bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate-to-severe atopic dermatitis: week 16 results of an open-label randomized efficacy assessor-blinded head-to-head phase IIIb/IV study (Level Up)
Authors: Silverberg Jonathan I , Bunick Christopher G , Hong H Chih-ho , Mendes-Bastos Pedro , Stein Gold Linda , Costanzo Antonio , Ibrahim Nadia , Sancho Cristina , Wu Xiaoqiang , Han Yu , Levy Gweneth , Altman Kathy , Calimlim Brian , Eyerich Kilian
Published: October 2024

Background

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden, despite ongoing systemic treatment.

Objectives

To assess the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) as per its label, and present the week 16 primary analysis results.

Methods

Level Up is a phase IIIb/IV global randomized open-label efficacy assessor-blinded study evaluating UPA vs. DUPI in adolescents and adults with moderate-to-severe AD who had an inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (period 1). Patients on UPA were started on 15 mg and dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥ 4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on or after week 4, or an EASI reduction of at least 75% (EASI 75) on or after week 8. The primary endpoint was simultaneous achievement of an EASI reduction of at least 90% (EASI 90) and WP-NRS 0/1 at week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study.

Results

Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at week 16 was demonstrated with UPA vs. DUPI (19.9% vs 8.9%, respectively; P < 0.001). UPA showed superiority over DUPI for all ranked secondary endpoints, with post hoc analyses exhibiting higher itch response rates as early as day 2. No new safety signals were identified in this period.

Conclusions

Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose-escalated based on clinical response, demonstrated superiority over DUPI per its label for the primary endpoint of simultaneous achievement of near-complete skin clearance (EASI 90) and little-to-no itch (WP-NRS 0/1) at week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. No new safety signals were identified vs. the previously reported safety profiles of UPA and DUPI.
Relationship between CT-derived cervical muscle mass and quality, systemic inflammation, and survival in symptomatic patients undergoing carotid endarterectomy
Authors: Bradley Nicholas A , Dosanj Karamonique , Chan Sharon Yen Ming , Wilson Alasdair , Siddiqui Tamim , Forsythe Rachel , Roxburgh Campbell S D , McMillan Donlad C , Guthrie Graeme J K
Published: October 2024

Background

Sarcopenia appears to be associated with inferior outcomes in surgical conditions. Chronic systemic inflammation confers an inferior long-term prognosis in cardiovascular disease and is associated with the development of sarcopenia. The aim of this study was to describe the prognostic role of sarcopenia assessed using computed tomography (CT)-derived body composition analysis and systemic inflammation in patients undergoing carotid endarterectomy for symptomatic carotid stenosis.

Methods

In this retrospective cohort study, patients undergoing carotid endarterectomy for symptomatic carotid stenosis between 1 January 2011 and 1 October 2021 at four referral centres were included. The C3 skeletal muscle index and C3 skeletal muscle density were recorded from preoperative CT images. Systemic inflammation was assessed using the preoperative systemic inflammatory grade (SIG). The primary outcome was overall mortality during the study interval.

Results

A total of 618 patients were included, with a median follow-up of 69 (interquartile range 34–85) months. On univariable analysis, age greater than or equal to 75 years (P < 0.001), American Society of Anesthesiologists (ASA) grade greater than II (P < 0.001), low C3 skeletal muscle index (P = 0.002), low C3 skeletal muscle density (P < 0.001), SIG greater than or equal to 2 (P < 0.001), and low L3 derived skeletal muscle index (P < 0.001) were associated with increased mortality, whereas body mass index greater than or equal to 25 kg/m2 was associated with decreased mortality (P = 0.023). On multivariable analysis, age 75 years or older (HR 2.17 (95% c.i. 1.58 to 2.97), P < 0.001), ASA grade greater than II (HR 2.06 (95% c.i. 1.35 to 3.12), P < 0.001), low C3 skeletal muscle density (HR 1.84 (95% c.i. 1.33 to 2.54), P < 0.001), and SIG greater than or equal to 2 (HR 1.63 (95% c.i. 1.33 to 1.99), P < 0.001) were independently associated with increased mortality.

Conclusion

Cervical CT-derived muscle mass and density, and markers of systemic inflammation, such as systemic inflammatory grade, may be associated with an inferior long-term prognosis after carotid endarterectomy.
Longitudinal association of depressive symptoms with cognition and neuroimaging biomarkers in cognitively unimpaired older adults, mild cognitive impairment, and Alzheimer’s disease
Authors: Hu Ying , Zhu Ting , Yuan Minlan , Zhu Hongru , Zhang Wei
Published: October 2024

We aimed to longitudinally examine the relationship between depression and cognitive function and investigate the mediating effects of imaging indicators in this relationship. 2,251 subjects with longitudinal assessment of geriatric depression scale, Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating–Sum of Boxes (CDRSB), Alzheimer’s Disease Assessment Scale11, Alzheimer’s Disease Assessment Scale13 and imaging of 3DT1, diffusion tensor imaging, fluid-attenuated inversion recovery, arterial spin labeling, fluorodeoxyglucose positron emission tomography, 18F-AV45-PET, and 18F-AV1451-PET were included from the Alzheimer’s Disease Neuroimaging Initiative database. The multivariate mixed-effects models were employed to analyze the correlation between geriatric depression scale scores, cognitive function, and imaging indicators. The sgmediation software package was utilized to analyze the mediating effects of imaging indicators. The geriatric depression scale was negatively correlated with Mini-Mental State Examination and Montreal Cognitive Assessment, and positively correlated with CDRSB, Alzheimer’s Disease Assessment Scale11, and Alzheimer’s Disease Assessment Scale13 when the subjects were not grouped. The geriatric depression scale was negatively correlated with Montreal Cognitive Assessment and positively correlated with Alzheimer’s Disease Assessment Scal13 in groups with baseline diagnosis of early mild cognitive impairment and late mild cognitive impairment. Furthermore, depression was associated with regional imaging indicators, while cognitive function was linked to broad imaging indicators. Some of these indicators were related to both depression and cognitive function, playing a mediating role in their relationship. Depression was related to cognitive function, especially in subjects with mild cognitive impairment. Some imaging indicators may represent the underlying basis for the association between depression and cognitive function.
Short- and long-term outcomes of patients with acute myocardial infarction complicated by cardiac arrest: a nationwide cohort study 2013–22
Authors: Jortveit Jarle , Andersen Geir Øystein , Halvorsen Sigrun
Published: October 2024

Aims

To assess short- and long-term outcomes of acute myocardial infarction (AMI) complicated by out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA) in a nationwide cohort.

Methods and results

Cohort study of AMI patients admitted to hospitals in Norway 2013–22 registered in the Norwegian Myocardial Infarction Registry. Outcomes were in-hospital and long-term mortality. Cumulative mortality was assessed with the Kaplan–Meier and the life-table methods. Cox regression was used for risk comparisons. Among 105 439 AMI patients (35% women), we identified 3638 (3.5%) patients with OHCA and 2559 (2.4%) with IHCA. The mean age was 65.7 (13.2), 70.9 (12.6), and 70.7 (13.6) years for OHCA, IHCA, and AMI without cardiac arrest (CA), respectively. The median follow-up time was 3.3 (25th, 75th percentile: 1.1, 6.3) years. In-hospital mortality was 28, 49, and 5%, in OHCA, IHCA, and AMI without CA, and the estimated 5-year cumulative mortality was 48% [95% confidence interval (CI) 46–50%], 69% (95% CI 67–71%), and 35% (95% CI 34–35%), respectively. Among patients surviving to hospital discharge, no significant difference in mortality during follow-up was found between OHCA and AMI without CA [adjusted hazard ratio (HR) 1.04, 95% CI 0.96–1.13], while the long-term mortality of AMI patients with IHCA was higher (age-adjusted HR 1.31, 95% CI 1.19–1.45).

Conclusion

In this large, contemporary cohort of AMI patients, in-hospital mortality of patients with OHCA or IHCA was still high. Among patients surviving to hospital discharge, long-term mortality was comparable between OHCA and AMI without CA, while the outcome of patients with IHCA was significantly worse.
Echocardiographic parameters for weaning from extracorporeal membrane oxygenation—the role of longitudinal function and cardiac time intervals
Authors: Tavazzi Guido , Colombo Costanza Natalia Julia , Klersy Catherine , Dammassa Valentino , Civardi Luca , Degani Antonella , Biglia Alessio , Via Gabriele , Camporotondo Rita , Pellegrini Carlo , Price Susanna
Published: October 2024

Aims

Limited data exist on echocardiographic predictors of weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). We aimed to test the performance of different echocardiographic indices to predict weaning from V-A ECMO and free survival after weaning

Methods and results

Observational study including patients with cardiogenic shock submitted to V-AECMO. Echocardiography was performed after V-AECMO placement and daily during the weaning trial to assess cardiac recovery. Echocardiography data after V-A ECMO implantation and during the last weaning trial before V-A ECMO removal were analysed. Besides traditional parameters, total isovolumic time (t-IVT, a left ventricular performance index) and mitral annular plane systolic excursion (MAPSE) were also tested. Seventy-six patients were included. A greater ventricular velocity time integral (LVOT VTI) at baseline was associated with a five-fold increase in weaning success (P < 0.001) as MAPSE lateral >6.15 mm (P = 0.001) did. TAPSE and S′ at tricuspid annulus showed an analogous association. During the weaning trial t-IVT, LVEF, MAPSE, LVOT VTI, and TAPSE all improved significantly (P < 0.001 for all). At regression analysis t-IVT <14.4 s/min (<0.001), LVOT VTI >12.3 cm (P < 0.001), MAPSE > 8.9 mm (P < 0.001), TAPSE > 16 mm (<0.001), and E/eʹ < 15.5 (P = 0.001) were associated with weaning success and free survival after weaning. LVEF did not predict the weaning success and survival at any time-point (P = 0.230).

Conclusion

Longitudinal function, t-IVT and native ejection, measured with LVOT VTI, are reliable parameters to predict weaning success in V-A ECMO whereas the LVEF, although dynamically changing during weaning trial, it is not.
Explosive eruption processes inferred from high-frequency seismic waveforms of eruption tremor and explosion events
Authors: Mori Azusa , Kumagai Hiroyuki
Published: October 2024

We investigated the relation between high-frequency seismic signals and eruption size and duration using seismic data of eruption tremor and explosion events generated during sub-Plinian and Vulcanian eruptions, respectively, at various volcanoes. We estimated source amplitude functions from seismic envelope seismograms in the 5–10 Hz band, in which S waves are assumed to radiate isotropically. Because seismic data associated with explosive eruptions can be contaminated by infrasound signals, we confirmed that contamination did not significantly affect the source amplitude functions quantified from our analysed waveforms. We approximated the source amplitude functions of eruption tremor and explosion events by quadrilateral and triangular shapes. For eruption tremor, the durations of the source amplitude functions increased with decreasing slope of the initial phase, that is between onset and maximum amplitude. For explosion events, both the maximum and cumulative amplitudes of the source amplitude functions increased with increasing slope of the initial phase, but the overall durations clustered around a typical value. Moreover, the initial phase durations of eruption tremor were longer than those of explosion events. Based on eruption models proposed by previous studies, Vulcanian and sub-Plinian eruptions have been thought to be triggered by accumulation of magma at a shallow part in a conduit and mixing of cool mushy magma with hot fresh magma in a reservoir, respectively. The above differences between the source amplitude functions of eruption tremor and explosion events can be explained by the distinct eruption triggering processes of sub-Plinian and Vulcanian eruptions. Our results suggest that source amplitude functions are useful for investigating eruption processes and estimating eruption sizes and durations for seismic eruption monitoring.
Möbius Invariant Y-systems (Cluster Structures) for Miquel Dynamics
Authors: Affolter Niklas C
Published: October 2024

Miquel dynamics is a discrete time dynamics for circle patterns, which relies on Miquel’s six circle theorem. Previous work shows that the evolution of the circle centers satisfy the dSKP equation on the octahedral lattice $A_{3}$. As a consequence, Miquel dynamics is a discrete integrable system. Moreover, Miquel dynamics give rise to a real-valued cluster structure. The evolution of the cluster variables under Miquel dynamics is also called a Y-system in the discrete integrable systems community. If the Y-system is real positive-valued then the circle pattern is accompanied by an invariant dimer model, an exactly solvable model studied in statistical physics. However, while circle patterns are Möbius invariant, the circle centers and the Y-system are not Möbius invariant, which violates the so called transformation group principle. In this article we show that half the intersection points satisfy the dSKP equation as well, and we introduce two new real-valued Y-systems for Miquel dynamics that involve only the intersection points. Therefore, the new Y-systems are Möbius invariant, and thus satisfy the transformation group principle. We also show that the circle centers and intersection points combined satisfy the dSKP equation on the 4-dimensional octahedral lattice $A_{4}$. In addition, we present two more complex-valued Y-systems for Miquel dynamics, which are real-valued in and only in the case of integrable circle patterns. We also investigate the special cases of harmonic embeddings and s-embeddings, which relate to the spanning tree and Ising model, respectively.
Review: Diagnostic Potential for Collaborative Pharyngitis Biomarkers
Authors: Ledeboer Nathan A , Caldwell Jane M , Boyanton Bobby L
Published: October 2024

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology.
Comparative analysis of biofilm bacterial communities developed on different artificial reef materials
Authors: Sajid Sumbal , Zhang Guoqiang , Zhang Zongyao , Chen Lianguo , Lu Yishan , Fang James Kar-Hei , Cai Lin
Published: October 2024

Aims

Artificial reefs play a vital role in restoring and creating new habitats for marine species by providing suitable substrates, especially in areas where natural substrates have been degraded or lost due to declining water quality, destructive fishing practices, and coral diseases. Artificial reef restoration aimed at coral larval settlement is gaining prominence and initially depends on the development of biofilms on reef surfaces. In this study, we hypothesized that different artificial reef materials selectively influence the composition of biofilm bacterial communities, which in turn affected coral larval settlement and the overall success of coral rehabilitation efforts. To test this hypothesis, we evaluated the impact of six different reef-made materials (porcelain, granite, coral skeleton, calcium carbonate, shell cement, and cement) on the development of biofilm bacterial communities and their potential to support coral larval settlement.

Methods and results

The biofilm bacterial communities were developed on different artificial reef materials and studied using 16S rRNA gene amplicon sequencing and analysis. The bacterial species richness and evenness were significantly (P < 0.05) low in the seawater, while these values were high in the reef materials. At the phylum level, the biofilm bacterial composition of all materials and seawater was majorly composed of Pseudomonadota, Cyanobacteria, and Bacteroidetes; however, significantly (P < 0.05) low Bacteroidetes were found in the seawater. At the genus level, Thalassomonas, Glaciecola, Halomicronema, Lewinella, Hyphomonas, Thalassospira, Polaribacter, and Tenacibaculum were significantly (P < 0.05) low in the coral skeleton and seawater, compared to the other reef materials. The genera Pseudoaltermonas and Thalassomonas (considered potential inducers of coral larval settlement) were highly abundant in the shell-cement biofilm, while low values were found in the biofilm of the other materials.

Conclusion

The biofilm bacterial community composition can be selective for different substrate materials, such as shell cement exhibited higher abundances of bacteria known to facilitate coral larval settlement, highlighting their potential in enhancing restoration outcomes.
Advancing patient-centered clinical decision support in today’s health care ecosystem: key themes from the Clinical Decision Support Innovation Collaborative’s 2023 Annual Meeting
Authors: Dullabh Prashila , Dhopeshwarkar Rina , Cope Elizabeth , Gauthreaux Nicole , Zott Courtney , Peterson Caroline , Leaphart Desirae , Hoyt Sarah , Hammer Amy , Ryan Sofia , Swiger James , Lomotan Edwin A , Desai Priyanka ,   CDSiC Annual Meeting Planning Committee, Adams Lauren , Catlett Marley , Correa Kiran , Dungan Rachel , Gordon Janna , Heaney-Huls Krysta , Jiménez Frances , Jones Troi , Weinberg Sarah
Published: October 2024

Objective

This perspective summarizes key themes that arose from stakeholder discussions at the inaugural Clinical Decision Support Innovation Collaborative (CDSiC) 2023 Annual Meeting. The CDSiC is an Agency for Healthcare Research and Quality (AHRQ)-funded innovation hub for patient-centered clinical decision support (PC CDS).

Materials and Methods

The meeting took place on May 16-17, 2023, and engaged 73 participants that represented a range of stakeholder groups including researchers, informaticians, federal representatives, clinicians, patients, and electronic health record developers. Each meeting session was recorded and had 2 notetakers. CDSiC leadership analyzed the compiled meeting notes to synthesize key themes.

Results

Participants discussed 7 key opportunities to advance PC CDS: (1) establish feedback loops between patients and clinicians; (2) develop new workflows; (3) expand the evidence base; (4) adapt the CDS Five Rights for the patient perspective; (5) advance health equity; (6) explore perceptions on the use of artificial intelligence; and (7) encourage widespread use and scalability of PC CDS.

Discussion and Conclusion

Innovative approaches are needed to ensure patients’ and caregivers’ voices are meaningfully included to advance PC CDS.
The Influence of Muscle Wasting on Patient Outcomes among Burn Patients: A Burn Care Quality Platform Study
Authors: Blears Elizabeth , Murton Andrew , Caffery Julie
Published: October 2024

The hypermetabolism that occurs after large burns leads to muscle wasting that can result in weakness, difficulty fighting infections, and other challenges to healing. Overall, rates of muscle wasting are not well established across burn centers. The Burn Care Quality Platform (BCQP), the largest available dataset on burn patients globally, was used to explore the rate of Muscle Wasting using data collected from more than 100 burn centers. “Muscle Wasting” was defined from relevant ICD codes (sarcopenia, muscle cachexia, protein malnutrition). Binomial and logistic regression were used to analyze the role of Muscle Wasting in burn mortality and other outcomes after controlling for demographic and comorbid characteristics. In total, the BCQP provided data from 84 438 adult and pediatric burn patients injured between 2000 and 2018. Only 2.6% (N = 2159) of the patients in the BCQP were diagnosed with having Muscle Wasting at some point during their admission. While Muscle Wasting was not associated with a statistically significant impact on mortality, it remained an independent predictor of inability to discharge to independent living, longer inpatient days, as well as an average of 10 additional surgical procedures (P < .001 for all) as compared to patients who did not have Muscle Wasting. Muscle Wasting is an independent risk factor for several adverse outcomes in burn patients, but not mortality in the BCQP. Confidence in these findings would be improved with more accurate data collection, as the diagnosis of Muscle Wasting is likely under-reported, under-diagnosed, or both.
Therapy with transitions from one bone-forming agent to another: a retrospective cohort study on teriparatide and romosozumab
Authors: Kobayakawa Tomonori , Kanayama Yasuhide , Hirano Yuji , Yukishima Toshitaka , Nakamura Yukio
Published: October 2024

This study aimed to evaluate the effectiveness of sequential therapy with a bone formation-promoting agent (either teriparatide or romosozumab) for osteoporosis treatment following prior treatment with the other bone-forming agent (teriparatide or romosozumab). This is a multicenter retrospective cohort study observing 2 groups for comparison: one with 69 patients transitioning from teriparatide to romosozumab (the T2R group) and the other with 25 patients transitioning from romosozumab to teriparatide (the R2T group), monitored for 12 months on the second drug. Key outcomes included changes in bone mineral density (BMD), bone turnover marker changes, and adverse events. The mean ages of each group were 72.3 years in the T2R group and 67.6 years in the R2T group, with the proportions of women being 91.3% and 80.0%, respectively. The percent changes of BMD in the lumbar spine after 12 months of sequential therapy were +10.8% in the T2R group (p < .001 versus baseline) and −0.0% in the R2T group (p = .875). The percent changes in BMD in the total hip and femoral neck were +4.4% and +4.4% in the T2R group, and −1.3% and −0.8% in the R2T group, respectively. When comparing the 2 groups, BMD changes at all sites in the T2R group were significantly higher than those in the R2T group (p < .001). Furthermore, when examining the changes in the proportion of patients who achieved the osteoporosis treatment goal of a T-score exceeding −2.5, no significant increase was observed in the R2T group, whereas a significant increase was observed in the lumbar spine in the T2R group. Regarding therapy switching between bone-forming agents, this study suggests that transitioning from teriparatide to romosozumab increases BMD more effectively than transitioning in the opposite sequence.
Computational analysis of unsteady oscillatory flow of nanofluid with variable electric conductivity: gear-generalized differential quadrature approach
Authors: Afridi Muhammad Idrees , Khan Muhammad Sabaoon , Qasim Muhammad , Chamkha Ali J
Published: October 2024

This study numerically investigated the entropy production in nanofluids’ dissipative unsteady oscillatory flow characterized by variable electric conductivity and magnetic heating effects. The imposition of the non-isothermal boundary condition on the oscillatory stretching sheet plays a crucial role in establishing the self-similar solution in the presence of viscous heating. An external magnetic field (uniform in space and time) is imposed perpendicular to the plane of the oscillating stretched boundary. The energy equation, incorporating viscous dissipation effects and momentum equation, is reduced to nonlinear coupled partial differential equations and numerically solved using the Gear-generalized differential quadrature scheme.Additionally, to ensure the precision and reliability of the outcomes, the numerical code undergoes a thorough validation process that involves comparing its outputs to the findings of previous available studies. The Corcione model is implemented to describe the nanofluid’s effective viscosity and thermal conductivity. Furthermore, expressions for entropy production and relative irreversibility parameter (Bejan number), considering variable electric conductivity, are derived and computed based on solutions obtained from momentum and energy equations. The impacts of parameters such as magnetic parameter, variable electric conductivity parameter, Eckert number, Strouhal number, Prandtl number and temperature difference parameters on flow, heat transfer, entropy generation, and Bejan number are systematically illustrated and examined. We observed that increasing the variable electric conductivity parameters reduces the velocity profiles while improving the thermal fields. Similar behavior is found when the strength of a magnetic field is increased. The skin friction coefficient exhibits an augmentation in response to the Eckert number, dimensionless time, Strouhal number, nanoparticle volume fraction, magnetic parameter, and variable thermal conductivity parameter. Conversely, the Nusselt number increases concerning the Strouhal number and nanoparticle volume fraction. At the same time, it declines in association with the magnetic parameter, dimensionless time, Eckert number, and variable electric conductivity parameter.This comprehensive investigation enhances our understanding of nanofluid dynamics and provides valuable insights for optimizing thermal management systems across various engineering disciplines.
Systematic review of associations between anxiety, depression, and functional/biological aging among cancer survivors
Authors: Streck Brennan Parmelee , Sass Dilorom , Brick Rachelle , Fisk Leah , Livinski Alicia A , Guida Jennifer L
Published: October 2024

Background

Evidence suggests a mind-body component to aging through which psychological distress from anxiety and depression drives molecular changes that promote early decline (ie, accelerated aging). Cancer survivors experience particularly high rates of anxiety and depression. Some survivors also have accelerated aging, though the relationships between anxiety and depression and aging are not clear. A synthesis of evidence is needed to understand the state of the science and impending priorities.

Methods

PubMed, Embase, CINAHL, Web of Science, and PsycNet databases were searched for studies that measured associations between depression, anxiety, and nonchronological aging in cancer survivors (2012-2022). Data were methodologically evaluated.

Results

Survivorship studies were included if they were peer reviewed, published in English from 2012 to 2022, and measured associations between anxiety and depression and aging. In total, 51 studies were included. Just over half were cross-sectional (53%). Foci included functional (n = 35 [69%]) and biological (n = 16 [31%]). Functional aging measures included frailty, sarcopenia, geriatric assessment, and cognition. Biological aging measures included telomere length, telomerase, age-related inflammatory blood-based biomarkers, renal insufficiency, anemia, and DNA methylation. We tested 223 associations. Associations between anxiety, depression, and aging were generally positive, though with varying strengths. Most compelling were associations between functional aging and depression. There were concerns for selection and measurement biases.

Conclusions

Findings suggest positive associations between anxiety, depression, and aging among cancer survivors. Future work is needed to clarify temporality, develop a consensus on the measurement of aging, and diversify cohorts.
Alleviating vascular calcification with Bushen Huoxue formula in rats with chronic kidney disease by inhibiting the PTEN/PI3K/AKT signaling pathway through exosomal microRNA-32
Authors: Guo Xingyun , Liu Shiwei , Wu Xiaoyi , Yang Ronglu , Ren Qiuyue , Zhou Yanyan , Shi Kaifeng , Yuan Lisha , Zhang Ning , Liu Shiyi
Published: October 2024

Background

Vascular calcification (VC) significantly raises cardiovascular mortality in chronic kidney disease (CKD) patients. VC is characterized by the phenotypic transformation of vascular smooth muscle cells (VSMCs) to osteoblast-like cells, mediated by exosomes derived from calcified VSMCs and the exosomal microRNAs (miRNA) which may trigger some signals to recipient VSMCs. Bushen Huoxue (BSHX) formula has demonstrated its clinical efficacy in CKD and its protective role in CKD-VC rats has also been observed. However, little is known about its underlying mechanism.

Methods

To establish a VC model, aortic VSMCs from rats were induced to osteogenic differentiation by high-level phosphate (HP) in vitro. The expression of exosome and calcification makers were analyzed by western blot, including CD9, CD63, α-SMA, BMP-2, and Runx2, respectively. Differential expression of exosomal miRNAs in normal and HP-induced VSMCs were identified by using whole miRNA microarray technology. GO and KEGG analyses were performed to determine the significant enrichment of functions and signaling pathways in the target genes. In vivo, the CKD-VC rat model was established by administering adenine gavage combined with a high phosphorus diet. The rats were divided into normal control, model, low-dose BSHX, medium-dose BSHX, high-dose BSHX groups, and sevelamer groups. The blood biochemical parameters were measured. Renal histopathology and aortic calcification were observed. Western blot detected the levels of the calcification markers. Quantitative real–time PCR (qPCR) assay detected exosomal microRNA-32 (miR-32) mRNA expression in the aorta, the most differentially expressed exosomal miRNA previously identified. Phosphatase and tensin homolog located on chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway components were also tested by western blot.

Results

Exosomal miRNA-32 and PI3K/AKT signaling pathways were highly differentially expressed between normal and HP-induced VSMCs. In vivo, BSHX improved blood biochemical parameters, renal histopathology, and aortic calcification in CKD-VC rats. BSHX increased the expression level of α-SMA and decreased the level of BMP-2 and Runx2. BSHX also lowered the expression level of exosomal miR-32 mRNA, enhanced PTEN expression, therefore, reduced p-PI3K and p-AKT levels in the aorta.

Conclusion

BSHX alleviated VC in CKD rats by downregulating exosomal miR-32 expression in the aorta, thereby promoting PTEN expression and inhibiting the PI3K/AKT signaling pathway.
Detection of extended gamma-ray emission in the vicinity of Cl Danks 1 and 2
Authors: Liu Jia-hao , Liu Bing , Yang Rui-zhi
Published: October 2024

We report the detection of high-energy gamma-ray emission towards the G305 star-forming region. Using almost 15 yr of observation data from Fermi Large Area Telescope, we detected an extended gamma-ray source in this region with a significance of $\sim 13 \sigma$. The gamma-ray radiation reveals a clear pion-bump feature and can be fitted with the power-law parent proton spectrum with an index of $-2.5$. The total cosmic ray (CR) proton energy in the gamma-ray production region is estimated to be of the order of $10^{49}\ \rm erg$. We further derived the CR radial distribution from both the gamma-ray emission and gas distribution and found it roughly obeys the $1/r$ type profile, though a constant profile is not ruled out. This is consistent with other similar systems and expected from the continuous injection of CRs by the central powerful young massive star cluster Danks 1 or Danks 2 in this region. Together with former detections of similar gamma-ray structures, such as Cygnus cocoon, Westerlund 1, Westerlund 2, NGC 3603, and W40, the detection supports the hypothesis that young massive star clusters are CR accelerators.
The decline in tropical land carbon sink drove high atmospheric CO2 growth rate in 2023
Authors: Gui Yanchen , Wang Kai , Jin Zhe , Wang Heyuan , Deng Hanzhi , Li Xiangyi , Tian Xiangjun , Wang Tao , Chen Wei , Wang Tengjiao , Piao Shilong
Published: October 2024

Atmospheric CO2 growth rate (CGR), reflecting the carbon balance between anthropogenic emissions and net uptake from land and ocean, largely determines the magnitude and speed of global warming. The CGR at Mauna Loa Baseline Observatory reached a record high in 2023. We quantified major components of the global carbon balance for 2023, by developing a framework that integrated fossil fuel CO2 emissions data and an atmospheric inversion from the Global ObservatioN-based system for monitoring Greenhouse GAses (GONGGA) with two artificial intelligence (AI) models derived from dynamic global vegetation models. We attributed the record high CGR increase in 2023 compared to 2022 primarily to the large decline in land carbon sink (1803 ± 197 TgC year−1), with minor contributions from a small reduction in ocean carbon sink (184 TgC year−1) and a slight increase in fossil fuel emissions (24 TgC year−1). At least 78% of the global decline in land carbon sink was contributed by the decline in tropical sink, with GONGGA inversion (1354 TgC year−1) and AI simulations (1578 ± 666 TgC year−1) showing similar declines in the tropics. We further linked this tropical decline to the detrimental impact of El Niño-induced anomalous warming and drying on vegetation productivity in water-limited Sahel and southern Africa. Our successful attribution of CGR increase within a framework combining atmospheric inversion and AI simulations enabled near-real-time tracking of the global carbon budget, which had a one-year reporting lag.
Updated systematic review of respiratory health surveillance: what is the evidence and what are the knowledge gaps?
Authors: McElvenny Damien M , Wiggans Ruth , Hoyle Jennie , Fishwick David , van Tongeren Martie
Published: October 2024

Occupational health surveillance of respiratory disease, if done properly, should contribute to reducing the burden of occupational lung diseases. However, this systematic review shows that the quality and extent of evidence on the effectiveness of occupational health surveillance for respiratory disease is very limited. Therefore, it is essential to expand the evidence base in order to make informed decisions on the need for any changes to established guidance on health surveillance.
Beyond Words: Enhancing Clinical Guideline Comprehension With Icons
Authors: Comba Isin Y , O’Horo John C , Gordon Joel E , Falck-Ytter Yngve , Moore Matthew M , Morgan Rebecca L , Mustafa Reem A , Bhimraj Adarsh
Published: October 2024

Background

The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance.

Methods

We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability.

Results

The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P > .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P < .01). In contrast, response time did not differ between versions for the second question (P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon.

Conclusions

This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience.
12 Access to paediatric maltreatment services through a northern community hospital
Authors: Ng Pamela , Corbeil Chantal
Published: October 2024

Background

Few studies have evaluated how paediatric maltreatment services based in community hospitals can provide access to care for populations who live far away from tertiary centres. The Violence Intervention Prevention Program (VIPP) and the Paediatric Abuse and Referral Evaluation (PARE) clinic based in a northern community hospital in Canada offer assessment for sexual and physical maltreatment.

Objectives

The aim of the study was to describe demographic and clinical characteristics of patients accessing VIPP and PARE services and to characterize the length of time required to access care.

Design/Methods

We conducted a retrospective chart review of patients, under 16 years of age, who attended PARE clinic for initial consultation between 2017-2019. Analyses were descriptive. This work was approved by the research ethics board at our hospital. There are no funding disclosures.

Results

Of 164 patients, 62.2% were female; 37.8% male. The mean age was 6.6 years, ranging from 1 month to 15.9 years. 54.3% of referrals were for suspected physical maltreatment, 44.4% for suspected sexual maltreatment and 1.2% for both. 87.5% of patients listed home addresses within the hospital’s city limits. The maximum distance travelled from home to access care was 171 km. 87.2% of patients presented through the emergency department; a minority presented through direct referral to outpatient services (11.5%) or through inpatient (1.2%). When called from the emergency department, on-call VIPP nurses responded within a mean of 32 minutes for initial assessment. These patients received a maltreatment assessment by a paediatrician through the PARE clinic a mean of 14.3 days later. If patients did not present through the emergency department, the mean wait time for a maltreatment assessment by a paediatrician was 16 days. 13.4% (22/164) required referral to other medical or multidisciplinary services. General paediatrics (11/22) was the most frequent referral, followed by community speech programs (5/22). A minority (3.0%) of cases required consultation with external maltreatment teams, where two cases were peer-reviewed with a tertiary care team, one with a paediatric maltreatment physician at another community hospital and two cases were reviewed with a paediatric tertiary care radiologist.

Conclusion

Our results suggest that community-based paediatric maltreatment services provide care for our regional northern population. There is timely on-call access to allied-health providers through the emergency department. All patients were able to be assessed locally and none were required to travel to a tertiary care hospital. Further study is needed to assess how our data compares to other community maltreatment programs.
44 Spotting the clotting: a 3-year national surveillance study of paediatric pulmonary thromboembolism
Authors: Ramsay Lily , Pike Meghan , Moorehead Paul , Chan Anthony K C , McMullen Sarah , Plint Amy C , Krmpotic Kristina
Published: October 2024

Background

Pulmonary thromboembolism (PE) is a rare event in the paediatric population but can be acutely life-threatening and result in chronic complications. Awareness of contemporary patterns of clinical presentation, diagnostic modalities, and management may aid clinicians in ensuring that patients are promptly identified and treated.

Objectives

To describe the risk factors, symptoms, diagnostic modalities, therapeutic interventions, and short-term outcomes in paediatric patients (neonate up to 18 years) with PE through national surveillance.

Design/Methods

Between January 2020 and December 2022, monthly surveillance was conducted with over 2,800 paediatricians and sub-specialists through the Canadian Paediatric Surveillance Program. Voluntary reporting of cases meeting a standardized definition of PE was followed up with a detailed questionnaire.

Results

58 confirmed cases were reported; 33 (57%) were females age 15 to 18 years. Detailed information was available for 31 (53%) of 58 cases. At least 1 risk factor was identified in 28 (90%) cases and 12 (39%) patients had 2 or more risk factors. The most common risk factors were oral contraceptive use (n=10 of 31; 32%) and obesity (n=9 of 31; 29%). Presentation was symptomatic in 28 (90%) cases; 24 (77%) patients presented with 2 or more symptoms. The most common symptoms were chest pain (n=18; 58%), dyspnea (n=13; 42%) and tachycardia (n=13; 42%). The most common diagnostic modality utilized was computed tomography pulmonary angiography (n=25; 81%). Initiation of systemic anticoagulation was reported for 24 (77%) of 31 cases; thrombolysis and surgical interventions were uncommon (< 5 cases). Treatment complications were common (n=8; 29%). Mortality was reported, but in fewer than 5 cases.

Conclusion

PE in children often presents with non-specific symptoms, but usually occurs in patients with known risk factors. Clinicians should maintain a high index of suspicion in symptomatic patients, particularly those with risk factors and in cases when other diagnoses that may explain symptoms have been excluded. Anticoagulation is the mainstay of treatment; complications can occur. Prompt recognition and management presumably reduce morbidity and mortality, but this cannot be inferred from our data.
45 Home-based phototherapy for neonatal hyperbilirubinemia: A one-time Canadian Paediatric Surveillance Program Survey
Authors: Holyer Karissa , Abdulsatar Farah , Miller Michael
Published: October 2024

Background

Home-based phototherapy (HP) has gained popularity as a viable alternative to hospital-based treatment for neonatal hyperbilirubinemia, with longstanding use internationally and availability in specific regions of Canada. HP has been shown to be cost-effective and beneficial for parent-infant bonding, but its safety remains unclear, especially with current use in Canada.

Objectives

The primary objective of this study was to identify adverse events related to HP within Canada over the past 12 months. Secondary objectives included identifying risk factors associated with these adverse outcomes and gathering information on the current status of HP in Canada.

Design/Methods

A one-time survey, distributed through the Canadian Paediatric Surveillance Program, collected retrospective data from paediatricians. The survey included questions about adverse events associated with HP and associated risk factors and outcomes, as well as the provision of HP. A descriptive statistical analysis was conducted.

Results

The survey response rate was 31% (844/2741). Among the 497 respondents providing care for neonatal hyperbilirubinemia, 15 (3%) physicians reported a total of 28 cases of adverse events associated with HP in the preceding 12 months. Most adverse events resulted in admissions or readmissions to the hospital for in-hospital phototherapy with no serious adverse events or long-term consequences. Risk factors were identified in 67% of cases, with infant-related factors being the most prevalent. HP was offered at the centre of 12% of the responding physicians, with formal protocols for patient assessment and follow-up at most centres.

Conclusion

This survey revealed no serious adverse related to HP in the preceding 12 months. The survey also revealed that while HP is available in Canada, there is a lack of standardization in its administration across the country. This study provides valuable insights into the safety and practice of HP for neonatal hyperbilirubinemia in Canada, contributing to evidence-based decision-making and optimization of care protocols.