ABSTRACT
BACKGROUND: More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway. METHODS: In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. RESULTS: A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%). CONCLUSIONS: Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.).
Subject(s)
Antibodies, Monoclonal, Humanized , Drug Tapering , Polymyalgia Rheumatica , Humans , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Interleukin-6/antagonists & inhibitors , Polymyalgia Rheumatica/drug therapy , Prednisone/administration & dosage , Prednisone/adverse effects , Recurrence , Treatment Outcome , Antibodies, Monoclonal, Humanized/therapeutic use , Drug Tapering/methods , C-Reactive Protein/analysisABSTRACT
Stretchable electroluminescent devices represent an emerging optoelectronic technology for future wearables. However, their typical construction on sub-millimeter-thick elastomers has limited moisture permeability, leading to discomfort during long-term skin attachment. Although breathable textile displays may partially address this issue, they often have distinct visual appearances with discrete emissions from fibers or fiber junctions. This study introduces a convenient procedure to create stretchable, permeable displays with continuous luminous patterns. The design utilizes ultrathin nanocomposite devices embedded in a porous elastomeric microfoam to achieve high moisture permeability. These displays also exhibit excellent deformability, low-voltage operation, and excellent durability. Additionally, the device is decorated with fluorinated silica nanoparticles to achieve self-cleaning and washable capabilities. The practical implementation of these nanocomposite devices is demonstrated by creating an epidermal counter display that allows intimate integration with the human body. These developments provide an effective design of stretchable and breathable displays for comfortable wearing.
ABSTRACT
Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.
ABSTRACT
Currently, a major target in the development of Na-ion batteries is the concurrent attainment of high-rate capacity and long cycling stability. Herein, an advanced Na-ion battery with high-rate capability and long cycle stability based on Li/Ti co-doped P2-type Na0.67Mn0.67Ni0.33O2, a host material with high-voltage zero-phase transition behavior and fast Na+ migration/conductivity during dynamic de-embedding process, is constructed. Experimental results and theoretical calculations reveal that the two-element doping strategy promotes a mutually reinforcing effect, which greatly facilitates the transfer capability of Na+. The cation Ti4+ doping is a dominant high voltage, significantly elevating the operation voltage to 4.4 V. Meanwhile, doping Li+ shows the function in charge transfer, improving the rate performance and prolonging cycling lifespan. Consequently, the designed P2-Na0.75Mn0.54Ni0.27Li0.14Ti0.05O2 cathode material exhibits discharge capacities of 129, 104, and 85 mAh g- 1 under high voltage of 4.4 V at 1, 10, and 20 C, respectively. More importantly, the full-cell delivers a high initial capacity of 198 mAh g-1 at 0.1 C (17.3 mA g-1) and a capacity retention of 73% at 5 C (865 mA g-1) after 1000 cycles, which is seldom witnessed in previous reports, emphasizing their potential applications in advanced energy storage.
ABSTRACT
BACKGROUND: Targeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19. METHODS: In this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored. RESULTS: Geometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49-1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia. CONCLUSIONS: Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo. GOV IDENTIFIER: NCT04469621, first posted on clinicaltrials.gov on July 14, 2020.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , C-Reactive Protein , Double-Blind Method , Protein Kinase Inhibitors/adverse effects , Biomarkers , Protein Kinases , Threonine , Serine , Treatment Outcome , Receptor-Interacting Protein Serine-Threonine KinasesABSTRACT
Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Biomarkers/analysis , Research Design , Clinical Trials as TopicABSTRACT
Synaptic vesicle (SV) exo- and endocytosis are tightly coupled to sustain neurotransmission in presynaptic terminals, and both are regulated by Ca(2+). Ca(2+) influx triggered by voltage-gated Ca(2+) channels is necessary for SV fusion. However, extracellular Ca(2+) has also been shown to be required for endocytosis. The intracellular Ca(2+) levels (<1 microM) that trigger endocytosis are typically much lower than those (>10 microM) needed to induce exocytosis, and endocytosis is inhibited when the Ca(2+) level exceeds 1 microM. Here, we identify and characterize a transmembrane protein associated with SVs that, upon SV fusion, localizes at periactive zones. Loss of Flower results in impaired intracellular resting Ca(2+) levels and impaired endocytosis. Flower multimerizes and is able to form a channel to control Ca(2+) influx. We propose that Flower functions as a Ca(2+) channel to regulate synaptic endocytosis and hence couples exo- with endocytosis.
Subject(s)
Calcium Channels/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Endocytosis , Exocytosis , Synaptic Vesicles/metabolism , Animals , Calcium Channels/analysis , Drosophila Proteins/analysis , Drosophila melanogaster/cytology , Protein Isoforms/analysis , Protein Isoforms/metabolism , Synaptic Vesicles/chemistryABSTRACT
BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.
Subject(s)
Stomach Neoplasms , Humans , Middle Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/drug therapy , Combined Modality Therapy , Chemotherapy, Adjuvant , Chemoradiotherapy , Gastrectomy , Neoplasm StagingABSTRACT
BACKGROUND: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. METHODS: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. RESULTS: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. CONCLUSION: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.
Subject(s)
Dermatologic Agents , Psoriasis , Humans , Methotrexate/therapeutic use , Dermatologic Agents/therapeutic use , Treatment Outcome , Psoriasis/drug therapy , Psoriasis/genetics , Psoriasis/chemically induced , Polymorphism, Single NucleotideABSTRACT
The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.
Subject(s)
Escherichia coli O157 , Nanoparticles , Animals , Mice , DNA, Complementary , DNA , Escherichia coli O157/genetics , Food MicrobiologyABSTRACT
BACKGROUND: The aim of this study was to evaluate the psychological distress pre-operatively, at 3, 6, and 12 months in patients who underwent lumbar spine fusion surgery. METHODS: A total of 440 patients received instrumented lumbar spine fusion were enrolled. Psychological distress was evaluated using the Modified Somatic Perception Questionnaire (MSPQ) and the Modified Zung Depressive Index (ZDI). The results of lumbar fusion surgery were evaluated using the Oswestry Disability Index (ODI), the Japanese Orthopedic Association (JOA-29), and the visual analog scale (VAS). RESULTS: Psychological distress was reported among 23% of patients and 7, 5.5, and 4.0% of the patients preoperatively, at 3, 6, and 12 months after lumbar surgery, respectively. The mean MSPQ score decreased from 8.78 (before surgery) to 4.30, 3.52, and 3.43 at 3, 6 and 12 months in after surgery, respectively, in patients with psychological distress patients (p < 0.001). The mean ZDI score decreased from 17.78 to 12.48, 10.35, and 9.61 (p < 0.001). The mean ODI score decreased from 22.91 to 11.78, 10.13, and 9.96 (P < 0.001). The mean JOA score increased from 13.65 to 22.30, 23.43, and 23.61 (P < 0.001). The mean low back pain (LBP) VAS score decreased from 4.48 to 1.96, 1.52, and 1.51 (P < 0.001); moreover, the mean leg pain (LP) VAS score decreased from 5.30 to 1.30, 1.04, and 1.03 (P < 0.001). CONCLUSIONS: Patients with psychological distress may experience surgical intervention benefits equal to those of ordinary patients. Moreover, reduced pain and disability after surgical intervention may also alleviate psychological distress. Hence, we highly recommend that patients with psychological distress undergo surgical intervention as normal patients do, but appropriate screening measures and interventions are necessary.
Subject(s)
Psychological Distress , Spinal Fusion , Humans , Spinal Fusion/adverse effects , Lumbosacral Region , Neurosurgical Procedures , PainABSTRACT
TM2 domain containing (TM2D) proteins are conserved in metazoans and encoded by three separate genes in each model organism species that has been sequenced. Rare variants in TM2D3 are associated with Alzheimer's disease (AD) and its fly ortholog almondex is required for embryonic Notch signaling. However, the functions of this gene family remain elusive. We knocked-out all three TM2D genes (almondex, CG11103/amaretto, CG10795/biscotti) in Drosophila and found that they share the same maternal-effect neurogenic defect. Triple null animals are not phenotypically worse than single nulls, suggesting these genes function together. Overexpression of the most conserved region of the TM2D proteins acts as a potent inhibitor of Notch signaling at the γ-secretase cleavage step. Lastly, Almondex is detected in the brain and its loss causes shortened lifespan accompanied by progressive motor and electrophysiological defects. The functional links between all three TM2D genes are likely to be evolutionarily conserved, suggesting that this entire gene family may be involved in AD.
Subject(s)
Drosophila Proteins , Membrane Proteins , Neurogenesis , Receptors, Notch , Animals , Drosophila melanogaster/genetics , Drosophila Proteins/genetics , Gene Knockout Techniques , Membrane Proteins/genetics , Mutation/genetics , Neurogenesis/genetics , Neurons/metabolism , Receptors, Notch/genetics , Signal Transduction/geneticsABSTRACT
BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.
Subject(s)
Bone Density Conservation Agents , Gastrointestinal Diseases , Osteoporosis, Postmenopausal , Osteoporosis , Humans , Female , Teriparatide/therapeutic use , Teriparatide/pharmacology , Retrospective Studies , Postmenopause , Glucocorticoids/therapeutic use , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Bone Density , Diphosphonates/therapeutic use , Lumbar Vertebrae/diagnostic imaging , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/drug therapyABSTRACT
BACKGROUND: Young adults engage in behaviors that place them at risk for skin cancer. Dissemination of digital health promotion interventions via social media is a potentially promising strategy to modify skin cancer risk behaviors by increasing UV radiation (UVR) protection and skin cancer examinations. OBJECTIVE: This study aimed to compare 3 digital interventions designed to modify UVR exposure, sun protection, and skin cancer detection behaviors among young adults at moderate to high risk of skin cancer. METHODS: This study was a hybrid type II effectiveness-implementation randomized controlled trial of 2 active interventions, a digital skin cancer risk reduction intervention (UV4.me [basic]) compared with an enhanced version (UV4.me2 [enhanced]), and an electronic pamphlet (e-pamphlet). Intervention effects were assessed over the course of a year among 1369 US young adults recruited primarily via Facebook and Instagram. Enhancements to encourage intervention engagement and behavior change included more comprehensive goal-setting activities, ongoing proactive messaging related to previously established mediators (eg, self-efficacy) of UVR exposure and protection, embedded incentives for module completion, and ongoing news and video updates. Primary outcome effects assessed via linear regression were UVR exposure and sun protection and protection habits. Secondary outcome effects assessed via logistic regression were skin self-exams, physician skin exams, sunscreen use, indoor tanning, and sunburn. RESULTS: The active interventions increased sun protection (basic: P=.02; enhanced: P<.001) and habitual sun protection (basic: P=.04; enhanced P=.01) compared with the e-pamphlet. The enhanced intervention increased sun protection more than the basic one. Each active intervention increased sunscreen use at the 3-month follow-up (basic: P=.03; enhanced: P=.01) and skin self-exam at 1 year (basic: P=.04; enhanced: P=.004), compared with the e-pamphlet. Other intervention effects and differences between the Basic and Enhanced Intervention effects were nonsignificant. CONCLUSIONS: The active interventions were effective in improving several skin cancer risk and skin cancer prevention behaviors. Compared with the basic intervention, the enhanced intervention added to the improvement in sun protection but not other behaviors. Future analyses will explore intervention engagement (eg, proportion of content reviewed). TRIAL REGISTRATION: ClinicalTrials.gov NCT03313492; http://clinicaltrials.gov/ct2/show/NCT03313492.
Subject(s)
Skin Neoplasms , Humans , Skin Neoplasms/prevention & control , Young Adult , Male , Female , Adult , Social Media , Health Promotion/methods , Adolescent , Risk-TakingABSTRACT
PURPOSE: The aim of this study was to investigate the distribution of coronal plane alignment of the knee (CPAK) classification and functional knee phenotypes in a Chinese osteoarthritis (OA) population and to compare different lower limb alignment targets according to the distribution characteristics to find suitable total knee arthroplasty (TKA) bone cut strategies for the Chinese OA patients. METHODS: The computed tomography (CT) images were retrospectively collected and the three-dimensional (3D) models were reconstructed from 434 Chinese OA patients, including 93 males and 341 females, with a mean age of 66.4 ± 9.3 years. Femoral mechanical angle (FMA), tibial mechanical angle (TMA) and mechanical hip-knee-ankle angle (mHKA) were measured on the 3D models. Arithmetic hip-knee-ankle angle (aHKA) was calculated using FMA plus TMA, and joint line obliquity was calculated as 180 + TMA-FMA. The CPAK according to MacDessi and the functional knee phenotypes according to Hirschmann were performed. In addition, the suitable TKA bone cut strategies were explored according to the phenotypes and based on the characteristics of different alignment targets, such as mechanical alignment, anatomic alignment (AA), kinematic alignment, restricted KA (rKA) and adjusted MA (aMA). Statistical differences were determined using the independent-samples t-test or the two independent-samples Wilcoxon test, with p < 0.05 considered statistically significant. RESULTS: The Chinese OA population showed a varus alignment tendency (mHKA = 172.1° ± 7.2°), to which the TMA was a major contributor (TMA = 84.7° ± 4.4° vs. FMA = 91.3° ± 3.2°). The mHKA was on average 3.9° more varus than the aHKA. A total of 140 functional knee phenotypes were found and 45.6% were concentrated in VARFMA3°-NEUFMA0° to VARTMA3°-NEUTMA0°. More than 70% of patients had different FMA and TMA phenotypes. There were 92.9% of CPAK distributed in types I to IV, with type I accounting for 53.9%. The FMA phenotypes were less changed if the aMA and rKA were chosen, and the TMA phenotypes were less changed if the AA and rKA were chosen. CONCLUSION: Compared with the CPAK, the functional knee phenotypes were more suitable for the Chinese OA population with a wide distribution and a varus tendency, and it seemed more appropriate to choose aMA and rKA as TKA alignment targets for resection. LEVEL OF EVIDENCE: Level â ¢.
Subject(s)
Arthroplasty, Replacement, Knee , Imaging, Three-Dimensional , Osteoarthritis, Knee , Phenotype , Tomography, X-Ray Computed , Humans , Female , Male , Aged , Osteoarthritis, Knee/surgery , Osteoarthritis, Knee/diagnostic imaging , Middle Aged , Arthroplasty, Replacement, Knee/methods , Retrospective Studies , China , Knee Joint/diagnostic imaging , Knee Joint/surgery , Asian People , East Asian PeopleABSTRACT
BACKGROUND/PURPOSE: Biomaterial implants are emerging as a treatment choice for pleurodesis; however, the optimal biomaterial and form for managing spontaneous pneumothorax, particularly post-video-assisted thoracic surgery, remain under investigation. This study evaluated the mechanical and biological properties of the poly-ε-caprolactone (PCL) membrane as a sclerosing agent for pleurodesis in Landrace pigs. METHODS: Twenty-four Landrace pigs were split into two groups for mechanical abrasion and PCL membrane pleurodesis, with the latter group's PCL meshes inserted using video-assisted thoracic surgery. The mechanical and biological properties of the PCL membrane were assessed in pigs at three, six, and 12 months after the procedure. This assessment involved a range of techniques, such as the T-Peel test, macroscopic evaluation with a scoring scale, microscopic examination, and biomechanical and molecular weight analysis. RESULTS: The PCL membrane group outperformed the traditional abrasion group, with stronger adhesions seen over longer implantation durations. This group also showed superior and more consistent results in both macroscopic and microscopic evaluations compared to the control group. The membrane-based method was easier and faster to perform than the control group's method, and importantly, no mortality occurred following membrane implantation. CONCLUSION: This study is the pioneering effort to present long-term findings regarding the mechanical and biological properties of the PCL membrane in an in vivo animal model. The membrane demonstrated better adhesion ability than that of traditional abrasion and showed reassuring biocompatibility in both the pig model, suggesting its potential as treatment for patients with primary spontaneous pneumothorax. Further clinical studies are needed to support these observations.
Subject(s)
Biocompatible Materials , Pleurodesis , Polyesters , Animals , Swine , Pleurodesis/methods , Biocompatible Materials/administration & dosage , Pneumothorax/therapy , Thoracic Surgery, Video-Assisted/methods , Membranes, Artificial , Materials Testing , Disease Models, AnimalABSTRACT
BACKGROUND/PURPOSE: The global incidence of lip and oral cavity cancer continues to rise, necessitating improved early detection methods. This study leverages the capabilities of computer vision and deep learning to enhance the early detection and classification of oral mucosal lesions. METHODS: A dataset initially consisting of 6903 white-light macroscopic images collected from 2006 to 2013 was expanded to over 50,000 images to train the YOLOv7 deep learning model. Lesions were categorized into three referral grades: benign (green), potentially malignant (yellow), and malignant (red), facilitating efficient triage. RESULTS: The YOLOv7 models, particularly the YOLOv7-E6, demonstrated high precision and recall across all lesion categories. The YOLOv7-D6 model excelled at identifying malignant lesions with notable precision, recall, and F1 scores. Enhancements, including the integration of coordinate attention in the YOLOv7-D6-CA model, significantly improved the accuracy of lesion classification. CONCLUSION: The study underscores the robust comparison of various YOLOv7 model configurations in the classification to triage oral lesions. The overall results highlight the potential of deep learning models to contribute to the early detection of oral cancers, offering valuable tools for both clinical settings and remote screening applications.
ABSTRACT
Stretchable conductive nanocomposites are essential for deformable electronic devices. These conductors currently face significant limitations, such as insufficient deformability, significant resistance changes upon stretching, and drifted properties during cyclic deformations. To tackle these challenges, we present an electrically self-healing and ultrastretchable conductor in the form of bilayer silver nanowire/liquid metal microcapsule nanocomposites. These nanocomposites utilize silver nanowires to establish their initial excellent conductivity. When the silver nanowire networks crack during stretching, the microcapsules are ruptured to release the encased liquid metal for recovering the electrical properties. This self-healing capability allows the nanocomposite to achieve ultrahigh stretchability for both uniaxial and biaxial strains, minor changes in resistance during stretching, and stable resistance after repetitive deformations. The conductors have been used to create skin-attachable electronic patches and stretchable light-emitting diode arrays with enhanced robustness. These developments provide a bioinspired strategy to enhance the performance and durability of conductive nanocomposites.
ABSTRACT
The age, growth, reproduction and resource development status of Ptychidio jordani, as a critically endangered freshwater fish in the Hongshui River, China, was studied in this work. A total of 525 specimens were collected monthly using the cages and gillnets from October 2021 to September 2022 in the Hongshui River. The scale was used for age determination, and the maximum age for both female and male was estimated to be 5 years and 3 years, respectively. Female and male P. jordani showed different growth patterns, which were expressed as Lt = 261.3 (1-e-0.4885(t-0.1476) ) and Lt = 251.2 (1-e-0.4758(t+0.9643) ), respectively. The overall sex ratio was 1:0.47 (female:male). Female attained sex maturity at 2.34 years (192 mm body length). Month variation of the gonad somatic index indicated that the spawning period occurred from April to October. The absolute fecundity was estimated at 9046 ± 3434 eggs per individual, and the relative fecundity was 38.08 ± 15.77 eggs per gram. The exploitation rate of female and male was 0.233 and 0.495, which indicated that P. jordani was not overfishing. This study provided data on the key life-history traits of P. jordani, which has not been known previously and is essential for conservation strategy and policy development.
Subject(s)
Reproduction , Rivers , Female , Male , Animals , Fertility , Fresh Water , Fishes , SeasonsABSTRACT
In this work, industrial Kambara reactor desulphurization slag (KR slag) was indirectly carbonated. The effects of leaching time, leaching temperature, leaching agent types, and leaching agent concentration on the leaching ratio of calcium from KR slag were investigated. Subsequently, precipitated calcium carbonate (PCC) was synthesized by bubbling CO2 gas (flow rate of 15 mL/min) into 400 mL leaching solutions at 40 °C for 120 min with magnetic stirring at 300 rpm. It is found that calcium in KR slag can be selectively extracted using a diluted solution of ammonium acetate (CH3COONH4) or ammonium chloride (NH4Cl), while ammonium sulfate ((NH4)2SO4) solution is not suitable as leaching agent due to the formation of slightly soluble calcium sulfate (CaSO4). The leaching ratio of calcium is improved by extending the leaching time or increasing the leaching solvent concentration. However, leaching temperature has little effect on calcium extraction. After carbonating the NH4Cl- and CH3COONH4-leachate for 120 min, calcite and vaterite type PCC with a purity of 99% is synthesized. Each gram of KR slag can produce 0.794 g and 0.803 g PCC using NH4Cl and CH3COONH4 leaching agents respectively. Calculations show that 349.6 kg CO2 is captured by per ton of KR slag. The CO2 capture capacity of KR slag is significantly higher compared with previously studied materials.