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microRNAs (miRNAs) are promising biomarkers for many diseases, including multiple sclerosis (MS). The neurofilament light chain (NfL) is a biomarker that can detect axonal damage in different neurological diseases. The objective of this study was to evaluate the association of the expression profile of pre-selected miRNAs and NfL levels with clinical and radiological variables in MS patients. We conducted a 1-year longitudinal prospective study in MS patients with different clinical forms. We measured clinical disability using the expanded disability status scale (EDSS), the magnetic resonance imaging (MRI) volumetry baseline, and cognitive functioning using the processing speed test (PST) at baseline and 1 year later. Selected serum miRNAs and serum NfL (sNfL) levels were quantified. Seventy-three patients were recruited. MiR-126.3p correlated with EDSS and cognitive status at baseline and miR-126.3p and miR-9p correlated with cognitive deterioration at 1 year. Correlations with regional brain volumes were observed between miR-126.3p and the cortical gray matter, cerebellum, putamen, and pallidum; miR-146a.5p with the cerebellum and pallidum; miR-29b.3p with white matter and the pallidum; miR-138.5p with the pallidum; and miR-9.5p with the thalamus. sNfL was correlated with miR-9.5p. miR-146a.5p was also associated with the MS phenotype. These data justify future studies to further explore the utility of miRNAs (mirR-126.3p, miR-146.5p, and miR.9-5p) and sNfL levels as biomarkers of MS.

The goal of this article is to analyse leisure time physical activity (LTPA) and health-driven motivations to engage in such activity among elderly people in the European Union. We use as a base the recommendations of the World Health Organisation (WHO) and the theory of the correlation between physical activity according to individual factors (age, gender, socio-economic status) and contextual factors (habitat, community infrastructures, the model of the welfare state of the country of residence). Data are taken from Eurobarometer 88.4. The Generalized Structural Equation Model (GSEM) methodology was used, with the STATA program. The results show that 65.3% of EU citizens over the age of 60 engage in some form of LTPA, that 40.4% do so for health reasons, and that only 32.3% engage in LTPA that meets the minimum guidelines set by the WHO. In addition, there are large differences based on individual and contextual characteristics. The following group was found to be those who practice the most: men, with high socio-economic status, belonging to the middle and upper social classes, living in rural areas where there is infrastructure for physical activity, and above all, in the countries of the Nordic model of social welfare.

Importance: The value of serum neurofilament light chain (sNfL) levels for predicting long-term disability in patients with multiple sclerosis (MS) remains controversial., Objective: To assess whether high sNfL values are associated with disability worsening in patients who underwent their first demyelinating MS event., Design, Setting, and Participants: This multicenter cohort study included patients who underwent their first demyelinating event suggestive of MS at Hospital Universitario Ramón y Cajal (development cohort; June 1, 1994, to September 31, 2021, with follow-up until August 31, 2022) and 8 Spanish hospitals (validation cohort; October 1, 1995, to August 4, 2020, with follow-up until August 16, 2022)., Exposures: Clinical evaluations at least every 6 months., Main Outcomes and Measures: The main outcomes were 6-month confirmed disability worsening (CDW) and an Expanded Disability Status Scale (EDSS) score of 3. Levels of sNfL were measured in blood samples obtained within 12 months after disease onset using a single molecule array kit. The cutoffs used were sNfL level of 10 pg/mL and a standardized score (z score) of 1.5. Multivariable Cox proportional hazards regression models were used to evaluate outcomes., Results: Of the 578 patients included in the study, 327 were in the development cohort (median age at sNfL analysis, 34.1 years [IQR, 27.2-42.7 years]; 226 female [69.1%]) and 251 patients were in the validation cohort (median age at sNfL analysis, 33.3 years [IQR, 27.4-41.5 years]; 184 female [73.3%]). The median follow-up was 7.10 years (IQR, 4.18-10.0 years). Levels of sNfL greater than 10 pg/mL were independently associated with higher risk of 6-month CDW and an EDSS of 3 in the development cohort (6-month CDW: hazard ratio [HR], 2.39; 95% CI, 1.39-4.12; P = .002; EDSS of 3: HR, 4.12; 95% CI, 2.18-7.77; P < .001) and the validation cohort (6-month CDW: HR, 1.61; 95% CI, 1.07-2.42; P = .02; EDSS of 3: HR, 2.03; 95% CI, 1.23-3.33; P = .005). Highly effective disease-modifying treatments were associated with lower risks of 6-month CDW and an EDSS of 3 in patients with high baseline sNfL values., Conclusions and Relevance: This cohort study found that high sNfL values obtained within the first year of disease were associated with long-term disability worsening in MS, suggesting that sNfL level measurement may help identify optimal candidates for highly effective disease-modifying treatments.

The objective of this study was to evaluate, in a group of Galician inmates, if there were variations in the levels of physical and mental health and anxiety-depressive symptomatology, depending on the sports' practice performed. The relationship between these constructs was also investigated. The sample was composed of 509 people deprived of liberty in prisons in the Autonomous Community of Galicia, Spain. A quantitative methodology was used, with the questionnaire as an information collection instrument, Student's t -tests, Pearson's correlation analysis and a stepwise regression analysis were carried out. The results indicated that those who performed physical activity during their stay in prison had higher levels of physical and mental health, as well as lower indicators of anxiety-depressive symptoms. People who did not practice sports showed a decrease in their perceived health levels when compared to those perceived in their pre-prison stage. A negative association was shown between perceived health levels and anxiety-depressive symptomatology. Perceived physical health, alone, explained 35% of the variance in perceived mental health. These results add to knowledge about the relationships between perceived health, anxiety-depressive symptoms and sports practice in the group of people deprived of liberty, highlighting the importance of promoting physical activity in penitentiary institutions.

Aim: Glioblastoma (GB) is an aggressive tumor type and the detection of circulating endothelial cells (CECs) in peripheral blood has been related to angiogenesis., Materials & Methods: A prospective single-center pilot study of CEC detection at diagnosis in 22 patients with GB was performed, using the US FDA-approved CellSearch system., Results: A CEC cutoff value was estimated using a receiver operating curve (ROC) and patients were classified into two groups: <40 CEC/4 ml and >40 CEC/4 ml blood. Median overall survival was 25.33 months for group 1 and 8.23 months for group 2 cases (p = 0.02). There was no correlation between CEC and PWI (perfusion-weighted imaging) RM., Conclusion: CEC detection has a prognostic value in GB cases at diagnosis., Competing Interests: Financial & competing interests disclosure The study was supported by Grupo Español de Investigación en Neurooncologia (GEINO). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2022 The Authors.)

Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS)., Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS)., Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25-38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72-3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54-5.71, p = 0.001; aHR 4.96, 95% CI 2.22-11.07, p < 0.001; and aHR 2.31, 95% CI 1.08-4.93, p = 0.03, respectively)., Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB., Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing-remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82-15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.

Introduction: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals., Methods: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents., Results: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments., Conclusions: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cassava ( Manihot esculenta Crantz) has been traditionally grown as a subsistence crop in Laos, but in recent years cassava cultivation in this country has expanded and is becoming a 'cash crop' for farmers (Malik et al., 2020). This also means that cassava vegetative seed (stakes) is rapidly multiplied and distributed. One of the most important diseases affecting cassava in the world is the Cassava Mosaic Disease (CMD), caused by several species of begomoviruses and disseminated by infected stakes or vectored by the whitefly Bemisia tabaci (Legg et al., 2014). Sri Lankan cassava mosaic virus (SLCMV), a bipartite begomovirus, is the virus species causing CMD in Southeast Asia (SEA) and is widespread in Cambodia, Vietnam, Thailand and south China (Siriwan et al., 2020). During field surveys on July 12 to 14, 2020, the team in south Laos, surveyed 8 fields along the border with Cambodia, in the southern provinces of Attapeu and Champassack and identified CMD symptoms (Supplementary Figure 1A) in only one of the fields, located at Kong District of the Champassack province (GPS coordinates 13.94325, 105.99102). From these 8 fields, samples were collected from every third plant in an X pattern. Photographs from each sampled plant were taken and uploaded into CIAT's PestDisPlace platform (https://pestdisplace.org), for CMD symptom confirmation (Supplementary Figure 1B). Leaf samples were sent to the laboratory for PCR using primers SLCMV-F 5'-ATGTCGAAGCGACCAGCAGATATAAT-3' and SLCMV-R 5'-TTAATTGCTGACCGAATCGTAGAAG-3' targeting the AV1 gene (Dutt et al., 2005), following the protocol described in Siriwan et al. (2020) and primers SLCMV-B-F1 5'-ACCGGATGGCCGCGCCCCCCTCT-3' and SLCMV-B-606R 5'-CACCTACCCTGTTATCGCTAAG-3' targeting part of the BV1 gene. Out of 60 samples collected for the field in Kong district, eleven (18.3%) resulted PCR positive to SLCMV (to DNA-A and DNA-B) but only four plants (6.7%) showed symptoms of CMD (see Supplementary Figure 1B and 1C). None of the samples in the other seven fields had CMD symptoms nor was SLCMV detected in any of these plants. Furthermore, the presence of CMD symptoms in the old leaves of the plants in the affected field suggests that the virus was introduced with contaminated stakes. The complete bipartite genome of one isolate (Champ1), was amplified by Rolling Circle Amplification and sequenced with the nanopore MinION technology as described by Leiva et al. (2020). The sequences were submitted to GenBank under accession nos MT946533 (DNA-A) and MT946534 (DNA-B). A phylogenetic tree for SLCMV and a link to the open SLCMV Nextstrain map (Hadfield et al., 2018) is included in Supplementary Figure 2. The sequences of the DNA-A and DNA-B components of the Champ1 isolate were nearly identical to those of anisolate of SLCMV from Ratanakiri, Cambodia (99.72% for DNA-A and 99.82 for DNA-B; Wang et al., 2016). Phylogenetic analysis (Supplementary Figure 2), grouped isolate Champ1 with those that form the cluster of SEA isolates that contain the shorter version of the rep gene (Siriwan et al., 2020). This short version of rep present a deletion of 7 amino acids at the C-terminus, which is involved in host responses to SLCMV (Wang et al., 2020). The confirmation of CMD and SLCMV in the border between Laos and Cambodia should be followed by disease containment and management strategies, particularly given that the majority cassava varieties grown in Laos are from neighbor countries, most of which have already reported the presence of CMD. Acknowledgements We thank all staff from the CIAT's Cassava Program and the Plant Protection Center of Laos in Vientiane. We acknowledge financial support from the Australian Centre for International Agricultural Research (ACIAR) and the CGIAR Research Program on Roots, Tubers and Bananas (RTB) (https://www.cgiar.org/funders/).

Despite the numerous benefits associated with sport practice, many children and adolescents end up quitting it year after year, with a stable dropout rate between 10 and 19 years of age. Among the causes of sport abandonment, the scientific literature highlights the presence of burnout as a fundamental factor. In this regard, the aim of the present study was to investigate the levels of the three components of sport burnout-emotional and physical exhaustion, reduced sense of accomplishment, and sport devaluation-reported by a sample of young (former) athletes, depending on whether their sport abandonment was relative (i.e., change to another sport modality) or definitive. In particular, participants were former agonist road cyclists, who have been divided into three groups on the basis of what they did after abandoning road bicycle racing, namely: (a) those still involved in cycling, either in a different specialty (e.g., mountain bike) or with a different role (e.g., coach for kids); (b) those who started practicing a different sport; and (c) those who definitively abandoned sports. The general hypothesis was that, with respect to those who changed sport and those who definitively abandoned it, those still involved in cycling would report experiencing lower levels of the three burnout components during the last year practicing it. To test this hypothesis, the Athlete Burnout Questionnaire (ABQ; Raedeke and Smith, 2001) was administered to 85 young former road cyclists. The results seem to support the hypothesis for two out of the three components, namely, emotional and physical exhaustion and sport devaluation; on the other hand, for reduced sense of accomplishment, no difference among the three groups emerged. Further research is needed to deepen the understanding of such processes, also in relation with other relevant constructs; yet, the results of the present study should already raise the awareness of sport organizations on the need to deal with this and related phenomena by adopting appropriate strategies to ensure the well-being of young athletes, thus trying to reduce early dropout., (Copyright © 2020 Sors, Tomé Lourido, Damonte, Santoro, Galmonte, Agostini and Murgia.)

The decision-making processes of referees in sports are affected by many factors, including the pressure of spectators. While the home/visitor bias has been previously investigated, the role of crowd noise has been less studied. In the present study, we investigated how the crowd noise (calm vs. pressing) influence the decisions of basketball referees, when examining videos of potential fouls. In doing so, we also considered the level of competitive anxiety of referees (low vs. high anxiety), as factor potentially interacting with the pressure exerted by the spectators. A 2 × 2 ANOVA (Crowd noise x Anxiety) revealed a significant interaction [ F (1,28) = 7.33; p < 0.05; η p 2 = 0.21; power = 0.74], with the highly anxious referees showing poorer performances in the pressing crowd condition [ t (14) = 2.24; p < 0.05; d = 0.64]. The results indicate that the crowd noise does not seem to affect the referees' decisions, unless we consider the anxiety. The present findings suggest that the decisions of referees with high anxiety might be more easily influenced by external factors like crowd noise. Based on these results, referees' federations should consider the possibility to develop training protocols dedicated to highly anxious referees, to avoid their decisions from being biased by spectators' pressure., (Copyright © 2019 Sors, Tomé Lourido, Parisi, Santoro, Galmonte, Agostini and Murgia.)

Background: The evaluation of psychological skills by athletes and their relationship with sports performance and satisfaction has been of great interest in recent decades. Likewise, there has been an emergent tendency to focus on developing specific psychological skills for each sport. The principal aim of this study was to determine the frequency with which athletes deploy psychological skills whilst competing and whether their frequency varies in accordance with the technical, tactical and physical characteristics of the sport in question. A further objective was to establish the connection between the frequency of use of psychological skills and athletes' degree of satisfaction with their performance., Methods: The study comprised 1003 athletes practicing 43 different sports, grouped into 7 categories based on the similarities between them. Frequency of use of the psychological skills was measured with the Test of Performance Strategies 3., Results: The data analyses allowed the following conclusions to be drawn: the degree to which psychological skills are used is dependent on the technical, tactical and physical characteristics of each sport; and the higher the frequency of the use of psychological skills, the greater the athletes' degree of satisfaction with their performance., Conclusions: These results allow athletes and coaches to increase levels of sports performance by working on the use of psychological skills, adapted to the technical, tactical or physical requirements of the category in which their sport is included. In addition, working on different psychological skills will improve their satisfaction with sports performance.

Background: In recent years, there has been a growing interest in the conceptualisation and assessment of athletes&rsquo; psychological skills and the study of their impact on sports performance. The aim of this study was to adapt the Test of Performance Strategies 3 competition subscale to the Spanish context., Method: The items included in the original test in English were translated using a double-back method, and the test was completed by a sample of 1,003 Spanish athletes of both sexes. Analyses of the factorial validity, reliability and invariance of the measurement model were carried out., Results: Favourable evidence was obtained for a measurement model comprising 36 items grouped in 9 factors, similar to the original model. Model fit was reasonable for both individual parameters and overall. Reliability rates were satisfactory for the overall test and for each factor. Evidence was also favourable for sex-based measurement model invariance., Conclusions: The adaptation is satisfactory and fit for use by sports psychology researchers and professionals in assessing the psychological skills employed by athletes in competition.

Introduction: It has been debated whether the penumbral pattern, as identified using multimodal imaging, is a specific marker of tissue viability in ischemic stroke. We assessed whether perfusion computed tomography (PCT) accurately identifies salvageable tissue and helps predict postreperfusion outcomes., Methods: A retrospective study of patients with anterior circulation stroke undergoing reperfusion therapies who had a PCT before treatment and an assessment of vessel recanalization post treatment was conducted. Tissue at risk was considered as that with reduced cerebral blood flow, whereas the infarct core was the region of reduced cerebral blood volume, the mismatch region being salvageable tissue. The volume of hypodensity in slices corresponding to perfusion acquisition cage in 24-hour computed tomography (partial lesion volume [PLV]) was measured. Outcome variables were the amount of preserved tissue, that is, the difference between volumes of tissue at risk and PLV expressed as a percentage, and the modified Rankin Scale (mRS) score at 3 months., Results: Patients (n = 34) meeting the inclusion criteria were included. Vessel recanalization was associated with a larger amount of tissue at risk preserved from definite lesion (89% [interquartile range {IQR}: 76-94] versus 46% [IQR: 23-86], P < .005). The amount of preserved tissue correlated with clinical outcome at 24 hours: for each 10% of preserved tissue, the National Institutes of Health Stroke Scale score improved by 3 points (95% confidence interval [CI]: -4.9 to -.8, P = .007) and was the only predictor of independency (mRS score 0-2) following adjustment for covariates (odds ratio 1.15, 95% CI: 1.04-1.28, P = .005)., Conclusions: PCT provides accurate markers of viability of tissue in acute ischemic stroke and could help predict the degree of improvement following reperfusion., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization., Methods: Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, time-lapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability)., Results: Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT + MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3-0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5-1.2). A score ≤5 in CTA-SI-ASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %)., Conclusions: CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies.

Chromatographic profiles of wines have been used as a fingerprint for the discrimination of Spanish wines based on oenological practices. In order to extract information of different families of phenolic compounds, profiles of different UV-vis absorption wavelengths (280, 310, 370 and 520nm) and fluorescence (ex=260nm; em=360nm) were analysed. A total of thirteen phenolic compounds which allowed the discrimination of wines of three different Spanish appellations (Penedes, Rioja and Ribera del Duero) were selected by means of principal component analysis (PCA). Afterwards, these compounds were used to build partial least squares discriminant analysis (PLS1-DA and PLS2-DA) models which allowed the discrimination of wines according to their appellation with classification rates for independent test sets higher than 96% and 93% for PLS1-DA and PLS2-DA models respectively. Finally, characteristic compounds of each appellation were tentatively identified by means of liquid chromatography-mass spectrometry (LC-MS) analysis. Thus, ten out of thirteen compounds (i.e., gallic acid for Penedes, trans-coumaroyltartaric and trans-caffeoyltartaric acids for Rioja and myricetin for Ribera del Duero wines) have been proposed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

PET imaging utilizes a dedicated camera system with multiple positron detector rings. PET/CT precisely aligns and combines metabolic PET mages with anatomical CT images, and is being increasingly preffered over PET scanning alone. FDG is the most widely used radiotracer in the management of cancer patients, and the prototypical PET/CT protocol used in other cancers can also be applied to the management of cervical carcinoma patients. The applications of PET/CT in cervical cancer patients include: assessing local tumor extension (information on metabolic tumor activity and possible endometrial involvement), evaluating pelvic nodal involvement (even in cases with negative CT or MRI studies), detection of distant metastases (PET/CT should be the first imaging technique used to evaluate extrapelvic disease before pelvic exenteration), radiation therapy planning (in patiens with PET scans positive for lymph nodes), identification of persistent/recurrent disease (especially in assessing response to neoadjuvant therapy and prognosis (with an inverse response-survival relationship.