High Efficiency Video Coding (HEVC) is the state-of-the-art video coding standard. It adopts a hierarchical quad-tree-based coding unit (CU) partitioning structure that is flexible in various texture ...and motion characteristics of a video signal. However, the exhaustive partitioning process for finding optimal CU partitions requires a dramatic increase in computational complexity of the HEVC encoder compared with previous video coding standards. In this paper, a fast CU partitioning algorithm is proposed for HEVC encoder, which early on terminates the CU partitioning process based on the Bayesian decision rule using joint online and offline learning. An online learning method is first presented based on the minimum error Bayesian decision rule using a training picture selection method with scene change detection. Next, a joint online and offline learning method is presented, which additionally trains the loss of decision making of the proposed method based on the minimum risk Bayesian decision rule. The proposed method is implemented on an HEVC test software 15.0. Experimental results show that the proposed method reduces the computational complexity of HEVC encoder to 53.6% on an average with a 0.71% acceptable Bjøntegaard delta bitrate loss in random access configuration. For other configurations, 48.4%, 48.5%, and 54.2% encoding time saving are obtained on an average for low delay, low delay-P, and all intra-configurations, respectively.
Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in ...gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner.
In late January, a worldwide crisis known as COVID-19 was declared a Public Health Emergency of International Concern by the WHO. Within only a few weeks, the outbreak took on pandemic proportions, ...affecting over 100 countries. It was a significant issue to prevent and control COVID-19 on both national and global scales due to the dramatic increase in confirmed cases worldwide. Government guidelines provide a fundamental resource for communities, as they guide citizens on how to protect themselves against COVID-19, however, they also provide critical guidance for policy makers and healthcare professionals on how to take action to decrease the spread of COVID-19. We aimed to identify the differences and similarities between six different countries' (US, China, South Korea, UK, Brazil and Haiti) government-provided community and healthcare system guidelines, and to explore the relationship between guideline issue dates and the prevalence/incidence of COVID-19 cases.
To make these comparisons, this exploratory qualitative study used document analysis of government guidelines issued to the general public and to healthcare professionals. Documents were purposively sampled (N = 55) and analyzed using content analysis.
The major differences in the evaluation and testing criteria in the guidelines across the six countries centered around the priority of testing for COVID-19 in the general population, which was strongly dependent on each country's healthcare capacity. However, the most similar guidelines pertained to the clinical signs and symptoms of COVID-19, and methods to prevent its contraction.
In the initial stages of the outbreak, certain strategies were universally employed to control the deadly virus's spread, including quarantining the sick, contact tracing, and social distancing. However, each country dealt with differing healthcare capacities, risks, threats, political and socioeconomic challenges, and distinct healthcare systems and infrastructure. Acknowledging these differences highlights the importance of examining the various countries' response to the COVID-19 pandemic with a nuanced view, as each of these factors shaped the government guidelines distributed to each country's communities and healthcare systems.
To assess incidence and risk factors of postoperative progressive nasal inner nuclear layer (INL) thickening after epiretinal membrane (ERM) surgery. Progressive nasal INL thickening was defined as ...1.5-fold increase in thickness of nasal INL after ERM surgery compared to preoperative examination. Kaplan-Meier survival analysis was done to compare the cumulative risk ratio between groups stratified by presence of progressive nasal INL thickening. Logistic regression was performed to identify possible risk factors. Progressive nasal INL thickening occurred in 13.0% of ERM removal patients. Patients without progressive nasal INL thickening showed better visual acuity recovery compared to patients with nasal INL thickening (p = 0.029). Presence of cystoid space in inner retinal layer before surgery (odds ratio OR = 0.143, 95% confidence interval CI 0.028-0.736; p = 0.020), older age (OR = 0.896, 95% CI 0.817-0.982, p = 0.020), and thicker preoperative central macular thickness (OR = 0.994, 95% CI 0.988-1.000, p = 0.039) were correlated inversely with thickening of nasal INL. Correlation between nasal INL thickness and postoperative visual outcome was significant. Absence of cystoid space before ERM surgery, younger age, and thinner central macular thickness were risk factors for progressive postoperative nasal INL thickening. Progressive nasal INL thickening may serve as a new biomarker for worsened visual symptom after ERM surgery.
Chronic inflammation of rheumatoid arthritis (RA) is promoted by proinflammatory cytokines and closely linked to angiogenesis. In the present study, we investigated the anti-inflammatory effects of ...emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) isolated from the root of Rheum palmatum L. in interleukin 1 beta (IL-1β) and lipopolysaccharide (LPS)-stimulated RA synoviocytes under hypoxia. Emodin significantly inhibited IL-1β and LPS-stimulated proliferation of RA synoviocytes in a dose-dependent manner under hypoxic condition. Also, enzyme linked immunosorbent assay (ELISA) revealed that emodin significantly reduced the production of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), IL-6 and IL-8, mediators prostagladin E2 (PGE2), matrix metalloproteinase (MMP)-1 and MMP-13 and vascular endothelial growth factor (VEGF) as an angiogenesis biomarker in IL-1β and LPS-treated synoviocytes under hypoxia. Consistently, emodin attenuated the expression of cyclooxygenase 2 (COX-2), VEGF, hypoxia inducible factor 1 alpha (HIF-1α), MMP-1 and MMP-13 at mRNA level in IL-1β and LPS-treated synoviocytes under hypoxia. Furthermore, emodin reduced histone deacetylase (HDAC) activity as well as suppressed the expression of HDAC1, but not HDAC2 in IL-1β and LPS-treated synoviocytes under hypoxia. Overall, these findings suggest that emodin inhibits proinflammatory cytokines and VEGF productions, and HDAC1 activity in hypoxic RA synoviocytes.
Various low-volume bowel cleansing formulations that improve compliance have been approved and are being used in clinical practice. This study aimed to compare the effectiveness of 1 L polyethylene ...glycol (PEG) with ascorbic acid with that of sodium picosulfate (PICO) with magnesium citrate. This was a multicenter, randomized controlled, non-inferiority study. Patients were randomized into a 1 L PEG with ascorbic acid group and a PICO with magnesium citrate group according to the bowel cleansing agent used. Colonoscopy was performed as a single-blind study wherein the endoscopist had no information about any bowel preparation agent. The efficacy of bowel cleansing was assessed using the Harefield Cleansing Scale (HCS), and adverse events, preferences, and satisfaction were evaluated using a patient-reported questionnaire before colonoscopy. A total of 254 participants were randomly assigned to two groups: 115 in the 1 L PEG with ascorbic acid group and 113 in the PICO with magnesium citrate group. Overall bowel cleansing success was not statistically different between the two groups (97.4 vs. 97.3%), confirming that 1 L PEG with ascorbic acid was not inferior to PICO with magnesium citrate (lower confidence limit, -4.15%; p = 1.00). High-quality bowel cleansing was achieved in 87% of the 1 L PEG with ascorbic acid group and 77% of the PICO with magnesium citrate group (Lower confidence limit, 1.29%, p = 0.05). In terms of patient satisfaction, PICO with magnesium citrate was better, but compliance and side effects were similar in both groups. The 1 L PEG with ascorbic acid showed similar efficacy and adverse events as PICO with magnesium citrate. Although 1 L PEG with ascorbic acid is very effective in bowel preparation despite its small volume, it is necessary to increase satisfaction such as taste and feeling.
Although Mycobacterium leprae (M.leprae) is usually found in macrophages and nerves of the dermis of patients with multibacillary leprosy, it is also present in all layers of the epidermis, basal, ...suprabasal, prickle cells, and keratin layers. However, the mechanism by which M.leprae invades the dermis remains unknown, whereas the underlying mechanism by which M.leprae invades peripheral nerves, especially Schwann cells, is well defined. M. leprae binds to the α-dystroglycan (DG) of Schwann cells via the interaction of α-DG and laminin (LN) -α2 in the basal lamina, thus permitting it to become attached to and invade peripheral nerves. In the current study, we investigated the issue of how M.leprae is phagocytosed by human epidermal keratinocytes, neonatal (HEKn). LN-5 is the predominant form of laminin in the epidermis and allows the epidermis to be stably attached to the dermis via its interaction with α/β-DG as well as integrins that are produced by keratinocytes. We therefore focused on the role of LN-5 when M. leprae is internalized by HEKn cells. Our results show that M.leprae preferentially binds to LN-5-coated slides and this binding to LN-5 enhances its binding to HEKn cells. The findings also show that pre-treatment with an antibody against α-DG, integrin-β1, or -β4 inhibited the binding of LN-5-coated M.leprae to HEKn cells. These results suggest that M. leprae binds to keratinocytes by taking advantage of the interaction of LN-5 in the basal lamina of the epidermis and a surface receptor of keratinocytes, such as α-DG, integrin-β1, or -β4.
Although
has been reported to have anti-cancer mechanisms, such as caspase activation, cell cycle arrest, an anti-angiogenesis effect, and Bcl-2 family regulation, its underlying mechanism of ...endoplasmic reticulum (ER) stress-mediated apoptosis has never been demonstrated. Thus, in this current study, ER stress-related apoptosis via miR-216b of the ethanol extract of
(SM) is elucidated for the first time. SM treatment inhibited the viability of U266 and U937 cells in a concentration-dependent manner. However, SM-exposed Raw264.7 cells were intact compared to U266 or U937 cells. Treatment with SM significantly elevated the generation of reactive oxygen species (ROS). The anti-proliferative effect of SM was reversed by pretreatment with the ROS scavenger,
-acetyl-l-cysteine (NAC), compared to cells treated only with SM. Also, SM treatment increased the ER stress by elevation of phosphorylated activating transcription factor 4 (p-ATF4), phosphorylated eukaryotic Initiation Factor 2 (p-eIF2), and phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK) expression. Caspase-3 and Poly (ADP-ribose) polymerase (PARP) were cleaved and CCAAT-enhancer-binding protein homologous protein (CHOP) was activated by SM treatment. PARP cleavage and CHOP activation were attenuated by NAC pretreatment. Furthermore, SM increased the tumor suppressor, miR-216b, and suppressed its target, c-Jun. miR-216b inhibitor attenuated the apoptotic effect of SM. Taken together, SM treatment induced apoptosis through regulation of miR-216b and ROS/ER stress pathways. SM could be a potential drug for treatment of multiple myeloma and myeloid leukemia.
Purpose
Casein kinase (CK) 2 activation has been implicated in the proliferation of various tumor types and resistance to chemotherapy. We investigated the mechanistic basis for the association ...between CK2 activation and paclitaxel resistance in a gastric cancer (GC).
Experimental design
CK2 expression was evaluated in 59 advanced GC patients treated with paclitaxel as the second-line therapy. The efficacy of a CK2 inhibitor, CX-4945, and paclitaxel was evaluated in GC cell lines and a xenograft model.
Results
Patients with high CK2 expression (29/59, 39%) showed lower disease control rates (47.7% vs. 72.3%,
p
= 0.017) and shorter progression-free survival (2.8 vs. 4.8 months,
p
= 0.009) than patients with low CK2 expression. CK2 protein expression was associated with sensitivity to paclitaxel in 49 GC cell lines. Combination therapy with CX-4945 and paclitaxel exerted synergistic antiproliferative effects and inhibited the downregulation of phosphatidylinositol 3-kinase/AKT signaling in SNU-1 cells. In the SNU-1 xenograft model, the combination treatment was significantly superior to either single agent, suppressing tumor growth without notable toxicities.
Conclusions
These results demonstrated that CK2 activation was related to paclitaxel resistance and that CX-4945 in combination with paclitaxel could be used as a potential treatment for paclitaxel resistance in GC.
Abstract
The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal ...vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018–2019 and 2020–July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018–2019 and 2020–2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018–2019 and 2020–2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence.