Risk factors for radiation pneumonitis after rotating gantry intensity-modulated radiation therapy for lung cancer

The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). Importantly, independent studies have documented that IGHV SHM status is also a predictor of responses to therapy, including both chemoimmunotherapy (CIT) and novel, targeted agents. Moreover, immunogenetic analysis in CLL has revealed that different patients may express (quasi)identical, stereotyped B cell receptor immunoglobulin (BcR IG) and are classified into subsets based on this common feature. Patients in certain stereotyped subsets display consistent biology, clinical presentation, and outcome that are distinct from other patients, even with concordant IGHV gene SHM status. All of the above highlights the relevance of immunogenetic analysis in CLL, which is considered a cornerstone for accurate risk stratification and clinical decision making. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering all test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL.

The study is to explore the role of ferroptosis-related genes (FRGs) in the occurrence and development of gastric cancer (GC), and to construct a new prognosis signature to predict the prognosis in GC. Clinical information and corresponding RNA data of GC patients were downloaded from TCGA and GEO databases. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, CIBERSORT, McpCounter and TIMER algorithm were used to analyze the infiltration of immune cells in two molecular subgroups. LASSO algorithm and multivariate Cox analysis were used to construct a prognostic risk signature. Functional analysis was conducted to elucidate the underlying mechanisms. Finally, the FRPGs were verified by Quantitative Real-Time PCR. We obtained 16 FRGs and divided GC patients into two subgroups by consistent clustering. Cluster C1 with a higher abundance of immune cell infiltration but lower probability in response to immunotherapy, it was reasonable to speculate that Cluster C1 was in accordance with the immune rejection type. Functional analysis showed that the biological process of DEGs in training cohort mainly included immune globulin, and human immune response mediated by circulating immune globulin. GSEA analysis showed that compared with Cluster C2, Cluster C1 showed lower expression in lipid metabolism. The nomogram combined with risk signature and clinical features can accurately predict the prognosis of GC patients. We identified two molecular subtypes, Clusters C1 and C2. In Cluster C1, patients with poor prognosis present with a hyperimmune status and low lipid metabolism, and we speculate that Cluster C1 was in accordance with the immune rejection type. The risk model based on FRPGs can accurately predict the prognosis of GC. These results indicated that ferroptosis is associated with TIME, and deserved considerable attention in determining immunotherapy treatment strategy for GC patients.

Cyclin E is frequently encoded by CCNE1 gene amplification in various malignancies. We reviewed the medical records of patients with solid tumors displaying CCNE1 amplification to determine the effect of this amplification for future therapeutic development. We reviewed the medical records of patients with advanced solid tumors harboring CCNE1 amplification who were seen at the phase I clinic between September 1, 2012, and December 31, 2019. Among 79 patients with solid tumors harboring CCNE1 amplification, 56 (71%) received phase 1 clinical trial therapy, 39 (49%) had 3 or more concurrent genomic aberrances, and 52 (66%) had a concurrent TP53 mutation. The median overall survival (OS) after patients' initial phase I visit was 8.9 months and after their initial metastasis diagnosis was 41.4 months. We identified four factors associated with poor risk: age"‰<"‰45 years, body mass index"‰â‰¥"‰25 kg/m2, presence of the TP53 mutation, and elevated LDH"‰>"‰upper limit of normal. In patients treated with gene aberration-related therapy, anti-angiogenic therapy led to significantly longer OS after their initial phase I trial therapy than those who did not: 26 months versus 7.4 months, respectively (P"‰="‰0.04). This study provided preliminary evidence that CCNE1 amplification was associated with frequent TP53 mutation and aggressive clinical outcomes. Survival benefit was observed in patients who received antiangiogenic therapy and gene aberration-related treatment, supporting the future development of a personalized approach to combine gene aberration-related therapy with antiangiogenesis for the treatment of advanced malignancies harboring CCNE1 amplification.

This study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.

The pharmaceutical company Pfizer has voluntary recalled a blood pressure medication for the second time in a month. Pfizer is recalling five lots of blood pressure medicine Accupril because of elevated levels of a nitrosamine, Nnitroso-quinapril, the company said in a news release posted Friday on the FDA website. Nitrosamines...

MILLIONS of Brits have been urged to take up a rapid test to see if they have bowel cancer. The Health Secretary has called on men over 60 to make sure they have the life-saving checkups. It couldn't be easier - with a home testing kit on offer, or use...

Christine Bronstein took at home colon cancer test after seeing blood in her stool. It was positive, but her doctor texted: "You don't have cancer :)"

Tragic events like wars, famines, earthquakes, and accidents create fearful memories in our brain. These memories continue to haunt us even after the actual event has passed. Luckily, researchers from Tokyo University of Science (TUS) have recently been able to understand the hidden biochemical mechanisms involved in the selective suppression of fearful memories, which is called fear extinction. The researchers, who had previously demonstrated fear extinction in mice using the chemically synthesized compound "KNT-127," have now identified the underlying mechanism of this compound's action. Their findings have been published recently in Frontiers in Behavioral Neuroscience.

We expanded a published mathematical model of SARS-CoV-2 transmission with complex, age-structured transmission and with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. The model was also improved to allow realistic age-structured transmission with a pre-specified R0 of transmission, and to include more compartments and parameters, e.g. for groups such as detected and undetected asymptomatic infectious cases who mask up at different rates. When masks are used at typically-observed population rates of 80% for those"‰â‰¥"‰65 years and 60% for those"‰<"‰65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks' source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number"‰â‰¤"‰1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2). For variants of concern similar to omicron (B.1.1.529) or the sub-lineage BA.2, modeled reductions in effective reproduction number due to similar high quality, high prevalence mask wearing is more modest (to 3.9 and 5.0 from an R0"‰="‰10.0 and 13.0, respectively). None-the-less, the ratio of incident risk for masked vs. non-masked populations still shows a benefit of wearing masks even with the higher R0 variants.

The original version of this Article contained errors in Table 3, where the mean and SD values were incorrect for "Clinical Composite Asymmetry |Δ2D:4D|"‰+"‰|Δ3D:5D|" for the controls. The incorrect and correct values appear below. The original article has been corrected. Plastic, Reconstructive and...

Nature Reviews Clinical Oncology (2022)Cite this article. Anti-PD-1/PD-L1 antibodies have dramatically improved the outcomes of many patients with non-small-cell lung cancers (NSCLCs) lacking actionable driver alterations. Nonetheless, the majority of patients do not derive long-term benefit from these agents. Now, data from the phase II CITYSCAPE trial demonstrate the superiority of the anti-TIGIT antibody tiragolumab plus the anti-PD-L1 antibody atezolizumab relative to atezolizumab alone in patients with advanced-stage NSCLC.

The aim of this study was to compare the prognosis of patients with acute respiratory failure (ARF) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant 501Y.V2 to that of patients with ARF due to the original strain. This retrospective matched cohort study included all consecutive patients who were hospitalized for ARF due to SARS-CoV-2 in Reunion Island University Hospital between March 2020 and March 2021. Twenty-eight in hospital mortality was evaluated before and after matching. A total of 218 patients with ARF due to SARS-CoV-2 were enrolled in the study. Of these, 83 (38.1%) were infected with the 501Y.V2 variant. During intensive care unit stay, 104 (47.7%) patients received invasive mechanical ventilation and 20 (9.2%) patients were supported by venovenous extracorporeal membrane oxygenation. Patients infected with the 501Y.V2 variant were younger (58 [51"“68] vs. 67 [56"“74] years old, P"‰="‰0.003), had less hypertension (54.2% vs 68.1%, P"‰="‰0.04), and had less chronic kidney disease (13.3% vs. 31.9%, P"‰="‰0.002) than patients infected with the original strain. After controlling for confounding variables (62 matched patients in each group), 28-day mortality was higher in the group of patients infected with the 501Y.V2 variant (30.6%) than in the group of patients infected with the original strain (19.4%, P"‰="‰0.04). In Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients with ARF infected with the 501Y.V2 variant than in patients infected with the original strain.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-022-11087-x, published online 02 May 2022. The original version of this Article contained an error in Affiliation 2, which was incorrectly given as 'Centre for SHARP Vision, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China'. The correct affiliation is listed below:. Research Centre...

Nitrogen substitutional doping in the Ï€-basal plane of graphene has been used to modulate the material properties and in particular the transition from hole to electron conduction, thus enlarging the field of potential applications. Depending on the doping procedure, nitrogen moieties mainly include graphitic-N, combined with pyrrolic-N and pyridinic-N. However, pyridine and pyrrole configurations of nitrogen are predominantly introduced in monolayer graphene:N lattice as prepared by CVD. In this study, we investigate the possibility of employing pyridinic-nitrogen as a reactive site as well as activate a reactive center at the adjacent carbon atoms in the functionalized C"“N bonds, for additional post reaction like oxidation. Furthermore, the photocatalytic activity of the graphene:N surface in the production of singlet oxygen (1O2) is fully exploited for the oxidation of the graphene basal plane with the formation of pyridine N-oxide and pyridone structures, both having zwitterion forms with a strong p-doping effect. A sheet resistance value as low as 100 Ω/â–¡ is reported for a 3-layer stacked graphene:N film.

Correction to: Heredity https://doi.org/10.1038/s41437-022-00529-x, published online 08 April 2022. The link https://doi.org/10.5061/dryad.p5hqbzkrc was added to the data availability section. The original article has been corrected. Author information. Author notes. These authors contributed equally: AM Carpenter, BA Graham. Authors and Affiliations. University of Lethbridge, Lethbridge, AB, Canada. A. M. Carpenter, B....

Aging is associated with a reduced magnitude of primary immune responses to vaccination. mRNA-based SARS-CoV-2 vaccines have shown efficacy in older adults but virus variant escape is still unclear. Here we analyze humoral and cellular immunity against an early-pandemic viral isolate and compare that to the P.1 (Gamma) and B.1.617.2 (Delta) variants in two cohorts (<50 and >55 age) of mRNA vaccine recipients. We further measure neutralizing antibody titers for B.1.617.1 (Kappa) and B.1.595, with the latter SARS-CoV-2 isolate bearing the spike mutation E484Q. Robust humoral immunity is measured following second vaccination, and older vaccinees manifest cellular immunity comparable to the adult group against early-pandemic SARS-CoV-2 and more recent variants. More specifically, the older cohort has lower neutralizing capacity at 7-14 days following the second dose but equilibrates with the younger cohort after 2-3 months. While long-term vaccination responses remain to be determined, our results implicate vaccine-induced protection in older adults against SARS-CoV-2 variants and inform thinking about boost vaccination.

In this article the grant number 200020_175700/1 relating to Swiss National Science Foundation for Jacopo Grazioli was omitted. The original article has been corrected. These authors contributed equally: Jacopo Grazioli, Gionata Ghiggi. Environmental Remote Sensing Laboratory, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Jacopo...

Society for Rural Development, Kakinada, India. Society for Rural Development, Kakinada, India. Institute for Enhanced Livelihoods, Montreal, Canada. None of the 21 targets of the United Nations’ Sustainable Development Goals (SDGs) set for 2020 was achieved. But, by our calculations, the target to protect 10% of the global ocean area (SDG14, target 5) could become a reality this year.

The immense potential of G protein-coupled receptors (GPCRs) as targets for drug discovery is not fully realized due to the enormous difficulties associated with structure elucidation of these profoundly unstable membrane proteins. The existing methods of GPCR stability-engineering are cumbersome and low-throughput; in addition, the scope of GPCRs that could benefit from these techniques is limited. Here, we present a yeast-based screening platform for a single-step isolation of GRCR variants stable in the presence of short-chain detergents, a feature essential for their successful crystallization using vapor diffusion method. The yeast detergent-resistant cell wall presents a unique opportunity for compartmentalization, to physically link the receptor's phenotype to its encoding DNA, and thus enable discovery of stable GPCR variants with unprecedent efficiency. The scope of mutations identified by the method reveals a surprising amenability of the GPCR scaffold to stabilization, and suggests an intriguing possibility of amending the stability properties of GPCR by varying the structural status of the C-terminus.

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. Understanding the nanoscopic chemical and structural changes that drive...