Johanssondemant8668

Colorectal cancer has one of the highest mortality rates among malignant tumors, and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors. Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy. Here, we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumor-specific cytotoxic T cell responses. Three HLA-A2-restricted neoepitopes (P31, P50, and P52) were immunogenic and could induce cytotoxic T lymphocytes in peripheral blood mononuclear cells from healthy donors and colorectal cancer patients. Cytotoxic T lymphocytes induced in HLA-A2.1/Kb transgenic mice could recognize and lyse mutant neoepitope-transfected HLA-A2+ cancer cells. Adoptive transfer of cytotoxic T lymphocytes induced by the peptide pool of these three neoepitopes effectively inhibited tumor growth and increased the therapeutic effects of anti-PD-1 antibody. click here These results revealed the potential of high-frequency mutation-specific peptide-based immunotherapy as a personalized treatment approach for patients with non-MSI-H colorectal cancer. The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors, such as anti-PD-1, could provide a promising treatment strategy for non-MSI-H colorectal cancer.Airborne particulate matter (PM) pollution, as a leading environmental health risk, causes millions of premature deaths globally every year. Lower respiratory infection (LRI) is a sensitive response to short-term exposure to outdoor PM pollution. The airborne transmission of etiological agents of LRI, as an important pathway for infection and morbidity, bridges the public health issues of air quality and pathogen infectivity, virulence, resistance, and others. Enormous efforts are underway to identify common pathogens and substances that are etiological agents for LRI and to understand the underlying toxicological and clinical basis of health effects by identifying mechanistic pathways. Seasonal variations and geographical disparities in the survival and infectivity of LRI pathogens are unsolved mysteries. Weather conditions in geographical areas may have a key effect, but also potentially connect LRI with short-term increases in ambient air PM pollution. Statistical associations show that short-term elevations in fine and coarse PM lead to increases in respiratory infections, but the causative agents could be chemical or microbiological and be present individually or in mixtures, and the interactions between chemical and microbiological agents remain undefined. Further investigations on high-resolution monitoring of airborne pathogens in relation to PM pollution for an integrated exposure-response assessment and mechanistic study are warranted. Improving our understanding of the spatiotemporal features of pathogenic bioaerosols and air pollutants and translating scientific evidence into effective policies is vital to reducing the health risks and devastating death toll from PM pollution.Common variable immunodeficiency disorders (CVID) are the most frequent symptomatic primary immune deficiencies in adults and children. In addition to recurrent and severe infections, patients with CVID are susceptible to autoimmune and inflammatory complications. The aetiologies of these uncommon conditions are, by definition, unknown. When the causes of complex disorders are uncertain, diagnostic criteria may offer valuable guidance to the management of patients. Over the last two decades, there have been four sets of diagnostic criteria for CVID in use. The original 1999 European Society for Immunodeficiencies and Pan-American Society for Immunodeficiency (ESID/PAGID) criteria are less commonly used than the three newer criteria Ameratunga et al (Clin Exp Immunol 174203-211, 2013), ESID (J Allergy Clin Immunol Pract, 2019) and ICON (J Allergy Clin Immunol Pract 438-59, 2016) criteria. The primary aim of the present study was to compare the utility of diagnostic criteria in a well-characterised cohort of CVCVID diagnostic criteria to patients on SCIG/IVIG may obviate the need to stop treatment for vaccine studies, to confirm the diagnosis.

Radical cystectomy with permanent urinary diversion is the gold standard treatment for invasive muscle bladder cancer. Hydronephrosis is common in these patients, but Ultrasound (US) or Computed Tomography Urography (CTU) scan are unable to discriminate obstructive from non-obstructive hydronephrosis. We used Diuresis Renography (DR) with F + 10 in seated position (sp) method in the identification of patients with a Uretero-ileal Anastomosis Stricture (UAS) who would benefit from surgical therapy.

We studied 39 asymptomatic patients, who underwent radical cystectomy and urinary diversion. Based on radiological findings (US, CTU) 44 kidneys were hydronephrotic. All patients underwent a

Tc-MAG3 DR with F + 10(sp) method. We acquired a DR for 20min with the patient in a seated position. Patient drank 400-500mL of water at 5min after tracer injection and received a 20mg bolus of Furosemide at 10min during dynamic acquisition. The indices Time to peak, diuretic half time, and 20min/peak ratio have been evalufindings of US or CTU, in management of bladder cancer patients with urinary diversion. The semiquantitative indices diuretic half time and 20 min/peak ratio evaluated in a condition of favorable gravity reduce uncertain responses improving interobserver concordance.

The EQ-5D-5L is a well-established health questionnaire that estimates health utilities by applying preference-based weights. Limited work has been done to examine alternative scoring approaches when utility weights are unavailable or inapplicable. We examined whether the Mokken scaling approach can elucidate 1) if the level summary score is appropriate for the EQ-5D-5L and 2) an interpretation of such a score.

The R package "mokken" was used to assess monotonicity (scaling coefficients H, automated item selection procedure) and manifest invariant item ordering (MIIO paired item response functions [IRF], H

). We used a rich dataset (the Multiple Instrument Comparison, MIC) which includes EQ-5D-5L data from six Western countries.

While all EQ-5D-5L items demonstrated monotonicity, the anxiety/depression (AD) item had weak scalability (H

 = 0.377). Without AD, scalability improved from H

 = 0.559 to H

 = 0.714. MIIO revealed that the 5 items can be ordered, and the ordering is moderately accurate in treveals additional limitations with self-care. Scalability and item ordering are even stronger when the anxiety/depression item is not included in the scale.

We evaluated the feasibility of machine learning analysis using diffusion tensor imaging (DTI) parameters to identify patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). We hypothesized that patients with idiopathic RBD could be identified via machine learning analysis based on DTI.

We enrolled 20 patients with newly diagnosed idiopathic RBD at a tertiary hospital. We also included 20 healthy subjects as a control group. All of the subjects underwent DTI. We obtained the conventional DTI parameters and structural connectomic profiles from the DTI. We investigated the differences in conventional DTI measures and structural connectomic profiles between patients with idiopathic RBD and healthy controls. We then used machine learning analysis using a support vector machine (SVM) algorithm to identify patients with idiopathic RBD using conventional DTI and structural connectomic profiles.

Several regions showed significant differences in conventional DTI measures and structural connectomic profiles between patients with idiopathic RBD and healthy controls. The SVM classifier based on conventional DTI measures revealed an accuracy of 87.5% and an area under the curve of 0.900 to identify patients with idiopathic RBD. Another SVM classifier based on structural connectomic profiles yielded an accuracy of 75.0% and an area under the curve of 0.833.

Our findings demonstrate the feasibility of machine learning analysis based on DTI to identify patients with idiopathic RBD. The conventional DTI parameters might be more important than the structural connectomic profiles in identifying patients with idiopathic RBD.

Our findings demonstrate the feasibility of machine learning analysis based on DTI to identify patients with idiopathic RBD. The conventional DTI parameters might be more important than the structural connectomic profiles in identifying patients with idiopathic RBD.

Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF).

The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (11) to receive 10mg empagliflozin or a placebo (once daily), 2weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24.

Overall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24weeks (-2.2 vs. + 0.1kg, P < 0.001, and -5.1 vs. -0.3%, P < 0.001, respectively). Decreased PVS, defined as a change in PVS of < -4.5%, was associated with the administration of empagliflozin (odds ratio 2.61, 95% confidence interval 1.11-6.15, P = 0.028). N-terminalprob-type natriuretic peptide levels decreased in both the empagliflozin and placebo groups (1028.7-370.3pg/mL, P < 0.001, and 1270.6-673.7pg/mL, P < 0.01, respectively).

Empagliflozin reduced the body weight and PVS. Early SGLT2 inhibitor administration in patients with AMI, CHF, and T2DM can therefore be effective in reducing the body weight and PVS.

UMIN 000030158.

UMIN 000030158.

Diabetes mellitus (DM) has a serious impact on people's lives in the world. Interventions that affect risk factors for prediabetes can prevent and reduce diabetes occurrence. Proinsulin (PI), true insulin (TI), and proinsulin to insulin ratio (PI/TI) are risk factors for diabetes. The roles of these indicators in prediabetes are unclear. This study aimed to evaluate the impact of PI, TI, PI/TI, 2-h proinsulin (2hPI), 2-h true insulin (2hTI), and 2hPI/2hTI on the risk of prediabetes among the Chinese Han population.

This cross-sectional study recruited 1688 subjects including 718 prediabetes cases and 970 non-prediabetes controls from Hainan Affiliated Hospital of Hainan Medical University. The cases involved 292 men and 426 women. The controls involved 324 men and 646 women. The mean age was 53.62 ± 12.43years in the prediabetes group and 44.24 ± 12.87years in the non-prediabetes group.

Our results showed that PI, TI, PI/TI, 2hPI, 2hTI, and 2hPI/2hTI were significantly correlated with prediabetes (all p < 0.