Temporal prediction of multiple sclerosis evolution from patient-centered outcomes

Multiple Sclerosis is a degenerative condition of the central nervous system that affects nearly 2.5 million of individuals in terms of their physical, cognitive, psychological and social capabilities. Despite the high variability of its clinical presentation, relapsing and progressive multiple sclerosis are considered the two main disease types, with the former possibly evolving into the latter. Recently, the attention of the medical community toward the use of patient-centered outcomes in multiple sclerosis has significantly increased. Such patient-friendly measures are devoted to the assessment of the impact of the disease on several domains of the patient life. In this work, we investigate on use of patient-centered outcomes to predict the evolution of the disease and to assess its impact on patients\u201a\uc4\uf4 lives. To this aim, we build a novel temporal model based on gradient boosting classification and multiple-output elastic-net regression. The model provides clinically interpretable results along with accurate predictions of the disease course evolution

Development and psychometric properties of a self-assessed knowledge questionnaire for caregivers of people with multiple sclerosis (CareKoMS): a cross-sectional study

ObjectivesKnowledge about multiple sclerosis (MS) is crucial for those who provide care and support as caregivers. However, despite the key benefits of acquiring relevant information to properly assume the caregiving role, caregivers' knowledge of MS is poorly investigated. The aim of this study was to develop and validate the Caregivers' Knowledge of Multiple Sclerosis (CareKoMS), a self-assessed questionnaire, to test MS knowledge in caregivers of people with MS. DesignCross-sectional study. SettingItaly. ParticipantsTwo-hundred caregivers (female: 49%) were asked to self-administer the 32-item CareKoMS questionnaire; they had a median age of 60 years (IQR: 51-68 years) and a medium-high educational level (36.5% primary school and 63.5% high school/university). Item analysis using item difficulty index, item discrimination index, Kuder-Richardson-20 coefficient and item-total correlation were assessed. Once excluding less useful items, reliability, floor and ceiling effects and construct validity were calculated on the 21-item CareKoMS final version. ResultsPsychometric evaluation indicates that the 21-item CareKoMS was a good questionnaire with no ceiling or floor effects registered. Internal consistency was satisfactory and acceptable as indicated by the mean value of 0.74 of Kuder-Richardson-20. No ceiling or floor effects have been observed. Interestingly, educational level and disease duration correlated with MS knowledge. ConclusionCareKoMS is a valid self-assessed questionnaire on MS knowledge for caregivers that may be used in clinical practice and research. Assessing knowledge of MS among caregivers is essential to facilitate their caregiving role and thus decrease the burden of disease management

The impact of different doses of indocyanine green on the sentinel lymph-node mapping in early stage endometrial cancer.

INTRODUCTION Aim of the study is to evaluate the impact of different doses of indocyanine green (ICG) on the sentinel lymph-node (SLN) mapping in endometrial cancer (EC). MATERIALS AND METHODS A retrospective analysis of EC patients undergoing a laparoscopic SLN mapping at two institutions was performed. Two different injection protocols were used (protocol # 1: 5 mg/ml and a volume of 8 ml; protocol # 2: 1.25 mg/ml and a volume of 4 ml). In every case, the injection was intracervical. The laparoscopic equipment adopted was the same among both institutions. Overall and bilateral detection rates (DR) and median number of retrieved SLNs were calculated. At uni- and multivariate analysis factors (including ICG dose) associated with DR and number of detected SLNs were investigated. RESULTS Overall, 168 patients were included. The overall and bilateral DR were 96.3 and 84.5%. Median number of removed SLNs was 3 (0-18). In 56% of the patients, a median number of 6 (1-93) non-SLNs (NSLNs) were removed. Seventeen (10.1%) patients had metastatic SLNs. At multivariate analysis, no factors were associated with bilateral DR. ICG dose was the only factor associated with number of removed SLNs at multivariate analysis. CONCLUSION A larger dose of ICG is associated with a higher number of retrieved SLNs but not with an increased bilateral DR

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CL(pro). The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was performed to ascertain the nature of the binding with the 3CL(pro). The compounds are slow-binding inactivators of 3CL(pro) with a K(i) of 3.95 μM and 3.77 μM for protocetraric and salazinic acid, respectively, and inhibitory efficiency k(inact)/K(i) at about 3 × 10(−5) s(−1)µM(−1). The mechanism of inhibition shows that both compounds act as competitive inhibitors with the formation of a stable covalent adduct. The viability assay on epithelial cells revealed that none of them shows cytotoxicity up to 80 μM, which is well below the K(i) values. By molecular modelling, we predicted that the catalytic Cys145 makes a nucleophilic attack on the carbonyl carbon of the cyclic ester common to both inhibitors, forming a stably acyl-enzyme complex. The computational and kinetic analyses confirm the formation of a stable acyl-enzyme complex with 3CL(pro). The results obtained enrich the knowledge of the already numerous biological activities exhibited by lichen secondary metabolites, paving the way for developing promising scaffolds for the design of cysteine enzyme inhibitors

The Theory of the Interleaving Distance on Multidimensional Persistence Modules

In 2009, Chazal et al. introduced $\epsilon$-interleavings of persistence modules. $\epsilon$-interleavings induce a pseudometric $d_I$ on (isomorphism classes of) persistence modules, the interleaving distance. The definitions of $\epsilon$-interleavings and $d_I$ generalize readily to multidimensional persistence modules. In this paper, we develop the theory of multidimensional interleavings, with a view towards applications to topological data analysis. We present four main results. First, we show that on 1-D persistence modules, $d_I$ is equal to the bottleneck distance $d_B$. This result, which first appeared in an earlier preprint of this paper, has since appeared in several other places, and is now known as the isometry theorem. Second, we present a characterization of the $\epsilon$-interleaving relation on multidimensional persistence modules. This expresses transparently the sense in which two $\epsilon$-interleaved modules are algebraically similar. Third, using this characterization, we show that when we define our persistence modules over a prime field, $d_I$ satisfies a universality property. This universality result is the central result of the paper. It says that $d_I$ satisfies a stability property generalizing one which $d_B$ is known to satisfy, and that in addition, if $d$ is any other pseudometric on multidimensional persistence modules satisfying the same stability property, then $d\leq d_I$. We also show that a variant of this universality result holds for $d_B$, over arbitrary fields. Finally, we show that $d_I$ restricts to a metric on isomorphism classes of finitely presented multidimensional persistence modules.Comment: Major revision; exposition improved throughout. To appear in Foundations of Computational Mathematics. 36 page

A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

Background Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.Foundation KiKaChildren's Neuroblastoma Cancer FoundationSKK FoundationDutch Cancer Societ

Small renal masses in kidney transplantation : Overview of clinical impact and management in donors and recipients

Kidney transplantation is the best replacement treatment for the end-stage renal disease. Currently, the imbalance between the number of patients on a transplant list and the number of organs available constitutes the crucial limitation of this approach. To expand the pool of organs amenable for transplantation, kidneys coming from older patients have been employed; however, the combination of these organs in conjunction with the chronic use of immunosuppressive therapy increases the risk of incidence of graft small renal tumors. This narrative review aims to provide the state of the art on the clinical impact and management of incidentally diagnosed small renal tumors in either donors or recipients. According to the most updated evidence, the use of grafts with a small renal mass, after bench table tumor excision, may be considered a safe option for high-risk patients in hemodialysis. On the other hand, an early small renal mass finding on periodic ultrasound-evaluation in the graft should allow to perform a conservative treatment in order to preserve renal function. Finally, in case of a renal tumor in native kidney, a radical nephrectomy is usually recommended