ABSTRACT
Existing panoramic layout estimation solutions tend to recover room boundaries from a vertically compressed sequence, yielding imprecise results as the compression process often muddles the semantics between various planes. Besides, these data-driven approaches impose an urgent demand for massive data annotations, which are laborious and time-consuming. For the first problem, we propose an orthogonal plane disentanglement network (termed DOPNet) to distinguish ambiguous semantics. DOPNet consists of three modules that are integrated to deliver distortion-free, semantics-clean, and detail-sharp disentangled representations, which benefit the subsequent layout recovery. For the second problem, we present an unsupervised adaptation technique tailored for horizon-depth and ratio representations. Concretely, we introduce an optimization strategy for decision-level layout analysis and a 1D cost volume construction method for feature-level multi-view aggregation, both of which are designed to fully exploit the geometric consistency across multiple perspectives. The optimizer provides a reliable set of pseudo-labels for network training, while the 1D cost volume enriches each view with comprehensive scene information derived from other perspectives. Extensive experiments demonstrate that our solution outperforms other SoTA models on both monocular layout estimation and multi-view layout estimation tasks.
ABSTRACT
Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5â¯mg/kg, 5 times/week) and moderate tibial loading (4.5â¯N peak load, 4â¯Hz, 300â¯cycles for 5â¯days/week), individually and combined, on mature mice (~50â¯weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by -4.3â¯% over four weeks and the bone deterioration occurred in the majority (64â¯%) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3â¯%, +9.5â¯%, +12.0â¯% and increased the % of samples with positive Ct.pMOI changes by +32â¯%, +26â¯%, and +43â¯%, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5â¯mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0â¯%, +15â¯%, and +29â¯% relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.
ABSTRACT
Currently, there are no commercially available plant-based products that replicate the flavor profile of roasted fish. As the increasing demand of plant-based meat in the recent years, the exploration of plant-based meat flavors holds significant importance. This study revealed that a blend of lysine, leucine, glutamic acid, alanine, cysteine, glucose, and algae oil (rich in docosahexaenoic acid, DHA), when subjected to heating in low pH, generated the distinct flavor like roasted mackerel. The precursor, mechanism and flavor note were investigated. Key aromatic compounds such as isovaleric acid, octanoic acid, 1,5-octadien-3-one, 2,4-octadienal, 2-octenal, furaneol, 2,5-furandicarboxaldehyde, and 2-pentenylfuran were found as important contributors in the reaction flavor model. These compounds primarily derived from heat-induced lipid oxidation, lipid degradation, and Maillard reaction of these plant-based ingredients. The development of plant-based meat flavors is crucial for promoting the substantial progress of plant-based meat products.
ABSTRACT
This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.
Subject(s)
Apoptosis , Cell Movement , Cell Proliferation , Colonic Neoplasms , GTPase-Activating Proteins , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , p21-Activated Kinases , Humans , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Cell Proliferation/genetics , GTPase-Activating Proteins/metabolism , GTPase-Activating Proteins/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , p21-Activated Kinases/metabolism , p21-Activated Kinases/genetics , Cell Movement/genetics , Apoptosis/genetics , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic , Male , Female , Middle Aged , PrognosisABSTRACT
Trace natural products (TNPs) are still the vital source of drug development. However, the mining of novel TNPs is becoming increasingly challenging due to their low abundance and complex interference. A comprehensive strategy was proposed in which the functionalized magnetic particles integrated with LC-MS for TNPs discovery. Under the guidance of the approach, fifteen trace Nuphar alkaloids including seven new ones, cyanopumiline A sulfoxide (1), cyanopumiline C sulfoxide (8) and cyanopumilines A-E (4-5, 10, 12-13) featuring an undescribed nitrile-containing 6/6/5/6/6 pentacyclic ring system were isolated from the rhizomes of Nuphar pumila. Their structures and absolute configurations were determined on the basis of detailed spectroscopic data analysis and single-crystal X-ray diffraction analysis. Notably, a concise method based on 13C NMR spectroscopy was established to determine the relative configurations of spiroatoms. Biologically, compounds 1-12 exhibited potent immunosuppressive activities with IC50 values ranging from 0.1-12.1 µM against anti-CD3/CD28 induced human peripheral T cell proliferation. Mechanistic studies revealed that 4 could dose-dependently decrease pro-inflammatory cytokines and the expression levels of CD25 and CD71.
Subject(s)
Alkaloids , Cell Proliferation , Dose-Response Relationship, Drug , Immunosuppressive Agents , Humans , Cell Proliferation/drug effects , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Molecular Structure , Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , Structure-Activity Relationship , Chromatography, Liquid , Drug Discovery , T-Lymphocytes/drug effects , Mass Spectrometry , Liquid Chromatography-Mass SpectrometryABSTRACT
Thin-plate spline (TPS) is a principal warp that allows for representing elastic, nonlinear transformation with control point motions. With the increase of control points, the warp becomes increasingly flexible but usually encounters a bottleneck caused by undesired issues, e.g., content distortion. In this paper, we explore generic applications of TPS in single-image-based warping tasks, such as rotation correction, rectangling, and portrait correction. To break this bottleneck, we propose the coupled thin-plate spline model (CoupledTPS), which iteratively couples multiple TPS with limited control points into a more flexible and powerful transformation. Concretely, we first design an iterative search to predict new control points according to the current latent condition. Then, we present the warping flow as a bridge for the coupling of different TPS transformations, effectively eliminating interpolation errors caused by multiple warps. Besides, in light of the laborious annotation cost, we develop a semi-supervised learning scheme to improve warping quality by exploiting unlabeled data. It is formulated through dual transformation between the searched control points of unlabeled data and its graphic augmentation, yielding an implicit correction consistency constraint. Finally, we collect massive unlabeled data to exhibit the benefit of our semi-supervised scheme in rotation correction. Extensive experiments demonstrate the superiority and universality of CoupledTPS over the existing state-of-the-art (SoTA) solutions for rotation correction and beyond. The code and data will be available at https://github.com/nie-lang/CoupledTPS.
ABSTRACT
Single-molecule localization microscopy (SMLM) based on temporal-focusing multiphoton excitation (TFMPE) and single-wavelength excitation is used to visualize the three-dimensional (3D) distribution of spontaneously blinking fluorophore-labeled subcellular structures in a thick specimen with a nanoscale-level spatial resolution. To eliminate the photobleaching effect of unlocalized molecules in out-of-focus regions for improving the utilization rate of the photon budget in 3D SMLM imaging, SMLM with single-wavelength TFMPE achieves wide-field and axially confined two-photon excitation (TPE) of spontaneously blinking fluorophores. TPE spectral measurement of blinking fluorophores is then conducted through TFMPE imaging at a tunable excitation wavelength, yielding the optimal TPE wavelength for increasing the number of detected photons from a single blinking event during SMLM. Subsequently, the TPE fluorescence of blinking fluorophores is recorded to obtain a two-dimensional TFMPE-SMLM image of the microtubules in cancer cells with a localization precision of 18±6 nm and an overall imaging resolution of approximately 51â nm, which is estimated based on the contribution of Nyquist resolution and localization precision. Combined with astigmatic imaging, the system is capable of 3D TFMPE-SMLM imaging of brain tissue section of a 5XFAD transgenic mouse with the pathological features of Alzheimer's disease, revealing the distribution of neurotoxic amyloid-beta peptide deposits.
Subject(s)
Fluorescent Dyes , Fluorescent Dyes/chemistry , Humans , Mice , Animals , Microscopy, Fluorescence, Multiphoton/methods , Single Molecule Imaging/methods , Photons , Microtubules/metabolism , Microtubules/chemistryABSTRACT
BACKGROUND AND OBJECTIVE: Local advanced rectal cancer (LARC) poses significant treatment challenges due to its location and high recurrence rates. Accurate early detection is vital for treatment planning. With magnetic resonance imaging (MRI) being resource-intensive, this study explores using artificial intelligence (AI) to interpret computed tomography (CT) scans as an alternative, providing a quicker, more accessible diagnostic tool for LARC. METHODS: In this retrospective study, CT images of 1070 T3-4 rectal cancer patients from 2010 to 2022 were analyzed. AI models, trained on 739 cases, were validated using two test sets of 134 and 197 cases. By utilizing techniques such as nonlocal mean filtering, dynamic histogram equalization, and the EfficientNetB0 algorithm, we identified images featuring characteristics of a positive circumferential resection margin (CRM) for the diagnosis of locally advanced rectal cancer (LARC). Importantly, this study employs an innovative approach by using both hard and soft voting systems in the second stage to ascertain the LARC status of cases, thus emphasizing the novelty of the soft voting system for improved case identification accuracy. The local recurrence rates and overall survival of the cases predicted by our model were assessed to underscore its clinical value. RESULTS: The AI model exhibited high accuracy in identifying CRM-positive images, achieving an area under the curve (AUC) of 0.89 in the first test set and 0.86 in the second. In a patient-based analysis, the model reached AUCs of 0.84 and 0.79 using a hard voting system. Employing a soft voting system, the model attained AUCs of 0.93 and 0.88, respectively. Notably, AI-identified LARC cases exhibited a significantly higher five-year local recurrence rate and displayed a trend towards increased mortality across various thresholds. Furthermore, the model's capability to predict adverse clinical outcomes was superior to those of traditional assessments. CONCLUSION: AI can precisely identify CRM-positive LARC cases from CT images, signaling an increased local recurrence and mortality rate. Our study presents a swifter and more reliable method for detecting LARC compared to traditional CT or MRI techniques.
ABSTRACT
BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.
Subject(s)
Aortic Dissection , Hospital Mortality , Shock , Humans , Female , Male , Aortic Dissection/surgery , Aortic Dissection/complications , Aortic Dissection/mortality , Middle Aged , Shock/mortality , Shock/surgery , Retrospective Studies , Prognosis , Aged , Risk Factors , Postoperative Complications/mortality , Postoperative Complications/etiology , Treatment Outcome , Preoperative Period , Aortic Aneurysm/surgery , Aortic Aneurysm/complications , Aortic Aneurysm/mortality , Acute DiseaseABSTRACT
BACKGROUND: Although indicator condition (IC)-guided HIV testing (IC-HIVT) is effective at facilitating timely HIV diagnosis, research on IC categories and the related HIV risk in Taiwan is limited. To improve the adoption and spread of IC-HIVT in Taiwan, this study compared the IC categories of people living with HIV (PLWH) and non-HIV controls and investigated delays in the diagnosis of HIV infection. METHODS: This nationwide, retrospective, 1:10-matched case-control study analyzed data from the Notifiable Diseases Surveillance System and National Health Insurance Research Database to evaluate 42 ICs for the 5-year period preceding a matched HIV diagnostic date from 2009 to 2015. The ICs were divided into category 1 ICs (AIDS-defining opportunistic illnesses [AOIs]), category 2 ICs (diseases associated with impaired immunity or malignancy but not AOIs), category 3 ICs (ICs associated with sexual behaviors), and category 4 ICs (mononucleosis or mononucleosis-like syndrome). Logistic regression was used to evaluate the HIV risk associated with each IC category (at the overall and annual levels) before the index date. Wilcoxon rank-sum test was performed to assess changes in diagnostic delays following an incident IC category by HIV transmission routes. RESULTS: Fourteen thousand three hundred forty-seven PLWH were matched with 143,470 non-HIV controls. The prevalence results for all ICs and category 1-4 ICs were, respectively, 42.59%, 11.16%, 15.68%, 26.48%, and 0.97% among PLWH and 8.73%, 1.05%, 4.53%, 3.69%, and 0.02% among non-HIV controls (all P < 0.001). Each IC category posed a significantly higher risk of HIV infection overall and annually. The median (interquartile range) potential delay in HIV diagnosis was 15 (7-44), 324.5 (36-947), 234 (13-976), and 74 (33-476) days for category 1-4 ICs, respectively. Except for category 1 for men who have sex with men, these values remained stable across 2009-2015, regardless of the HIV transmission route. CONCLUSIONS: Given the ongoing HIV diagnostic delay, IC-HIVT should be upgraded and adapted to each IC category to enhance early HIV diagnosis.
Subject(s)
HIV Infections , Sexual and Gender Minorities , Male , Humans , HIV Infections/diagnosis , HIV Infections/epidemiology , Case-Control Studies , Retrospective Studies , Taiwan/epidemiology , Delayed Diagnosis , Homosexuality, Male , HIV TestingABSTRACT
The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.
Subject(s)
Biomarkers , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Proto-Oncogene Proteins c-myc , Receptors, Interleukin-6 , Humans , Apoptosis , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
Purpose: Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu®, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP in vitro and in vivo, little information is known about the effect of OP use on cancers in humans. Methods: A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018. Results: The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis. Conclusion: These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.
ABSTRACT
BACKGROUND: Acute type A aortic intramural hematoma (ATAIMH) is a variant of acute type A aortic dissection (ATAAD), exhibiting an increased risk of hemopericardium and cardiac tamponade. It can be life-threatening without emergency treatment. However, comprehensive studies of the clinical features and surgical outcomes of preoperative hemopericardium in patients with ATAIMH remain scarce. This retrospective study aims to investigate the clinical features and early and late outcomes of patients who underwent aortic repair surgery for ATAIMH complicated with preoperative hemopericardium. METHODS: We investigated 132 consecutive patients who underwent emergency ATAIMH repair at this institution between February 2007 and August 2020. These patients were dichotomized into the hemopericardium (n = 58; 43.9%) and non-hemopericardium groups (n = 74; 56.1%). We compared the clinical demographics, surgical information, postoperative complications, 5-year cumulative survival rates, and freedom from reoperation rates. Furthermore, multivariable logistic regression analysis was utilized to identify independent risk factors for patients who underwent re-exploration for bleeding. RESULTS: In the hemopericardium group, 36.2% of patients presented with cardiac tamponade before surgery. Moreover, the hemopericardium group showed higher rates of preoperative shock and endotracheal intubation and was associated with an elevated incidence of intractable perioperative bleeding, necessitating delayed sternal closure for hemostasis. The hemopericardium group exhibited higher blood transfusion volumes and rates of re-exploration for bleeding following surgery. However, the 5-year survival (59.5% vs. 75.0%; P = 0.077) and freedom from reoperation rates (93.3% vs. 85.5%; P = 0.416) were comparable between both groups. Multivariable analysis revealed that hemopericardium, cardiopulmonary bypass time, and delayed sternal closure were the risk factors for bleeding re-exploration. CONCLUSIONS: The presence of hemopericardium in patients with ATAIMH is associated with an elevated incidence of cardiac tamponade and unstable preoperative hemodynamics, which could lead to perioperative bleeding tendencies and high complication rates. However, patients of ATAIMH complicated with hemopericardium undergoing aggressive surgical intervention exhibited long-term surgical outcomes comparable to those without hemopericardium.
Subject(s)
Cardiac Tamponade , Pericardial Effusion , Humans , Retrospective Studies , Pericardial Effusion/surgery , Treatment Outcome , Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Aortic Intramural Hematoma , Hematoma/complications , Hematoma/surgeryABSTRACT
Introduction: Postoperative pain and complications pose significant challenges following a hemorrhoidectomy. Attaining effective anesthesia with minimal complications is crucial. The ideal anesthesia method for ambulatory hemorrhoidectomy remains uncertain. This study aimed to investigate whether the combination of general anesthesia plus local infiltration (GAL) is associated with lower complications and reduced pain compared to spinal anesthesia (SA) in the context of hemorrhoidectomy. Methods: This retrospective single-center cohort study, conducted in a tertiary medical center in East Asia, evaluated excisional hemorrhoidectomies performed between January 1, 2017, and March 31, 2023, utilizing GAL or SA. Data on the six most common complications-pain, constipation, acute urine retention (AUR), bleeding, nausea, and headache-were extracted from medical records. A total of 550 hemorrhoidectomies were included: 220 in the GAL group and 330 in the SA group. Patient characteristics were comparable between the two groups. Results: The AUR rate was significantly lower in the GAL group compared to the SA group (15.5% vs. 32.1%, P < 0.001). Although the proportion of pain scores ≥4 did not differ significantly between the GAL and SA groups (36.2% vs. 39.8%, P = 0.429), the pain score curve indicated a stable trend. Overall, the GAL group exhibited a lower rate of adverse effects (56.9% vs. 67.4%, P = 0.023). There were no significant differences in the rates of other complications and emergency department readmission between the GAL and SA groups. Discussion: GAL emerges as a favorable choice for anesthesia in hemorrhoidectomy, demonstrating a lower incidence of urine retention and a prolonged analgesic effect in multiple hemorrhoidectomies. These findings support the conclusion that GAL represents an optimal anesthetic method for enhancing the postoperative experience in patients undergoing hemorrhoidectomy.
ABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is a major risk factor for osteoporosis/osteoporotic fractures. We aimed to elucidate the role of treatment choices among osteoporosis/osteoporotic fractures. METHODOLOGY: We utilized the Chang-Gung Research Database to assess the risks of osteoporosis/osteoporotic fractures among independently treated RA patients, using retrospective time-to-event outcomes analysis. RESULTS: A total of 3509 RA patients with a mean of 63.1 ± 8.6 years were analyzed. Among all, 1300 RA patients (37%) were diagnosed with newly diagnosed osteoporosis. The crude incidence of newly diagnosed osteoporosis was the highest among those treated with other conventional disease-modifying anti-rheumatic drugs (cDMARDs; 74.1 events/1000-PYs, 95%CI 66.0-82.3), followed by those with a non-treatment period (68 events/1000-PYs, 95%CI 63.1-72.9), methotrxate (MTX) monotherapy (60.7 events/1000-PYs, 95%CI 41.2-80.3), MTX plus other cDMARDs (51.9 events/1000-PYs, 95%CI 43.4-60.3), and abatacept/rituximab (48.6 events/1000-PYs, 95%CI 14.9-82.3). The lowest crude incidence was found in patients treated with anti-TNFi biologics (40.4 events/1000-PYs, 95%CI 28.6-52.2) and other biologic disease-modifying anti-rheumatic drugs (bDMARDs; 40.1 events/1000-PYs, 95%CI 8.0-72.1). A total of 270 patients (20.8%) suffered from an incident fracture during follow-ups. The crude incidence of fracture was the highest among those treated with abatacept/rituximab (49.0 events/1000-PYs, 95%CI 6.0-91.9), followed by those with non-treatment periods (24.3 events/1000-PYs, 95%CI 19.3-29.4), other cDMARDs (24.2 events/1000-PYs, 95%CI 18.1-30.2), anti-TNFi biologics (20.2 events/1000-PYs, 95%CI 8.8-31.6). Other bDMARDs (13.3 events/1000-PYs, 95%CI 0-39.2), MTX mono (12.5 events/1000-PYs, 95%CI 0.3-24.8), and MTX plus other cDMARDs (11.4 events/1000-PYs, 95%CI 5.4-17.4) were low incidences. CONCLUSION: The treatment option has emerged as a critical determinant in the context of future osteoporosis and osteoporotic fracture risks among RA. These findings offer a valuable resource for clinicians, empowering them to tailor bespoke treatment strategies for RA patients, thereby mitigating the potential for future osteoporosis and fractures.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Osteoporosis , Osteoporotic Fractures , Humans , Abatacept/therapeutic use , Rituximab/therapeutic use , Methotrexate/therapeutic use , Osteoporotic Fractures/diagnosis , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Retrospective Studies , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Antirheumatic Agents/adverse effects , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Biological Products/adverse effectsABSTRACT
PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.
Subject(s)
Bacterial Infections , Bronchiectasis , Methicillin-Resistant Staphylococcus aureus , Respiratory Insufficiency , Adult , Humans , Escherichia coli , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bronchiectasis/drug therapy , Bronchiectasis/epidemiology , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Fibrosis , Respiratory Insufficiency/drug therapy , Drug Resistance, Multiple, BacterialABSTRACT
Deep learning-based computer-generated holography (DeepCGH) has the ability to generate three-dimensional multiphoton stimulation nearly 1,000 times faster than conventional CGH approaches such as the Gerchberg-Saxton (GS) iterative algorithm. However, existing DeepCGH methods cannot achieve axial confinement at the several-micron scale. Moreover, they suffer from an extended inference time as the number of stimulation locations at different depths (i.e., the number of input layers in the neural network) increases. Accordingly, this study proposes an unsupervised U-Net DeepCGH model enhanced with temporal focusing (TF), which currently achieves an axial resolution of around 5â µm. The proposed model employs a digital propagation matrix (DPM) in the data preprocessing stage, which enables stimulation at arbitrary depth locations and reduces the computation time by more than 35%. Through physical constraint learning using an improved loss function related to the TF excitation efficiency, the axial resolution and excitation intensity of the proposed TF-DeepCGH with DPM rival that of the optimal GS with TF method but with a greatly increased computational efficiency.
ABSTRACT
Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent studies have indicated the activation of Sigma-1 receptor plays an important role in providing neuroprotection, especially in ALS and Alzheimer's disease. Nevertheless, the mechanisms underlying Sigma-1R activation and its effect on (G4C2)n-RNA-induced cell death remain unclear. In this study, we demonstrated that fluvoxamine is a Sigma-1R agonist that can increase chaperone activity and stabilize the protein expression of Pom121 in (G4C2)31-RNA-expressing NSC34 cells, leading to increased colocalization at the nuclear envelope. Interestingly, fluvoxamine treatment increased Pom121 protein expression without affecting transcription. In C9orf72-ALS, the nuclear translocation of TFEB autophagy factor decreased owing to nucleocytoplasmic transport defects. Our results showed that pretreatment of NSC34 cells with fluvoxamine promoted the shuttling of TFEB into the nucleus and elevated the expression of LC3-II compared to the overexpression of (G4C2)31-RNA alone. Additionally, even when used alone, fluvoxamine increases Pom121 expression and TFEB translocation. To summarize, fluvoxamine may act as a promising repurposed medicine for patients with C9orf72-ALS, as it stabilizes the nucleoporin Pom121 and promotes the translocation of TFEB in (G4C2)31-RNA-expressing NSC34 cells.