bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study
Authors: Salmela Birgitta , Jaakkola Jussi , Kalatsova Ksenia , Inkovaara Jaakko , Aro Aapo L , Teppo Konsta , Penttilä Tero , Halminen Olli , Haukka Jari , Putaala Jukka , Linna Miika , Mustonen Pirjo , Hartikainen Juha , Airaksinen K E Juhani , Lehto Mika
Published: October 2024

Aims

Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF.

Methods and results

The nationwide Finnish anticoagulation in AF registry-based linkage study covers all patients with new-onset AF in Finland during 2007–2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AADs), cardioversion, or catheter ablation. The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups [adjusted subdistribution hazard ratio (aSHR) 1.223, 95% confidence interval (CI) 1.187–1.261]. Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95% CI 0.695–0.749), more often in patients ≥ 75 years (aSHR 1.166, 95% CI 1.108–1.227), while no difference between the sexes existed in patients aged 65–74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95% CI 0.826–0.998) and ≥75 years (aSHR 0.521, 95% CI 0.354–0.766), whereas there was no difference in patients aged 65–74 years.

Conclusion

Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.
Explaining extreme differences in species richness among co-occurring palm clades in Madagascar
Authors: Eiserhardt Wolf L , Hansen Lars Emil S F , Couvreur Thomas L P , Dransfield John , Ferreira Paola de Lima , Rakotoarinivo Mijoro , Bellot Sidonie , Baker William J
Published: October 2024

Imbalance in species richness among related clades is a pervasive, yet incompletely understood feature of biodiversity. Comparison of species-poor and species-rich clades that have evolved within the same region can shed light on the mechanisms underlying this phenomenon. The long-isolated island of Madagascar is an ideal place for doing this. Madagascar harbours at least ten clades of palms (Arecaceae) that have colonized the island independently and diversified to widely differing degrees, ranging from one to 180 known species. We estimated colonization times and diversification rates for these clades based on an extensive phylogenomic dataset and tested the degree to which clades that arrived in Madagascar earlier have more species (time-for-speciation effect), finding a moderate effect. For context, we tested for time-for-speciation effects in other plant and animal lineages, finding variable but qualitatively similar results. Our findings suggest that variation in diversification rate (i.e. speciation and/or extinction rate) is a major driver of species richness imbalance among Malagasy clades, both in palms and elsewhere. We demonstrate that in palms, differences in diversification rates originated long before colonization of the island, suggesting a minor role of classical ‘island radiation’ and a stronger role of heritable traits driving diversification rate. Ability to colonize new climates also appears to play a role. Future work should address the interplay between the dynamic environment of Madagascar and the inherited traits of colonizing lineages to fully explain the island’s intriguing mix of species-poor and species-rich clades.
Array analysis of P-wave polarization data for constraining near-surface shear wave speeds: Application to the Valley of Mexico seismic network
Authors: Ruelas Adrián , Park Sunyoung , Sánchez-Sesma Francisco J
Published: October 2024

We present an array method for constraining near-surface shear wave speed values from P-wave polarization data. As the direction of P-wave particle motion is determined both by the incident ray parameter and the local surficial shear wave speed, the latter can be inferred from three-component seismic records if the ray parameter is estimated first. Previous studies have analysed data recorded at a single station from various earthquakes in order to estimate near-surface shear wave speed. In contrast, this paper analyses data recorded at an array of stations. As such, this method can estimate both ray parameter data for the recorded earthquakes and near-surface shear wave speed values at the studied sites. And as an advantage, the method can analyse records of local and regional earthquakes where ray parameter information cannot be reliably estimated using 1D reference velocity models. Additionally, by processing polarization data spanning multiple events and stations, our method provides robust estimates for near-surface shear wave speed values. We apply this array-based method to a seismic array covering the Valley of Mexico. Analysed records correspond to regional earthquakes with epicentral distances of roughly 300 km. The corresponding ray parameter values for all earthquakes were estimated from the delay of the seismic waves arrival throughout the network as all stations have a reliable time reference. Near-surface shear wave speed values estimated from the array-based polarization analysis are correlated with major geological features of the area such as the Trans-Mexican Volcanic Belt and the local basin. We also apply the presented method to a minimal data scenario. The flexibility of this method allows it to employ a single ray parameter value as input, producing robust estimates for near-surface shear wave speed values within our case study. This feature becomes useful in a variety of scenarios, such as utilizing seismic data lacking timing information. The presented method constitutes an accessible and inexpensive alternative to study shallow seismic structure, opening opportunities to expand and complement current tools and techniques to assess seismic hazards.
Joint measurement of cosmic-ray muons and seismic waves at laboratory scale
Authors: Matsushima Jun , Kodama Masashi , Ali Mohammed Y , Bouchaala Fateh , Tanaka Hiroyuki K M , Kin Tadahiro , Basiri Hamid , Yokota Toshiyuki , Suzuki Makoto
Published: October 2024

Current geophysical exploration methods face challenges in accurately determining gas saturation levels and elastic constants with adequate spatial resolution. Seismic wave velocity is a critical physical property in these techniques, but it introduces uncertainties because of its composite nature involving density and two elastic constants (e.g. bulk and shear modulus), which exhibit a trade-off relationship. We propose a novel approach that integrates cosmic-ray muon detection with seismic exploration to independently resolve P- and S-wave velocities into their constituent elastic constants and densities. First, we utilized a fluid substitution approach based on Gassmann's model to illustrate the benefits of incorporating density information in predicting gas saturation levels in pores. This supports the advantage of decomposing seismic wave velocity into density and two elastic constants. Second, to validate the applicability and performance of the proposed method, which involves separating seismic wave velocity into density and two types of elastic constants, muon and ultrasonic data were collected in laboratory experiments on two different targets: an acrylic block and an aluminium block. Upon muon observation, a relationship is established to convert muon flux into density length, considering the characteristics of the building housing the laboratory and the direction of muon arrival at specific positions within the building. Although there is potential for enhancing the accuracy of the derived physical properties such as density, bulk modulus, and shear modulus, the feasibility of this method has been successfully demonstrated at the laboratory scale.
Salutogenic mechanisms in nature-based work: fostering sense of coherence for employees with limited capability for work
Authors: Hiemstra Sanne Renske , Naaldenberg Jenneken , de Jonge A , Vaandrager Lenneke
Published: October 2024

Having a job is important for the well-being and inclusion of people with limited capability for work (LCW) due to physical and/or mental disability. This study explores salutogenic mechanisms that contribute to work-related sense of coherence (Work-SoC) of employees with LCW, i.e. perceiving their work in nature as manageable, comprehensible and meaningful. Semi-structured interviews (26 in total) were conducted with employees with LCW, employee supervisors, job coaches and foresters, all working in nature management. Interviews were held at four worksites of a governmental organisation in the Netherlands that provides permanent jobs for people with LCW. Employees with LCW contributed to the design and analysis of the study as co-researchers. Thematic analysis was used and member checks were carried out on preliminary findings. We identified six salutogenic mechanisms that contribute to nature-based Work-SoC of employees with LCW: (i) having constructive working relationships, (ii) experiencing structure and clarity, (iii) receiving practical and emotional support, (iv) support in the creation of meaning, (v) experiencing and learning in practice and (vi) physical activity and (absence of) stimuli. Identified mechanisms can create a positive effect when leveraged, thereby boosting (new) salutogenic mechanisms. Our findings illustrate that nature-based work can provide resources that promote Work-SoC of employees with LCW through the identified mechanisms. However, employees with LCW, colleagues, supervisors and stakeholders must recognize, mobilize and use these resources to leverage identified mechanisms in order to facilitate health-promoting workplaces for people with LCW. This, in turn, can contribute to sustainable inclusion through enablement.
Inequalities in health literacy between European population and newly arrived male sub-Saharan migrants in Europe
Authors: Ferreira-Alfaya Francisco Javier
Published: October 2024

Increases in migration pressure from sub-Saharan Africa to Europe have increased in recent years. Despite this trend, the health literacy needs of migrants in host communities have not been sufficiently studied. This research aims to explore the health literacy of migrants newly arriving in Europe and compare it with the health literacy levels of the European population, utilizing data obtained from the European health literacy survey. A convenience sampling cross-sectional study was conducted at the Temporary Immigrant Stay Center in Melilla (Spain) in June 2022 using a validated French and Arabic version of the 16-item European health literacy survey questionnaire. A total of 106 sub-Saharan migrants ≥ 18 years of age were surveyed. The general health literacy index of the migrants was 30.02 points (on a scale of 50), placing it in the ‘problematic’ level. Of the participants, 57.54% had a limited ability to obtain, understand and apply health information and make appropriate health-related decisions. The largest gap compared to European citizens was observed in skills to understand information related to disease prevention. These results reinforce that migrant status is a social determinant of low health literacy and suggest that health professionals should extend their educational role to this vulnerable group.
Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR)
Authors: Gachet Benoit , Dechartres Agnès , Senneville Eric , Robineau Olivier
Published: October 2024

Background

The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy.

Objective

Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR.

Methods

We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate.

Results

Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients’ populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible.

Conclusion

The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.
Pyruvate stimulates transamination of leucine into α-ketoisocaproic acid and supports 3-methylbutanal production by Lactococcus lactis
Authors: Brandsma Johannes B , Brinkman Judith , Wolkers-Rooijackers Judith C M , van Swam Iris , van Uitert Kim , Zwietering Marcel H , Smid Eddy J
Published: October 2024

Aim

To investigate the effect of pyruvate and glucose on leucine transamination and 3-methylbutanal production by Lactococcus lactis, including the comparison with cells possessing glutamate dehydrogenase (GDH) activity.

Methods and results

Lactococcus lactis cells were incubated in chemically defined medium (CDM) with the pH controlled at 5.2 to mimic cheese conditions. Pyruvate supplementation stimulated the production of the key flavour compound 3-methylbutanal by 3–4 times after 72 h of incubation. Concurrently, alanine production increased, demonstrating the involvement of pyruvate in transamination reactions. Glucose-metabolizing cells excreted α-ketoisocaproic acid and produced even 3 times more 3-methylbutanal after 24 h than pyruvate-supplemented cells. Conjugal transfer technique was used to transfer the plasmid pGdh442 carrying the gdh gene encoding for GDH to L. lactis. Introducing GDH did not stimulate the excretion of α-ketoisocaproic acid and the production of 3-methylbutanal.

Conclusions

These results demonstrate that Lactococcus uses pyruvate to transaminate leucine into α-ketoisocaproic acid which supports 3-methylbutanal production. Surprisingly, GDH activity did not stimulate leucine transamination and 3-methylbutanal production.
Physical activity, metabolites, and breast cancer associations
Authors: Watts Eleanor L , Moore Steven C , Abar Leila , Hong Hyokyoung G , Saint-Maurice Pedro F , O’Connell Caitlin , Matthews Charles E , Loftfield Erikka
Published: October 2024

Background

The effects of usual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites, and breast cancer risk.

Methods

Physical activity levels were assessed using doubly labeled water, accelerometers, and 24-hour recalls in the Interactive Diet and Activity Tracking in AARP (IDATA) Study (N = 707 participants, ages 50-74 years, 51% women), with 1 to 6 assessments over 12 months and 2 blood sample collections. Partial Spearman correlations were used to estimate associations between physical activity and 843 serum metabolites, corrected for multiple testing. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolites with postmenopausal breast cancer in a nested case-control study (621 cases, 621 controls); all statistical tests were 2-sided.

Results

Physical activity was associated with 164 metabolites spanning numerous pathways, including amino acid and fatty acid metabolism. Twelve of these metabolites were also associated with breast cancer risk, 10 of which supported a protective role of physical activity. Notably, higher physical activity was associated with lower 16alpha-hydroxy dehydroepiandrosterone 3-sulfate (sulfated steroid) and adipoylcarnitine (fatty acid), both of which were associated with increased breast cancer risk (OR per 1 standard deviation [SD] = 1.34, 95% CI = 1.16 to 1.55 and 1.26, 1.11 to 1.42, respectively). Higher physical activity energy expenditure was also associated with lower sphingomyelin (d18:1/20:1, d18:2/20:0), which was associated with a reduced breast cancer risk (OR = 0.82, 95% CI = 0.73 to 0.93).

Conclusion

Physical activity is associated with a broad range of metabolites, many of which are consistent with a protective effect against breast cancer. Our findings highlight potential metabolic pathways for cancer prevention.
Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening
Authors: Hu Ping , Prorok Philip C , Katki Hormuzd A
Published: October 2024

Background

Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs.

Methods

We used the Hu-Zelen model, previously used to plan the National Lung Screening Trial (NLST), to estimate mortality reductions, sample size, and power for 9 cancers for different RCT design parameters and MCD test parameters.

Results

Our base-case RCT with 5 yearly screens and 100 000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87%-89% power to detect a 9%-10% mortality reduction (Number Needed to Screen [NNS] = 578-724) over 7-9 years. The majority of prevented deaths were from lung cancers (base-case [64%-66%] and all sensitivity analyses), 8%-10% from colorectal cancer, and 26% from the other 7 cancers, mostly from stomach or ovary or esophagus (due to excellent stage 1 survival) and less from liver or pancreas (poor stage 1 survival) or head and neck or lymphoma (excellent stage 4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage shifts, and mean sojourn times in the preclinical state (especially for lung cancer), but 90% power could be recovered by recruiting a substantially higher risk population.

Conclusions

Large-scale MCD RCTs would have 89% power to detect an approximate 10% cancer mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably with mammographic screening. Most prevented cancer deaths in a well-powered MCD RCT would likely be from lung cancer. Non-lung and non-colorectal cancer sites could be a meaningful proportion of prevented cancer deaths, but power is insufficient to isolate non-lung-cancer mortality reductions.
Precision preclinical modeling to advance cancer treatment
Authors: Gutmann David H , Boehm Jesse S , Karlsson Elinor K , Padron Eric , Seshadri Mukund , Wallis Deeann , Snyder Joshua C
Published: October 2024

A new era of cancer management is underway in which treatments are being developed for the entire continuum of the disease process. The availability of genetically engineered and naturally occurring preclinical models serves as instructive platforms for evaluating therapeutic mechanisms. However, a major clinical challenge is that the entire malignancy process occurs across multiple scales including genetic mutations, malignant changes in cell behavior, dysregulated tumor microenvironments, and systemic adaptations in the host. A multidisciplinary group of investigators coalesced at the National Cancer Institute Oncology Models Forum with the overall goal to provide updates on the use of precision preclinical models of cancer. The benefits and limitations of preclinical models were discussed to identify strategies for maximizing opportunities in modeling that could inform future cancer prevention and treatment approaches. Our shared perspective is that the continuum of single cell, multicell, organoid, and in situ models are remarkable resources for the clinical challenges ahead. We provide a roadmap for parsing already available models and include preliminary recommendations for the application of next-generation preclinical modeling in cancer intervention.
Posttreatment surveillance intensity and overall survival in prostate cancer survivors (AFT-30)
Authors: Chen Ronald C , Basak Ramsankar , Dusetzina Stacie , Usinger Deborah S , Mohammed Zahed , Falchook Aaron D , Schumacher Jessica R , Francescatti Amanda B , Cuddy Amanda , Chang George J , Kozower Benjamin D , Greenberg Caprice C , Barber Anne K , Katz Aaron J
Published: October 2024

Background

Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

Methods

Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer–accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of prostate-specific antigen (PSA) tests in the first year after primary treatment (categorized as 0-1 [low intensity], 2 [medium], or ≥3 [high intensity] PSA tests) was associated with overall survival. Secondary outcomes included recurrence-free survival (RFS) and subsequent use of imaging tests, biopsy procedures, and salvage treatment.

Results

Median follow-up exceeded 8 years from prostate cancer diagnosis. Overall survival was not statistically significantly different across surveillance intensity groups among radiation therapy (P = .59) or radical prostatectomy (P = .29) patients. RFS was not statistically significantly different across surveillance intensity groups for radiation therapy (P = .13) patients but was for radical prostatectomy (P = .01) patients with high intensity associated with the worst RFS. In both treatments, higher surveillance intensity was associated with more procedures and salvage treatments.

Conclusions

In patients with localized prostate cancer, more frequent PSA surveillance testing after radical prostatectomy or radiation therapy was associated with increased procedures and salvage treatments but not overall survival.
Anaerobe-Targeted Antibiotic Therapy in the Neonatal Intensive Care Unit
Authors: Green Matthew B , Zevallos Barboza Alvaro , Mukhopadhyay Sagori , Gerber Jeffrey S , Morowitz Michael J , Puopolo Karen M , Flannery Dustin D
Published: October 2024

Anaerobe-targeted antibiotic (ATA) therapy may adversely impact the developing neonatal microbiome. We describe utilization patterns, potential indications, and related outcomes of ATA therapy in neonatal intensive care units across the United States over 13 years. While overall antibiotic use decreased, ATA use was unchanged. Potentially associated indications were inconsistent.
Media representations of Venezuelan migration in Portugal and Argentina: Between exceptionalism and a returning diaspora
Authors: Padilla Beatriz , França Thais , Melella Cecilia
Published: October 2024

Since the Venezuelan humanitarian crisis, Venezuelan migration to Portugal and Argentina has increased significantly, generating media reactions. Even if media discourses about immigrants in general tend to be negative, Venezuelans seem to be an exception, as the image portrayed tends to be positive, associated either with their highly skilled profile or with their European ancestors. By applying mass-media critical discourse analysis, this article analyses dominant media representations of Venezuelan migrants in Portugal and Argentina between 2015 and 2019, and shows how discourses represent them according to the leading policies that frame migrations in each context of destination. In Portugal, Venezuelans are perceived as Luso-descendants returning home, so they are not specifically targeted by immigration policies but are rather ambiguously included in diaspora policies while abroad; even upon return, they are considered national citizens. In Argentina, Venezuelans are seen as talented migrants who bring along qualifications and entrepreneurship capacity to the country, thus deserving exceptional treatment and solidarity due to the humanitarian crisis caused by the Chavez–Maduro regime. Both examples illustrate how positive media images carry different connotations depending on ideological and policy discourses shaped by local–global historical processes and contexts.
Chemical abundances for a sample of FGK dwarfs in the Pleiades open cluster from APOGEE
Authors: Grilo Vinicius , Souto Diogo , Cunha Katia , Guerço Rafael , Vieira Rodrigo , Smith Verne , Vilar Deusalete , Silva-Andrade Anderson , Wanderley Fábio , Daflon Simone , Silva João Victor Sales
Published: October 2024

This paper presents chemical abundances of 12 elements (C, Na, Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, and Fe) for 80 FGK dwarfs in the Pleiades open cluster, which span a temperature range of $\sim$2000 K in T$_{\rm eff}$, using the high-resolution (R$\sim$22 500) near-infrared SDSS (Sloan Digital Sky Survey)-IV/APOGEE (Apache Point Observatory Galactic Evolution Experiment) spectra ($\lambda$1.51–1.69 $\mu$m). Using a 1D local thermodynamic equilibrium abundance analysis, we determine an overall metallicity of [Fe/H]  = +0.03 $\pm$ 0.04 dex, with the elemental ratios [$\alpha$/Fe]  = +0.01 $\pm$ 0.05, [odd-z/Fe]  = –0.04 $\pm$ 0.08, and [iron peak/Fe]  = –0.02 $\pm$ 0.08. These abundances for the Pleiades are in line with the abundances of other open clusters at similar galactocentric distances as presented in the literature. Examination of the abundances derived from each individual spectral line revealed that several of the stronger lines displayed trends of decreasing abundance with decreasing $T_{\rm eff}$. The list of spectral lines that yield abundances that are independent of $T_{\rm eff}$ are presented and used for deriving the final abundances. An investigation into possible causes of the temperature-dependent abundances derived from the stronger lines suggests that the radiative codes and the APOGEE line list we employ may inadequately model van der Waals broadening, in particular in the cooler K dwarfs.
How to infer ocean freezing rates on icy satellites from measurements of ice thickness
Authors: Shibley Nicole C , Lai Ching-Yao , Culberg Riley
Published: October 2024

Liquid-water oceans likely underlie the ice shells of Europa and Enceladus, but ocean properties are challenging to measure due to the overlying ice. Here, we consider gravity-driven flow of the ice shells of icy satellites and relate this to ocean freeze and melt rates. We employ a first-principles approach applicable to conductive ice shells in a Cartesian geometry. We derive a scaling law under which ocean freeze/melt rates can be estimated from shell-thickness measurements. Under a steady-state assumption, ocean freeze/melt rates can be inferred from measurements of ice thickness, given a basal viscosity. Depending on a characteristic thickness scale and basal viscosity, characteristic freeze/melt rates range from around O(10$^{-1}$) to O(10$^{-5}$) mm/yr. Our scaling is validated with ice-penetrating radar measurements of ice thickness and modelled snow accumulation for Roosevelt Island, Antarctica. Our model, coupled with observations of shell thickness, could help estimate the magnitudes of ocean freeze/melt rates on icy satellites.
Revisiting the effect of lens mass models in cosmological applications of strong gravitational lensing
Authors: Harvey-Hawes Christopher , Wiltshire David L
Published: October 2024

Strong gravitational lens system catalogues are typically used to constrain a combination of cosmological and empirical power-law lens mass model parameters, often introducing additional empirical parameters and constraints from high resolution imagery. We investigate these lens models using Bayesian methods through a novel alternative that treats spatial curvature via the non-FLRW timescape cosmology. We apply Markov Chain Monte Carlo methods using the catalogue of 161 lens systems of Chen et al., in order to constrain both lens and cosmological parameters for: (i) the standard $\Lambda$CDM model with zero spatial curvature; and (ii) the timescape model. We then generate large mock data sets to further investigate the choice of cosmology on fitting simple power-law lens models. In agreement with previous results, we find that in combination with single isothermal sphere parameters, models with zero FLRW spatial curvature fit better as the free parameter approaches an unphysical empty universe, $\Omega _{\mathrm{M}0}\rightarrow 0$. By contrast, the timescape cosmology is found to prefer parameter values in which its cosmological parameter, the present void fraction, is driven to $f_{\mathrm{v}0}\rightarrow 0.73$ and closely matches values that best fit independent cosmological data sets: supernovae Ia distances and the cosmic microwave background. This conclusion holds for a large range of seed values $f_{\mathrm{v}0}\in \lbrace 0.1,0.9\rbrace$, and for timescape fits to both timescape and FLRW mocks. Regardless of cosmology, unphysical estimates of the distance ratios given from power-law lens models result in poor goodness of fit. With larger data sets soon available, separation of cosmology and lens models must be addressed.
How do the successive buckling events affect a galaxy bar and stellar disc? Potential observable signatures for spotting the buckling action – I
Authors: Kataria Sandeep Kumar
Published: October 2024

Until now, observations have caught up only a handful of galaxies in ongoing buckling action. Interestingly, N-body simulations over the past several decades show that almost every bar buckles or vertically thickens as soon as it reaches its peak strength during its evolution and leads to box/peanut/x (BPX) shapes. In order to understand the effect of multiple buckling events on the observable properties of galactic bar and disc, we perform an N-body simulation of a Milky Way-type disc. The axisymmetric galaxy disc forms a bar within a Gyr of its evolution and the bar undergoes two successive buckling events. We report that the time-spans of these two buckling events are 220 Myr and 1 Gyr, which have almost similar strengths of the bending modes. As a result of these two buckling events, the full lengths of BPX shapes are around 5.8 and 8.6 kpc, which are around two-thirds of the full bar length at the end of each buckling event. We find that the first buckling occurs at a smaller scale (radius $\lt $3 kpc) with a shorter time-span affecting the larger length-scales of the disc, which is quantified in terms of changes in $m=$2 and $m=$ 4 Fourier modes. While the second buckling occurs at larger scales (radius $\approx$6 kpc) affecting the inner disc the most. Finally, we provide observable kinematic signatures (i.e. quadrupolar patterns of the line-of-sight velocities), which can potentially differentiate the successive buckling events.
Taurine hypomodification underlies mitochondrial tRNATrp-related genetic diseases
Authors: Lu Jia-Li , Dai Yichen , Ji Kunqian , Peng Gui-Xin , Li Hong , Yan Chuanzhu , Shen Bin , Zhou Xiao-Long
Published: October 2024

Escherichia coli MnmE and MnmG form a complex (EcMnmEG), generating transfer RNA (tRNA) 5-carboxymethylaminomethyluridine (cmnm5U) modification. Both cmnm5U and equivalent 5-taurinomethyluridine (τm5U, catalyzed by homologous GTPBP3 and MTO1) are found at U34 in several human mitochondrial tRNAs (hmtRNAs). Certain mitochondrial DNA (mtDNA) mutations, including m.3243A > G in tRNALeu(UUR) and m.8344A > G in tRNALys, cause genetic diseases, partially due to τm5U hypomodification. However, whether other mtDNA variants in different tRNAs cause a defect in τm5U biogenesis remains unknown. Here, we purified naturally assembled EcMnmEG from E. coli. Notably, EcMnmEG was able to incorporate both cmnm5U and τm5U into hmtRNATrp (encoded by MT-TW), providing a valuable basis for directly monitoring the effects of mtDNA mutations on U34 modification. In vitro, several clinical hmtRNATrp pathogenic mutations caused U34 hypomodification. A patient harboring an m.5541C > T mutation exhibited hmtRNATrp τm5U hypomodification. Moreover, using mtDNA base editing, we constructed two cell lines carrying m.5532G > A or m.5545C > T mutations, both of which exhibited hmtRNATrp τm5U hypomodification. Taurine supplementation improved mitochondrial translation in patient cells. Our findings describe the third hmtRNA species with mutation-related τm5U-hypomodification and provide new insights into the pathogenesis and intervention strategy for hmtRNATrp-related genetic diseases.
GWAShug: a comprehensive platform for decoding the shared genetic basis between complex traits based on summary statistics
Authors: Cao Chen , Tian Min , Li Zhenghui , Zhu Wenyan , Huang Peng , Yang Sheng
Published: October 2024

The shared genetic basis offers very valuable insights into the etiology, diagnosis and therapy of complex traits. However, a comprehensive resource providing shared genetic basis using the accessible summary statistics is currently lacking. It is challenging to analyze the shared genetic basis due to the difficulty in selecting parameters and the complexity of pipeline implementation. To address these issues, we introduce GWAShug, a platform featuring a standardized best-practice pipeline with four trait level methods and three molecular level methods. Based on stringent quality control, the GWAShug resource module includes 539 high-quality GWAS summary statistics for European and East Asian populations, covering 54 945 pairs between a measurement-based and a disease-based trait and 43 902 pairs between two disease-based traits. Users can easily search for shared genetic basis information by trait name, MeSH term and category, and access detailed gene information across different trait pairs. The platform facilitates interactive visualization and analysis of shared genetic basic results, allowing users to explore data dynamically. Results can be conveniently downloaded via FTP links. Additionally, we offer an online analysis module that allows users to analyze their own summary statistics, providing comprehensive tables, figures and interactive visualization and analysis. GWAShug is freely accessible at http://www.gwashug.com.
A compact stem-loop DNA aptamer targets a uracil-binding pocket in the SARS-CoV-2 nucleocapsid RNA-binding domain
Authors: Esler Morgan A , Belica Christopher A , Rollie Joseph A , Brown William L , Moghadasi Seyed Arad , Shi Ke , Harki Daniel A , Harris Reuben S , Aihara Hideki
Published: October 2024

SARS-CoV-2 nucleocapsid (N) protein is a structural component of the virus with essential roles in the replication and packaging of the viral RNA genome. The N protein is also an important target of COVID-19 antigen tests and a promising vaccine candidate along with the spike protein. Here, we report a compact stem-loop DNA aptamer that binds tightly to the N-terminal RNA-binding domain of SARS-CoV-2 N protein. Crystallographic analysis shows that a hexanucleotide DNA motif (5′-TCGGAT-3′) of the aptamer fits into a positively charged concave surface of N-NTD and engages essential RNA-binding residues including Tyr109, which mediates a sequence-specific interaction in a uracil-binding pocket. Avid binding of the DNA aptamer allows isolation and sensitive detection of full-length N protein from crude cell lysates, demonstrating its selectivity and utility in biochemical applications. We further designed a chemically modified DNA aptamer and used it as a probe to examine the interaction of N-NTD with various RNA motifs, which revealed a strong preference for uridine-rich sequences. Our studies provide a high-affinity chemical probe for the SARS-CoV-2 N protein RNA-binding domain, which may be useful for diagnostic applications and investigating novel antiviral agents.
MicroEpitope: an atlas of immune epitopes derived from cancer microbiomes
Authors: Li Donghao , Cai Yangyang , Liu Kefan , Lv Dezhong , Zeng Mengqian , Wen Luan , Lv Chongwen , Guo Jiyu , Xu Kang , Ding Na , Li Yongsheng , Xu Juan
Published: October 2024

The majority of human cancers harbor molecular evidence of intratumoral microbiota. Microbiota-derived epitopes as molecular mimics of tumor antigens can bind human leukocyte antigen (HLA), thereby modulating host immunity. However, many questions remain regarding the mechanisms underlying the interactions between microbiota and the host's immune system in cancer. Here, MicroEpitope (http://bio-bigdata.hrbmu.edu.cn/MicroEpitope) was developed to provide and analyze the atlas of microbiota-derived epitopes in cancer. We manually collected available mass spectrometry (MS)-based HLA immunopeptidomes of 1190 samples across 24 cancer types. Alignment was performed against an in-house constructed theoretical library of human and intratumor microbiome encoded proteins, including 1298 bacterial and 124 viral species. Currently, MicroEpitope contains 51 497 bacteria and 767 virus-derived epitopes, mainly originating from Bacillus subtilis, Buchnera aphidicola and human cytomegalovirus. The common immunogenic features of epitopes were calculated, as well as their biochemical properties and the clinical relevance of corresponding bacteria and viruses across cancers. MicroEpitope also provides five analytical tools, and multiple visualization methods to facilitate understanding of the roles of microbiota-derived epitopes in cancer immunity. In summary, MicroEpitope represents a vital resource for investigating HLA-presented immunopeptidomes derived from cancer microbiomes, and could further enable rich insight in tumor antigen prioritization strategies.
Visualization of Type IV-A1 CRISPR-mediated repression of gene expression and plasmid replication
Authors: Sanchez-Londono Mariana , Rust Selina , Hernández-Tamayo Rogelio , Gomes-Filho José Vicente , Thanbichler Martin , Randau Lennart
Published: October 2024

Type IV CRISPR–Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins) effector complexes are often encoded on plasmids and are proposed to prevent the replication of competing plasmids. The Type IV-A1 CRISPR–Cas system of Pseudomonas oleovorans additionally harbors a CRISPR RNA (crRNA) that tightly regulates the transcript levels of a chromosomal target and represents a natural CRISPR interference (CRISPRi) tool. This study investigates CRISPRi effects of this system using synthetic crRNAs against genome and plasmid sequences. Targeting of reporter genes revealed extended interference in P. oleovorans and Escherichia coli cells producing recombinant CRISPR ribonucleoprotein (crRNP) complexes. RNA sequencing (RNA-seq) analyses of Type IV-A1 CRISPRi-induced transcriptome alterations demonstrated highly effective long-range downregulation of histidine operon expression, whereas CRISPRi effects of dCas9 remained limited to the vicinity of its binding site. Single-molecule microscopy uncovered the localization dynamics of crRNP complexes. The tracks of fluorescently labeled crRNPs co-localized with regions of increased plasmid replication, supporting efficient plasmid targeting. These results identify mechanistic principles that facilitate the application of Type IV-A1 CRISPRi for the regulation of gene expression and plasmid replication.
Effectiveness and Experience of Implementing Digital Interventions to Promote Smoking Cessation Among Adults With Severe Mental Illness: A Systematic Review and Meta-analysis
Authors: Huddlestone Lisa , Shoesmith Emily , Pervin Jodi , Stevens Rosie , Gilbody Simon , Ratschen Elena
Published: October 2024

Introduction

Digital technology is increasingly used to support interventions targeting smoking cessation in people with severe mental illness (SMI). However, little is known about their implementation and effectiveness in this population. We aimed to determine the effectiveness, stakeholder experiences, factors influencing implementation, and quality of reporting of digital interventions for smoking cessation in adults living with SMI.

Methods

Five online bibliographic databases were searched for articles published between December 31, 2000 and January 31, 2023. Studies involving adults accessing treatment for alcohol and substance use disorders, neurocognitive disorders, and terminal illnesses were excluded. Risk of bias was assessed using the Mixed Methods Appraisal Tool. A Mantel–Haenszel random-effects meta-analysis of randomized controlled trials was conducted. Participant experience and intervention implementation were explored using a narrative synthesis. Quality of reporting of interventions was assessed using the Template for Intervention Description and Replication checklist.

Results

Thirty-one studies enrolling 3794 participants were included. Meta-analysis of biochemically verified abstinence at longest follow-up (month 1 to month 6) did not find an overall effect in favour of intervention (risk ratio = 0.66, 95% confidence interval = −0.005 to 1.37). Interventions tailored to people with SMI were perceived as acceptable. Implementation strategies concentrated on overcoming practical challenges at the participant/user level.

Conclusions

No evidence of the effectiveness of digital interventions to support smoking cessation in people with SMI was found. The importance of tailoring interventions to the needs of people with SMI is highlighted. Robust reporting of implementation is required to enhance future efforts to support smoking cessation in adults with SMI.

Implications

The findings of this review add to the emerging evidence on digital interventions to support smoking cessation among people with SMI. We highlight the importance of tailoring interventions to the population, particularly considering the role of mental illness and the side effects of psychotropic medication in the accessibility and usability of digital interventions.
Attenuated melanopsin-mediated post-illumination pupillary response is associated with reduced actigraphic amplitude and mesor in older adults
Authors: Chan Joey W Y , Li Chun-Tung , Chau Steven Wai Ho , Chan Ngan Yin , Li Tim Man-ho , Huang Bei , Tsoh Joshua , Li Shirley X , Chong Kelvin K L , Roecklein Kathryn A , Wing Yun Kwok
Published: October 2024

Study Objectives

This study aimed to explore the relationship between post-illumination pupillary response (PIPR) with sleep and circadian measures in a community sample of healthy older adults.

Methods

Eligible participants were invited to complete a 1 week sleep diary and actigraphy, and provide an overnight urine sample to measure urinary 6-sulfatoxymelatonin (aMT6s). PIPR was defined as the (1) pupil constriction at 6 second poststimulus (PIPR-6s) and (2) for -30s beginning 10 seconds after stimulus (PIPR-30s), normalized as a percentage to the baseline pupil diameter, after 1 second of blue and 1 second of red light stimulus, respectively. The Net-PIPRs were reported by subtracting the PIPR to red stimulus from the PIPR to blue stimulus. The relationship between PIPR metrics to aMT6s and actigraphic rest-activity rhythm parameters was examined by generalized linear models.

Results

A total of 48 participants were recruited (mean age: 62.6 ± 7.1 years, male: 44%). Both Net PIPR-6s and Net PIPR-30s were significantly associated with actigraphic rest-activity amplitude (B = 0.03, p = .001 and B = 0.03, p = .01, respectively) and actigraphic rest-activity mesor (B = 0.02, p = .001 and B = 0.03, p = .004, respectively). Additionally, the Net PIPR-30s were positively associated with overnight aMT6s level (B = 0.04, p = .03) and negatively associated with actigraphic rest-activity acrophase (B = −0.01, p = .004) in the fully adjusted models.

Conclusions

Attenuated PIPR is associated with a reduced actigraphic amplitude and mesor. The reduced retinal light responsivity may be a potential pathway contributing to impaired photic input to the circadian clock and resulted in age-related circadian changes in older adults.
3Digital Humanities
Authors: Roy Dibyadyuti , Deshbandhu Aditya
Published: October 2024

Current conversations around the manifestations of artificial intelligence have led to binary viewpoints that either predict apocalyptic visions of imminent human obsolescence or forthcoming machinic sentience and technological singularity. Amid these polarized perspectives, the materiality of massive digital infrastructures that regularly exploit vulnerable labour forces and the environmental costs driving such emerging forms of digitality are being systematically erased. As a field bridging humanistic enquiry and computational methods, digital humanities finds itself at the epicentre of such debates around the potentials and pitfalls of what artificial intelligence and its futures imply for scholarly and humanistic practices. Therefore, this chapter identifies and reviews interventions from 2023 and early 2024, across both discursive and physical locations, to show how current disciplinary conversations in digital humanities must emerge from both traditional and unconventional sites, which navigate the intersections between artificial and human domains, while emphasizing the provocations and issues that will shape the future of the field.
New theropod dinosaur remains from the Upper Cretaceous of the Kem Kem Group (Eastern Morocco) clarify spinosaurid morphology
Authors: Lacerda Mauro B S , Isasmendi Erik , Delcourt Rafael , Fernandes Marcelo A , Hutchinson John R
Published: October 2024

The Kem Kem Group is a lowermost lithostratigraphic unit from the Upper Cretaceous that extends along the border between Algeria and Morocco, in the northern region of Africa. This geological unit has yielded several tetrapod fossils, including a well-represented assemblage of theropod dinosaurs, after more than eight decades of research. Here, we report new occurrences of spinosaurid theropods from the spinosaurine clade in the Kem Kem Group by providing anatomical descriptions and taxonomic identifications of 11 new specimens derived from the Tafilalt region of Morocco. Among the findings, we describe a cervical vertebra of Sigilmassasaurus, in addition to several cranial, axial, and appendicular elements that can safely be attributed to Spinosaurinae. Moreover, based on a unique combination of characteristics, we also describe an isolated and partial ischium belonging to an indeterminate carcharodontosaurid. We also deliver a detailed redescription of one of the most complete snouts of a spinosaurine known to date. Therefore, the theropod dinosaurs of the Kem Kem Group show considerable diversity, but many questions, especially related to the diversity of spinosaurids and the general abundance of carnivorous dinosaurs in this region, remain unclear until new materials are discovered and complete descriptions are made.