Comparative efficacy evaluation of disinfectants against severe acute respiratory syndrome coronavirus-2.

BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

Dynamically disordered hydrogen bonds in the hureaulite-type phosphatic oxyhydroxide Mn5[(PO4)2(PO3(OH))2](HOH)4.

We report the temperature evolution of hydrogen bond (HB) chains and rings in Mn5[(PO4)2(PO3(OH))2](HOH)4 to reveal conduction pathways based on difference Fourier maps with neutron- and synchrotron x-ray diffraction data. Localized proton dynamics for the five distinct hydrogen sites were observed and identified in this study. Their temperature evaluation over ten orders of magnitude in time was followed by means of quasielastic neutron scattering, dielectric spectroscopy, and ab initio molecular dynamics. Two out of the five hydrogen sites are geometrically isolated and are not suitable for long-range proton conduction. Nevertheless, the detected dc conductivity points to long-range charge transport at elevated temperatures, which occurs most likely (1) over H4-H4 sites between semihelical HB chains (interchain-exchanges) and (2) by rotations of O1-H1 and site-exchanging H4-O10-O5 groups along each semihelical HB chain (intrachain-exchanges). The latter dynamics freeze into a proton-glass state at low temperatures. Rotational and site-exchanging motions of HOH and OH ligands seem to be facilitated by collective motions of framework polyhedra, which we detected by inelastic neutron scattering.

Punzi-loss:: a non-differentiable metric approximation for sensitivity optimisation in the search for new particles.

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

Re-evaluation of the prognostic significance of oropharyngeal dysphagia in idiopathic inflammatory myopathies.

OBJECTIVE: To investigate the prognostic significance of videofluorographic swallowing study (VFSS)-confirmed oropharyngeal dysphagia in idiopathic inflammatory myopathies (IIMs). METHOD: We reviewed the medical records of patients who were diagnosed with IIM between 2009 and 2020 at Seoul St Mary's Hospital. All oropharyngeal dysphagia cases were limited to VFSS-confirmed dysphagia found during the initial diagnostic work-up for IIM. We described the findings on VFSS and the course of the dysphagic symptoms. Logistic regression and survival analyses were performed to evaluate the risk of pneumonia and mortality, respectively. RESULTS: We found 88 patients with IIM who met the criteria. Among them, 17 patients (19%) had oropharyngeal dysphagia. Except for two cases lost to follow-up and one deceased case, all of the patients with dysphagia (14 of 14) had swallowing function restored within 6 months. The risk of pneumonia within 3 months from the diagnosis of IIM was significant [odds ratio = 4.49, 95% confidence interval (CI) 1.07-18.88]. The median follow-up duration was 34 and 27 months for the groups without and with dysphagia, respectively. The survival analysis failed to demonstrate that the presence of oropharyngeal dysphagia increased the risk of death (hazard ratio = 0.77, 95% CI: 0.085-7.00). CONCLUSIONS: Oropharyngeal dysphagia found at the initial diagnosis of IIM improved within 3-6 months in nearly all cases. Furthermore, IIM patients who had oropharyngeal dysphagia at the initial diagnosis of IIM were not likely to have shorter survival, even if the risk of pneumonia was increased in the short term.

Indole-3-carbinol inhibits the proliferation of colorectal carcinoma LoVo cells through activation of the apoptotic signaling pathway.

Indole-3-carbinol (I3C) is a phytochemical that exhibits growth-inhibitory activity against various cancer cells. However, there are limited studies on the effects of I3C on colon cancer cells. In this study, the growth-inhibitory activity of I3C against the human colorectal carcinoma cell line (LoVo) was examined. The results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, colony formation, and cell counting assays revealed that I3C suppressed the proliferation of LoVo cells. Microscopy and wound-healing analyses revealed that I3C affected the morphology and inhibited the migration of LoVo cells, respectively. I3C induced apoptosis and DNA fragmentation as evidenced by the results of fluorescein isothiocyanate-conjugated annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay, respectively. Additionally, I3C arrested the cell cycle at the G0/G1 phase and enhanced the reactive oxygen species levels. Western blotting analysis revealed that treatment with I3C resulted in the activation of apoptotic proteins, such as poly(ADP-ribose) polymerase, caspase-3, caspase-7, caspase-9, Bax, Bim, and p53 in LoVo cells. These results indicate that I3C induces apoptosis in LoVo cells by upregulating p53, leading to the activation of Bax and caspases. Taken together, I3C exerts cytotoxic effects on LoVo cells by activating apoptosis.

MGMT Promoter Methylation Status in Initial and Recurrent Glioblastoma: Correlation Study with DWI and DSC PWI Features.

BACKGROUND AND PURPOSE: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate MGMT promoter methylation status changes with DWI and DSC PWI features in patients with recurrent glioblastoma after standard treatment. MATERIALS AND METHODS: Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the MGMT promoter methylation status for the initial and recurrent tumors: 2 groups whose MGMT promoter methylation status remained, group methylated (n = 13) or group unmethylated (n = 18), and 1 group whose MGMT promoter methylation status changed from methylated to unmethylated (n = 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The t test and Mann-Whitney U test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups. RESULTS: Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all P < .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (P < .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594. CONCLUSIONS: MGMT promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the MGMT promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.

Change in the Shrinkage Forces of Composite Resins According to Controlled Deflection.

The aim of this study was to investigate how the polymerization shrinkage forces of composite resins change with change in deflection. Five composites, SDR (Dentsply Caulk, Milford, DE, USA), EcuSphere-Shape (DMG, Hamburg, Germany), Tetric N-Ceram Bulk Fill (Ivoclar Vivadent, Schaan, Liechtenstein), CLEARFIL AP-X (Kuraray Noritake Dental Inc., Sakazu, Kurashiki, Okayama, Japan), and Filtek Z350 XT (3M Dental Products, St Paul, MN, USA), were tested in this experiment. The polymerization shrinkage forces of the composites were measured using a custom-made tooth-deflection-mimicking device and software (R&B Inc, Daejon, Korea). In all measurements, six modes were tested: maximum-deflection, zero-deflection, and four deflection-controlled modes. For each deflection mode, the shrinkage forces were recorded continuously every 0.1 second for 180 seconds. Polymerization shrinkage and flexural modulus were also measured. Eight specimens of each material were allocated for each test. For each material, six groups of shrinkage force values were compared using one-way ANOVA and Tukey post hoc tests at a 95% confidence level. The polymerization shrinkage force of each material in each of the six deflection modes was analyzed with 95% confidence using one-way ANOVA and Tukey post hoc tests. The relationship between the force measured in the six deflection modes and the linear polymerization shrinkage and flexural modulus was analysed with 95% confidence using Pearson correlation analysis. For each material, the following held true: the shrinkage force was highest in zero-deflection mode, the force decreased as deflection increased, and the smallest force appeared in maximum-deflection mode (p<0.05). There was a high negative correlation between allowable deflection and shrinkage force in all materials.

Relationship between faecal calprotectin and inflammation in peripheral joints and entheses in axial spondyloarthritis.

Objectives: To compare faecal calprotectin levels according to the type of manifestation and to investigate factors associated with increases in faecal calprotectin in patients with axial spondyloarthritis (axSpA). Method: The study enrolled 190 patients fulfilling the imaging arm of the Assessment of SpondyloArthritis international Society axSpA criteria. Faecal calprotectin levels were measured in an enzyme-linked immunosorbent assay. Systemic inflammatory markers and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were also assessed. Peripheral joint involvement was assessed using the 44-joint examination and Spondyloarthritis Research Consortium of Canada Enthesitis Index. Results: Of 190 patients, 34 (18%) had increased faecal calprotectin levels. These patients were more likely to have ongoing peripheral arthritis and enthesitis (p = 0.016 and 0.001, respectively). A history of psoriasis and uveitis, or current uveitis symptoms, had no bearing on faecal calprotectin levels. Faecal calprotectin levels increased along with ASDAS-C-reactive protein (CRP), and correlated with ASDAS-erythrocyte sedimentation rate (ESR) (r = 0.240, p = 0.001), ASDAS-CRP (r = 0.162, p = 0.025), ESR (r = 0.228, p = 0.002), and CRP levels (0.258, p < 0.001). Tender joint and swollen joint counts also correlated with faecal calprotectin levels (r = 0.252 and 0.205, p < 0.001 and p = 0.005, respectively). Faecal calprotectin levels were higher in patients with current peripheral symptoms (p = 0.003). Peripheral symptoms were independently associated with increased faecal calprotectin levels (odds ratio = 4.083; 95% confidence interval 1.580-10.556). Conclusions: Faecal calprotectin levels in axSpA patients were associated with disease activity. Subclinical gut inflammation (assessed by measuring faecal calprotectin) in axSpA is more closely related to peripheral joint inflammation than to axial joint inflammation.

Inactivation of Escherichia coli, Salmonella enterica serovar Typhimurium, and Bacillus cereus in roasted grain powder by radio frequency heating.

AIMS: The objective of this study was to evaluate the antimicrobial effects of radio frequency (RF) heating and the combination treatment of RF heating with ultraviolet (UV) radiation against foodborne pathogens in roasted grain powder (RGP). METHODS AND RESULTS: Foodborne pathogens inoculated on RGP were subjected to RF heating or RF-UV combination treatments. After 120 s of RF heating, 4·68, 3·89 and 4·54 log reductions were observed for Escherichia coli, Salmonella Typhimurium and Bacillus cereus vegetative cells respectively. The combined RF-UV treatment showed synergistic effects of over 1 log unit compared to the sum of individual treatment for E. coli and S. Typhimurium, but not for B. cereus vegetative cells because of their high UV resistance. Germinated B. cereus cells were not significantly inactivated by RF heating (<1 log CFU per gram), and increased heat resistance compared to the vegetative cells was verified with mild heat treatment. The colour of RGP was not significantly affected by the RF or RF-UV treatments. CONCLUSIONS: Applying RF heating to grain-based food products has advantages for the inactivation of E. coli and S. Typhimurium in RGP. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study could be used as a basis for determining the treatment conditions for inactivating E. coli and other foodborne pathogens such as S. Typhimurium and B. cereus in RGP.

Trabecular bone score value is associated with new bone formation independently of fat metaplasia on spinal magnetic resonance imaging in patients with ankylosing spondylitis.

OBJECTIVE: To evaluate the association between trabecular bone score (TBS) and new bone formation in ankylosing spondylitis (AS) patients, and to investigate whether TBS is independently associated with new bone formation. METHOD: Sixty-eight patients with AS underwent spinal magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density at baseline. Lateral radiographs of the cervical and lumbar spine (baseline and 2 years) were assessed for new bone formation (syndesmophyte formation and/or growth combined), and spinal MRIs were assessed for the presence or absence of fat metaplasia (FM) at the first to fourth lumbar vertebrae. The factors associated with new bone formation were analysed at the patient level and the vertebral level. RESULTS: New bone formation had developed in 17 patients (25%) at 2 year follow-up. Patients with new bone formation had a higher prevalence of FM and lower TBS at baseline than patients without new bone formation (p = 0.013 and p = 0.041). At the patient level, FM on MRI and low TBS (< 1.23) were significantly associated with new bone formation. At the vertebral level, new bone formation had developed in 25 out of 231 vertebrae (11%) after 2 years. Vertebrae with both FM on MRI and low TBS tended to have more new bone formation (p < 0.001). Syndesmophytes and low TBS (< 1.23) independently increased the risk of new bone formation at the level of individual vertebrae. CONCLUSION: At both patient and individual vertebral levels, low TBS was associated with new bone formation independently of FM on MRI.

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). CONCLUSIONS: Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Prone positioning before extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: A retrospective multicenter study / Decúbito prono previo a la oxigenación de membrana extracorpórea para el síndrome de dificultad respiratoria aguda: un estudio retrospectivo multicéntrico

Objective: To evaluate the clinical outcomes of patients with severe acute respiratory distress syndrome (ARDS) subjected to prone positioning before extracorporeal membrane oxygenation (ECMO). Design: A retrospective analysis of a multicenter cohort was carried out. Setting: Patients admitted to the Intensive Care Units of 11 hospitals in Korea. Patients: Patients were divided into those who underwent prone positioning before ECMO (n=28) and those who did not (n=34). Interventions: None. Variables of interest: Thirty-day mortality, ECMO weaning failure rate, mechanical ventilation weaning success rate, mechanical ventilation-free days at day 60. Results: The prone group had lower median peak inspiratory pressure and lower median dynamic driving pressure before ECMO. Thirty-day mortality was 21% in the prone group and 41% in the non-prone group (p=0.098). The prone group also showed a lower ECMO weaning failure rate, and a higher mechanical ventilation weaning success rate and more mechanical ventilation-free days at day 60. In the non-prone group, median dynamic compliance marginally decreased shortly after ECMO, but no significant change was observed in the prone group. Conclusions: Prone positioning before ECMO was not associated to increased mortality and tended to exert a protective effect

Objetivo: Evaluar los resultados clínicos de pacientes con síndrome de dificultad respiratoria aguda (SDRA) quienes fueron colocados en decúbito prono previo a la oxigenación con membrana extracorpórea (ECMO). Diseño: Análisis retrospectivo de una cohorte multicéntrico. Escenario: Pacientes admitidos en las unidades de cuidado intensivo de 11 hospitales en Corea. Pacientes: Los pacientes fueron divididos en aquellos que fueron colocados en decúbito prono antes de la ECMO (n=28) y aquellos que no fueron colocados en decúbito prono antes de la ECMO (n=34). Intervenciones: Ninguna. Variables de interés principales: Mortalidad a los 30 días, tasa de fracaso de retirada gradual de la ECMO, tasa de éxito de retirada gradual de la ventilación mecánica, días sin ventilación mecánica a los 60 días. Resultados: El grupo prono tuvo una mediana más baja de la presión inspiratoria máxima y una mediana más baja de la presión de conducción dinámica antes de la ECMO. La mortalidad a los 30 días fue 21% en el grupo prono y 41% en el grupo no prono (P = 0.098). El grupo prono también mostró un valor numérico menor de tasa de fracaso de retirada progresiva de la ECMO, y valores más altos de tasa de éxito de destete de la ventilación mecánica y días sin ventilación mecánica a los 60 días. En el grupo no prono, la mediana del cumplimiento dinámico descendió marginalmente, poco después de ECMO, pero no se observó un cambio significativo en el grupo prono. Conclusiones: La colocación en decúbito prono antes de la ECMO no se asoció con un incremento en mortalidad y tendió a ser de protección

Ultrashort laser induced spatial redistribution of silver species and nano-patterning of etching selectivity in silver-containing glasses.

Femtosecond laser-induced spatial redistribution of silver species (ions, clusters, and hole centers) in a silver-containing phosphate glass is investigated by correlative means of near-field scanning optical microscopy (NSOM) images, numerical simulations, chemical micro-probe analysis, and nanoscale spatial profiles after soft etching. In particular, we found that the chemical etching selectivity for nanoscale patterning is strongly dependent upon the irradiation of femtosecond laser due to the spatial redistribution of silver species within the affected area. These results strongly indicate that controlling the distribution of silver species by femtosecond laser irradiation may open new routes for surface nanoscale chemical and/or spatial patterning for the fabrication of 2D surface photonic crystals.

Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer.

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.

Magnetic resonance imaging assessment of the substrate for hyposmia in patients with Parkinson's disease.

AIM: To assess whether multimodal magnetic resonance imaging (MRI) could detect neuroanatomical substrates that are distinctive to hyposmic Parkinson's disease (PD). MATERIALS AND METHODS: Among 102 PD patients, 62 were hyposmic and 40 were normosmic. For each patient, a sagittal structural three-dimensional (3D) T1-weighted image was obtained with the magnetisation-prepared rapid acquisition of the gradient-echo sequence to generate subcortical grey matter masking templates and to perform a voxel-based morphometry analysis of the subcortical grey matter volumes. A 3D multi-echo gradient sequence was run to obtain axial magnitude and phase images to produce a quantitative susceptibility map (QSM), and a diffusion-weighted image was acquired to generate an apparent diffusion coefficient (ADC) map. The volumes and average QSM and ADC values of the 15 subcortical grey matter structures were calculated, and the group differences were evaluated using a one-way analysis of covariance with age and gender as covariates. RESULTS: The QSM of the left thalamus significantly increased, while that of the right thalamus significantly decreased in hyposmia. No effects on the cortical volume changes were found other than aging. CONCLUSION: The present results suggest that accumulation of disease-related substances in the left and right thalamus and the increasing asymmetry between the two sides are associated with hyposmia in PD.

Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca and salivary gland dysfunction in patients with Sjögren's syndrome: a longitudinal analysis of the Korean Initiative of primary Sjögren's Syndrome (KISS) cohort.

OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.

Anticarcinogenic effect of indole-3-carbinol (I3C) on human hepatocellular carcinoma SNU449 cells.

Many cruciferous vegetables, including cabbage, contain indole-3-carbinol (I3C), which is a known anticarcinogen. However, the anticarcinogenic effects of I3C on liver cancer have not been investigated. Therefore, this study was conducted to evaluate the anticarcinogenic effects of I3C in human hepatocellular carcinoma (HCC) SNU449 cells. The results of MTT and WST-1 assays indicated that treatment of SNU449 cells with I3C decreased viability in dose- and time-dependent manners, while colony formation assays indicated that I3C also inhibited proliferation of SNU449 cells. Moreover, fluorescence-activated cell sorter analysis showed that I3C induced apoptosis in SNU449 cells in dose- and time-dependent manners. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling revealed that I3C induced DNA fragmentation in SNU449 cells in a time-dependent manner, while Western blotting showed that apoptotic proteins such as p53, cleaved PARP, caspase-3, and caspase-7 were activated in SNU449 cells following treatment with I3C. Finally, reactive oxygen species-related protein peroxiredoxin-1 and thioredoxin-1 expression decreased in I3C-treated SNU449 cells. The aim of our study is to investigate the unknown mechanisms responsible for the apoptotic effects of I3C on human HCC SNU449 cells, and the results suggest that I3C may be useful for the prevention and treatment of liver cancer.

Theoretical spin-wave dispersions in the antiferromagnetic phase AF1 of MnWO4 based on the polar atomistic model in P2.

The spin wave dispersions of the low temperature antiferromagnetic phase (AF1) MnWO4 have been numerically calculated based on the recently reported non-collinear spin configuration with two different canting angles. A Heisenberg model with competing magnetic exchange couplings and single-ion anisotropy terms could properly describe the spin wave excitations, including the newly observed low-lying energy excitation mode [Formula: see text] meV appearing at the magnetic zone centre. The spin wave dispersion and intensities are highly sensitive to two differently aligned spin-canting sublattices in the AF1 model. Thus this study reinsures the otherwise hardly provable hidden polar character in MnWO4.

Influences of age and sex on the validity of bone scintigraphy for the diagnosis of temporomandibular joint osteoarthritis.

Bone scintigraphy has been used for the diagnosis of early-stage temporomandibular joint (TMJ) osteoarthritis (OA) owing to its high sensitivity. However, the diagnostic value of bone scintigraphy may be compromised when applied to patients in an age range with high bone metabolism rates. The aim of this study was to investigate the validity of bone scintigraphy as an appropriate diagnostic modality for TMJ OA. A total of 406 subjects (145 male, 261 female; age range 14-87 years) were selected, and all subjects underwent both bone scintigraphy and computed tomography (CT). The diagnosis of TMJ OA was confirmed with CT. Images obtained with bone scintigraphy were analyzed by visual and quantitative methods using the TMJ-to-skull ratio. The TMJ-to-skull ratio was significantly higher during adolescence and elderly adulthood, but differences between the sexes were not significant. The diagnostic value of the TMJ-to-skull ratio was lower in elderly adulthood in both males and females. The diagnostic utility of visual assessment was also compromised during late adulthood in both males and females. Thus bone scintigraphy has little value in the detection of TMJ OA, because the results could be influenced by age-related bone metabolism rates.