bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring cis-to-trans isomerization of azobenzene using Brillouin microscopy
Authors: Wang Zhe , Jiang Qiyang , Barwig Chantal , Mishra Ankit , Ramesh Krishna , Selhuber-Unkel Christine
Published: June 2024

Brillouin spectroscopy is commonly used to study the acoustic properties of materials. Here we explored its feasibility in studying the photoinduced isomerization of azobenzene. The isomerization of azobenzene changes the solution elastic modulus, and Brillouin scattering is sensitive to these changes. In this study, we experimentally demonstrated the photoswitching of azobenzene in DMSO using our home-made virtually imaged phased array-based high-resolution optical Brillouin spectrometer, and confirmed the results by ultraviolet–visible spectrophotometry. Remarkable Brillouin frequency shift variations were quantitatively recorded upon irradiation, and it was found that this method can indeed be used to monitor the isomerization process in situ. Importantly, our strategy also allows us to provide the relationship between the fraction of trans- and cis- azobenzene and the Brillouin frequency shift. This shows that Brillouin spectroscopy has broad prospects for the characterization of azobenzene isomerization and other photoresponsive materials.
Packaging of micro-lens arrays to photonic integrated circuits using beam shape evaluation
Authors: Gradkowski Kamil , Morrissey Padraic E , O’Brien Peter
Published: June 2024

We propose a method for aligning and attaching micro-lens arrays to photonic integrated circuits (PICs). Unlike the conventional approach of assessing power coupled to a fiber directly, our method utilizes a beam profiler. This profiler allows us to optimize the lens position by analyzing the transmitted beam shape from the PIC edge coupler through the lens. In conjunction, we employ grating couplers to introduce external light, acting as a ‘beacon’ for optimization. The use of grating couplers enables efficient coupling of external light into the PIC, providing a reference point for alignment. Importantly, our method accommodates both regular waveguide-side-up and upside-down (through-Silicon) orientations of the PIC. This versatility allows us to reproduce coupling results across a 6-channel array, demonstrating robust performance. This innovative approach not only ensures precise alignment and attachment but also opens up new possibilities for photonic packaging. The flexibility to work in different orientations is likely to lead to advancements in the design and assembly of photonic devices.
Synergistically biomimetic platform that enables droplets to be self-propelled
Authors: Li Minghao , Lu Yao , Wang Yujie , Huang Shuai , Feng Kai
Published: June 2024

Droplet transport still faces numerous challenges, such as a limited transport distance, large volume loss, and liquid contamination. Inspired by the principle of ‘synergistic biomimetics’, we propose a design for a platform that enables droplets to be self-propelled. The orchid leaf-like three-dimensional driving structure provides driving forces for the liquid droplets, whereas the lotus leaf-like superhydrophobic surface prevents liquid adhesion, and the bamboo-like nodes enable long-distance transport. During droplet transport, no external energy input is required, no fluid adhesion or residue is induced, and no contamination or mass loss of the fluid is caused. We explore the influence of various types and parameters of wedge structures on droplet transportation, the deceleration of droplet speed at nodal points, and the distribution of internal pressure. The results indicate that the transport platform exhibits insensitivity to pH value and temperature. It allows droplets to be transported with varying curvatures in a spatial environment, making it applicable in tasks like target collection, as well as load, fused, anti-gravity, and long-distance transport. The maximum droplet transport speed reached (58 ± 5) mm·s−1, whereas the transport distance extended to (136 ± 4) mm. The developed platform holds significant application prospects in the fields of biomedicine and chemistry, such as high-throughput screening of drugs, genomic bioanalysis, microfluidic chip technology for drug delivery, and analysis of biological samples.
Random forest based robust human activity detection system using hybrid feature
Authors: Shankar Bharti Shambhu , Rai Rajesh Kumar , Dwivedi Neelam
Published: June 2024

Human Activity Recognition is analyzing surveillance videos of a person’s activity. Tracking and identifying activities is essential in various applications like fight detection, mob lynching, etc. Human activity recognition may be the primary or secondary goal of a significant problem target. Surveillance for fight detection, crowd violence, public attacks, mob lynching, public robbery, etc, are few to list. The researchers are getting done in this direction, and algorithms are being proposed for automatic activity recognition. These are typically restricted to the recordings made by stationary cameras, though. For automated Human Activity Recognition, a novel skeleton-based feature called ‘Orientation Invariant Skeleton Feature (OISF)’ was introduced in the earlier work. This work uses a hybrid feature, which is a combination of ‘OISF’ features (proposed by Neelam Dwivedi et al) and ‘FV1’ features (proposed by S Kumar et al) for human activity detection systems. The hybrid features used in this paper have a low dependence on changes in camera orientation, according to experimental results. The accuracy obtained is higher than that of earlier studies using existing features and is roughly 99.50% with the ViHASi dataset and 97.25% with the KTH dataset. This demonstrates that the proposed study is suitable for commercial use.
Biogenic Bovine Serum Albumin/Zn3(PO4)2/Cr2O3 hybrid electrocatalyst for improved oxygen evolution reaction
Authors: Raj Ritu , Ahmed Imtiaz , Kumar Vikash , Singh Gajendra Prasad , Haldar Krishna Kanta
Published: June 2024

The fabrication of nanostructured protein-inorganic hybrid materials is crucial for the development of advanced multifunctional materials. Protein-inorganic mesoporous composites are gaining attention due to their remarkable properties, including large surface areas and active surface functional groups. We have successfully synthesized mesoporous BSA/Zn3(PO4)2/Cr2O3 catalysts to improve the kinetics of the oxygen evolution reaction (OER) in electrocatalytic water splitting for sustainable energy generation. This approach utilizes BSA in the synthesis process and is environmentally friendly. By adjusting the BSA quantity, we could control the yield of BSA/Zn3(PO4)2/Cr2O3 mesoporous. We employed various techniques, including FE-SEM, XRD, and FTIR, to analyze the morphology and structural characteristics of the biogenic BSA/Zn3(PO4)2/Cr2O3 electrocatalyst. Our comprehensive evaluation of the electrocatalytic OER activity of the BSA/Zn3(PO4)2/Cr2O3 hybrid structure demonstrated its remarkable performance. The biologically synthesized catalyst exhibited exceptional OER efficiency, maintaining a high current density of 10 mA cm−2 at very low overpotentials (only 216 mV) under alkaline conditions. The elongated peptide backbone of BSA significantly facilitated ion and electron transport, contributing to improved OER activity. The synergistic interaction between various amino acids from BSA and the metal ions within Zn3(PO4)2/Cr2O3 can be attributed to this enhancement, highlighting the potential of this hybrid structure in electrocatalytic OER applications.
Socialism, Community, and Limiting Leviathan
Authors: Browning Gary
Published: June 2024

Murdoch’s non-fiction exploration of the political is matched by the inclusion within her novels of a number of political themes. In the early novels Murdoch’s radical utopianism is explored. For instance, in Under the Net, the nature of socialism is debated by the major protagonist, Jake Donaghue, and a political radical, Lefty Todd. Their conversation raises major questions about the popularity and character of socialism in the post-war world. Freedom is discussed by the character Bill Mor in The Sandcastle, and a radical community experimenting with non-capitalist modes of work is described in The Bell. Revolutionary Irish Nationalism is explored in The Red and the Green, along with more moderate Anglo-Irish sentiments. In subsequent novels more pessimistic readings of the political are offered, notably in The Book and the Brotherhood where a great critical work of political theory is being written, and characters discuss its prospects and meaning. Notwithstanding her increasing criticism of radical politics, the novel appears to support lively debate on politics, in which radicalism is espoused alongside more conservative views.
Cause-specific survival analysis of gynecological cancers among a non-White population: a SEER-based study
Authors: Priyadarshini Subhadra , Swain Prafulla Kumar , Padhee Sourav , Agarwal Khushi
Published: June 2024

Gynecological cancers are the most prevalent cancers in women, making them a major public health concern for decades. Health disparities and inequalities in access to care among different racial groups have been a major concern in the US healthcare system. This study was aimed at investigating cause-specific survival rates among non-White women with gynecological cancer and to identify risk factors associated with gynecological cancer mortality by race. The Kaplan–Meier method was used to calculate 5-year survival estimates and various risk factors for gynecological cancer among non-White women were analyzed using Cox proportional hazard model. The findings of this study highlight the need for targeted interventions to improve access to care and reduce health disparities for non-White women with gynecological cancer.

This article is part of a Special Collection on Gynecological Cancer.
Long-Term Effects of Intensive Rehabilitation on Memory Functions in Acquired Brain-Damaged Patients
Authors: Anaki David , Devisheim Haim , Goldenberg Rosalind , Feuerstein Rafael
Published: June 2024

Objective

Memory difficulties after brain injury are a frequent and concerning outcome, affecting a wide range of daily activities, employment, and social reintegration. Despite the importance of functional memory capacities throughout life, most studies examined the short-term effects of memory interventions in brain-damaged patients who underwent a rehabilitation program. In the present study, we investigated the long-term outcomes and intensity of memory interventions in acquired (traumatic brain injury [TBI] and non-TBI) brain-damaged patients who participated in an intensive cognitive rehabilitation program and either suffered or did not suffer from memory impairments.

Method

We measured pre-post-treatment memory performance of patiients (N = 24) suffering from memory deficits in four common and validated memory tasks (e.g. ROCFT). We compared them to other acquired brain injury patients treated at the same rehabilitation facility who did not suffer from memory impairments (N = 16).

Results

Patients with memory deficits showed long-term improvements in three out of four tasks, while patients without memory deficits showed memory enhancements in only one task. In addition, rehabilitation intensity and type of brain damage predicted the extent of the memory change over time.

Discussion

Long-term improvements in objective memory measures can be observed in patients suffering from brain injury. These improvements can be enhanced by intensifying the treatment program. Findings also suggest that these memory improvements are more pronounced in non-TBI than TBI patients. We discuss the implications of these results in designing optimal memory rehabilitation interventions.
Interplay between subthalamic nucleus and spinal cord controls parkinsonian nociceptive disorders
Authors: Charles Keri-Ann , Molpeceres Sierra Elba , Bouali-Benazzouz Rabia , Tibar Houyam , Oudaha Khalid , Naudet Frédéric , Duveau Alexia , Fossat Pascal , Benazzouz Abdelhamid
Published: June 2024

Pain is a non-motor symptom that impairs quality of life in patients with Parkinson's disease. Pathological nociceptive hypersensitivity in patients could be due to changes in the processing of somatosensory information at the level of the basal ganglia, including the subthalamic nucleus (STN), but the underlying mechanisms are not yet defined. Here, we investigated the interaction between the STN and the dorsal horn of the spinal cord (DHSC), by first examining the nature of STN neurons that respond to peripheral nociceptive stimulation and the nature of their responses under normal and pathological conditions. Next, we studied the consequences of deep brain stimulation (DBS) of the STN on the electrical activity of DHSC neurons. Then, we investigated whether the therapeutic effect of STN-DBS would be mediated by the brainstem descending pathway involving the rostral ventromedial medulla. Finally, to better understand how the STN modulates allodynia, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in the STN.

The study was carried out on the 6-OHDA rodent model of Parkinson's disease, obtained by stereotactic injection of the neurotoxin into the medial forebrain bundle of rats and mice. In these animals, we used motor and nociceptive behavioural tests, in vivo electrophysiology of STN and wide dynamic range (WDR) DHSC neurons in response to peripheral stimulation, deep brain stimulation of the STN and the selective DREADD approach. Vglut2-ires-cre mice were used to specifically target and inhibit STN glutamatergic neurons.

STN neurons are able to detect nociceptive stimuli, encode their intensity and generate windup-like plasticity, like WDR neurons in the DHSC. These phenomena are impaired in dopamine-depleted animals, as the intensity response is altered in both spinal and subthalamic neurons. Furthermore, as with L-DOPA, STN-DBS in rats ameliorated 6-OHDA-induced allodynia, and this effect is mediated by descending brainstem projections leading to normalization of nociceptive integration in DHSC neurons. Furthermore, this therapeutic effect was reproduced by selective inhibition of STN glutamatergic neurons in Vglut2-ires-cre mice.

Our study highlights the centrality of the STN in nociceptive circuits, its interaction with the DHSC and its key involvement in pain sensation in Parkinson's disease. Furthermore, our results provide for the first-time evidence that subthalamic DBS produces analgesia by normalizing the responses of spinal WDR neurons via descending brainstem pathways. These effects are due to direct inhibition, rather than activation of glutamatergic neurons in the STN or passage fibres, as shown in the DREADDs experiment.
Distinct transcriptional alterations distinguish Lewy body disease from Alzheimer’s disease
Authors: Olney Kimberly C , Rabichow Benjamin E , Wojtas Aleksandra M , DeTure Michael , McLean Pamela J , Dickson Dennis W , Chang Rui , Ross Owen A , Fryer John D
Published: June 2024

Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by α-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, AD is characterized by amyloid plaques and neurofibrillary tangles. Both conditions often co-occur with additional neuropathological changes, such as vascular disease and TDP-43 pathology.

To elucidate shared and distinct molecular signatures underlying these mixed neuropathologies, we extensively analysed transcriptional changes in the anterior cingulate cortex, a brain region critically involved in cognitive processes. We performed bulk tissue RNA sequencing from the anterior cingulate cortex and determined differentially expressed genes (q-value <0.05) in control (n = 81), LBD (n = 436), AD (n = 53) and pathological amyloid cases consisting of amyloid pathology with minimal or no tau pathology (n = 39). We used gene set enrichment and weighted gene correlation network analysis to understand the pathways associated with each neuropathologically defined group.

LBD cases had strong upregulation of inflammatory pathways and downregulation of metabolic pathways. The LBD cases were further subdivided into either high Thal amyloid, Braak NFT, or low pathological burden cohorts. Compared to the control cases, the LBD cohorts consistently showed upregulation for genes involved in protein folding and cytokine immune response, as well as downregulation of fatty acid metabolism. Surprisingly, concomitant tau pathology within the LBD cases resulted in no additional changes. Some core inflammatory pathways were shared between AD and LBD but with numerous disease-specific changes. Direct comparison of LBD cohorts versus AD cases revealed strong enrichment of synaptic signalling, behaviour and neuronal system pathways. Females had a stronger response overall in both LBD and AD, with several sex-specific changes.

Overall, the results identify genes commonly and uniquely dysregulated in neuropathologically defined LBD and AD cases, shedding light on shared and distinct molecular pathways. Additionally, the study underscores the importance of considering sex-specific changes in understanding the complex transcriptional landscape of these neurodegenerative diseases.
Central involvement in peripheral disease: melanopsin pathway impairment in chronic inflammatory demyelinating polyneuropathy
Authors: Steiner Oliver L , Klostermann Fabian
Published: June 2024

Chronic inflammatory demyelinating polyneuropathy (CIDP) compromises functions of the peripheral nervous system (PNS). Recently, however, symptoms such as cognitive deficits, visual dysfunction and circadian disorders were reported, compatible with additional involvement of the central nervous system (CNS) in CIDP. Against this background, we were interested in the functional state of melanopsin-expressing retinal ganglion cells (mRGCs) as a potential biomarker for sleep–wake abnormalities and CNS involvement in CIDP. Based on a chromatic pupillometry protocol, we examined the integrity of the melanopsin system in a prospective case–control study in 20 persons with CIDP compared to 20 controls without CIDP. The results were referred to clinical measures of disease severity and sleep behaviour. Patients with CIDP had a significantly reduced melanopsin-mediated post-illumination pupil response (PIPR) compared to healthy controls (25% versus 36%; P < 0.01). This reduction correlated with disease severity (r = 0.478, P < 0.05). Further, patients with CIDP reported diminished sleep quality (P < 0.05); however, there was no significant correlation with the melanopsin-mediated PIPR. The results demonstrate an impairment of mRGC function related to CIDP. Since the PIPR reduction correlated with disease severity, it could be an easily available biomarker for CNS affection in CIDP, a condition defined as PNS disorder.
Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans
Authors: Woodrow Rebecca E , Menon David K , Stamatakis Emmanuel A ,   CENTER-TBI MRI Sub-study Participants and Investigators, Amrein Krisztina , Andelic Nada , Andreassen Lasse , Anke Audny , Azouvi Philippe , Bellander BoMichael , Benali Habib , Buki Andras , Caccioppola Alessio , Calappi Emiliana , Carbonara Marco , Citerio Giuseppe , Clusmann Hans , Coburn Mark , Coles Jonathan , Correia Marta , Czeiter Endre , De Keyser Véronique , Degos Vincent , Depreitere Bart , Eikenes Live , Ezer Erzsébet , Foks Kelly , Frisvold Shirin , Galanaud Damien , Ghuysen Alexandre , Glocker Ben , Haberg Asta , Haitsma Iain , Helseth Eirik , Hutchinson Peter J , Kornaropoulos Evgenios , Kovács Noémi , Kowark Ana , Laureys Steven , Ledoux Didier , Lingsma Hester , Maas Andrew I R , Manley Geoffrey , Menon David K , Menovsky Tomas , Misset Benoit , Muraleedharan Visakh , Nakken Ingeborg , Newcombe Virginia , Nordhøy Wibeke , Nyirádi József , Ortolano Fabrizio , Parizel Paul M , Perlbarg Vincent , Persona Paolo , Peul Wilco , Posti Jussi P , Puybasset Louis , Richter Sophie , Roe Cecilie , Roise Olav , Rossaint Rolf , Ross Sandra , Rueckert Daniel , Singh Ranjit D , Skandsen Toril , Sorinola Abayomi , Stamatakis Emmanuel , Steyerberg Ewout W , Stocchetti Nino , Takala Riikka , Tamás Viktória , Tenovuo Olli , Thibaut Aurore , Vámos Zoltán , Van der Steen Gregory , van Erp Inge A , Van Hecke Wim , Vande Vyvere Thijs , Verheyden Jan , Vik Anne , Volovici Victor , Westlye Lars T , Whitehouse Daniel , Williams Guy , Winzeck Stefan , Ylén Peter , Zoerle Tommaso
Published: June 2024

Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury (n = 21) to that of single injury (n = 21) and healthy controls (n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury.
Navigating the Med-Peds Maze: Considerations for the Combined Adult and Pediatric Infectious Diseases Fellowship Application Process
Authors: McCluskey James M
Published: June 2024

Navigating the combined adult and pediatric infectious disease (ID) fellowship application, interview, and matching process requires careful consideration from applicants and programs alike. Currently, it is functional but not streamlined, and as the ID community is facing recruitment and workforce challenges, it is important to be transparent about this process for applicants while emphasizing areas of potential improvement for fellowship programs. As it stands, this process requires foresight from the applicant and coordination between the adult and pediatric fellowship programs. This perspective article provides an anecdote and discusses issues and suggestions for troubleshooting, including, but not limited to: strategic approach to applications, interviews, and ranking; mentorship; geographic preference; and program saturation.
Risk Factors and Outcome Associated With Fungal Infections in Patients With Severe Burn Injury: 10-year Retrospective IFI-BURN Study
Authors: Dudoignon Emmanuel , Chevret Sylvie , Tsague Sorel , Hamane Samia , Chaouat Marc , Plaud Benoit , Vicault Eric , Mebazaa Alexandre , Legrand Matthieu , Alanio Alexandre , Denis Blandine , Dépret Francois , Dellière Sarah
Published: June 2024

Background

In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients.

Methods

This retrospective cohort study includes adult patients admitted to the burn intensive care unit (BICU) between April 2014 and May 2023 with total burn surface area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage or ≥2 positive blood specific-quantitative polymerase chain reactions (qPCRs) or a combination of both.

Results

Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n = 30; IMI n = 43; both n = 14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence proven/putative (pr/pu) IFD was 26.4% (95% confidence interval [CI], 21.4%–31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (ie, from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (P < .0001). IFD was independently associated with a risk of death (hazard ratio [HR]: 1.94 for pr/pu IFD; 95% CI, 1.12–3.36; P = .019).

Conclusions

This study describes twenty-first-century characteristics of IFDs in severe burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores.
Explainable artificial intelligence in deep learning–based detection of aortic elongation on chest X-ray images
Authors: Ribeiro Estela , Cardenas Diego A C , Dias Felipe M , Krieger Jose E , Gutierrez Marco A
Published: June 2024

Aims

Aortic elongation can result from age-related changes, congenital factors, aneurysms, or conditions affecting blood vessel elasticity. It is associated with cardiovascular diseases and severe complications like aortic aneurysms and dissection. We assess qualitatively and quantitatively explainable methods to understand the decisions of a deep learning model for detecting aortic elongation using chest X-ray (CXR) images.

Methods and results

In this study, we evaluated the performance of deep learning models (DenseNet and EfficientNet) for detecting aortic elongation using transfer learning and fine-tuning techniques with CXR images as input. EfficientNet achieved higher accuracy (86.7% ± 2.1), precision (82.7% ± 2.7), specificity (89.4% ± 1.7), F1 score (82.5% ± 2.9), and area under the receiver operating characteristic (92.7% ± 0.6) but lower sensitivity (82.3% ± 3.2) compared with DenseNet. To gain insights into the decision-making process of these models, we employed gradient-weighted class activation mapping and local interpretable model-agnostic explanations explainability methods, which enabled us to identify the expected location of aortic elongation in CXR images. Additionally, we used the pixel-flipping method to quantitatively assess the model interpretations, providing valuable insights into model behaviour.

Conclusion

Our study presents a comprehensive strategy for analysing CXR images by integrating aortic elongation detection models with explainable artificial intelligence techniques. By enhancing the interpretability and understanding of the models’ decisions, this approach holds promise for aiding clinicians in timely and accurate diagnosis, potentially improving patient outcomes in clinical practice.
Left atrial deformation analysis in patients with non-ischaemic dilated cardiomyopathy in atrial fibrillation
Authors: Ródenas-Alesina Eduard , Lozano-Torres Jordi , Tobías-Castillo Pablo Eduardo , Badia-Molins Clara , Vila-Olives Rosa , Calvo-Barceló Maria , Casas Guillem , Soriano-Colomé Toni , San Emeterio Aleix Olivella , Fernández-Galera Rubén , Méndez-Fernández Ana B , Barrabés José A , Ferreira-González Ignacio , Rodríguez-Palomares José
Published: June 2024

Aims

Atrial fibrillation (AF) is a common comorbidity in non-ischaemic dilated cardiomyopathy (NIDCM) affecting conventional measures of left atrial (LA) function. We aimed to determine whether LA function analysis could identify patients at higher risk of major cardiovascular events (MACEs).

Methods and results

A retrospective study of patients with NIDCM in AF referred to a single centre for transthoracic echocardiography (TTE) between 2015 and 2019. Peak atrial longitudinal strain (PALS) was measured along with LA emptying fraction and LA filling index (LAFI = E wave/PALS). Cox regression analysis was conducted. A total of 153 patients were included [median age 74 years, left ventricular ejection fraction (LVEF) 35%], and 57 (37.3%) had MACE after a median follow-up of 3.2 years. LAFI was the only independent TTE parameter associated with MACE after adjustment for age, diabetes, LVEF, left ventricular global longitudinal strain (LV-GLS), and LA volume index [adjusted hazard ratio (HR) = 1.02 per point increase, P = 0.024], with the best cut-off at ≥15. LAFI ≥15 predicted each of MACE components when separately analysed: MACE HR = 1.95, 95% confidence interval (CI) 1.16–3.30; cardiovascular death HR = 3.68, 95% CI 1.41–9.56, heart failure admission HR = 2.13, 95% CI 1.19–3.80, and ventricular arrhythmia HR = 4.72, 95% CI 1.52–14.67. Higher LAFI was associated with worsening LV-GLS, E/e′, systolic pulmonary artery (PA) pressure, tricuspid annular plane systolic excursion, and right ventricular to PA coupling.

Conclusion

LA deformation analysis is feasible in patients with NIDCM presenting with AF. LAFI may identify patients at higher risk of MACE and correlates with higher pulmonary pressures and worse right ventricular function, suggesting an elevation of left-sided ventricular pressures in patients with higher LAFI.
Testosterone therapy in older men: clinical implications of recent landmark trials
Authors: Grossmann Mathis , Anawalt Bradley D , Yeap Bu B
Published: June 2024

Testosterone therapy for men with hypogonadism due to identifiable hypothalamic-pituitary-testicular (HPT) pathology is uncontroversial. However, the risks and benefits of testosterone for men with clinical features of hypogonadism in the absence of identifiable HPT axis pathology have been uncertain. Recent landmark placebo-controlled trials assessed the benefits and risks of testosterone therapy (≤3 years) for middle-aged and older men with symptoms and possible signs of hypogonadism or end-organ androgen deficiency, low or low-normal serum testosterone concentrations, but no HPT pathology: Testosterone therapy (1) had modest—but clinically significant—benefits on average self-reported energy and mood, sexual function, and satisfaction; (2) in conjunction with a lifestyle programme, reversed or reduced incident type 2 diabetes mellitus (T2D) in men at high risk of or newly diagnosed with T2D; (3) modestly improved objectively assessed muscle strength and timed walking distance; (4) increased bone density and strength, but did not reduce falls or typical osteoporotic fractures and surprisingly increased the risk of fractures typically attributable to trauma; and (5) did not significantly increase the risk of myocardial infarction, stroke, or prostate cancer. These landmark trials help to inform clinical decision-making about testosterone therapy for men.
Variants in both the N- or C-terminal domains of IHH lead to defective secretion causing short stature and skeletal defects
Authors: Díaz-González Francisca , Sentchordi-Montané Lucía , Lucas-Castro Elsa , Modamio-Høybjør Silvia , Heath Karen E
Published: June 2024

Background

Heterozygous Indian Hedgehog gene (IHH) variants are associated with brachydactyly type A1 (BDA1). However, in recent years, numerous variants have been identified in patients with short stature and more variable forms of brachydactyly. Many are located in the C-terminal domain of IHH (IHH-C), which lacks signaling activity but is critical for auto-cleavage and activation of the N-terminal (IHH-N) peptide. The absence of functional studies of IHH variants, particularly for those located in IHH-C, has led to these variants being classified as variants of uncertain significance (VUS).

Objective

To establish a simple functional assay to determine the pathogenicity of IHH VUS and confirm that variants in the C-terminal domain affect protein function.

Design/Methods

In vitro studies were performed for 9 IHH heterozygous variants, to test their effect on secretion and IHH intracellular processing by western blot of cells expressing each variant.

Results

IHH secretion was significantly reduced in all mutants, regardless of the location. Similarly, intracellular levels of N-terminal and C-terminal IHH peptides were severely reduced in comparison with the control. Two variants present at a relatively high frequency in the general population also reduced secretion but to a lesser degree in the heterozygous state.

Conclusions

These studies provide the first evidence that variants in the C-terminal domain affect the secretion capacity of IHH and thus, reduce availability of IHH ligand, resulting in short stature and mild skeletal defects. The secretion assay permits a relatively easy test to determine the pathogenicity of IHH variants. All studied variants affected secretion and interestingly, more frequent population variants appear to have a deleterious effect and thus contribute to height variation.
Feasibility study on atrial fibrillation ablation with pulsed field ablation and concomitant occlusion of the left atrial appendage
Authors: Beney Jennifer , Galea Roberto , Siontis Georgios , Gräni Christoph , Kueffer Thomas , Brugger Nicolas , Reichlin Tobias , Räber Lorenz , Roten Laurent
Published: June 2024

Aims

Atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) are increasingly performed as individual procedures. Pulsed field ablation (PFA) has significantly reduced procedure duration and may be advantageous for the combined approach.

Methods and results

We have launched a programme for simultaneous AF ablation using PFA and LAAO for patients qualifying for both treatments and excluding those with a complex anatomy. We compare procedure duration and fluoroscopy time against individual procedures (either AF ablation or LAAO alone), all performed by the same operators and using consistent technologies. We performed the combined procedure in 10 patients (50% males; median age 70 years) and excluded 2 patients (17%) because of a complex left atrial appendage anatomy. No death, stroke, or major bleeding events, including pericardial effusion, occurred. For single-procedure comparison, 207 AF ablation procedures and 61 LAAO procedures were available. The total median procedure duration was 79 min (range 60–125) for the combined procedure, 71 min (25–241) for individual AF ablation (51 min without and 78 min with 3-dimensional electroanatomic mapping), and 47 min (15–162) for individual LAAO. The respective fluoroscopy times were 21 (15–26), 15 (5–44), and 10 (3–50) min. For the combined procedure, femoral vein access to last PFA application lasted 49 min (34–93) and LAAO added 20 min (15–37).

Conclusion

Simultaneous PFA-based AF ablation and LAAO in carefully selected patients is feasible and safe and can be executed within a short overall procedure duration.
A common ericoid shrub modulates the diversity and structure of fungal communities across an arbuscular to ectomycorrhizal tree dominance gradient
Authors: Polussa Alexander , Ward Elisabeth B , Bradford Mark A , Oliverio Angela M
Published: June 2024

Differences between arbuscular (AM) and ectomycorrhizal (EcM) trees strongly influence forest ecosystem processes, in part through their impact on saprotrophic fungal communities. Ericoid mycorrhizal (ErM) shrubs likely also impact saprotrophic communities given that they can shape nutrient cycling by slowing decomposition rates and intensifying nitrogen limitation. We investigated the depth distributions of saprotrophic and EcM fungal communities in paired subplots with and without a common understory ErM shrub, mountain laurel (Kalmia latifolia L.), across an AM to EcM tree dominance gradient in a temperate forest by analyzing soils from the organic, upper mineral (0–10 cm), and lower mineral (cumulative depth of 30 cm) horizons. The presence of K. latifolia was strongly associated with the taxonomic and functional composition of saprotrophic and EcM communities. Saprotrophic richness was consistently lower in the Oa horizon when this ErM shrub species was present. However, in AM tree-dominated plots, the presence of the ErM shrub was associated with a higher relative abundance of saprotrophs. Given that EcM trees suppress both the diversity and relative abundance of saprotrophic communities, our results suggest that separate consideration of ErM shrubs and EcM trees may be necessary when assessing the impacts of plant mycorrhizal associations on belowground communities.
Ambient noise imaging for municipal solid waste landfill structure detection based on the common-midpoint two-station analysis with distributed acoustic sensing
Authors: Chen Hepu , Sun Shangrao , Li Fangyu , Cao Danping , Xu Kaijun , Yin Bingxiang , Yin Jiaojian , He Yongbo
Published: June 2024

Distributed acoustic sensing (DAS) enables high-density sampling of seismic wavefields at low cost compared to conventional geophones. This capability facilitates structural detection of a municipal solid waste (MSW) landfill, which is important for protecting the surrounding ecosystem. However, processing the vast amount of data from DAS array for ambient noise imaging can be computationally intensive. To address this, we employed the common-midpoint two-station (CMP-TS) analysis to enhance the efficiency of ambient noise imaging in the MSW landfill. CMP-TS analysis involves selecting pairs of traces at equal distances on both sides with the subarray midpoint as symmetry, which reduces the number of DAS array recordings for cross-correlation calculations. After positioning the DAS arrays linearly on top of the MSW landfill to automatically collect ambient noise, we used the CMP-TS analysis in the cross-correlation calculations to speed up the measurement of dispersion. The S-wave velocity structure of the study region was obtained quickly by inverting the extracted dispersion curves using the gradient optimization method. Ambient noise imaging based on CMP-TS analysis with DAS was applied to a test of an area-type MSW landfill. The resulting S-wave velocity section revealed a discontinuous low-velocity zone, validated by the high-density resistivity method. This low-velocity zone was interpreted as containing leachate from waste decomposition, and its discontinuity may be caused by excessive differences in the waste residues settling rates under compaction. Employing CMP-TS analysis in ambient noise data collected by DAS offers more cost-effective monitoring and a reliable basis for environmental pollution prevention and control.
Physicians working with physician assistants and nurse practitioners: perceived effects on clinical practice
Authors: Hu Xiaochu , Coplan Bettie , Barnes Hilary , Smith Noël , Essary Alison , Dill Michael
Published: June 2024

Physicians in the United States are increasingly working with physician assistants (PAs) and nurse practitioners (NPs), but little is known about how they perceive working with PAs and NPs affects their clinical practice. We used a new national survey to examine physicians’ perceptions of working with PAs and/or NPs on their patient volume, care quality, time use, and workload. Among our analytical sample of 5823 physicians, 59% reported working with PAs and/or NPs. Most reported that PAs and NPs positively affected their clinical practice. Among several findings, physicians working in medical schools and with higher incomes were more likely to indicate that PAs improve their clinical practices in all 4 aspects, while being in specialties with higher women's representation was associated with lower ratings for working with PAs. Native Hawaiian and Pacific Islander physicians and those with higher incomes were more likely to signify that NPs improved their clinical practices in all 4 aspects. These findings provide valuable insights, from the physicians’ perspective, on care delivery reform.
Understanding ethnic inequities associated with tobacco use in Aotearoa New Zealand: a quantitative analysis
Authors: Gurram Niveditha , Carroll Felix , Elers Christine Ngā Hau , Fox Ririwai , Minster Sara Tepaeru , Wikaire Erena , Brown Lynsey
Published: June 2024

Despite the inclusion of both individual interventions and population-based measures in the Aotearoa New Zealand (Aotearoa NZ) Tobacco Control Programme, the gap between Māori, Pacific peoples and European/Asian/Other (EAO) populations in tobacco use has not decreased significantly. Tobacco control interventions that focus on individual behaviour change have produced little impact towards reducing tobacco smoking inequities for Māori and Pacific peoples in Aotearoa NZ. Using data from the New Zealand Health Survey (NZHS), this research investigates the impact of the wider determinants of health and individual-level factors on inequities in tobacco use between Māori, Pacific peoples and EAO. A conceptual framework was developed to support the theoretical positioning of this research and to inform data categorization, framing, discourse, analyses and interpretation. We conducted hierarchical regression to examine the effect of factors from each domain on ethnic inequities in tobacco use. We found that socioeconomic factors accounted for a significant amount of the disparity in adults currently smoking between Māori and Pacific peoples and EAO. Our results suggest that socioeconomic factors may be a more effective target of intervention than individual behaviours for reducing tobacco-related inequities. Addressing the broader determinants of health through comprehensive cross-agency cooperation to reduce ethnic inequities in tobacco use in Aotearoa NZ is likely to be more effective than individual behaviour change approaches.
Convexity of shock polars
Authors: Elling Volker W
Published: June 2024

We show that the shock polars of compressible full potential flow are strictly convex if the enthalpy per mass is a convex function of volume per mass, in particular when the sound speed is a non-decreasing function of density. Counterexamples are given for some cases that violate the condition on enthalpy. For the full Euler equations with convex equation of state satisfying the ideal gas law, polars are strictly convex if heat capacity is constant, but counterexamples are given in variable cases, showing no useful generalizations are possible.
Asymptotically compatible energy of variable-step fractional BDF2 scheme for the time-fractional Cahn–Hilliard model
Authors: Liao Hong-lin , Liu Nan , Zhao Xuan
Published: June 2024

A novel discrete gradient structure of the variable-step fractional BDF2 formula approximating the Caputo fractional derivative of order $\alpha \in (0,1)$ is constructed by a local-nonlocal splitting technique, that is, the fractional BDF2 formula is split into a local part analogue to the two-step backward differentiation formula (BDF2) of the first derivative and a nonlocal part analogue to the L1-type formula of the Caputo derivative. Then a local discrete energy dissipation law of the variable-step fractional BDF2 implicit scheme is established for the time-fractional Cahn–Hilliard model under a weak step-ratio constraint $0.3960\le \tau _{k}/\tau _{k-1}<r^{*}(\alpha )$, where $\tau _{k}$ is the $k$th time-step size and $r^{*}(\alpha )\ge 4.660$ for $\alpha \in (0,1)$. The present result provides a practical answer to the open problem in [SINUM, 57: 218-237, Remark 6] and significantly relaxes the severe step-ratio restriction [Math. Comp., 90: 19–40, Theorem 3.2]. More interestingly, the discrete energy and the corresponding energy dissipation law are asymptotically compatible with the associated discrete energy and the energy dissipation law of the variable-step BDF2 method for the classical Cahn–Hilliard equation, respectively. To the best of our knowledge, such type energy dissipation law is established at the first time for the variable-step L2 type formula of Caputo’s derivative. Numerical examples with an adaptive stepping procedure are provided to demonstrate the accuracy and the effectiveness of our proposed method.
Concentration–resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model
Authors: Lu Ting-Yin , Sun Zhen , Liang Liu-Yan , Zhang Jing , Guo Wen-Long , Wang Zi-Ye , Sun Jian , Liao Xiao-Ping , Zhou Yu-Feng
Published: June 2024

Aims

This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis.

Methods and Results

Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration–time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants.

Conclusions

The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg−1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.
Yttrium immobilization through biomineralization with phosphate by the resistant strain Mesorhizobium qingshengii J19
Authors: Coimbra Carina , Branco Rita , da Silva Pedro S P , Paixão José A , Martins Jean M F , Spadini Lorenzo , Morais Paula V
Published: June 2024

Aims

Yttrium (Y) holds significant industrial and economic importance, being listed as a critical element on the European list of critical elements, thus emphasizing the high priority for its recovery. Bacterial strategies play a crucial role in the biorecovery of metals, offering a promising and environmentally friendly approach. Therefore, gaining a comprehensive understanding of the underlying mechanisms behind bacterial resistance, as well as the processes of bioaccumulation and biotransformation, is of paramount importance.

Methods and results

A total of 207 Alphaproteobacteria strains from the University of Coimbra Bacteria Culture Collection were tested for Y-resistance. Among these, strain Mesorhizobium qingshengii J19 exhibited high resistance (up to 4 mM Y) and remarkable Y accumulation capacity, particularly in the cell membrane. Electron microscopy revealed Y-phosphate interactions, while X-ray diffraction identified Y(PO3)3·9H2O biocrystals produced by J19 cells.

Conclusion

This study elucidates Y immobilization through biomineralization within phosphate biocrystals using M. qingshengii J19 cells.