bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study
Authors: Veltmann Christian , Duncker David , Doering Michael , Gummadi Siva , Robertson Michael , Wittlinger Thomas , Colley Byron J , Perings Christian , Jonsson Orvar , Bauersachs Johann , Sanchez Robert , Maier Lars S
Published: June 2024

Background and Aims

In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days.

Methods

Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180.

Results

A total of 598 patients with de novo HFrEF [59 years (interquartile range 51–68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin–angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%–50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%–52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%–72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%–81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers.

Conclusions

Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.
Electroanatomical adaptations in the guinea pig heart from neonatal to adulthood
Authors: Haq Kazi T , McLean Kate , Salameh Shatha , Swift Luther M , Posnack Nikki Gillum
Published: June 2024

Aims

Electroanatomical adaptations during the neonatal to adult phase have not been comprehensively studied in preclinical animal models. To explore the impact of age as a biological variable on cardiac electrophysiology, we employed neonatal and adult guinea pigs, which are a recognized animal model for developmental research.

Methods and results

Electrocardiogram recordings were collected in vivo from anaesthetized animals. A Langendorff-perfusion system was employed for the optical assessment of action potentials and calcium transients. Optical data sets were analysed using Kairosight 3.0 software. The allometric relationship between heart weight and body weight diminishes with age, it is strongest at the neonatal stage (R2 = 0.84) and abolished in older adults (R2 = 1E−06). Neonatal hearts exhibit circular activation, while adults show prototypical elliptical shapes. Neonatal conduction velocity (40.6 ± 4.0 cm/s) is slower than adults (younger: 61.6 ± 9.3 cm/s; older: 53.6 ± 9.2 cm/s). Neonatal hearts have a longer action potential duration (APD) and exhibit regional heterogeneity (left apex; APD30: 68.6 ± 5.6 ms, left basal; APD30: 62.8 ± 3.6), which was absent in adults. With dynamic pacing, neonatal hearts exhibit a flatter APD restitution slope (APD70: 0.29 ± 0.04) compared with older adults (0.49 ± 0.04). Similar restitution characteristics are observed with extrasystolic pacing, with a flatter slope in neonates (APD70: 0.54 ± 0.1) compared with adults (younger: 0.85 ± 0.4; older: 0.95 ± 0.7). Neonatal hearts display unidirectional excitation–contraction coupling, while adults exhibit bidirectionality.

Conclusion

Postnatal development is characterized by transient changes in electroanatomical properties. Age-specific patterns can influence cardiac physiology, pathology, and therapies for cardiovascular diseases. Understanding heart development is crucial to evaluating therapeutic eligibility, safety, and efficacy.
Superior vena cava isolation using a pentaspline pulsed-field ablation catheter: feasibility and safety in patients undergoing atrial fibrillation catheter ablation
Authors: Ollitrault Pierre , Chaumont Corentin , Font Jonaz , Manninger Martin , Conti Sergio , Matusik Paweł T , Mulder Bart A , Ferchaud Virginie , Pellissier Arnaud , Al Khoury Mayane , Milliez Paul , Champ-Rigot Laure , Anselme Frédéric
Published: June 2024

Aims

Superior vena cava (SVC) isolation during atrial fibrillation catheter ablation is limited by the risk of collateral damage to the sinus node and/or the phrenic nerve. Due to its tissue-specificity, we hypothesized the feasibility and safety of pulsed-field ablation (PFA)–based SVC isolation.

Methods and results

One hundred and five consecutive patients undergoing PFA-based AF catheter ablation were prospectively included. After pulmonary vein isolation (±posterior wall isolation and electrical cardioversion), SVC isolation was performed using a standardized workflow. Acute SVC isolation was achieved in 105/105 (100%) patients after 6 ± 1 applications. Transient phrenic nerve stunning occurred in 67/105 (64%) patients but without phrenic nerve palsy at the end of the procedure and at hospital discharge. Transient high-degree sinus node dysfunction occurred in 5/105 (4.7%) patients, with no recurrence at the end of the procedure and until discharge. At the 3-month follow-up visit, no complication occurred.

Conclusion

SVC isolation using a pentaspline PFA catheter is feasible and safe.
Mid-term performance of His bundle pacing and usefulness of backup leads
Authors: Herbert Julia , Kovacsovics Arianne , Brito Rita , Masson Nicolas , Burri Haran
Published: June 2024

Ventricular backup leads may be considered in selected patients with His bundle pacing (HBP), but it remains unknown to what extent this is useful. A total of 184 HBP patients were studied. At last follow-up, 147 (79.9%) patients retained His bundle capture at programmed output. His bundle pacing lead revision was performed in 5/36 (13.9%) patients without a backup lead and in 3/148 (2.0%) patients with a backup lead (P = 0.008). One patient without a backup lead had syncope due to atrial oversensing. Thus, implantation of ventricular backup leads may avoid lead revision and adverse events in selected HBP patients.
A temporal sequence of heterochronic gene activities promotes stage-specific developmental events in Caenorhabditis elegans
Authors: Ivanova Maria , Moss Eric G
Published: June 2024

The heterochronic genes of the nematode Caenorhabditis elegans control the succession of postembryonic developmental events. The 4 core heterochronic genes lin-14, lin-28, hbl-1, and lin-41 act in a sequence to specify cell fates specific to each of the 4 larval stages. It was previously shown that lin-14 has 2 activities separated in time that promote L1 and L2 developmental events, respectively. Using the auxin-inducible degron system, we find that lin-28 and hbl-1 each have 2 activities that control L2 and L3 events which are also separated in time. Relative to events they control, both lin-28 and hbl-1 appear to act just prior to or concurrently with events of the L2. Relative to each other, lin-28 and hbl-1 appear to act simultaneously. By contrast, the lin-14 activity controlling L2 events precedes those of lin-28 and hbl-1 controlling the same events, suggesting that lin-14's regulation of lin-28 is responsible for the delay. Likewise, the activities of lin-28 and hbl-1 controlling L3 fates act well in advance of those fates, suggesting a similar regulatory gap. lin-41 acts early in the L3 to affect fates of the L4, although it was not possible to determine whether it too has 2 temporally separated activities. We also uncovered a feedback phenomenon that prevents the reactivation of heterochronic gene activity late in development after it has been downregulated. This study places the heterochronic gene activities into a timeline of postembryonic development relative to one another and to the developmental events whose timing they control.
Medicare Advantage enrollment and outcomes of post-acute nursing home care among patients with dementia
Authors: Kim Daeho , Meyers David J , Keohane Laura M , Varma Hiren , Achola Emma M , Trivedi Amal N
Published: June 2024

Enrollment in Medicare Advantage (MA) has been rapidly growing. We examined whether MA enrollment affects the outcomes of post-acute nursing home care among patients with Alzheimer's disease and related dementias (ADRD). We exploited year-to-year changes in MA penetration rates within counties from 2012 through 2019. After adjusting for patient-level characteristics and county fixed effects, we found that MA enrollment was not associated with days spent at home, nursing home days, likelihood of becoming a long-stay resident, hospital days, hospital readmission, or 1-year mortality. There was a modest increase in successful discharge to the community by 0.73 percentage points (relative increase of 2.4%) associated with a 10-percentage-point increase in MA enrollment. The results are consistent among racial/ethnic subgroups and dual-eligible patients. These findings suggest an imperative need to monitor and improve quality of managed care among enrollees with ADRD.
Age validation of yellowfin and bigeye tuna using post-peak bomb radiocarbon dating confirms long lifespans in the western and central Pacific Ocean
Authors: Andrews Allen H , Eveson J Paige , Welte Caroline , Okamoto Kei , Satoh Keisuke , Krusic-Golub Kyne , Lougheed Bryan C , Macdonald Jed I , Roupsard Francois , Farley Jessica H
Published: June 2024

Age-reading protocols for tuna species using annual growth zones in thin-cut transverse otolith sections have produced greater age estimates than previous methods. Lifespan estimates for yellowfin (YFT) and bigeye (BET) tuna (Thunnus albacares and T. obesus) were validated up to 16–18 years in the western North Atlantic Ocean using bomb 14C dating and the current study extends the approach to YFT and BET of the western and central Pacific Ocean (WCPO). Archived otoliths from young-of-the-year (YOY) tuna caught in the WCPO were analysed for 14C to establish a reference chronology covering 30 years (1989–2019). This YOY 14C time series exhibited strong concordance with existing coral-otolith 14C references for the tropical-subtropical Pacific Ocean and was combined as a single chronology. Otolith cores from YFT aged 1–14 years and BET aged 1–13 years from presumed annual counts were analysed for 14C. These measurements aligned with the reference chronology for the calculated hatch years for both species. These findings provide strong evidence that growth zones in thin-sectioned otoliths are deposited annually for YFT and BET of the WCPO and that age interpretation is correct using the current age reading protocol with little to no bias.
Precise error bounds for numerical approximations of fractional HJB equations
Authors: Chowdhury Indranil , Jakobsen Espen R
Published: June 2024

We prove precise rates of convergence for monotone approximation schemes of fractional and nonlocal Hamilton–Jacobi–Bellman equations. We consider diffusion-corrected difference-quadrature schemes from the literature and new approximations based on powers of discrete Laplacians, approximations that are (formally) fractional order and second-order methods. It is well known in numerical analysis that convergence rates depend on the regularity of solutions, and here we consider cases with varying solution regularity: (i) strongly degenerate problems with Lipschitz solutions and (ii) weakly nondegenerate problems where we show that solutions have bounded fractional derivatives of order $\sigma \in (1,2)$. Our main results are optimal error estimates with convergence rates that capture precisely both the fractional order of the schemes and the fractional regularity of the solutions. For strongly degenerate equations, these rates improve earlier results. For weakly nondegenerate problems of order greater than one, the results are new. Here we show improved rates compared to the strongly degenerate case, rates that are always better than $\mathcal{O}\big (h^{\frac{1}{2}}\big )$.
On the Picard Group of the Stable Module Category for Infinite Groups
Authors: Gómez Juan Omar
Published: June 2024

We introduce the stable module $\infty $-category for groups of type $\Phi $ as an enhancement of the stable category defined by N. Mazza and P. Symonds. For groups of type $\Phi $ that act on a tree, we show that the stable module $\infty $-category decomposes in terms of the associated graph of groups. For groups that admit a finite-dimensional cocompact model for the classifying space for proper actions, we exhibit a decomposition in terms of the stable module $\infty $-categories of their finite subgroups. We use these decompositions to provide methods to compute the Picard group of the stable module category. In particular, we provide a description of the Picard group for countable locally finite $p$-groups.
Varied Prevalence of Antimalarial Drug Resistance Markers in Different Populations of Newly Arrived Refugees in Uganda
Authors: Tukwasibwe Stephen , Garg Shreeya , Katairo Thomas , Asua Victor , Kagurusi Brian A , Mboowa Gerald , Crudale Rebecca , Tumusiime Gerald , Businge Julius , Alula David , Kasozi Julius , Wadembere Ibrahim , Ssewanyana Isaac , Arinaitwe Emmanuel , Nankabirwa Joaniter I , Nsobya Samuel L , Kamya Moses R , Greenhouse Bryan , Dorsey Grant , Bailey Jeffrey A , Briggs Jessica , Conrad Melissa D , Rosenthal Philip J
Published: June 2024

Newly arrived refugees offer insights into malaria epidemiology in their countries of origin. We evaluated asymptomatic refugee children within 7 days of arrival in Uganda from South Sudan and the Democratic Republic of Congo (DRC) in 2022 for parasitemia, parasite species, and Plasmodium falciparum drug resistance markers. Asymptomatic P. falciparum infections were common in both populations. Coinfection with P. malariae was more common in DRC refugees. Prevalences of markers of aminoquinoline resistance (PfCRT K76T, PfMDR1 N86Y) were much higher in South Sudan refugees, of antifolate resistance (PfDHFR C59R and I164L, PfDHPS A437G, K540E, and A581G) much higher in DRC refugees, and of artemisinin partial resistance (ART-R; PfK13 C469Y and A675V) moderate in both populations. Prevalences of most mutations differed from those seen in Ugandans attending health centers near the refugee centers. Refugee evaluations yielded insights into varied malaria epidemiology and identified markers of ART-R in 2 previously little-studied countries.
Whole-Genome Sequencing of Invasive Neonatal Escherichia coli From Uppsala County, Sweden
Authors: Heydecke Anna , Myrelid Åsa , Normann Erik , Gullsby Karolina , Tano Eva , Sütterlin Susanne
Published: June 2024

Background

This study sought to investigate associations between virulence factors and phylogeny in all neonatal Escherichia coli bloodstream infections from patients admitted to the neonatal intensive care unit at Uppsala University Hospital between 2005 and 2020.

Methods

A total of 37 E. coli isolates from 32 neonates were whole-genome sequenced and analyzed for virulence factors related to extraintestinal E. coli; patient-related data were collected retrospectively from the medical records.

Results

E. coli isolates that belong to phylogroup B2 were associated with mortality (odds ratio [OR], 26; P < .001), extreme prematurity with delivery before gestational week 28 (OR, 9; P < .05), and shock (OR, 9; P < .05) compared with isolates of non-B2 group. Female neonates were more often infected with isolates of phylogroup B2 E. coli compared with male neonates (OR, 7; P = .05). The identification of the genotoxin determinant clb coding for colibactin exhibited strong associations with mortality (OR, 67; P < .005), gestational age (OR, 18; P < .005), and shock (OR, 26; P < .005).

Discussion

The study highlighted the correlation between neonatal E. coli bacteremia caused by phylogroup B2 and the role of colibactin. Results emphasize difference between male and female neonates in E. coli populations in bloodstream infections.
A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study
Authors: De la Rosa-Riestra Sandra , López-Hernández Inmaculada , Pérez-Rodríguez María Teresa , Sousa Adrián , Goikoetxea Agirre Josune , Reguera Iglesias José María , León Eva , Armiñanzas Castillo Carlos , Sánchez Gómez Leticia , Fernández-Natal Isabel , Fernández-Suárez Jonathan , Boix-Palop Lucía , Cuquet Pedragosa Jordi , Jover-Sáenz Alfredo , Sánchez Calvo Juan Manuel , Martín-Aspas Andrés , Natera-Kindelán Clara , del Arco Jiménez Alfonso , Bahamonde Carrasco Alberto , Smithson Amat Alejandro , Vinuesa García David , Martínez Pérez-Crespo Pedro María , López-Cortés Luis Eduardo , Rodríguez-Baño Jesús ,   PROBAC/GEIRAS-SEIMC/SAMICEI, Retamar-Gentil Pilar , Ferrer José Bravo , Reche Isabel , Gea-Lázaro Isabel , Pérez-Camacho Inés , Porto Antonio Sánchez , García Marcos Guzmán , Carral Berta Becerril , de Lucas Esperanza Merino
Published: June 2024

Objectives

Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort.

Methods

A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC.

Results

Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%–14% for 3–7 points, 26%–45% for 8–12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79–0.83) in the DC and 0.80 (0.78–0.83) in the VC.

Conclusions

A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.
Chromosomal and plasmid localization of ileS2 in high-level mupirocin-resistant Staphylococcus pseudintermedius and Staphylococcus aureus isolated from canine and feline origins
Authors: Chanchaithong Pattrarat , Chueahiran Surawit , Pinpimai Komkiew , Sroithongkham Parinya , Leelapsawas Chavin , Indra Rusmin , Yindee Jitrapa , Chuanchuen Rungtip
Published: June 2024

Objectives

To characterize the mobile genetic elements and genetic localization of ileS2 in high-level mupirocin-resistant (Hi-MupR) methicillin-resistant Staphylococcus pseudintermedius (MRSP) and MRSA isolates recovered from canine and feline clinical samples.

Methods

The identification of bacterial species and presence of mecA and ileS2 genes in MRSP and MRSA isolates were performed using MALDI-TOF MS and PCR, respectively. Antimicrobial resistance (AMR) phenotypes were determined by broth microdilution assays. The genome characteristics, ileS2-containing elements and staphylococcal cassette chromosome mec (SCCmec) were illustrated using complete circular genomes obtained from hybrid assembly of Illumina short-reads and Oxford Nanopore Technologies long-reads. These were analysed through phylogenetic and bioinformatics approaches.

Results

A total of 18 MRSP clinical isolates and four MRSA clinical isolates exhibited the Hi-MupR phenotype and carried multiple AMR genes, including mecA and ileS2 genes. MRSP ST182-SCCmec V (n = 6) and ST282-ΨSCCmec57395-t10 (n = 4) contained the ileS2 transposable unit associated with IS257 on the chromosome. Three MRSA ST398-SCCmec V-t034/t4652 isolates carried ∼42 kb pSK41-like ileS2 plasmids, whereas similar ileS2 plasmids lacking tra genes were found in MRSP ST282-ΨSCCmec57395-t72/t21 isolates. Furthermore, a new group of ileS2 plasmids, carried by MRSP ST45-ΨSCCmec57395, ST433-ΨSCCmecKW21-t05 and ST2165-SCCmec IV-t06, and by one MRSA ST398-SCCmec V-t034 strain, shared the plasmid backbone with the cfr/fexA-carrying plasmid pM084526_1 in MRSA ST398.

Conclusions

This study provides the first evidence of ileS2 integration into the S. pseudintermedius chromosome, which is a rare occurrence in staphylococcal species, and plasmids played a pivotal role in dissemination of ileS2 in both staphylococcal species.
Impact of an antimicrobial stewardship programme on antibiotic utilization and resistance burden in patients with acute leukaemia: an 11-year longitudinal cohort study using interrupted time-series analysis
Authors: Lee Raeseok , Nho Dukhee , Cho Sung-Yeon , Park Silvia , Cho Byung-Sik , Kim Hee-Je , Yoon Jae-Ho , Lee Seok , Kim Yoo-Jin , Lee Dong-Gun
Published: June 2024

Background

Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia.

Objectives

To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms.

Methods

We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions.

Results

A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [−70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (−11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: −0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of −0.06 BSI/1000 PD and −0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased.

Conclusions

Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.
FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury
Authors: Penatzer Julia , Steele Lisa , Breuer Julie , Fabia Renata , Hall Mark , Thakkar Rajan K
Published: June 2024

Pediatric burn injuries are a leading cause of morbidity with infections being the most common acute complication. Thermal injuries elicit a heightened cytokine response while suppressing immune function; however, the mechanisms leading to this dysfunction are still unknown. Our aim was to identify extracellular proteins and circulating phosphoprotein expression in the plasma after burn injury to predict the development of nosocomial infection (NI). Plasma was collected within 72 hours after injury from 64 pediatric burn subjects; of these, 18 went on to develop an NI. Extracellular damage-associated molecular proteins, FAS(APO), and protein kinase b (AKT) signaling phosphoproteins were analyzed. Subjects who went on to develop an NI had elevated high-mobility group box 1, heat shock protein 90 (HSP90), and FAS expression than those who did not develop an NI after injury (NoNI). Concurrently, phosphorylated (p-)AKT and mammalian target of rapamycin (p-mTOR) were elevated in those subjects who went on to develop an NI. Quadratic discriminant analysis revealed distinct differential profiles between NI and NoNI burn subjects using HSP90, FAS, and p-mTOR. The area under the receiver-operator characteristic curves displayed significant ability to distinguish between these 2 burn subject cohorts. These findings provide insight into predicting the signaling proteins involved in the development of NI in pediatric burn patients. Further, these proteins show promise as a diagnostic tool for pediatric burn patients at risk of developing infection while additional investigation may lead to potential therapeutics to prevent NI.
AI-powered fire engineering design and smoke flow analysis for complex-shaped buildings
Authors: Zeng Yanfu , Zheng Zhe , Zhang Tianhang , Huang Xinyan , Lu Xinzheng
Published: June 2024

This paper aims to automatize the performance-based design of fire engineering and the fire risk assessment of buildings with large open spaces and complex shapes. We first establish a database of high-quality fire simulations for diverse building shapes with heights up to 60 m and complex atriums with volumes up to 22 400 m³. Then, artificial intelligence (AI) models are trained to predict the soot visibility slices for new fire cases in buildings of different atrium shapes, symmetricities, and volumes. Two deep learning models were demonstrated: the pix2pix generative adversarial network (GAN) and image-prompt diffusion model. Compared with high-fidelity computational fluid dynamics fire modeling, the available safe egress time predicted by both models shows a high accuracy of 92% for random atrium shapes that are not distinct from the training cases, proving their performance in actual design practices. The diffusion model reproduces more flow details of the smoke visibility profiles than GAN, but it takes a longer computational time to render the fire scene. This work demonstrates the potential of leveraging AI technologies in building fire safety design, offering significant cost and time reductions and optimal solution identification.
Franseen needle in endobronchial ultrasound-guided transbronchial needle aspiration: a phase II prospective study
Authors: Shikano Kohei , Ikari Jun , Nakajima Takahiro , Ota Masayuki , Shiko Yuki , Naito Akira , Abe Mitsuhiro , Kawasaki Takeshi , Ikeda Jun-Ichiro , Ozawa Yoshihito , Suzuki Takuji
Published: June 2024

Background

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing.

Methods

A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing.

Results

Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported.

Conclusions

The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study.

Key findings

What is known and what is new? 

What is the implication, and what should change now?
The Original Presidency: A Conception of Administrative Control
Authors: Wurman Ilan
Published: June 2024

The two predominant conceptions of executive power and supervision over the administrative state are inadequate. One maintains that all administrative discretion is the President’s, and that by virtue of the grant of executive power the President can both remove and control the discretion of all subordinate officers. That poses a possible textual problem: it seems to make the Opinions Clause superfluous. The other conception maintains that the President is, at best, a “persuader-in-chief,” with no constitutional right to control administrative discretion or to remove officers tasked with implementing statutory duties. Although this view makes sense of the Opinions Clause, there is no historical evidence for it. The proponents of these two schools of thought have thus been locked in a decades-long stalemate, with competing and irreconcilable paradigms of total control or no control. This Article recovers another, lost way of thinking about presidential power. According to this conception, Congress can insulate inferior officers from removal because they must follow orders. As for principal officers, the President can remove but not control them, at least not directly. There is no constitutional obligation on the part of principal officers to obey; the only inducement is the threat of removal. The Opinions Clause, far from being superfluous, then assures the President the power to acquire information to exercise intelligently the power to remove. In addition to this account’s textual and structural virtues, it appears to have been a relatively widely shared understanding of presidential power at the Founding, enough so to be within the range of plausible original meanings. This understanding of executive power may seem overly formalistic, but it is functionally more desirable than the two competing accounts that allow for total control or total balkanization.
Digitally filtered resonant arguments for deep learning classification of asteroids in secular resonances
Authors: Carruba V , Aljbaae S , Domingos R C , Caritá G , Alves A , Delfino E M D S
Published: June 2024

Node secular resonances, or s-type secular resonances, occur when the precession frequencies of the node of an asteroid and some planets are in commensurability. They are important for changing the proper inclination of asteroids interacting with them. Traditionally, identifying the asteroid resonant status was mostly performed by visual inspection of plots of the time series of the asteroid resonant argument to check for oscillations around an equilibrium point. Recently, deep learning methods based on convolutional neural networks (CNNs) for the automatic classification of images have become more popular for these kinds of tasks, allowing for the classification of thousands of orbits in a few minutes. In this work, we study 11 s-type resonances in the asteroid main belt and in the Hungaria region and focus on the four most diffusive ones. Two secular resonances in the Hungaria region, the 2 · s − s4 − s6 and the s − 2 · s6 + s7 − g6 + g8 overlap, but this has negligible effects in terms of chaotic dynamics. Here, we obtained filtered images of the resonant arguments by filtering out all low-frequency signals with a Butterworth filter. A simple method based on amplitudes and periods of librations can perform a preliminary selection of asteroids in librating orbits. Our results show that CNN models applied to filtered images are much more effective in terms of metrics like accuracy, Precision, Recall, and F1-score than those that use images of osculating resonant arguments. Filtered resonant arguments should be preferentially used to identify asteroids interacting with secular resonances.
Detection of open cluster members inside and beyond tidal radius by machine learning methods based on Gaia DR3
Authors: Noormohammadi M , Khakian Ghomi M , Javadi A
Published: June 2024

In our previous work, we introduced a method that combines two unsupervised algorithms: Density-based spatial clustering of applications with noise (DBSCAN) and Gaussian mixture model (GMM). We applied this method to 12 open clusters based on Gaia Early Data Release 3 (EDR3) data, demonstrating its effectiveness in identifying reliable cluster members within the tidal radius. However, for studying cluster morphology, we need a method capable of detecting members both inside and outside the tidal radius. By incorporating a supervised algorithm into our approach, we successfully identified members beyond the tidal radius. In our current work, we initially applied DBSCAN and GMM to identify reliable members of cluster stars. Subsequently, we trained the random forest algorithm using DBSCAN- and GMM-selected data. Leveraging the random forest, we can identify cluster members outside the tidal radius and observe cluster morphology across a wide field of view. Our method was then applied to 15 open clusters based on Gaia DR3, which exhibit a wide range of metallicity, distances, members, and ages. Additionally, we calculated the tidal radius for each of the 15 clusters using the King profile and detected stars both inside and outside this radius. Finally, we investigated mass segregation and luminosity distribution within the clusters. Overall, our approach significantly improved the estimation of the tidal radius and detection of mass segregation compared to the previous work. We found that in Collinder 463, low-mass stars do not segregate in comparison to high-mass and intermediate-mass stars. Additionally, we detected a peak of luminosity in the clusters, some of which were located far from the centre, beyond the tidal radius.
Mapping the structural landscape of the yeast Ty3 retrotransposon RNA genome
Authors: Andrzejewska-Romanowska Angelika , Gumna Julita , Tykwińska Ewa , Pachulska-Wieczorek Katarzyna
Published: June 2024

Long terminal repeat (LTR)-retrotransposons are significant contributors to the evolution and diversity of eukaryotic genomes. Their RNA genomes (gRNA) serve as a template for protein synthesis and reverse transcription to a DNA copy, which can integrate into the host genome. Here, we used the SHAPE-MaP strategy to explore Ty3 retrotransposon gRNA structure in yeast and under cell-free conditions. Our study reveals the structural dynamics of Ty3 gRNA and the well-folded core, formed independently of the cellular environment. Based on the detailed map of Ty3 gRNA structure, we characterized the structural context of cis-acting sequences involved in reverse transcription and frameshifting. We also identified a novel functional sequence as a potential initiator for Ty3 gRNA dimerization. Our data indicate that the dimer is maintained by direct interaction between short palindromic sequences at the 5′ ends of the two Ty3 gRNAs, resembling the model characteristic for other retroelements like HIV-1 and Ty1. This work points out a range of cell-dependent and -independent Ty3 gRNA structural changes that provide a solid background for studies on RNA structure-function relationships important for retroelement biology.
International regime uncertainty
Authors: Milner Helen V , Voeten Erik
Published: June 2024

Questions about the future of US supremacy, the global spread of liberal democracy, and liberal international economic institutions create what we call ‘international regime uncertainty’: doubts about the fundamental principles, rules, norms, and decision-making procedures that govern areas of international affairs. This includes both probabilistic assessments of the risk that prevailing principles and institutions cease to function but also fundamental uncertainty over what alternative institutional arrangements and governing principles may emerge. Irrespective of actual systemic change, international regime uncertainty can affect transnational economic and political activities by increasing structural policy uncertainty and the probability of bargaining failures. The political uproar over energy transition policies that seemingly violate core principles of the international trade regime illustrates these points.
Cities on a Hill: American Religious Exceptionalism and White Christian Nationalism
Authors: Wilcox Clyde
Published: June 2024

Scholarly attention has shifted from a focus on white evangelicals and the Christian Right to the more pressing threat of white Christian nationalism. In The Everyday Crusade: Christian Nationalism in American Politics, Eric L. McDaniel, Irfan Nooruddin, and Allyson F. Shortle explore the antecedent ideology of American religious exceptionalism. They report that many elements of this ideology are present across the political spectrum, but the strongest believers are distinctive in many ways. American religious exceptionalism can be a basis for a variety of political mobilizations, but it has most recently been used primarily in an effort to deliver Christian nationalist votes to Republican candidates, including Donald Trump.
Syngeneic mesenchymal stem cells loaded with telomerase-dependent oncolytic adenoviruses enhance anti-metastatic efficacy
Authors: Yang Mei-Lin , Hu Che-Yuan , Lee Ya-Che , Chang Chao-Ching , Chen Yi-Cheng , Lee Pei-Ru , Su Bing-Hua , Chen Pi-Che , Shiau Ai-Li , Shieh Gia-Shing , Wu Chao-Liang , Wu Pensee
Published: June 2024

Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites. Since telomerase activity is found in ~90% of human carcinomas, but undetected in normal adult cells, the human telomerase reverse transcriptase gene (TERT) promoter can be exploited for regulating the replication of oncolytic adenoviruses. Here, we evaluated the antitumor effects of syngeneic murine MSCs loaded with the luciferase-expressing, telomerase-dependent oncolytic adenovirus Ad.GS2 (MSC-Ad.GS2) and Ad.GS2 alone on metastatic MBT-2 bladder tumors. MSCs supported a low degree of Ad.GS2 replication, which could be augmented by coculture with MBT-2 cells or tumor-conditioned medium (TCM), suggesting that viral replication is increased when MSC-Ad.GS2 migrates to tumor sites. MBT-2 cells and TCM enhanced viral replication in Ad.GS2-infected MSCs. SDF-1 is a stem cell homing factor. Our results suggest that the SDF-1/STAT3/TERT signaling axis in MSCs in response to the tumor microenvironment may contribute to the enhanced replication of Ad.GS2 carried by MSCs. Notably, we demonstrate the potent therapeutic efficacy of systemically delivered MSC-Ad.GS2 in pleural disseminated tumor and experimental metastasis models using intrapleural and tail vein injection of MBT-2 cells, respectively. Treatment with MSC-Ad.GS2 significantly reduced tumor growth and prolonged the survival of mice bearing metastatic bladder tumors. Since telomerase is expressed in a broad spectrum of cancers, this therapeutic strategy may be broadly applicable.
Effects of Obesity on Systemic Complications After Operative Pelvic Ring Fractures
Authors: Patel Mihir , Fairburn Stevan , McGwin Gerald , Spitler Clay
Published: June 2024

OBJECTIVES:

To determine the effect of obesity on systemic complications after operative pelvic ring injuries.

METHODS:

Design:

Retrospective cohort study.

Setting:

Single level 1 trauma center.

Patient Selection Criteria:

All patients at a level 1 trauma center who underwent operative fixation of a pelvic ring injury from 2015 to 2022 were included. Patients were grouped based on body mass index (BMI) into 4 categories (normal = BMI <25, overweight = BMI 25–30, obese = BMI 30–40, and morbidly obese BMI >40).

Outcome Measures and Comparisons:

Systemic complications including acute respiratory distress syndrome, pneumonia, sepsis, deep venous thrombosis (DVT), pulmonary embolism, ileus, acute kidney injury (AKI), myocardial infarction, and mortality were recorded. Patients who developed a complication were compared with those who did not regarding demographic and clinical parameters to determine risk factors for each complication.

RESULTS:

A total of 1056 patients underwent pelvic ring fixation including 388 normal BMI, 267 overweight, 289 obese, and 112 morbidly obese patients. The average age of all patients was 36.9 years, with a range from 16 to 85 years. Overall, 631 patients (59.8%) were male. The overall complication and mortality rates were 23.2% and 1.4%, respectively. BMI was a significant independent risk factor for all-cause complication with an odds ratio of 1.67 for overweight, 2.30 for obese, and 2.45 for morbidly obese patients. The risk of DVT and AKI was also significantly increased with every weight class above normal with ORs of 5.06 and 3.02, respectively, for morbidly obese patients (BMI >40).

CONCLUSIONS:

This study demonstrated that among patients undergoing pelvic ring fixation, higher BMI was associated with increased risks of overall complication, specifically DVT and AKI. As the prevalence of obesity continues to increase in the population, surgeons should be cognizant that these patients may be at higher risk of certain postoperative complications during the initial trauma admission.

LEVEL OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Lower Extremity Amputation in Fracture-Related Infection
Authors: Carter Karen J. , Yeager Matthew T. , Rutz Robert W. , Benson Elizabeth Marks , Gross Evan G. , Campbell Collier , Johnson Joseph P. , Spitler Clay A.
Published: June 2024

OBJECTIVES:

To analyze demographics, comorbidities, fracture characteristics, presenting characteristics, microbiology, and treatment course of patients with fracture-related infections (FRIs) to determine risk factors leading to amputation.

METHODS:

Design:

Retrospective cohort.

Setting:

Single Level I Trauma Center (2013–2020).

Patient Selection Criteria:

Adults with lower extremity (femur and tibia) FRIs were identified through a review of an institutional database. Inclusion criteria were operatively managed fracture of the femur or tibia with an FRI and adequate documentation present in the electronic medical record. This included patients whose primary injury was managed at this institution and who were referred to this institution after the onset of FRI as long as all characteristics and risk factors assessed in the analysis were documented. Exclusion criteria were infected chronic osteomyelitis from a non-fracture-related pathology and a follow-up of less than 6 months.

Outcome Measures and Comparisons:

Risk factors (demographics, comorbidities, and surgical, injury, and perioperative characteristics) leading to amputation in patients with FRIs were evaluated.

RESULTS:

A total of 196 patients were included in this study. The average age of the study group was 44±16 years. Most patients were men (63%) and White (71%). The overall amputation rate was 9.2%. There were significantly higher rates of chronic kidney disease (CKD; P = 0.039), open fractures (P = 0.034), transfusion required during open reduction internal fixation (P = 0.033), Gram-negative infections (P = 0.048), and FRI-related operations (P = 0.001) in the amputation cohort. On multivariate, patients with CKD were 28.8 times more likely to undergo amputation (aOR = 28.8 [2.27 to 366, P = 0.010). A subanalysis of 79 patients with either a methicillin-sensitive Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) infection showed that patients with MRSA were significantly more likely to undergo amputation compared with patients with methicillin-sensitive Staphylococcus aureus (P = 0.031). MRSA was present in all cases of amputation in the Staphylococcal subanalysis.

CONCLUSIONS:

Findings from this study highlight CKD as a risk factor of amputation in the tibia and femur with fracture-related infection. In addition, MRSA was present in all cases of Staphylococcal amputation. Identifying patients and infection patterns that carry a higher risk of amputation can assist surgeons in minimizing the burden on these individuals.

LEVEL OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study
Authors: Hu Ziwei , Hu Yangyang , Zhang Shuoqi , Dong Li , Chen Xiaoqi , Yang Huiqin , Su Linchong , Hou Xiaoqiang , Huang Xia , Shen Xiaolan , Ye Cong , Tu Wei , Chen Yu , Chen Yuxue , Cai Shaozhe , Zhong Jixin , Dong Lingli
Published: June 2024

Background:

Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.

Methods:

In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.

Results:

In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.

Conclusion:

ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.

Trial Registration:

Chictr.org.cn: ChiCTR2200059599.