This guideline is structured to provide a clinical framework stratified by cancer severity to facilitate care decisions and guide the specifics of implementing the selected management options. The ...summary presented represents Part I of the two-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer severity.
The systematic review utilized in the creation of this guideline was completed by the Agency for Healthcare Research and Quality and through additional supplementation by ECRI Institute. This review included articles published between January 2007 and March 2014 with an update search conducted through August 2016. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. Additional information is provided as Clinical Principles and Expert Opinions (table 2 in supplementary unabridged guideline, http://jurology.com/).
The AUA (American Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated an evidence-based guideline based on a risk stratified clinical framework for the management of localized prostate cancer.
This guideline attempts to improve a clinician’s ability to treat patients diagnosed with localized prostate cancer, but higher quality evidence in future trials will be essential to improve the level of care for these patients. In all cases, patient preferences should be considered when choosing a management strategy.
The COVID-19 pandemic led to sharp declines in cancer screening. However, the total deficit in screening in the US associated with the pandemic and the differential impact on individuals in different ...geographic regions and by socioeconomic status (SES) index have yet to be fully characterized.
To quantify the screening rates for breast, colorectal, and prostate cancers associated with the COVID-19 pandemic in different geographic regions and for individuals in different SES index quartiles and estimate the overall cancer screening deficit in 2020 across the US population.
This retrospective cohort study uses the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information covering approximately 60 million people in Medicare Advantage and commercial health plans from across geographically diverse regions of the US. Participants were individuals in the database in January through July of 2018, 2019, and 2020 without diagnosis of the cancer of interest prior to the analytic index month.
Analytic index month and year.
Receipt of breast, colorectal, or prostate cancer screening.
Screening for all 3 cancers declined sharply in March through May of 2020 compared with 2019, with the sharpest decline in April (breast, -90.8%; colorectal, -79.3%; prostate, -63.4%) and near complete recovery of monthly screening rates by July for breast and prostate cancers. The absolute deficit across the US population in screening associated with the COVID-19 pandemic was estimated to be 3.9 million (breast), 3.8 million (colorectal), and 1.6 million (prostate). Geographic differences were observed: the Northeast experienced the sharpest declines in screening, while the West had a slower recovery compared with the Midwest and South. For example, percentage change in breast cancer screening rate (2020 vs 2019) for the month of April ranged from -87.3% (95% CI, -87.9% to -86.7%) in the West to -94.5% (95% CI, -94.9% to -94.1%) in the Northeast (decline). For the month of July, it ranged from -0.3% (95% CI, -2.1% to 1.5%) in the Midwest to -10.6% (-12.6% to -8.4%) in the West (recovery). By SES, the largest screening decline was observed in individuals in the highest SES index quartile, leading to a narrowing in the disparity in cancer screening by SES in 2020. For example, prostate cancer screening rates per 100 000 enrollees for individuals in the lowest and highest SES index quartiles, respectively, were 3525 (95% CI, 3444 to 3607) and 4329 (95% CI, 4271 to 4386) in April 2019 compared with 1535 (95% CI, 1480 to 1589) and 1338 (95% CI, 1306 to 1370) in April 2020. Multivariable analysis showed that telehealth use was associated with higher cancer screening.
Public health efforts are needed to address the large cancer screening deficit associated with the COVID-19 pandemic, including increased use of screening modalities that do not require a procedure.
To endorse Cancer Care Ontario's guideline on Active Surveillance for the Management of Localized Prostate Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures ...for endorsing clinical practice guidelines developed by other professional organizations.
The Active Surveillance for the Management of Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and the recommendations.
The ASCO Endorsement Panel determined that the recommendations from the Active Surveillance for the Management of Localized Prostate Cancer guideline, published in May 2015, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Active Surveillance for the Management of Localized Prostate Cancer guideline with added qualifying statements. The Cancer Care Ontario recommendation regarding 5-alpha reductase inhibitors was not endorsed by the ASCO panel.
For most patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the recommended disease management strategy. Factors including younger age, prostate cancer volume, patient preference, and ethnicity should be taken into account when making management decisions. Select patients with low-volume, intermediate-risk (Gleason 3 + 4 = 7) prostate cancer may be offered active surveillance. Active surveillance protocols should include prostate-specific antigen testing, digital rectal examinations, and serial prostate biopsies. Ancillary radiologic and genomic tests are investigational but may have a role in patients with discordant clinical and/or pathologic findings. Patients who are reclassified to a higher-risk category (Gleason score ≥ 7) or who have significant increases in tumor volume on subsequent biopsies should be offered active therapy.
This guideline is structured to provide a clinical framework stratified by cancer severity to facilitate care decisions and guide the specifics of implementing the selected management options. The ...summary presented herein represents Part II of the two-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer severity. Please refer to Part I for discussion of specific care options and outcome expectations and management.
The systematic review utilized in the creation of this guideline was completed by the Agency for Healthcare Research and Quality and through additional supplementation by ECRI Institute. This review included articles published between January 2007 and March 2014 with an update search conducted through August 2016. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. Additional information is provided as Clinical Principles and Expert Opinions (table 2 in supplementary unabridged guideline, http://jurology.com/).
The AUA (American Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated an evidence-based guideline based on a risk stratified clinical framework for the management of localized prostate cancer.
This guideline attempts to improve a clinician’s ability to treat patients diagnosed with localized prostate cancer, but higher quality evidence in future trials will be essential to improve the level of care for these patients. In all cases, patient preferences should be considered when choosing a management strategy.
Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved ...rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser
within its DNA binding domain occurs in response to infection by the fungus
and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene
and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.
Since its discovery over 100 years ago, insulin has been recognized as a key hormone in control of glucose homeostasis. Deficiencies of insulin signaling are central to diabetes and many other ...disorders. The brain is among the targets of insulin action, and insulin resistance is a major contributor to many diseases, including brain disorders. Here, we summarize key roles of insulin action in the brain and how this involves different brain cell types. Disordered brain insulin signaling can also contribute to neuropsychiatric diseases, affecting brain circuits involved in mood and cognition. Understanding of insulin signaling in different brain cell types/circuits and how these are altered in disease may lead to the development of new therapeutic approaches to these challenging disorders.
Insulin is a key hormone in regulation of energy metabolism. Insulin resistance, a state when cells become unresponsive to insulin, is a key feature of type 2 diabetes (T2D), obesity, and many other metabolic disorders.The brain is an insulin-sensitive tissue. Insulin signaling plays a key role in different brain cell types.Insulin modulates neuronal and glial function, resulting in changes in mood, cognition, and behavior.Dysfunction in brain insulin signaling underlies comorbidity of T2D and disorders such as depression and Alzheimer’s disease.Better understanding of brain insulin actions may lead to new therapeutic targets for the treatment of brain disorders
Purpose
Spot‐scanning arc therapy (SPArc) is an emerging proton modality that can potentially offer a combination of advantages in plan quality and delivery efficiency, compared with traditional IMPT ...of a few beam angles. Unlike IMPT, frequent low‐to‐high energy layer switching (so called switch‐up (SU)) can degrade delivery efficiency for SPArc. However, it is a tradeoff between the minimization of SU times and the optimization of plan quality. This work will consider the energy layer optimization (ELO) problem for SPArc and develop a new ELO method via energy matrix (EM) regularization to improve plan quality and delivery efficiency.
Methods
The major innovation of EM method for ELO is to design an EM that encourages desirable energy‐layer map with minimal SU during SPArc, and then incorporate this EM into the SPArc treatment planning to simultaneously minimize the number of SU and optimize plan quality. The EM method is solved by the fast iterative shrinkage‐thresholding algorithm and validated in comparison with a state‐of‐the‐art method, so‐called energy sequencing (ES).
Results
EM is validated and compared with ES using representative clinical cases. In terms of delivery efficiency, EM had fewer SU than ES with an average of 35% reduction of SU. In terms of plan quality, compared with ES, EM had smaller optimization objective values and better target dose conformality, and generally lower dose to organs‐at‐risk and lower integral dose to body. In terms of computational efficiency, EM was substantially more efficient than ES by at least 10‐fold.
Conclusion
We have developed a new ELO method for SPArc using EM regularization and shown that this new method EM can improve both delivery efficiency and plan quality, with substantially reduced computational time, compared with ES.
Plants are foundational for global ecological and economic systems, but most plant proteins remain uncharacterized. Protein interaction networks often suggest protein functions and open new avenues ...to characterize genes and proteins. We therefore systematically determined protein complexes from 13 plant species of scientific and agricultural importance, greatly expanding the known repertoire of stable protein complexes in plants. By using co-fractionation mass spectrometry, we recovered known complexes, confirmed complexes predicted to occur in plants, and identified previously unknown interactions conserved over 1.1 billion years of green plant evolution. Several novel complexes are involved in vernalization and pathogen defense, traits critical for agriculture. We also observed plant analogs of animal complexes with distinct molecular assemblies, including a megadalton-scale tRNA multi-synthetase complex. The resulting map offers a cross-species view of conserved, stable protein assemblies shared across plant cells and provides a mechanistic, biochemical framework for interpreting plant genetics and mutant phenotypes.
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•A global snapshot of protein organization in plants from deep proteomics profiling•Biochemical fractionation reveals stable protein complexes conserved across plants•Many observed complexes have previously only been inferred in plants by gene content•Known molecular modules are elaborated in plants with novel subunits and organization
This massive plant proteomics project, using co-fractionation mass spectrometry to measure the amounts and associations of over two million proteins from 13 diverse plant species, reveals stable protein complexes shared across plant cells and provides a framework for interpreting plant genetics and mutant phenotypes.
Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical ...cystectomy (RC) versus bladder-sparing trimodality therapy (TMT).
This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancer Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching.
The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study limitations included missing baseline QOL data and different follow-up times.
Both TMT and RC result in good long-term QOL outcomes in MIBC survivors, supporting TMT as a good alternative to RC for selected patients. Whether TMT leads to superior QOL requires prospective validation.
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