Goal: Chest auscultations offer a non-invasive and low-cost tool for monitoring lung disease. However, they present many shortcomings, including inter-listener variability, subjectivity, and ...vulnerability to noise and distortions. This work proposes a computer-aided approach to process lung signals acquired in the field under adverse noisy conditions, by improving the signal quality and offering automated identification of abnormal auscultations indicative of respiratory pathologies. Methods: The developed noise-suppression scheme eliminates ambient sounds, heart sounds, sensor artifacts, and crying contamination. The improved high-quality signal is then mapped onto a rich spectrotemporal feature space before being classified using a trained support-vector machine classifier. Individual signal frame decisions are then combined using an evaluation scheme, providing an overall patient-level decision for unseen patient records. Results: All methods are evaluated on a large dataset with >1000 children enrolled, 1-59 months old. The noise suppression scheme is shown to significantly improve signal quality, and the classification system achieves an accuracy of 86.7% in distinguishing normal from pathological sounds, far surpassing other state-of-the-art methods. Conclusion: Computerized lung sound processing can benefit from the enforcement of advanced noise suppression. A fairly short processing window size (<;1 s) combined with detailed spectrotemporal features is recommended, in order to capture transient adventitious events without highlighting sharp noise occurrences. Significance: Unlike existing methodologies in the literature, the proposed work is not limited in scope or confined to laboratory settings: This work validates a practical method for fully automated chest sound processing applicable to realistic and noisy auscultation settings.
Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional ...therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.
Fractional Chern insulators (FCIs) are lattice analogues of fractional quantum Hall states that may provide a new avenue towards manipulating non-Abelian excitations. Early theoretical studies
have ...predicted their existence in systems with flat Chern bands and highlighted the critical role of a particular quantum geometry. However, FCI states have been observed only in Bernal-stacked bilayer graphene (BLG) aligned with hexagonal boron nitride (hBN)
, in which a very large magnetic field is responsible for the existence of the Chern bands, precluding the realization of FCIs at zero field. By contrast, magic-angle twisted BLG
supports flat Chern bands at zero magnetic field
, and therefore offers a promising route towards stabilizing zero-field FCIs. Here we report the observation of eight FCI states at low magnetic field in magic-angle twisted BLG enabled by high-resolution local compressibility measurements. The first of these states emerge at 5 T, and their appearance is accompanied by the simultaneous disappearance of nearby topologically trivial charge density wave states. We demonstrate that, unlike the case of the BLG/hBN platform, the principal role of the weak magnetic field is merely to redistribute the Berry curvature of the native Chern bands and thereby realize a quantum geometry favourable for the emergence of FCIs. Our findings strongly suggest that FCIs may be realized at zero magnetic field and pave the way for the exploration and manipulation of anyonic excitations in flat moiré Chern bands.
Gravitational waves from the merger of binary neutron stars (BNSs) are accompanied by electromagnetic counterparts, making it possible to identify the associated host galaxy. In this work, we explore ...how properties of the hosts relate to the astrophysical processes leading to the mergers. It is thought that the BNS merger rate within a galaxy at a given epoch depends primarily on the galaxy's star formation history, as well as the underlying merger time-delay distribution of the binary systems. The stellar history of a galaxy, meanwhile, depends on the cosmological evolution of the galaxy through time, and is tied to the growth of structure in the universe. We study the hosts of BNS mergers in the context of structure formation by populating the UniverseMachine simulations with gravitational wave (GW) events, based on a simple time-delay model. We find that different time-delay distributions predict different properties of the associated host galaxies, including the distributions of stellar mass, star formation rate, halo mass, and local and large-scale clustering of hosts. Moreover, BNSs merging today with short delay times occur preferentially in hosts with high star formation rates, while those with long delay times live in dense regions within massive halos that have low star formation. We show that with events from current GW detector networks, it is possible to make preliminary distinctions between formation channels which trace stellar mass, halo mass, or star formation rate. We also find that strategies to follow-up GW events with electromagnetic telescopes can be significantly optimized using the clustering properties of their hosts.
Objective
T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic ...sclerosis (dcSSc).
Methods
In this 12‐month, randomized, double‐blind, placebo‐controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets.
Results
Among 88 participants, the adjusted mean change in the MRSS at 12 months was −6.24 units for those receiving abatacept and −4.49 units for those receiving placebo, with an adjusted mean treatment difference of −1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal‐like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively.
Conclusion
In this phase II trial, abatacept was well‐tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.
The interplay between strong electron–electron interactions and band topology can produce electronic states that spontaneously break symmetries. The discovery of flat bands in magic-angle twisted ...bilayer graphene (MATBG)1–3 with non-trivial topology4–7 has provided a compelling platform in which to search for new symmetry-broken phases. Recent scanning tunnelling microscopy8,9 and transport experiments10–13 have revealed a sequence of topological insulating phases in MATBG near integer filling of the electronic bands produced by the moiré pattern. These correspond to a simple pattern of flavour-symmetry-breaking Chern insulators that fill bands of different flavours one after the other. Here we report the high-resolution local compressibility measurements of MATBG with a scanning single-electron transistor, which reveal an additional sequence of incompressible states with unexpected Chern numbers observed down to zero magnetic field. We find that the Chern numbers for eight of the observed incompressible states are incompatible with the simple picture in which the bands are sequentially filled. We show that the emergence of these unusual incompressible phases can be understood as a consequence of broken translation symmetry that doubles the moiré unit cell and splits each flavour band in two. Our findings expand the known phase diagram of MATBG, and shed light on the origin of the close competition between different correlated phases in the system.In addition to the broken time-reversal symmetry that typifies Chern insulators, twisted bilayer graphene hosts a set of topological states with broken translational symmetry.
Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC). ...Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.
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•Metastatic TNBC is dependent on mitochondrial FAO energy metabolism•FAO activates c-Src via autophosphorylation at residue Y419•CPT genes are critical in TNBC tumor progression and metastasis•Reduction of fat or FAO may provide clinical benefit to TNBC patients
Park et al. show that mitochondrial fatty acid β oxidation is an important energy pathway in metastatic triple-negative breast cancer. Their results uncover the significance of mitochondrial energy reprogramming in the tumor properties of triple-negative breast cancer and regulation of the Src cancer pathway by post-translational modification.
Abstract Herein we combine cell sheet technology and electrospun scaffolding to rapidly generate circumferentially aligned tubular constructs of human aortic smooth muscles cells with contractile ...gene expression for use as tissue engineered blood vessel media. Smooth muscle cells cultured on micropatterned and N-isopropylacrylamide-grafted (pNIPAm) polydimethylsiloxane (PDMS), a small portion of which was covered by aligned electrospun scaffolding, resulted in a single sheet of unidirectionally aligned cells. Upon cooling to room temperature, the scaffold, its adherent cells, and the remaining cell sheet detached and were collected on a mandrel to generating tubular constructs with circumferentially aligned smooth muscle cells which possess contractile gene expression and a single layer of electrospun scaffold as an analogue to a small diameter blood vessel's internal elastic lamina (IEL). This method improves cell sheet handling, results in rapid circumferential alignment of smooth muscle cells which immediately express contractile genes, and introduction of an analogue to small diameter blood vessel IEL.
Plasmodium vivax, one of the five species of Plasmodium parasites that cause human malaria, is responsible for 25-40% of malaria cases worldwide. Malaria global elimination efforts will benefit from ...accurate and effective genotyping tools that will provide insight into the population genetics and diversity of this parasite. The recent sequencing of P. vivax isolates from South America, Africa, and Asia presents a new opportunity by uncovering thousands of novel single nucleotide polymorphisms (SNPs). Genotyping a selection of these SNPs provides a robust, low-cost method of identifying parasite infections through their unique genetic signature or barcode. Based on our experience in generating a SNP barcode for P. falciparum using High Resolution Melting (HRM), we have developed a similar tool for P. vivax. We selected globally polymorphic SNPs from available P. vivax genome sequence data that were located in putatively selectively neutral sites (i.e., intergenic, intronic, or 4-fold degenerate coding). From these candidate SNPs we defined a barcode consisting of 42 SNPs. We analyzed the performance of the 42-SNP barcode on 87 P. vivax clinical samples from parasite populations in South America (Brazil, French Guiana), Africa (Ethiopia) and Asia (Sri Lanka). We found that the P. vivax barcode is robust, as it requires only a small quantity of DNA (limit of detection 0.3 ng/μl) to yield reproducible genotype calls, and detects polymorphic genotypes with high sensitivity. The markers are informative across all clinical samples evaluated (average minor allele frequency > 0.1). Population genetic and statistical analyses show the barcode captures high degrees of population diversity and differentiates geographically distinct populations. Our 42-SNP barcode provides a robust, informative, and standardized genetic marker set that accurately identifies a genomic signature for P. vivax infections.
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