Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).

Rhizophagus intraradices and Azospirillum brasilense improve growth of herbaceous plants and soil biological activity in revegetation of a recovering coal-mining area.

We assessed, in a field experiment, the effects of arbuscular mycorrhizal fungi (Rhizophagus intraradices) and plant growth-promoting bacteria (Azospirillum brasilense) on the soil biological activity and the growth of key pioneer species used in the revegetation of coal-mining areas undergoing recovery. We applied four inoculation treatments to the pioneer plant species (Lablab purpureus, Paspalum notatum, Crotalaria juncea, Neonotonia wightii, Stylosanthes guianensis, Andropogon gayanus and Trifolium repens) used in the recovery process: NI (Control - Non-inoculated), AZO (A. brasilense), AMF (R. intraradices), and co-inoculation of AZO and AMF. On the 75th and 180th days, we measured plant dry mass, mycorrhizal colonization, N and P concentration, and accumulation in plant tissue. We collected soil to quantify glomalin content and soil enzyme activity. After 180 days, we did a phytosociological characterization of the remaining spontaneous plants.The both microorganisms, singly or co-inoculated, promoted increases in different fractions of soil glomalin, acid phosphatase activity, and fluorescein diacetate activity at 75 and 180 days. The inoculation was linked to higher plant biomass production (62-89%) and increased plant P and N accumulation by 34-75% and 70-85% at 180 days, compared with the non-inoculated treatment. Among the pioneer species sown Crotalaria juncea produced the highest biomass at the 75th and 180th days (67% and 76% of all biomass), followed by Lablab purpureus (3% and 0.5%), while the other species failed to establish. At 180 days, we observed twenty spontaneous plant species growing in the area, primarily from the Poaceae family (74%). That suggests that the pioneer species present in the area do not hinder the ecological succession process. Inoculation of R. intraradices and A. brasilense, isolated or combined, increases soil biological activity, growth, and nutrient accumulation in key pioneer plant species, indicating the potential of that technique for the recovery of lands degraded by coal mining.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

PURPOSE: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology. METHODS AND MATERIALS: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible. The maximally tolerated dose was defined as the dose of radiation therapy associated with a ≤30% rate of grade (G) 3 to 5 prespecified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume; tumors with endobronchial invasion were excluded. This primary analysis occurred 2 years after completion of accrual. RESULTS: Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range, 65-87) and 17 (57%) were female. Planning tumor volume was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%), and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range, 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia. The latter had computed tomography findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% CI, 52.3%-85.3%), progression-free survival 66.1% (95% CI, 46.1%-80.2%), local control 89.6% (95% CI, 71.2%-96.5%), regional control 96.4% (95% CI, 77.2%-99.5%), and distant control 85.9% (95% CI, 66.7%-94.5%). Quality-of-life scores declined numerically over time, but the decreases were not clinically or statistically significant. CONCLUSIONS: Sixty Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the prespecified acceptability criteria and results in excellent control for ultracentral tumors.

The radiation of nodulated Chamaecrista species from the rainforest into more diverse habitats has been accompanied by a reduction in growth form and a shift from fixation threads to symbiosomes.

All non-Mimosoid nodulated genera in the legume subfamily Caesalpinioideae confine their rhizobial symbionts within cell wall-bound 'fixation threads' (FTs). The exception is the large genus Chamaecrista in which shrubs and subshrubs house their rhizobial bacteroids more intimately within symbiosomes, whereas large trees have FTs. This study aimed to unravel the evolutionary relationships between Chamaecrista growth habit, habitat, nodule bacteroid type, and rhizobial genotype. The growth habit, bacteroid anatomy, and rhizobial symbionts of 30 nodulated Chamaecrista species native to different biomes in the Brazilian state of Bahia, a major centre of diversity for the genus, was plotted onto an ITS-trnL-F-derived phylogeny of Chamaecrista. The bacteroids from most of the Chamaecrista species examined were enclosed in symbiosomes (SYM-type nodules), but those in arborescent species in the section Apoucouita, at the base of the genus, were enclosed in cell wall material containing homogalacturonan (HG) and cellulose (FT-type nodules). Most symbionts were Bradyrhizobium genotypes grouped according to the growth habits of their hosts, but the tree, C. eitenorum, was nodulated by Paraburkholderia. Chamaecrista has a range of growth habits that allow it to occupy several different biomes and to co-evolve with a wide range of (mainly) bradyrhizobial symbionts. FTs represent a less intimate symbiosis linked with nodulation losses, so the evolution of SYM-type nodules by most Chamaecrista species may have (i) aided the genus-wide retention of nodulation, and (ii) assisted in its rapid speciation and radiation out of the rainforest into more diverse and challenging habitats.

Physical and functional evaluations in oncological patients elective to medium and large operations.

PURPOSE: To evaluate the risk of sarcopenia on the length of hospital stay and deaths in preoperative cancer patients as well its relation to physical and functional capacity. METHODS: Preoperative patients admitted to the Cancer Hospital of Mato Grosso comprised the sample. Sociodemographic data, lifestyle data, and a questionnaire for sarcopenia screening were collected. Subsequently, total body mass, height, muscle strength, muscle mass, and physical performance were evaluated. The primary, secondary and tertiary outcomes were sarcopenia, length of stay and death, respectively. The data were tabulated and analyzed using the statistical software SPSS (25.0). The significance level was 5%. RESULTS: We observed 12 (7.4%) patients with low muscle strength, 20 (12.3%) patients with low muscle mass, 11 (6.8%) patients with low physical performance, and 18 (11.1%) patients with scores for possible sarcopenia. When the risk of sarcopenia was observed, 44 (27.2%) patients had at least one risk related to muscle disorder. When analyzing the prevalence and association of sarcopenia with sociodemographic variables, we observed that education level was associated with sarcopenia (p = 0.031). In addition, there was an association between preoperative sarcopenia and postoperative death (p = 0.006). Finally, there were important correlations between muscle strength and physical performance (p < 0.05), between muscle strength and the sarcopenia questionnaire (p < 0.001), and between physical performance and the sarcopenia questionnaire (p < 0.05). CONCLUSION: The results suggest the need for counseling and the need to evaluate patients for risk of sarcopenia, since early intervention, such as dietary supplementation and physical exercise, may favor a better postoperative prognosis, possibly corresponding to shorter hospital stays and longer survival and quality of life for patients, especially those who will undergo surgical procedures.

Lossy Image Compression in a Preclinical Multimodal Imaging Study.

The growing use of multimodal high-resolution volumetric data in pre-clinical studies leads to challenges related to the management and handling of the large amount of these datasets. Contrarily to the clinical context, currently there are no standard guidelines to regulate the use of image compression in pre-clinical contexts as a potential alleviation of this problem. In this work, the authors study the application of lossy image coding to compress high-resolution volumetric biomedical data. The impact of compression on the metrics and interpretation of volumetric data was quantified for a correlated multimodal imaging study to characterize murine tumor vasculature, using volumetric high-resolution episcopic microscopy (HREM), micro-computed tomography (µCT), and micro-magnetic resonance imaging (µMRI). The effects of compression were assessed by measuring task-specific performances of several biomedical experts who interpreted and labeled multiple data volumes compressed at different degrees. We defined trade-offs between data volume reduction and preservation of visual information, which ensured the preservation of relevant vasculature morphology at maximum compression efficiency across scales. Using the Jaccard Index (JI) and the average Hausdorff Distance (HD) after vasculature segmentation, we could demonstrate that, in this study, compression that yields to a 256-fold reduction of the data size allowed to keep the error induced by compression below the inter-observer variability, with minimal impact on the assessment of the tumor vasculature across scales.

Neighborhood Deprivation and Rurality Associated With Patient-Reported Outcomes and Survival in Men With Prostate Cancer in NRG Oncology RTOG 0415.

PURPOSE: Rurality and neighborhood deprivation can contribute to poor patient-reported outcomes, which have not been systematically evaluated in patients with specific cancers in national trials. Our objective was to examine the effect of rurality and neighborhood socioeconomic and environmental deprivation on patient-reported outcomes and survival in men with prostate cancer in NRG Oncology RTOG 0415. METHODS AND MATERIALS: Data from men with prostate cancer in trial NRG Oncology RTOG 0415 were analyzed; 1,092 men were randomized to receive conventional radiation therapy or hypofractionated radiation therapy. Rurality was categorized as urban or rural. Neighborhood deprivation was assessed using the area deprivation index and air pollution indicators (nitrogen dioxide and particulate matter with a diameter less than 2.5 micrometers) via patient ZIP codes. Expanded Prostate Cancer Index Composite measured cancer-specific quality of life. The Hopkins symptom checklist measured anxiety and depression. EuroQoL-5 Dimension assessed general health. RESULTS: We analyzed 751 patients in trial NRG Oncology RTOG 0415. At baseline, patients from the most deprived neighborhoods had worse bowel (P = .011), worse sexual (P = .042), and worse hormonal (P = .015) scores; patients from the most deprived areas had worse self-care (P = .04) and more pain (P = .047); and patients from rural areas had worse urinary (P = .03) and sexual (P = .003) scores versus patients from urban areas. Longitudinal analyses showed that the 25% most deprived areas (P = .004) and rural areas (P = .002) were associated with worse EuroQoL-5 Dimension visual analog scale score. Patients from urban areas (hazard ratio, 1.81; P = .033) and the 75% less-deprived neighborhoods (hazard ratio, 0.68; P = .053) showed relative decrease in risk of recurrence or death (disease-free survival). CONCLUSIONS: Patients with prostate cancer from the most deprived neighborhoods and rural areas had low quality of life at baseline, poor general health longitudinally, and worse disease-free survival. Interventions should screen populations from deprived neighborhoods and rural areas to improve patient access to supportive care services.

Lung SBRT credentialing in the Canadian OCOG-LUSTRE randomized trial.

Purpose: To report on the Stereotactic Body Radiation Therapy (SBRT) credentialing experience during the Phase III Ontario Clinical Oncology Group (OCOG) LUSTRE trial for stage I non-small cell lung cancer. Methods: Three credentialing requirements were required in this process: (a) An institutional technical survey; (b) IROC (Imaging and Radiation Oncology Core) thoracic phantom end-to-end test; and (c) Contouring and completion of standardized test cases using SBRT for one central and one peripheral lung cancer, compared against the host institution as the standard. The main hypotheses were that unacceptable variation would exist particularly in OAR definition across all centres, and that institutions with limited experience in SBRT would be more likely to violate per-protocol guidelines. Results: Fifteen Canadian centres participated of which 8 were new, and 7 were previously established (≥2 years SBRT experience), and all successfully completed surveys and IROC phantom testing. Of 30 SBRT test plans, 10 required replanning due to major deviations, with no differences in violations between new and established centres (p = 0.61). Mean contouring errors were highest for brachial plexus in the central (C) case (12.55 ± 6.62 mm), and vessels in the peripheral (P) case (13.01 ± 12.55 mm), with the proximal bronchial tree (PBT) (2.82 ± 0.78 C, 3.27 ± 1.06 P) as another variable structure. Mean dice coefficients were lowest for plexus (0.37 ± 0.2 C, 0.37 ± 0.14 P), PBT (0.77 ± 0.06 C, 0.75 ± 0.09 P), vessels (0.69 ± 0.29 C, 0.64 ± 0.31 P), and esophagus (0.74 ± 0.04 C, 0.76 ± 0.04 P). All plans passed per-protocol planning target volume (PTV) coverage and maximum/volumetric organs-at-risk constraints, although variations existed in dose gradients within and outside the target. Conclusions: Clear differences exist in both contouring and planning with lung SBRT, regardless of centre experience. Such an exercise is important for studies that rely on high precision radiotherapy, and to ensure that implications on trial quality and outcomes are as optimal as possible.

Cervical Cancer Prevention on Instagram: Content and Social Interaction Analysis of Brazilian Accounts.

OBJECTIVE: The aim of the present study was to analyse the content of posts on Instagram about cervical cancer. METHODS: It was conducted a qualitative analysis using the 50 most popular publicly available Portuguese-language Instagram posts, containing the hashtags #cervicalcancer, #papsmear, #hpv, #papillomavirus, and #hpvvac-cine, during the Brazilian national cervical cancer prevention campaign in March 2018. RESULTS: Posts recruited using #cervicalcancer provided 60% of posts with contents related to secondary prevention; the #papsmear provided 46% of posts with irrelevant contents; the #hpv and #papillomavirus provided 50% and 64% of posts with informative content, respectively; and the #hpvvaccine provided 58% of posts with content related to primary prevention. The posts that received the highest number of likes were those from the hashtags #hpv and #papillomavirus with 151.33 and 78.00 likes/post, respectively. The majority of posts presented less than 05 comments/post, except for the #hpv, which had 64.76 comments/post. According to the users' profiles, the majority of the posts, regardless of the hashtag used, were made by health professionals. CONCLUSION: The focus of Instagram posts about cervical cancer is on secondary prevention, which can contribute to the promotion of health behaviours not directed to aspects of primary prevention of the disease.

High-precision 14C measurements of parenchyma-rich Hymenolobium petraeum tree species confirm bomb-peak atmospheric levels and reveal local fossil-fuel CO2 emissions in the Central Amazon.

Atmospheric radiocarbon (14C) recorded in tree rings has been widely used for atmospheric 14C calibration purposes and climate studies. But atmospheric 14C records have been limited along tropical latitudes. Here we report a sequence from 1938 to 2007 of precisely measured 14C dates in tree rings of the parenchyma-rich Hymenolobium petraeum tree species (Porto Trombetas, 1°S, 56°W) from the Central Brazilian Amazon. H. petraeum has discernible growth ring boundaries that allow dating techniques to be employed to produce calendrical dates. Bomb-peak tree-ring 14C reconstruction coincides with the broader changes associated with reported values of the Southern Hemisphere atmospheric 14C curve (SH zone 3; values within the ±2σ interval), suggesting that inter-hemispheric air-mass transport of excess-14C injected into the stratosphere during intensive atmospheric nuclear tests is relatively uniform across distinct longitudinal regions. From the early 1980s onwards, H. petraeum had lower 14C values than other pantropical 14C records. Through 14C-based estimation, we found a strong influence of fossil-fuel CO2 contributions from Porto Trombetas mining operations and shipping traffic on inland waterways. An increase of at least 6.3 ± 0.8 ppm of fossil-fuel CO2 has been detected by 14C. Our findings invite further 14C analyses using tree rings of tropical tree species as a potential tracer for a wide range of environmental sources of atmospheric 14C-variability.

The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes.

Nitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2 -fixing clade retained nodulation and diversified as stable nodulators, while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades. We characterize two nodule anatomy types across 128 species in 56 of the 152 genera of the legume subfamily Caesalpinioideae: fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads, and symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes (SYMs). Using a robust phylogenomic tree based on 997 genes from 147 Caesalpinioideae genera, we show that losses of nodulation are more prevalent in lineages with FTs than those with SYMs. We propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through tighter compartmentalization of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical legume clade.

The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.

BACKGROUND: In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. METHODS: The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. FINDINGS: Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. INTERPRETATION: The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. FUNDING: National Cancer Institute.

Lossless Coding of Light Fields Based on 4D Minimum Rate Predictors.

Common representations of light fields use four-dimensional data structures, where a given pixel is closely related not only to its spatial neighbours within the same view, but also to its angular neighbours, co-located in adjacent views. Such structure presents increased redundancy between pixels, when compared with regular single-view images. Then, these redundancies are exploited to obtain compressed representations of the light field, using prediction algorithms specifically tailored to estimate pixel values based on both spatial and angular references. This paper proposes new encoding schemes which take advantage of the four-dimensional light field data structures to improve the coding performance of Minimum Rate Predictors. The proposed methods expand previous research on lossless coding beyond the current state-of-the-art. The experimental results, obtained using both traditional datasets and others more challenging, show bit-rate savings no smaller than 10%, when compared with existing methods for lossless light field compression.

Melanoma classification using light-Fields with morlet scattering transform and CNN: Surface depth as a valuable tool to increase detection rate.

Medical image classification through learning-based approaches has been increasingly used, namely in the discrimination of melanoma. However, for skin lesion classification in general, such methods commonly rely on dermoscopic or other 2D-macro RGB images. This work proposes to exploit beyond conventional 2D image characteristics, by considering a third dimension (depth) that characterises the skin surface rugosity, which can be obtained from light-field images, such as those available in the SKINL2 dataset. To achieve this goal, a processing pipeline was deployed using a morlet scattering transform and a CNN model, allowing to perform a comparison between using 2D information, only 3D information, or both. Results show that discrimination between Melanoma and Nevus reaches an accuracy of 84.00, 74.00 or 94.00% when using only 2D, only 3D, or both, respectively. An increase of 14.29pp in sensitivity and 8.33pp in specificity is achieved when expanding beyond conventional 2D information by also using depth. When discriminating between Melanoma and all other types of lesions (a further imbalanced setting), an increase of 28.57pp in sensitivity and decrease of 1.19pp in specificity is achieved for the same test conditions. Overall the results of this work demonstrate significant improvements over conventional approaches.

Skin lesion classification using features of 3D border lines.

Machine learning algorithms are progressively assuming important roles as computational tools to support clinical diagnosis, namely in the classification of pigmented skin lesions using RGB images. Most current classification methods rely on common 2D image features derived from shape, colour or texture, which does not always guarantee the best results. This work presents a contribution to this field, by exploiting the lesions' border line characteristics using a new dimension - depth, which has not been thoroughly investigated so far. A selected group of features is extracted from the depth information of 3D images, which are then used for classification using a quadratic Support Vector Machine. Despite class imbalance often present in medical image datasets, the proposed algorithm achieves a top geometric mean of 94.87%, comprising 100.00% sensitivity and 90.00% specificity, using only depth information for the detection of Melanomas. Such results show that potential gains can be achieved by extracting information from this often overlooked dimension, which provides more balanced results in terms of sensitivity and specificity than other settings.

Framework for Intelligent Swimming Analytics with Wearable Sensors for Stroke Classification.

Intelligent approaches in sports using IoT devices to gather data, attempting to optimize athlete's training and performance, are cutting edge research. Synergies between recent wearable hardware and wireless communication strategies, together with the advances in intelligent algorithms, which are able to perform online pattern recognition and classification with seamless results, are at the front line of high-performance sports coaching. In this work, an intelligent data analytics system for swimmer performance is proposed. The system includes (i) pre-processing of raw signals; (ii) feature representation of wearable sensors and biosensors; (iii) online recognition of the swimming style and turns; and (iv) post-analysis of the performance for coaching decision support, including stroke counting and average speed. The system is supported by wearable inertial (AHRS) and biosensors (heart rate and pulse oximetry) placed on a swimmer's body. Radio-frequency links are employed to communicate with the heart rate sensor and the station in the vicinity of the swimming pool, where analytics is carried out. Experiments were carried out in a real training setup, including 10 athletes aged 15 to 17 years. This scenario resulted in a set of circa 8000 samples. The experimental results show that the proposed system for intelligent swimming analytics with wearable sensors effectively yields immediate feedback to coaches and swimmers based on real-time data analysis. The best result was achieved with a Random Forest classifier with a macro-averaged F1 of 95.02%. The benefit of the proposed framework was demonstrated by effectively supporting coaches while monitoring the training of several swimmers.

Nodulation of the neotropical genus Calliandra by alpha or betaproteobacterial symbionts depends on the biogeographical origins of the host species.

The neotropical genus Calliandra is of great importance to ecology and agroforestry, but little is known about its nodulation or its rhizobia. The nodulation of several species from two restricted diversity centres with native/endemic species (Eastern Brazil and North-Central America) and species widespread in South America, as well as their nodule structure and the molecular characterization of their rhizobial symbionts based on phylogeny of the 16S rRNA, recA and nodC gene, is reported herein. Species representative of different regions were grown in Brazilian soil, their nodulation observed, and their symbionts characterized. Calliandra nodules have anatomy that is typical of mimosoid nodules regardless of the microsymbiont type. The rhizobial symbionts differed according to the geographical origin of the species, i.e. Alphaproteobacteria (Rhizobium) were the exclusive symbionts from North-Central America, Betaproteobacteria (Paraburkholderia) from Eastern Brazil, and a mixture of both nodulated the widespread species. The symbiont preferences of Calliandra species are the result of the host co-evolving with the "local" symbiotic bacteria that thrive in the different edaphoclimatic conditions, e.g. the acidic soils of NE Brazil are rich in acid-tolerant Paraburkholderia, whereas those of North-Central America are typically neutral-alkaline and harbour Rhizobium. It is hypothesized that the flexibility of widespread species in symbiont choice has assisted in their wider dispersal across the neotropics.

Computational search for drug repurposing to identify potential inhibitors against SARS-COV-2 using Molecular Docking, QTAIM and IQA methods in viral Spike protein - Human ACE2 interface.

With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic density of the BCP O4-N10. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-Glu37 site, acting on the BCPs H30-H33 and O8-H31 while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O8-H31 of that same interactive site. Thus, the data suggest laboratory tests of a combination of molecules that can act at two sites of interaction simultaneously, using the combination of 1629/2542 and 1629/2600 ligands.

Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer.

PURPOSE: Moderate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique. METHODS AND MATERIALS: Patients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan-Meier from the date of last radiation treatment until date of event. RESULTS: We report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively. CONCLUSIONS: The longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.