Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5-10% of all human cancers, although this ...frequency increases to 10-30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.
Some reports of supernova (SN) discoveries turn out not to be true core-collapse explosions. One such case was SN 2009ip, which was recognized to be the eruption of a luminous blue variable (LBV) ...star. This source had a massive (50-80 M), hot progenitor star identified in pre-explosion data; it had documented evidence of pre-outburst variability and it was subsequently discovered to have a second outburst in 2010. In 2012, the source entered its third known outburst. Initial spectra showed the same narrow-line profiles as before, suggesting another LBV-like eruption. We present new photometry and spectroscopy of SN 2009ip, indicating that the 2012 outburst transitioned into a genuine SN explosion. The most striking aspect of these data is that unlike any previous episodes, the spectrum developed Balmer lines with very broad P-Cygni profiles characteristic of normal Type II supernovae (SNe II), in addition to overlying narrow emission components. The emission lines exhibit unprecedented (for any known non-terminal LBV-like eruption) full width at half-maximum intensity values of ∼8000 km s−1, while the absorption components seen just before the main brightening had blue wings extending out to −13 000 km s−1. These velocities are typical of core-collapse SN explosions, but have never been associated with emission lines from a non-terminal LBV-like eruption. SN 2009ip is the first object to have both a known massive blue progenitor star and LBV-like eruptions with accompanying spectra observed a few years prior to becoming a SN. Immediately after the broad lines first appeared, the peak absolute magnitude of M
V
−14.5 was fainter than that of normal SNe II. However, after a brief period of fading, the source quickly brightened again to M
R
= −17.5 mag in ∼2 d, suggesting a causal link to the prior emergence of the broad-line spectrum. Once the bright phase began, the broad lines mostly disappeared, and the spectrum resembled the early optically thick phases of luminous SNe IIn. The source reached a peak brightness of −18 mag about 2 weeks later, after which broad emission lines again developed in the spectrum as the source faded. We conclude that the most recent 2012 outburst of SN 2009ip was the result of a true core-collapse SN IIn that occurred when the progenitor star was in an LBV-like outburst phase, and where the SN was initially faint and then rapidly brightened due to interaction with circumstellar material. The pulsational pair instability, LBV-like eruptions or other instabilities due to late nuclear burning phases in massive stars may have caused the multiple pre-SN eruptions.
Background
Radiotherapy (RT) combined with cetuximab is the standard treatment for patients with inoperable head and neck cancers. Segmentation of head and neck (H&N) tumors is a prerequisite for ...radiotherapy planning but a time‐consuming process. In recent years, deep convolutional neural networks (DCNN) have become the de facto standard for automated image segmentation. However, due to the expensive computational cost associated with enlarging the field of view in DCNNs, their ability to model long‐range dependency is still limited, and this can result in sub‐optimal segmentation performance for objects with background context spanning over long distances. On the other hand, Transformer models have demonstrated excellent capabilities in capturing such long‐range information in several semantic segmentation tasks performed on medical images.
Purpose
Despite the impressive representation capacity of vision transformer models, current vision transformer‐based segmentation models still suffer from inconsistent and incorrect dense predictions when fed with multi‐modal input data. We suspect that the power of their self‐attention mechanism may be limited in extracting the complementary information that exists in multi‐modal data. To this end, we propose a novel segmentation model, debuted, Cross‐modal Swin Transformer (SwinCross), with cross‐modal attention (CMA) module to incorporate cross‐modal feature extraction at multiple resolutions.
Methods
We propose a novel architecture for cross‐modal 3D semantic segmentation with two main components: (1) a cross‐modal 3D Swin Transformer for integrating information from multiple modalities (PET and CT), and (2) a cross‐modal shifted window attention block for learning complementary information from the modalities. To evaluate the efficacy of our approach, we conducted experiments and ablation studies on the HECKTOR 2021 challenge dataset. We compared our method against nnU‐Net (the backbone of the top‐5 methods in HECKTOR 2021) and other state‐of‐the‐art transformer‐based models, including UNETR and Swin UNETR. The experiments employed a five‐fold cross‐validation setup using PET and CT images.
Results
Empirical evidence demonstrates that our proposed method consistently outperforms the comparative techniques. This success can be attributed to the CMA module's capacity to enhance inter‐modality feature representations between PET and CT during head‐and‐neck tumor segmentation. Notably, SwinCross consistently surpasses Swin UNETR across all five folds, showcasing its proficiency in learning multi‐modal feature representations at varying resolutions through the cross‐modal attention modules.
Conclusions
We introduced a cross‐modal Swin Transformer for automating the delineation of head and neck tumors in PET and CT images. Our model incorporates a cross‐modality attention module, enabling the exchange of features between modalities at multiple resolutions. The experimental results establish the superiority of our method in capturing improved inter‐modality correlations between PET and CT for head‐and‐neck tumor segmentation. Furthermore, the proposed methodology holds applicability to other semantic segmentation tasks involving different imaging modalities like SPECT/CT or PET/MRI. Code:https://github.com/yli192/SwinCross_CrossModalSwinTransformer_for_Medical_Image_Segmentation
A Spitzer survey for dust-obscured supernovae Fox, Ori D; Khandrika, Harish; Rubin, David ...
Monthly notices of the Royal Astronomical Society,
09/2021, Letnik:
506, Številka:
3
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Supernova (SN) rates serve as an important probe of star formation models and initial mass functions. Near-infrared seeing-limited ground-based surveys typically discover a factor of 3–10 ...fewer SNe than predicted from far-infrared luminosities owing to sensitivity limitations arising from both a variable point-spread function (PSF) and high dust extinction in the nuclear regions of star-forming galaxies. This inconsistency has potential implications for our understanding of star-formation rates and massive-star evolution, particularly at higher redshifts, where star-forming galaxies are more common. To resolve this inconsistency, a successful SN survey in the local universe must be conducted at longer wavelengths and with a space-based telescope, which has a stable PSF to reduce the necessity for any subtraction algorithms and thus residuals. Here, we report on a 2-yr Spitzer/IRAC 3.6 $\mu$m survey for dust-extinguished SNe in the nuclear regions of forty luminous infrared galaxies (LIRGs) within 200 Mpc. The asymmetric Spitzer PSF results in worse than expected subtraction residuals when implementing standard template subtraction. Forward-modelling techniques improve our sensitivity by several ∼1.5 mag. We report the detection of 9 SNe, five of which were not discovered by optical surveys. After adjusting our predicted rates to account for the sensitivity of our survey, we find that the number of detections is consistent with the models. While this search is none the less hampered by a difficult-to-model PSF and the relatively poor resolution of Spitzer, it will benefit from future missions, such as Roman and the James Webb Space Telescope, with higher resolution and more symmetric PSFs.
Using Smartphones for Indoor Fire Evacuation Kuo, Tzu-Wen; Lin, Ching-Yuan; Chuang, Ying-Ji ...
International journal of environmental research and public health,
05/2022, Letnik:
19, Številka:
10
Journal Article
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Fire smoke reduces the visibility of emergency direction signs, rendering them ineffective for providing appropriate guidance along evacuation routes in a fire situation. This is problematic because ...civilians may select evacuation routes that expose them to smoke or fire in a burning building. This study proposed using a smartphone voice-guided evacuation system (SVGES) to provide alternative evacuation routes for civilians trapped at a fire scene. To verify the efficacy of the SVGES, experiments were conducted with 26 participants in a simulated fire scenario. The experimental results showed that when using the SVGES, the participants chose the safest evacuation route with a 100% successful evacuation rate.
Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an ...oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the frequency of NTRK1 rearrangements in NSCLC and to assess the clinical activity of entrectinib.
We screened 1378 cases of NSCLC using anchored multiplex polymerase chain reaction (AMP). A patient with an NTRK1 gene rearrangement was enrolled onto a Phase 1 dose escalation study of entrectinib in adult patients with locally advanced or metastatic tumors (NCT02097810). We assessed safety and response to treatment.
We identified NTRK1 gene rearrangements at a frequency of 0.1% in this cohort. A patient with stage IV lung adenocrcinoma with an SQSTM1-NTRK1 fusion transcript expression was treated with entrectinib. Entrectinib was well tolerated, with no grade 3–4 adverse events. Within three weeks of starting on treatment, the patient reported resolution of prior dyspnea and pain. Restaging CT scans demonstrated a RECIST partial response (PR) and complete resolution of all brain metastases. This patient has continued on treatment for over 6 months with an ongoing PR.
Entrectinib demonstrated significant anti-tumor activity in a patient with NSCLC harboring an SQSTM1-NTRK1 gene rearrangement, indicating that entrectinib may be an effective therapy for tumors with NTRK gene rearrangements, including those with central nervous system metastases.
Myocardial fibrosis plays an important role in coxsackievirus B3 (CVB3) induced dilated cardiomyopathy. Excessive transforming growth factor (TGF)-β1 contributes to a pathologic excess of tissue ...fibrosis. We investigated the effect of astragaloside IV on myocardial fibrosis in CVB3-induced dilated cardiomyopathy. BALB/c mice were inoculated with CVB3 to induce acute viral myocarditis on day 7 (acute VMC group), monthly for 3
months to induce chronic myocarditis (chronic VMC group), and monthly for 9
months to induce dilated cardiomyopathy (DCM group). The same method was used for the DCM+Astra group as that of the DCM group, but former group was given with astragaloside IV-containing drinking water. Compared to DCM group, astragaloside IV treatment significantly increased the survival rate. Histological findings and the collagen volume fraction showed that astragaloside IV decreased fibrosis in heart tissues. Astragaloside IV decreased the level of the serum carboxy-terminal propeptide of procollagen type I (PICP) and the ratio of PICP/ N-terminal type I procollagen propeptide (PINP). Ameliorated myocardial fibrosis was consistent with the downregulated expression of TGF-β1 and its downstream pSmad2/3 and Smad4 in the myocardium of the DCM+Astra group compared to the DCM group. The level of type I collagen was lower in the DCM+Astra group than the DCM group. The same effect was found in the
in vitro study. These findings showed that astragaloside IV had a potent preventive effect on myocardial fibrosis in CVB3-induced dilated cardiomyopathy that might be due to downregulation of TGF-β1-Smad signaling.
Antibody-drug conjugates (ADC) have emerged as potent antitumor drugs that provide increased efficacy, specificity, and tolerability over chemotherapy for the treatment of cancer. ADCs generated by ...targeting cysteines and lysines on the antibody have shown efficacy, but these products are heterogeneous, and instability may limit their dosing. Here, a novel technology is described that enables site-specific conjugation of toxins to antibodies using chemistry to produce homogeneous, potent, and highly stable conjugates. We have developed a cell-based mammalian expression system capable of site-specific integration of a non-natural amino acid containing an azide moiety. The azide group enables click cycloaddition chemistry that generates a stable heterocyclic triazole linkage. Antibodies to Her2/neu were expressed to contain N6-((2-azidoethoxy)carbonyl)-l-lysine at four different positions. Each site allowed over 95% conjugation efficacy with the toxins auristatin F or a pyrrolobenzodiazepine (PBD) dimer to generate ADCs with a drug to antibody ratio of >1.9. The ADCs were potent and specific in in vitro cytotoxicity assays. An anti Her2/neu conjugate demonstrated stability in vivo and a PBD containing ADC showed potent efficacy in a mouse tumor xenograph model. This technology was extended to generate fully functional ADCs with four toxins per antibody. The high stability of the azide-alkyne linkage, combined with the site-specific nature of the expression system, provides a means for the generation of ADCs with optimized pharmacokinetic, biological, and biophysical properties.
Underground pipeline safety is a concern among civilians in populated urban cities. Due to the potential for considerable damage from underground pipeline leakages, it is critical to identify ...potential risk areas. This study developed a simplified risk value using risk assessment software (ALOHA) and geography information systems (SuperGIS and Surfer) to produce potential risk maps for underground pipeline leakage in a major urban city. A risk assessment of areas affected by underground pipeline leakage was performed for vapor diffusion, thermal radiation from combustion, and overpressure from an explosion. The results are applicable to disaster management departments and agencies in highly populated cities.
People tend to take their spatial cognition and wayfinding behaviors for granted while moving about in familiar spaces or traversing regular routes (e.g., the way to work). However, when an emergency ...occurs, even if people evacuate from a familiar venue, they are still likely to experience unexpected and irreparable tragedy. This study conducted an on-site experiment and a survey investigation. First-person view (FPV) floor plans were adopted to develop a relevant experiment, which was then used to investigate the relationship between wayfinding behavior and two influencing factors: floor plan cognition and distance. The t-tests for the accompanying questionnaire indicated that women (31%) are better than men (5.3%) in legend recognition and men (25.5%) outperform women (7.1%) in orientation; both findings achieved significance and are consistent with the results of previous studies conducted by neuroscientists. One-way ANOVA showed that when participants read a floor plan that was difficult to understand (not FPV), they took considerably more time (153.82 s) to reach the closer staircase than those who read a floor plan that was easy to understand and headed to the farther staircase (113.40 s). The understandability of floor plans is key to affecting the public’s evacuation time.
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