Search Results (39)

Background: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). Methods: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. Results: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2–4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3–28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8–21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. Conclusions: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort. Full article

Introduction: Arthrodesis of the sacroiliac joint (SIJ) has evolved over the last 5 years, with many trajectory strategies emerging. Innovation has outpaced data generation on the safety and efficacy of novel SIJ arthrodesis techniques. This retrospective review of the use of a SiLO TFX SIJ fusion system provides 12-month post-implant outcome data that can be compared with other techniques from published literature. Methods: A retrospective analysis was performed on patients that underwent the SiLO TFX sacroiliac joint fusion procedure at eight sites with data on pain reduction and functional improvement from baseline, as measured by a numerical rating scale (NRS) and Oswestry Disability Index (ODI), along with some safety and device integrity assessments recorded at 12 months post-implant. Safety was assessed by identifying key serious adverse events (bleeding, infection, nerve injury), and device integrity was assessed by evaluating misplaced or malfunctioned devices. ODI and NRS outcomes were compared with published rates from the literature. Results: Between 16 March 2023 and 20 February 2024, 42 subjects with 12-month ODI data available were enrolled. The subjects had a mean age of 60 ± 11 years, and 71% were female. The mean ODI score of 33 ± 15 at baseline improved to 17 ± 11 at 12 months, with a statistically significant improvement from baseline of 16 ± 15 (p < 0.0001). Furthermore, 52% of subjects had a 15-point absolute ODI improvement. Mean NRS of 7.1 ± 2.8 at baseline improved to 2.9 ± 2.2 at 12 months with a statistically significant reduction in pain of 4.2 ± 3.4 (p < 0.0001). No key serious adverse events or device integrity complications were noted. Subgroup analyses for a cohort of subjects with baseline ODI ≥ 30 and VAS pain ≥ 50 demonstrated that performance was similar to that in previously published literature with a mean improvement in ODI of 23.3 ± 12.7 (p < 0.0001) with 78% of subjects achieving a 15-point improvement at 12 months, and mean NRS improving by 4.7 ± 3.0 (p < 0.0001) with 88.9% achieving an improvement of 2 points. Conclusions: This data supports the safety and efficacy of SiLO TFX for SIJ fusion. The retrospective outcomes are comparable to those published for lateral-approach SIJ fusion. As follow up is limited to 12 months in this retrospective dataset; long-term fusion and cost-effectiveness remain to be addressed. Prospective, randomized controlled trials with a larger cohort are needed further to compare SiLO TFX to other available SIJ fusion techniques. Full article

Background/Objectives: Additive manufacturing (AM) enables the production of cementless acetabular cups with porous surfaces that facilitate early osseointegration. Directed energy deposition (DED), a form of AM, allows the direct welding of porous structures onto metal substrates without requiring a vacuum environment, offering advantages over conventional powder bed fusion methods. Despite growing interest in DED, no prospective clinical studies evaluating DED-based acetabular components have been published to date. This study assessed short-term outcomes of a DED-based 3D-printed acetabular cup in total hip arthroplasty (THA). Methods: A total of 120 patients who underwent primary cementless THA using the Corentec Mirabo Z^® acetabular cup were prospectively enrolled. Among them, 124 hips from 100 patients who had completed a minimum of 24 months of follow-up were included in the analysis. Clinical outcomes were assessed using the Harris hip score (HHS), WOMAC, EQ-5D-5L, and pain NRS. Radiographic evaluation included measurements of cup position, osseointegration, and detection of interfacial or polar gaps on CT and plain radiographs. Implant-related complications were also recorded. Results: At a mean follow-up of 34.6 months, the implant survival rate was 99.3%, with one revision due to suspected osseointegration failure. The HHS improved from 56.6 to 91.4 at 24 months, and the NRS decreased from 6.2 to 1.1 (both p < 0.001). Interfacial gaps were observed in 58.1% of cases on CT, though most were <1 mm and not clinically significant. Common postoperative issues included greater trochanteric pain syndrome, squeaking, and iliotibial band tightness, all of which were resolved with conservative treatment. Conclusions: DED-based 3D-printed acetabular cups demonstrated favorable short-term clinical and radiographic outcomes, with high survivorship and reliable early osseointegration in cementless THA. Full article

The eri silkworm Samia cynthia ricini (S. ricini) is an economically and scientifically significant lepidopteran species, though its genomic resources have remained limited. Here, we present a chromosome-level genome assembly for S. ricini generated through integrated long-read, short-read, and Hi-C sequencing data. The final 456.16 Mb assembly spans 14 chromosomes, exhibiting 98.5% BUSCO completeness and a 48.51% repetitive content. Functional annotation of the 15,729 protein-coding genes against five major databases (NR, SwissProt, Pfam, GO, and KEGG) revealed a maximum annotation rate of 92.71%, demonstrating high gene set quality. Comparative genomics with B. mori uncovered conserved syntenic blocks interspersed with chromosomal fusion/fission events and inversions. We further identified 4.27 million SNPs, 1.02 million InDels, and 53,367 SVs, establishing the first comprehensive variation map for this species. These genomic variations provide a foundation for marker-assisted breeding programs and trait association studies. All the genomic resources and interactive visualization tools were integrated into the SilkMeta database. This study establishes S. ricini as a pivotal resource for comparative lepidopteran genomics and accelerates molecular breeding programs for this agriculturally valuable insect. Full article

To enhance positioning capability and reliability within existing Communication Navigation Fusion Systems (CNFSs), this paper proposes an Asymmetric Double-Sideband Composite Localization Signal (ADCLS) and a dual-carrier aggregation dual-code loop tracking mechanism with fuzzy control. By organically integrating an embedded signal into the original positioning signal, the code loop is optimized via fuzzy control, while the ADCLS signal is processed as an asymmetric double-sideband signal for joint signal extraction. Experimental validation employs the 5G New Radio (NR) Time-Delay Line (TDL) channel model to simulate multipath propagation effects. The results show that this method improves the tracking accuracy of the code loop and the main carrier loop, thereby enhancing the ranging accuracy. Full article

Pain assessment is a challenging task for clinicians due to its subjective nature, particularly in individuals with communication difficulties, cognitive impairments, or severe disabilities. Traditional methods such as the Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), and Verbal Rating Scale (VRS) rely heavily on patient feedback, which can be inconsistent and subjective. To address these limitations, developing objective and reliable pain assessment tools that incorporate advanced technologies, such as multimodal data integration from video and fNIRS, is important for improving clinical outcomes. However, challenges such as noise susceptibility in fNIRS signals must be carefully addressed to realize their full potential. Recent studies have explored automatic pain assessment using machine learning and deep learning techniques, which require high-quality data that can accurately represent pain categories. In response to the introduction of a new dataset in the AI4Pain Challenge, we proposed a multimodal neural network model utilizing attention-based fusion to improve overall accuracy (MMAPA). Our model leverages video and fNIRS modalities as well as manually extracted statistical features. We also implemented fNIRS signal preprocessing and artifact noise filtering, which significantly improved performance on both the fNIRS and statistical feature branches. On the hidden test set, our model achieved an accuracy of 51.33%, outperforming the official baseline of 43.33%. To evaluate generalizability, we further tested our method on the BioVid Heat Pain Database, where our fusion model achieved the highest accuracy in the 10-fold cross-validation setting, outperforming PainAttNet and unimodal variants. These results highlight the effectiveness of our multimodal attention-based approach in improving pain classification performance across datasets. Full article

Introduction: Adolescent/young adult (AYA) patients with metastatic soft tissue sarcoma (STS) typically face a dismal prognosis. However, a subset of patients with incurable disease lives beyond two years. Due to the rarity of diagnoses and inherent heterogeneity within this population, a paucity of data exists regarding the experiences of AYAs with an indolent course (and how to best capture these experiences). With increasing biological insight and clinical experience, including the use of targeted or immune therapies, it is anticipated that more such patients will experience prolonged survival. Our pilot study aimed to describe the clinical characteristics and illness experiences of AYAs with incurable yet indolent metastatic STS who were living two years after their diagnoses. Our exploratory aim was to generate a conceptual framework that could subsequently be tested in a multi-center study with a larger cohort of patients. Materials and Methods: Patients with metastatic incurable STS, aged 15–39 years at diagnosis, and at least two years from diagnosis, were eligible. Patients were recruited over a two-year period at a quaternary children’s hospital with a comprehensive AYA oncology program. Participants completed a demographic form and PROMIS short form questionnaires for seven domains and answered an open-ended question. Responses to open-ended questions were coded independently by two authors and utilized to generate themes. Clinical variables were collected from medical records. Results: Five patients completed questionnaires. Mean age was 29.4 years (18.5–39.8 years) at diagnosis and 34 years (23.2–45.7 years) at study. Three patients were female; two were male; four were White; and one was Black/African American. Diagnoses included ASPSCR1::TFE3 alveolar soft part sarcoma; WWTR1::CAMTA1 epithelioid hemangioendothelioma; INI-1 deficient epithelioid sarcoma; EWSR1::NR4A3 extra-skeletal myxoid chondrosarcoma; and low-grade ARHGAP23::FER spindle cell malignancy, a novel fusion-driven sarcoma. Mean time since diagnosis was 4.5 years (2.6–6 years), and mean treatment duration was 4.2 years (1.5–6 years). On average, patients received 4.8 lines (range 2–8 lines) of antineoplastic therapy. All patients received at least one targeted therapy or immune checkpoint inhibitor. Patients reported increased fatigue and anxiety and decreased physical function compared to the standardized US reference population. Themes emerging from qualitative responses included managing physical symptoms, navigating feelings of guilt and inadequacy, self-reflection generating gratitude, and changing illness experiences over time. Conclusions: AYA patients living with incurable metastatic soft tissue sarcoma for more than two years were treated with multiple lines of antineoplastic therapy longitudinally. PROMIS data identified fatigue, anxiety, and decreased physical function within this population. Exploratory thematic analysis of qualitative responses generated concepts that could be further tested in an expanded cohort of patients. Full article

The large number of tires produced annually demands new recycling methods. A key challenge associated with recycling elastomers is their crosslinking structure that prevents fusion. It is possible to reverse crosslinking through a process called devulcanization. Devulcanized elastomers can be blended with fresh rubber and revulcanized for reuse. This paper examines samples made from natural rubber (NR), styrene–butadiene rubber (SBR), and nitrile butadiene rubber (NBR), blended with varying proportions of devulcanized ground tire rubber (dGTR) and newly revulcanized rubber. SiO₂, commonly present in tire formulations, is also added. Samples of these materials, with 0, 10, 20, and 40 phr of dGTR are subjected to accelerated degradation for 0, 30, 60, 120, and 240 h. The effects of this treatment, the influence of SiO₂, and the presence of a silane-based devulcanization agent (TESPT) that promotes the interaction between the rubber and silica, are analyzed at the microstructural level (FTIR, TGA, SEM) and through mechanical properties testing. The microstructural results of the spectroscopy and thermal analysis show that interactions between dGTR, silica, and silane compounds form aggregates that impact the material properties and degradation of the tires. Mechanically, when the sample contained up to 20 phr of dGTR, the compound presented a more brittle behavior, due to the crosslinking induced by the degradation. Full article

Background: Restoring electrical synchrony with cardiac resynchronization therapy (CRT) reverses the heart failure phenotype developed by left-ventricular (LV) dyssynchrony. This study aimed to identify new predictors of response to LV-only fusion pacing CRT. Methods: A select group of patients with CRT-P indications received a right atrium (RA)/LV DDD pacing system. LV dyssynchrony was assessed via offline TDI timing focusing on the temporal difference between peak septal (E″T) and lateral wall (A“T) motion. CRT effectiveness was evaluated at each follow-up, involving the heart rate recovery index (HRRI) parameter (acceleration/deceleration time) derived from exercise testing along with the echocardiographic parameters. Patients were classified into super-responders (SR), responders (R), and non-responders (NR). Results: Baseline initial characteristics: 62 patients (35 male) aged 62 ± 11 y.o. with non-ischemic dilated cardiomyopathy (DCM). Ejection fraction (EF) 27 ± 5.2%; QRS 164 ± 18 ms; 29% had type III diastolic dysfunction (DD), 63% type II DD, and 8% type I DD. Average follow-up was 45 ± 19 months: 34% of patients were SR, 61% R, and 5% NR. The E″T decreased from 90 ± 20 ms to 25 ± 10 ms in SR, with a shorter deceleration time (DT) during exercise test compared to NR (109 ± 68 ms vs. 330 ± 30 ms; p < 0.0001). The responders present a higher HRRI (2.87 ± 1.47 vs. 0.98 ± 0.08; p = 0.03) compared to NR and a significantly decrease in E“T and A“T from 76 ± 13 ms to 51 ± 11 ms (p < 0.0001). Prolonged DT was associated with an accentuated LV dyssynchrony and nonoptimal response to CRT. Conclusions: The study identified new parameters for assessing responsiveness to LV-only fusion pacing CRT, which could improve candidate selection and CRT implementation. Full article

Background/Objectives: Enhanced recovery after surgery (ERAS) protocols optimize perioperative care and improve recovery. This study evaluated the effectiveness of ERAS in one- or two-level posterior lumbar fusion surgeries, focusing on perioperative medication use, pain management, and functional outcomes. Methods: Eighty-eight patients undergoing lumbar fusion surgery between March 2021 and February 2022 were allocated into pre-ERAS (n = 41) and post-ERAS (n = 47) groups. Outcomes included opioid and antiemetic consumption, pain scores (numerical rating scale (NRS)), functional recovery (Oswestry Disability Index (ODI) and EuroQol 5 Dimension (EQ-5D)), and complication rates. Pain was assessed daily for the first four postoperative days and at 6 months. Linear Mixed Effects Model analysis evaluated pain trajectories. Results: The post-ERAS group showed significantly lower opioid (p = 0.005) and antiemetic (p < 0.001) use. No significant differences were observed in NRS pain scores in the first 4 postoperative days. At 6 months, the post-ERAS group reported significantly lower leg pain (p = 0.002). The time:group interaction was not significant for back (p = 0.848) or leg (p = 0.503) pain. Functional outcomes at 6 months, particularly ODI and EQ-5D scores, showed significant improvement in the post-ERAS group. Complication rates were lower in the post-ERAS group (4.3% vs. 19.5%, p = 0.024), while hospital stay and fusion rates remained similar. Conclusions: The ERAS protocol significantly reduced opioid and antiemetic use, improved long-term pain management and functional recovery, and lowered complication rates in lumbar fusion patients. These findings support the implementation of ERAS protocols in spinal surgery, emphasizing their role in enhancing postoperative care. Full article

Despite recent notable advancements in highlight image restoration techniques, the dearth of annotated data and the lightweight deployment of highlight removal networks pose significant impediments to further advancements in the field. In this paper, to the best of our knowledge, we first propose a semi-supervised learning paradigm for highlight removal, merging the fusion version of a teacher–student model and a generative adversarial network, featuring a lightweight network architecture. Initially, we establish a dependable repository to house optimal predictions as pseudo ground truth through empirical analyses guided by the most reliable No-Reference Image Quality Assessment (NR-IQA) method. This method serves to assess rigorously the quality of model predictions. Subsequently, addressing concerns regarding confirmation bias, we integrate contrastive regularization into the framework to curtail the risk of overfitting on inaccurate labels. Finally, we introduce a comprehensive feature aggregation module and an extensive attention mechanism within the generative network, considering a balance between network performance and computational efficiency. Our experimental evaluations encompass comprehensive assessments on both full-reference and non-reference highlight benchmarks. The results demonstrate conclusively the substantive quantitative and qualitative enhancements achieved by our proposed algorithm in comparison to state-of-the-art methodologies. Full article

This study aimed to evaluate the safety and efficacy of a novel Poly-Ether-Ether-Ketone (PEEK) expandable vertebral body replacement (VBR) for anterior cervico-thoracic vertebral column reconstruction in patients with metastatic, traumatic, or degenerative diseases. Radiographic and clinical outcomes, as well as complication rates, were analyzed in a retrospective analysis of 28 patients (61 ± 13 years; 64% female) who underwent an anterior cervical corpectomy and fusion (ACCF) with the Expandable Corpectomy Device (ECD) from DePuy/Synthes (2011–2020). Correction of the bisegmental kyphotic angle (BKA) was chosen as the primary outcome. Bony fusion, loss of device height, and implant subsidence were evaluated additionally. Clinical outcome was assessed using Odom’s criteria, the numerical pain rating scale (NRS), the American Spinal Injury Association Impairment Scale (AIS), and the Karnofsky Performance Status Scale (KPSS). Our study found a significant improvement in the BKA (12.3° ± 9.6°; p = 0.0002) at the last follow-up with no statistically relevant loss of device height (p = 0.96) or implant subsidence (p = 0.99). Successful bony fusion was observed in all patients. The KPSS significantly improved in patients with a tumorous disease at the time of discharge (p = 0.0009), and the sensation of pain showed significant improvement at six months post-operatively and at the final follow-up (p = 0.004; p = 0.021). However, four patients needed further secondary posterior stabilization, and one ECD was explanted due to a severe surgical site infection after an accidental esophageal lesion. In conclusion, the ECD proofed the radiographic stability for the anterior column reconstruction of the cervico-thoracic spine with significantly improved clinical outcome. Full article

Image preprocessing and fusion are commonly used for enhancing remote-sensing images, but the resulting images often lack useful spatial features. As the majority of research on image fusion has concentrated on the satellite domain, the image-fusion task for Unmanned Aerial Vehicle (UAV) images has received minimal attention. This study investigated an image-improvement strategy by integrating image preprocessing and fusion tasks for UAV images. The goal is to improve spatial details and avoid color distortion in fused images. Techniques such as image denoising, sharpening, and Contrast Limited Adaptive Histogram Equalization (CLAHE) were used in the preprocessing step. The unsharp mask algorithm was used for image sharpening. Wiener and total variation denoising methods were used for image denoising. The image-fusion process was conducted in two steps: (1) fusing the spectral bands into one multispectral image and (2) pansharpening the panchromatic and multispectral images using the PanColorGAN model. The effectiveness of the proposed approach was evaluated using quantitative and qualitative assessment techniques, including no-reference image quality assessment (NR-IQA) metrics. In this experiment, the unsharp mask algorithm noticeably improved the spatial details of the pansharpened images. No preprocessing algorithm dramatically improved the color quality of the enhanced images. The proposed fusion approach improved the images without importing unnecessary blurring and color distortion issues. Full article

Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. EWSR1 is a ‘promiscuous’ gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of EWSR1 translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving EWSR1 in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3′ partners, NR4A2 and RORB, which have not been previously reported. NR4A2 may functionally replace NR4A3, the usual 3′ partner in extraskeletal myxoid chondrosarcoma. The third GF, EWSR1::BEND2, has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing EWSR1 fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting. Full article

The Chinese soft-shelled turtle (Pelodiscus sinensis), an economically important aquatic species in China, displays considerable sexual dimorphism: the male P. sinensis is larger and, thus, more popular in the market. In this study, we obtained the full-length (FL) transcriptome data of P. sinensis by using Pacific Biosciences (PacBio)’s isoform sequencing and analyzed the transcriptome structure. In total, 1,536,849 high-quality FL transcripts were obtained through single-molecule real-time (SMRT) sequencing, which were then corrected using Illumina sequencing data. Next, 89,666 nonredundant FL transcripts were generated after mapping to the reference genome of P. sinensis; 291 fusion genes and 17,366 novel isoforms were successfully annotated using data from the nonredundant protein sequence database (NR), eukaryotic orthology groups (KOG), the Gene Ontology (GO) project, and the KEGG Orthology (KO) database. Additionally, 19,324 alternative polyadenylation sites, 101,625 alternative splicing events, 12,392 long noncoding RNAs, and 5916 transcription factors were identified. Smad4, Wif1, and 17-β-hsd were identified as female-biased genes, while Nkd2 and Prp18 held a higher expression level in males than females. In summary, we found differences between male and female P. sinensis individuals in AS, lncRNA, genes, and transcripts, which relate to the Wnt pathway, oocyte meiosis, and the TGF-β pathway. Female-biased genes such as Smad4, Wif1, and 17-β-hsd and male-biased genes such as Nkd2 and Prp18 played important roles in the sex determination of P. sinensis. FL transcripts are a precious resource for characterizing the transcriptome of P. sinensis, laying the foundation for further research on the sex-determination mechanisms of P. sinensis. Full article