease Activity Index, platelet count, and hematocrit and fecal calprotectin levels. In HT29 cells, Yoda1 triggered calcium influx, which was inhibited by GsMTx4 treatment and small interfering RNA–mediated PIEZO1 knockdown. Increased calcium concentrations resulted in increased reactive oxygen species accumulation and decreased mitochondrial membrane potential, whereas decreased calcium concentrations caused by GsMTx4 and PIEZO1 knockdown had the opposite effect. Mechanistically, molecules in the NLRP3 pathway were activated in patients with CD and HT29 cells were stimulated by lipopolysaccharide; these effects were reversed by the knockdown of PIEZO1. Finally, PIEZO1 and NLRP3 knockdown decreased proinflammatory cytokine levels in HT29 cells.

Conclusions

PIEZO1 in intestinal epithelial cells caused calcium influx, which resulted in mitochondrial dysfunction and activated the NLRP3 inflammasome, mediating intestinal inflammation.
Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study
Authors: Ong Yi Ying , Tint Mya-Thway , Aris Izzuddin M , Yuan Wen Lun , Chen Ling-Wei , Fortier Marielle V , Choo Jonathan , Ling Lieng Hsi , Shek Lynette , Tan Kok Hian , Gluckman Peter D , Yap Fabian , Chong Yap-Seng , Godfrey Keith M , Chong Mary F-F , Chan Shiao-Yng , Eriksson Johan G , Wlodek Mary E , De Lucia Rolfe Emanuella , Ong Ken K , Michael Navin , Lee Yung Seng
Published: July 2022

Background

Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers.

Methods

In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3–6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child’s sex, gestational age, age at follow-up, and other maternal factors.

Results

Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): −1.31 mmHg (−2.57, −0.06); DBP: −0.79 mmHg (−1.74, 0.15)] and body fat percentage [SBP: −1.46 mmHg (−2.73, −0.19); DBP: −0.80 mmHg (−1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (−1.29, 1.83)]; DBP: −0.14 mmHg (−1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk.

Conclusions

At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.
Histone Deacetylase Inhibition Restores Behavioral and Synaptic Function in a Mouse Model of 16p11.2 Deletion
Authors: Wang Wei , Tan Tao , Cao Qing , Zhang Freddy , Rein Benjamin , Duan Wei-Ming , Yan Zhen
Published: July 2022

Background

Microdeletion of the human 16p11.2 gene locus confers risk for autism spectrum disorders and intellectual disability. How 16p11.2 deletion is linked to these neurodevelopmental disorders and whether there are treatment avenues for the manifested phenotypes remain to be elucidated. Emerging evidence suggests that epigenetic aberrations are strongly implicated in autism.

Methods

We performed behavioral and electrophysiological experiments to examine the therapeutic effects of epigenetic drugs in transgenic mice carrying 16p11.2 deletion (16p11del/+).

Results

We found that 16p11del/+ mice exhibited a significantly reduced level of histone acetylation in the prefrontal cortex (PFC). A short (3-day) treatment with class I histone deacetylase (HDAC) inhibitor MS-275 or Romidepsin led to the prolonged (3–4 weeks) rescue of social and cognitive deficits in 16p11del/+ mice. Concomitantly, MS-275 treatment reversed the hypoactivity of PFC pyramidal neurons and the hyperactivity of PFC fast-spiking interneurons. Moreover, the diminished N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents and the elevated GABAA receptor-mediated synaptic currents in PFC pyramidal neurons of 16p11del/+ mice were restored to control levels by MS-275 treatment.

Conclusions

Our results suggest that HDAC inhibition provides a highly effective therapeutic strategy for behavioral deficits and excitation/inhibition imbalance in 16p11del/+ mice, likely via normalization of synaptic function in the PFC.
Viral Load Dynamics in SARS-CoV-2 Omicron Breakthrough Infections
Authors: Dewald Felix , Detmer Susanne , Pirkl Martin , Hellmich Martin , Heger Eva , Herrmann Maximilian , Lehmann Clara , Zweigner Janine , Klein Florian
Published: July 2022

To determine viral dynamics in Omicron breakthrough infections, we measured severe acute respiratory syndrome coronavirus 2 RNA in 206 double-vaccinated or boostered individuals. During the first 3 days following the onset of symptoms, viral loads were significantly higher (cycle threshold [Ct], 21.76) in vaccinated compared to boostered (Ct, 23.14) individuals (P = .029). However, by performing a longitudinal analysis on 32 individuals over 14 days, no difference in the viral load trajectory was observed between double-vaccinated and boostered patients. Our results indicate that booster immunization results in a reduction in detectable viral loads without significantly changing viral load dynamics over time.
Using a National Burn Registry to Develop a Model for Risk-Adjusted Length of Stay Benchmarking
Authors: Thompson Callie M , Phillips Matthew H , Bessey Palmer Q , Higginson Sara , Hoarle Kimberly , Hsu Naiwei , Phillips Bart , Weber Joan M , Weichmann-Murata Erica , Mandell Samuel P
Published: July 2022

Length of stay (LOS) is a frequently reported outcome after a burn injury. LOS benchmarking will benefit individual burn centers as a way to measure their performance and set expectations for patients. We sought to create a nationwide, risk-adjusted model to allow for LOS benchmarking based on the data from a national burn registry. Using data from the American Burn Association’s Burn Care Quality Platform, we queried admissions from 7/2015 to 6/2020 and identified 130,729 records reported by 103 centers. Using 22 predictor variables, comparisons of unpenalized linear regression and Gradient boosted (CatBoost) regressor models were performed by measuring the R2 and concordance correlation coefficient on the application of the model to the test dataset. The CatBoost model applied to the bootstrapped versions of the entire dataset was used to calculate O/E ratios for individual burn centers. Analyses were run on 3 cohorts: all patients, 10–20% TBSA, >20% TBSA. The CatBoost model outperformed the linear regression model with a test R2 of 0.67 and CCC of 0.81 compared with the linear model with R2=0.50, CCC=0.68. The CatBoost was also less biased for higher and lower LOS durations. Gradient-boosted regression models provided greater model performance than traditional regression analysis. Using national burn data, we can predict LOS across contributing burn centers while accounting for patient and center characteristics, producing more meaningful O/E ratios. These models provide a risk-adjusted LOS benchmarking using a robust data source, the first of its kind, for burn centers.
The Legalization of Cannabis and the Question of Reparations
Authors: Koram Kojo
Published: July 2022

This article surveys the dramatic sea change in the legal status of both the domestic and international cannabis trade over the past decade and asks whether legalization challenges or complements racial capitalism. As the changing status of prohibited drugs not only seeks to correct a historical wrong but also gives rise to a new, highly profitable cross-border commodities market, I analyse whether the variety of policies that are currently being implemented alongside cannabis legalization—from import restrictions to social equity licences—is sufficient to appease the demand for reparations by the communities who suffered the most through the past century of the ‘War on Drugs’. This ‘War on Drugs’ was both historically and structurally weighted towards the reinforcement of racial hierarchies. As it enters into its twilight, I find that an overview of both the international and domestic laws that are being passed in order to introduce a new age of legal, commercial cannabis threatens to lock in the racial inequalities of our global economy, rather than serve as a tool for the advancement of reparative racial justice.
TaGSNE, a WRKY transcription factor, overcomes the trade-off between grain size and grain number in common wheat and is associated with root development
Authors: Khan Nadia , Zhang Yanfei , Wang Jingyi , Li Yuying , Chen Xin , Yang Lili , Zhang Jie , Li Chaonan , Li Long , Ur Rehman Shoaib , Reynolds Matthew P , Zhang Lichao , Zhang Xueyong , Mao Xinguo , Jing Ruilian
Published: July 2022

Wheat is one of the world’s major staple food crops, and breeding for improvement of grain yield is a priority under the scenarios of climate change and population growth. WRKY transcription factors are multifaceted regulators in plant growth, development, and responses to environmental stimuli. In this study, we identify the WRKY gene TaGSNE (Grain Size and Number Enhancer) in common wheat, and find that it has relatively high expression in leaves and roots, and is induced by multiple abiotic stresses. Eleven single-nucleotide polymorphisms were identified in TaGSNE, forming two haplotypes in multiple germplasm collections, named as TaGSNE-Hap-1 and TaGSNE-Hap-2. In a range of different environments, TaGSNE-Hap-2 was significantly associated with increases in thousand-grain weight (TGW; 3.0%) and spikelet number per spike (4.1%), as well as with deeper roots (10.1%) and increased root dry weight (8.3%) at the mid-grain-filling stage, and these were confirmed in backcross introgression populations. Furthermore, transgenic rice lines overexpressing TaGSNE had larger panicles, more grains, increased grain size, and increased grain yield relative to the wild-type control. Analysis of geographic and temporal distributions revealed that TaGSNE-Hap-2 is positively selected in China and Pakistan, and TaGSNE-Hap-1 in Europe. Our findings demonstrate that TaGSNE overcomes the trade-off between TGW/grain size and grain number, leading us to conclude that these elite haplotypes and their functional markers could be utilized in marker-assisted selection for breeding high-yielding varieties.
Digital Humanities and disability: A systematic literature review of cultural accessibility for people with disability
Authors: Pirrone Maria , Centorrino Marco , Galletta Antonino , Sicari Christian , Villari Massimo
Published: July 2022

In recent times, Digital Humanities (DH), together with the discoveries of Information and Communications Technology, have enabled the rediscovery and usability of cultural content with the support of various technologies. However, it was found that not everyone is able to access web platforms or visit cultural sites easily. In particular, the epidemiological Covid-19 crisis has highlighted the retrograde state of culture in terms of accessibility and usability, conditioned by the physical and web browsing limitations that for years weighed on people with disabilities. Therefore, it was decided to investigate how DH might support the cultural accessibility of people with disabilities. In particular, it was decided to carry out a systematic review of the cultural innovations of DH together with a survey on disability and supporting technologies in order to present how to improve the quality of the cultural experience of such a target. This study proceeded with the research and selection of literature on the subject of DH and disability, with the selection, analysis, and correlation of the scientific works included. The reference time frame includes the works produced between 2018 and 2022 consulted on main databases such as Scopus and Web of Science (WoS), screened using the Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement.
The effect of quasar redshift errors on Lyman-α forest correlation functions
Authors: Youles Samantha , Bautista Julian E , Font-Ribera Andreu , Bacon David , Rich James , Brooks David , Davis Tamara M , Dawson Kyle , de la Macorra Axel , Dhungana Govinda , Doel Peter , Fanning Kevin , Gaztañaga Enrique , Gontcho A Gontcho Satya , Gonzalez-Morales Alma X , Guy Julien , Honscheid Klaus , Iršič Vid , Kehoe Robert , Kirkby David , Kisner Theodore , Landriau Martin , Le Guillou Laurent , Levi Michael E , Martini Paul , Muñoz-Gutiérrez Andrea , Palanque-Delabrouille Nathalie , Pérez-Ràfols Ignasi , Poppett Claire , Ramírez-Pérez César , Schubnell Michael , Tarlé Gregory , Walther Michael
Published: July 2022

Using synthetic Lyman-α forests from the Dark Energy Spectroscopic Instrument (DESI) survey, we present a study of the impact of errors in the estimation of quasar redshift on the Lyman-α correlation functions. Estimates of quasar redshift have large uncertainties of a few hundred km s−1 due to the broadness of the emission lines and the intrinsic shifts from other emission lines. We inject Gaussian random redshift errors into the mock quasar catalogues, and measure the auto-correlation and the Lyman-α-quasar cross-correlation functions. We find a smearing of the BAO feature in the radial direction, but changes in the peak position are negligible. However, we see a significant unphysical correlation for small separations transverse to the line of sight which increases with the amplitude of the redshift errors. We interpret this contamination as a result of the broadening of emission lines in the measured mean continuum, caused by quasar redshift errors, combined with the unrealistically strong clustering of the simulated quasars on small scales.
A quantum mechanical calculation of the CN radiative association
Authors: Zhang Shuai , Qin Zhi , Liu Linhua
Published: July 2022

Radiative association of CN is investigated through the quantum mechanical method, including the cross sections and rate coefficients. The ab initio potential energy curves, transition dipole moments, and permanent dipole moments of CN are obtained by the internally contracted multireference configuration interaction method with Davidson correction and aug-cc-pwCV5Z-DK basis set. For the collision of the ground state C (3Pg) and N (4Su) atoms, except for the four previously studied processes including the A2Π → X2Σ+, X2Σ+ → A2Π, A2Π → A2Π, and X2Σ+ → X2Σ+ transitions, four other radiative association processes including b4Π → a4Σ+, a4Σ+ → b4Π, b4Π → b4Π, and a4Σ+ → a4Σ+ transitions are considered. We also considered the collision of the excited C (1Dg) and the ground N (4Su) atoms including the 24Π → 14Σ− process and the collision of the ground C (3Pg) and the excited N (2Du) atoms including 22Π → B2Σ+, 32Π → B2Σ+, and 42Π → B2Σ+ transitions. The temperature population factor is considered to describe the thermal population of the three different dissociation asymptotic energies. The results show that the contribution of the A2Π → X2Σ+ and b4Π → a4Σ+ transitions to the total rate coefficients is significant over the entire temperature range. While considering the collision of C and N involving excited states, the contribution of the 22Π → B2Σ+, 32Π → B2Σ+, and 42Π → B2Σ+ transitions to the total rate coefficients cannot be ignored at the temperature range larger than 10 000 K. Finally, the rate coefficients are fitted to an analytical function for astrochemical reaction modelling.
Chemical abundance of LINER galaxies – metallicity calibrations based on SDSS-IV MaNGA
Authors: Oliveira C B , Krabbe A C , Hernandez-Jimenez J A , Dors O L , Zinchenko I A , Hägele G F , Cardaci M V , Monteiro A F
Published: July 2022

The ionizing source of low-ionization nuclear emission-line regions (LINERs) is uncertain. Because of this, an empirical relation to determine the chemical abundances of these objects has not been proposed. In this work, for the first time, we derived two semi-empirical calibrations based on photoionization models to estimate the oxygen abundance of LINERS as a function of the N2 and O3N2 emission-line intensity ratios. These relations were calibrated using oxygen abundance estimations obtained by comparing the observational emission-line ratios of 43 LINER galaxies (taken from the MaNGA survey) and grids of photoionization models built with the cloudy code assuming post-asymptotic giant branch stars with different temperatures. We found that the oxygen abundance of LINERs in our sample is in the $\rm 8.48 \: \lesssim \: 12+log(O/H) \: \lesssim 8.84$ range, with a mean value of $\rm 12+\log (O/H)=8.65$. We recommend the use of the N2 index to estimate the oxygen abundances of LINERs, since the calibration with this index presented a much smaller dispersion than the O3N2 index. In addition, the estimated metallicities are in good agreement with those derived by extrapolating the disc oxygen abundance gradients to the centre of the galaxies showing that the assumptions of the models are suitable for LINERs. We also obtained a calibration between the logarithm of the ionization parameter and the [O iii]/[O ii] emission-line ratio.
Reaching for the Edge I: probing the outskirts of massive galaxies with HSC, DECaLS, SDSS, and Dragonfly
Authors: Li Jiaxuan , Huang Song , Leauthaud Alexie , Moustakas John , Danieli Shany , Greene Jenny E , Abraham Roberto , Ardila Felipe , Kado-Fong Erin , Lokhorst Deborah , Lupton Robert , Price Paul
Published: July 2022

The outer light (stellar haloes) of massive galaxies has recently emerged as a possible low scatter tracer of dark matter halo mass. To test the robustness of outer light measurements across different data sets, we compare the 1D azimuthally averaged surface brightness profiles of massive galaxies using four independent data sets: the Hyper Suprime-Cam survey (HSC), the Dark Energy Camera Legacy Survey (DECaLS), the Sloan Digital Sky Survey (SDSS), and the Dragonfly Wide Field Survey (Dragonfly). We test the sky subtraction and proposed corrections for HSC and DECaLS. For galaxies at z < 0.05, Dragonfly has the best control of systematics, reaching surface brightness levels of μr ≈ 30 mag arcsec−2. At 0.19 < z < 0.50, HSC can reliably recover individual surface brightness profiles to μr ≈ 28.5 mag arcsec−2 (R = 100–150 kpc in semimajor axis). In a statistical sense, DECaLS agrees with HSC to R > 200 kpc. DECaLS and HSC measurements of the stellar mass contained within 100 kpc agree within 0.05 dex. Finally, we use weak lensing to show that measurements of outer light with DECaLS at 0.19 < z < 0.50 show a similar promise as HSC as a low scatter proxy of halo mass. The tests and results from this paper represent an important step forward for accurate measurements of the outer light of massive galaxies and demonstrate that outer light measurements from DECam imaging will be a promising method for finding galaxy clusters.
Investigating star-formation activity towards the southern H ii region RCW 42
Authors: Kumar Vipin , Vig S , Veena V S , Mohan S , Ghosh S K , Tej A , Ojha D K
Published: July 2022

The star-forming activity in the H ii region RCW 42 is investigated using multiple wavebands, from near-infrared to radio wavelengths. Located at a distance of 5.8 kpc, this southern region has a bolometric luminosity of 1.8 × 106 L⊙. The ionized gas emission has been imaged at low radio frequencies of 610 and 1280 MHz using the Giant Metrewave Radio Telescope, India, and shows a large expanse of the H ii region, spanning 20 × 15 pc2. The average electron number density in the region is estimated to be ∼70 cm−3, which suggests an average ionization fraction of the cloud to be 11 % . An extended green object EGO G274.0649-01.1460 and several young stellar objects have been identified in the region using data from the 2MASS and Spitzer surveys. The dust emission from the associated molecular cloud is probed using Herschel Space Telescope, which reveals the presence of five clumps, C1-C5, in this region. Two millimetre emission cores of masses 380 and 390 M⊙ towards the radio emission peak have been identified towards C1 from the ALMA map at 1.4 mm. The clumps are investigated for their evolutionary stages based on association with various star-formation tracers, and we find that all the clumps are in active/evolved stage.
Forecast of neutrino cosmology from the CSST photometric galaxy clustering and cosmic shear surveys
Authors: Lin Hengjie , Gong Yan , Chen Xuelei , Chan Kwan Chuen , Fan Zuhui , Zhan Hu
Published: July 2022

China Space Station Telescope (CSST) is a forthcoming powerful Stage IV space-based optical survey equipment. It is expected to explore a number of important cosmological problems in extremely high precision. In this work, we focus on investigating the constraints on neutrino mass and other cosmological parameters under the model of cold dark matter with a constant equation of state of dark energy (wCDM), using the mock data from the CSST photometric galaxy clustering and cosmic shear surveys (i.e. 3 × 2 pt). The systematics from galaxy bias, photometric redshift uncertainties, intrinsic alignment, shear calibration, baryonic feedback, non-linear, and instrumental effects are also included in the analysis. We generate the mock data based on the COSMOS catalogue considering the instrumental and observational effects of the CSST, and make use of the Markov chain Monte Carlo method to perform the constraints. Comparing to the results from current similar measurements, we find that CSST 3 × 2 pt surveys can improve the constraints on the cosmological parameters by one order of magnitude at least. We can obtain an upper limit for the sum of neutrino mass Σmν ≲ 0.36 (0.56) eV at 68 per cent (95 per cent) confidence level (CL), and Σmν ≲ 0.23 (0.29) eV at 68 per cent (95 per cent) CL if we ignore the baryonic effect, which is comparable to the Planck results and much better than the current photometric surveys. This indicates that the CSST photometric surveys can provide stringent constraints on the neutrino mass and other cosmological parameters, and the results also can be further improved by including data from other kinds of CSST cosmological surveys.
Bayesian Phylogenetic Inference using Relaxed-clocks and the Multispecies Coalescent
Authors: Flouri Tomáš , Huang Jun , Jiao Xiyun , Kapli Paschalia , Rannala Bruce , Yang Ziheng
Published: July 2022

The multispecies coalescent (MSC) model accommodates both species divergences and within-species coalescent and provides a natural framework for phylogenetic analysis of genomic data when the gene trees vary across the genome. The MSC model implemented in the program bpp assumes a molecular clock and the Jukes–Cantor model, and is suitable for analyzing genomic data from closely related species. Here we extend our implementation to more general substitution models and relaxed clocks to allow the rate to vary among species. The MSC-with-relaxed-clock model allows the estimation of species divergence times and ancestral population sizes using genomic sequences sampled from contemporary species when the strict clock assumption is violated, and provides a simulation framework for evaluating species tree estimation methods. We conducted simulations and analyzed two real datasets to evaluate the utility of the new models. We confirm that the clock-JC model is adequate for inference of shallow trees with closely related species, but it is important to account for clock violation for distant species. Our simulation suggests that there is valuable phylogenetic information in the gene-tree branch lengths even if the molecular clock assumption is seriously violated, and the relaxed-clock models implemented in bpp are able to extract such information. Our Markov chain Monte Carlo algorithms suffer from mixing problems when used for species tree estimation under the relaxed clock and we discuss possible improvements. We conclude that the new models are currently most effective for estimating population parameters such as species divergence times when the species tree is fixed.
Combined Working Memory Training and Transcranial Magnetic Stimulation Demonstrates Low Feasibility and Potentially Worse Outcomes on Delay to Smoking and Cognitive Tasks: A Randomized 2 × 2 Factorial Design Pilot and Feasibility Study
Authors: Lechner William V , Philip Noah S , Kahler Christopher W , Houben Katrijn , Tirrell Eric , Carpenter Linda L
Published: July 2022

Introduction

Repetitive Transcranial Magnetic Stimulation (rTMS) has shown promising results in treating several Substance Use Disorders including Tobacco Use Disorder. However, questions remain regarding how to optimize treatment outcomes. Enhancement of working memory by rTMS is a potential therapeutic mechanism. The current pilot study examined whether rTMS plus a cognitive training program could enhance the effects of rTMS on smoking behaviors using a controlled, factorial design.

Aims and Methods

We hypothesized that cognitive training plus stimulation would improve control over smoking behaviors, resulting in enhanced cognitive performance and increased latency to smoke on a delay to smoking analog task. Using a 2 × 2 factorial design, nicotine dependent smokers (n = 43) were randomized to receive 10 sessions of active (10 Hz) or sham rTMS delivered to the left dorsolateral prefrontal cortex, plus active or sham working memory training (WMT) prior to and following stimulation.

Results

Contrary to hypotheses, we observed a significant interaction effect, indicating that combining the two active interventions (rTMS+WMT) resulted in worse performance on the smoking analog task (B = −33.0, 95% CI = −64.39, −1.61, p < .05), compared to delivering either intervention alone. Additionally, although active rTMS (compared to sham rTMS) improved letter-sequencing performance (B = 1.23, 95% CI = 0.08–2.38, p < .05), and active WMT (compared to sham WMT) improved back-digit task performance (B = 1.53, 95% CI = 0.02–3.05, p < .05), combining interventions worsened the effect of each on a back-digit task (B = −3.01, 95% CI = −5.96, −0.052, p < .05).

Conclusions

These preliminary findings indicate potential iatrogenic effects of combining rTMS and this working memory training intervention and underscore the need for rigorous evaluation of substance specific conceptual frameworks when selecting future combination interventions.

Implications

Counter to hypothesis, this study found no additional benefit of adding a working memory training program to a rTMS protocol in a sample of daily smokers. The combination condition (active rTMS + active training) resulted in worse performance on a delay to smoking analog task and a measure of working memory performance compared to delivering either intervention alone. These preliminary findings inform strategies for optimizing rTMS in smokers and highlight the need for future studies to consider several key components of candidate combination interventions, including effects on regulation of substance use.

Clinical Trial Registration (if any)

The trial was registered at ClinicalTrials.gov (NCT03337113).
A Psychometric Evaluation of the Stanford Expectations of Treatment Scale (SETS) in the Context of a Smoking Cessation Trial
Authors: Ferkin Adam C , Tonkin Sarah S , Maguin Eugene , Mahoney Martin C , Colder Craig R , Tiffany Stephen T , Hawk Larry W
Published: July 2022

Introduction

Although treatment outcome expectancies (TOEs) may influence clinical outcomes, TOEs are rarely reported in the smoking cessation literature, in part because of the lack of validated measures. Therefore, we conducted a psychometric evaluation of TOEs scores with the Stanford Expectations of Treatment Scale (SETS) in the context of a smoking cessation clinical trial.

Methods

Participants were 320 adults enrolled in a randomized controlled trial of extended versus standard pre-quit varenicline treatment for smoking cessation (clinicaltrials.gov ID: NCT03262662). Across an 8-week treatment period, we examined the nature and stability of the factor structure using confirmatory factor analysis (CFA), evaluated discriminant validity by examining correlations with abstinence self-efficacy and positive/negative affect (PA/NA), and assessed internal consistency and test–retest reliability of SETS scores.

Results

CFAs supported a 2-factor structure that was stable (ie, invariant) across weeks. Positive and negative TOEs were each reflected in three-item subscales that exhibited acceptable to excellent internal consistency (Cronbach’s alphas ≥ .77). Positive and negative TOEs were modestly correlated with PA and NA (all |rs| <.27, p < .05). Positive TOEs, but not negative TOEs, were moderately correlated with abstinence self-efficacy (rs = .45 to .61, p < .01). Both positive and negative TOEs scores demonstrated moderate test-retest reliability between assessments (rs = .54 to .72).

Conclusions

SETS scores generally reflect a valid and reliable assessment of positive and negative TOEs in a sample of adults enrolled in a smoking cessation trial. The SETS appears to be a reasonable option for assessing TOEs in future smoking treatment studies.

Implications

Assessments of treatment outcome expectancies are rarely reported in the smoking cessation literature. The present results support the validity and reliability of the SETS scores among adults seeking treatment for their smoking behavior.
The Impact of Standardized Infectious Diseases Consultation on Postsplenectomy Care and Outcomes
Authors: Hale Andrew J , Depo Benjamin , Khan Sundas , Whitman Timothy J , Bullis Sean , Singh Devika , Peterson Katherine , Hyson Peter , Catoe Laura , Tompkins Bradley J , Alston W Kemper , Dejace Jean
Published: July 2022

Background

Patients who receive splenectomy are at risk for overwhelming postsplenectomy infection (OPSI). Guidelines recommend that adult asplenic patients receive a complement of vaccinations, education on the risks of OPSI, and on-demand antibiotics. However, prior literature suggests that a majority of patients who have had a splenectomy receive incomplete asplenic patient care and thus remain at increased risk. This study assessed the impact of standardized involvement of infectious diseases (ID) providers on asplenic patient care outcomes in patients undergoing splenectomy.

Methods

A quasi-experimental study design compared a prospective cohort of patients undergoing splenectomy from August 2017 to June 2021 who received standardized ID involvement in care of the asplenic patient with a historic control cohort of patients undergoing splenectomy at the same institution from January 2010 through July 2017 who did not. There were 11 components of asplenic patient care defined as primary outcomes. Secondary outcomes included the occurrence of OPSI, death, and death from OPSI.

Results

Fifty patients were included in the prospective intervention cohort and 128 in the historic control cohort. There were significant improvements in 9 of the 11 primary outcomes in the intervention arm as compared with the historic controls. Survival analysis showed no statistically significant difference in the incidence of OPSI-free survival between the groups (P = .056), though there was a trend toward improvement in the prospective intervention arm.

Conclusions

Standardized involvement of an ID provider in the care of patients undergoing splenectomy improves asplenic patient care outcomes. Routine involvement of ID in this setting may be warranted.
Applying Lessons Learned From COVID-19 Therapeutic Trials to Improve Future ALI/ARDS Trials
Authors: Wu Qun , Pennini Meghan E , Bergmann Julie N , Kozak Marina L , Herring Kristen , Sciarretta Kimberly L , Armstrong Kimberly L
Published: July 2022

Host-directed therapeutics targeting immune dysregulation are considered the most promising approach to address the unmet clinical need for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). To better understand the current clinical study landscape and gaps in treating hospitalized patients with severe or critical COVID-19, we identified COVID-19 trials developing host-directed therapies registered at ClinicalTrials.gov and discussed the factors contributing to the success vs failure of these studies. We have learned, instead of the one-size-fits-all approach, future clinical trials evaluating a targeted immunomodulatory agent in heterogeneous patients with ALI/ARDS due to COVID-19 or other infectious diseases can use immune-based biomarkers in addition to clinical and demographic characteristics to improve patient stratification and inform clinical decision-making. Identifying distinct patient subgroups based on immune profiles across the disease trajectory, regardless of the causative pathogen, may accelerate evaluating host-directed therapeutics in trials of ALI/ARDS and related conditions (eg, sepsis).
Κey Role of Early Source Control in Candidemic Patients With Sepsis or Septic Shock
Authors: Papadimitriou-Olivgeris Matthaios , Battistolo Julien , Poissy Julien , Coste Alix , Bochud Pierre-Yves , Calandra Thierry , Senn Laurence , Lamoth Frédéric
Published: July 2022

Background

Despite advances in diagnostic and therapeutic approaches, candidemia remains associated with high mortality rates. This study aimed at identifying predictors of mortality among patients with candidemia, with a focus on early interventions that can improve prognosis.

Methods

This was a single-center retrospective study including all adult patients with at least 1 positive blood culture for Candida species from 2014 to 2021.

Results

A total of 222 episodes of candidemia were included. Most candidemias were of unknown origin (36%) or vascular catheter related (29%). Septic shock developed in 29% episodes. Overall, 14-day mortality rate was 23%. In univariate analyses, septic shock was associated with higher 14-day mortality, whereas catheter-related candidemia and early (<72 hours) interventions, such as appropriate antifungal therapy, source control, and infectious diseases consultation, were associated with improved survival. In a Cox multivariate regression model, septic shock (odds ratio [OR], 3.62 [95% confidence interval {CI}, 2.05–6.38]) was associated with higher mortality. While the impact of early antifungal therapy did not reach statistical significance, early (<72 hours) infectious diseases consultation (OR, 0.46 [95% CI, .23–.91]) and early source control (OR, 0.15 [95% CI, .08–.31]) were associated with better survival. Subanalyses showed that the benefits of early source control, specifically catheter removal, were significant among patients with sepsis or septic shock, but not among those without sepsis. These associations remained significant after exclusion of patients who died prematurely or were in palliative care.

Conclusions

Early source control, in particular catheter removal, was a key determinant of outcome among candidemic patients with sepsis or septic shock.
Role of Therapeutic Drug Monitoring in the Treatment of Persistent Mycobacterium abscessus Central Nervous System Infection: A Case Report and Review of the Literature
Authors: Wu En-Ling , Al-Heeti Omar , Hoff Brian M , Williams Janna L , Krueger Karen M , Santoiemma Phillip P , Rhodes Nathaniel J
Published: July 2022

A patient presenting with recurrent ventriculoperitoneal shunt infection was found to have Mycobacterium abscessus growing from cerebrospinal fluid (CSF), which remained persistently positive. Therapeutic monitoring of clarithromycin, imipenem, and linezolid in CSF and plasma revealed lower than expected concentrations, prompting alternative therapy and culture clearance on hospital day 42.
The Role of Imagination and Anticipation in the Acceptance of Computability Proofs: A Challenge to the Standard Account of Rigor
Authors: Weber Keith
Published: July 2022

In a 2022 paper, Hamami claimed that the orthodox view in mathematics is that a proof is rigorous if it can be translated into a derivation. Hamami then developed a descriptive account that explains how mathematicians check proofs for rigor in this sense and how they develop the capacity to do so. By exploring introductory texts in computability theory, we demonstrate that Hamami’s descriptive account does not accord with actual mathematical practice with respect to computability theory. We argue instead for an alternative account in which imagination, anticipation, and interpretations of natural language play roles in establishing mathematical rigor.
Significant fluctuation in the global sulfate reservoir and oceanic redox state during the Late Devonian event
Authors: Cai Chunfang , Xu Chenlu , Fakhraee Mojtaba , Chen Daizhao , Peng Yanyan
Published: July 2022

Ocean sulfate concentration might have fluctuated greatly throughout the Earth’s history and may serve as a window into perturbations in the ocean–atmosphere system. Coupling high-resolution experimental results with an inverse modeling approach, we, here, show an unprecedented dynamic in the global sulfate reservoir during the Frasnian–Famennian (F–F) boundary event, as one of the “Big five” Phanerozoic biotic crises. Notably, our results indicate that, in a relatively short-time scale (∼200 thousand years), seawater sulfate concentration would have dropped from several mM before the Upper Kellwasser Horizon (UKH) to an average of 235 ± 172 μM at the end of the UKH (more than 100 times lower than the modern level) as the result of evaporite deposition and euxinia, and returned to around mM range after the event. Our findings indicate that the instability in the global sulfate reservoir and nutrient-poor oceans may have played a major role in driving the Phanerozoic biological crises.
Measuring racial and ethnic disparities in traffic enforcement with large-scale telematics data
Authors: Cai William , Gaebler Johann , Kaashoek Justin , Pinals Lisa , Madden Samuel , Goel Sharad
Published: July 2022

Past studies have found that racial and ethnic minorities are more likely than White drivers to be pulled over by the police for alleged traffic infractions, including a combination of speeding and equipment violations. It has been difficult, though, to measure the extent to which these disparities stem from discriminatory enforcement rather than from differences in offense rates. Here, in the context of speeding enforcement, we address this challenge by leveraging a novel source of telematics data, which include second-by-second driving speed for hundreds of thousands of individuals in 10 major cities across the United States. We find that time spent speeding is approximately uncorrelated with neighborhood demographics, yet, in several cities, officers focused speeding enforcement in small, demographically nonrepresentative areas. In some cities, speeding enforcement was concentrated in predominantly non-White neighborhoods, while, in others, enforcement was concentrated in predominately White neighborhoods. Averaging across the 10 cities we examined, and adjusting for observed speeding behavior, we find that speeding enforcement was moderately more concentrated in non-White neighborhoods. Our results show that current enforcement practices can lead to inequities across race and ethnicity.
Large-time asymptotics to solutions of a generalized Burgers equation with linear damping on half-line
Authors: Samanta P , Rao Ch. Srinivasa
Published: July 2022

In this article, we investigate an initial-boundary value problem posed for generalized Burgers equation (GBE) with linear damping via the method of matched asymptotic expansions. Asymptotic solutions are constructed for different sub-regions of the domain $x > 0,~ t > 0$. A special solution is derived, and it describes the large-time asymptotic behavior of the solutions of the GBE for certain parametric ranges. We also observe that a stationary solution of the GBE describes the large-time behavior of solutions for certain parametric ranges. The existence and uniqueness of the relevant stationary solution are proved using a shooting argument. A numerical study is presented comparing the numerical solutions (obtained by the method of lines) with the asymptotic solutions constructed.
Comparison of a modified Mogen clamp and classic dorsal slit circumcision under local anesthesia: A clinical study
Authors: Güler Yavuz
Published: July 2022

Background

Currently, although various methods are used, there is no gold standard method for circumcision. Therefore, we developed a modified circumcision clamp inspired by the Mogen clamp suitable for circumcisions performed under local anesthesia in our country. To evaluate its success and complications, we compared our modified Mogen clamp with a dorsal slit circumcision.

Materials and methods

From 2013 to 2017, we retrospectively evaluated 1309 patients who had undergone circumcision; of these, 832 used the modified Mogen clamp method (Group 1) and 477 used the dorsal slit method (Group 2). The patients’ age, surgery duration, minor hemorrhage (not requiring suture or repeated surgical exploration after circumcision but with buffer or clotting solution used), major hemorrhage (hemorrhage requiring suture or exploration), redundant prepuce skin remnants, revision numbers, and family satisfaction values were evaluated and compared between the 2 groups.

Results

Patients were assessed at least 3 times: 1day, 1week, and 1month after circumcision. The mean ages in Groups 1 and 2 were 16.5±22.8 versus 15.5±18.8 months, respectively. The surgical procedure durations were 9.2±1.7 and 15.4±2.5 minutes in Groups 1 and 2, respectively (p < 0.001). Complications were found in 164 (19.7%) versus 81 patients (17.0%) (p = 0.522), including redundant skin in 42 (5.4%) versus 15 patients (3.14%) (p = 0.105) and major hemorrhage in 20 (2.4%) versus 15 patients (3.3%) (p = 0.230) in Groups 1 and 2, respectively.

Conclusion

Under local anesthesia, the circumcision procedure with the modified Mogen clamp can be performed more rapidly than with the dorsal slit, and the cosmetic results are better as the incision line is more regular. All postoperative complications were similar, with problems related to redundant skin occurring more frequently with clamp circumcision.
Penile metastasis in prostate cancer patients: Two case reports, surgical excision technique, and literature review
Authors: Landen Lucas , Devos Gaëtan , Joniau Steven , Albersen Maarten
Published: July 2022

Two cases of penile metastasis from primary prostate cancer in a single center are presented, along with a literature review and description of the excision technique. Despite its rich vascularization, penile metastasis is rare, with 72 new cases from September 2006 to March 2021. There is a wide variety of diagnoses, treatments, and prognoses for penile metastatic lesions. Ga-68 prostatespecific membrane antigen positron emission tomography/computed tomography is the most sensitive imaging tool for detecting metastasis from primary prostate cancer. Magnetic resonance imaging of the penis is the most reliable technique for differentiating penile lesions. Histological diagnosis is mostly performed using fine-needle biopsy aspiration.

Metastasis-directed treatment is not considered to contribute to prolonged survival. Local treatment is feasible and can be offered to symptomatic patients. Owing to a heterogeneous group, defining overall survival is difficult. Survival until 46months after detecting penile metastases is described.
Deep Learning vs manual techniques for assessing left ventricular ejection fraction in 2D echocardiography: validation against CMR
Authors: Saloux Eric , Popoff Alexandre , Langet Hélène , Piro Paolo , Ropert Camille , Gauriau Romane , Stettler Romain , Amzulescu Mihaela Silvia , Pizaine Guillaume , Allain Pascal , Bernard Olivier , Hodzic Amir , Manrique Alain , Craene Mathieu De , Gerber Bernhard L.
Published: July 2022

Structured Abstract

Objective

To evaluate accuracy and reproducibility of 2D echocardiography (2DE) left ventricular (LV) volumes and ejection fraction (LVEF) estimates by Deep Learning (DL) vs. manual contouring and against CMR.

Background

2DE LV manual segmentation for LV volumes and LVEF calculation is time consuming and operator dependent.

Methods

A DL-based convolutional network (DL1) was trained on 2DE data from centre A, then evaluated on 171 subjects with a wide range of cardiac conditions (49 healthy) – 31 subjects from centre A (18%) and 140 subjects from centre B (82%) – who underwent 2DE and CMR on the same day. Two senior (A1 and B1) and one junior (A2) cardiologists manually contoured 2DE end-diastolic (ED) and end-systolic (ES) endocardial borders in the cycle and frames of their choice. Selected frames were automatically segmented by DL1 and two DL algorithms from the literature (DL2 and DL3), applied without adaptation to verify their generalizability to unseen data. Interobserver variability of DL was compared to manual contouring. All ESV, EDV and EF values were compared to CMR as reference.

Results

50% of 2DE images were of good quality. Interobserver agreement was better by DL1 and DL2 than by manual contouring for EF (Lin’s concordance = 0.9 and 0.91 vs. 0.84), EDV (0.98 and 0.99 vs. 0.82), and ESV (0.99 and 0.99 vs. 0.89). LVEF bias was similar or reduced using DL1 (-0.1) vs. manual contouring (3.0), and worse for DL2 and DL3. Agreement between 2DE and CMR LVEF was similar or higher for DL1 vs. manual contouring (Cohen’s kappa = 0.65 vs. 0.61) and degraded for DL2 and DL3 (0.48 and 0.29).

Conclusion

DL contouring yielded accurate EF measurements and generalized well to unseen data, while reducing interobserver variability. This suggests that DL contouring may improve accuracy and reproducibility of 2DE LVEF in routine practice.