Attempted suicide among adolescents: A stepwise discriminant analysis.

A sample of 40 adolescents (aged 13–17 yrs), some of whom had attempted suicide (n?=?20) and some who had not (n?=?20), were compared on a number of life history and psychological variables (affective and cognitive). Stepwise discriminant analyses produced 1 discriminant function (the lack of emotional significant other) that differentiated between the groups. This single discriminant function accounted for 77% of the variance in the data. These results are interpreted within the context of the early loss hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.     

Aspects of nucleosomal positional flexibility and fluidity

Nucleosomes have been considered until recently to be stable and uniquely localized particles. We focus here on two properties of nucleosomes that are emerging as central attributes of their functions: mobility and multiplicity of localization. The biological relevance of these phenomena is based on the fact that chromatin functions depend on the relative stability of nucleosomes, on their covalent or conformational modifications, their dynamics, their localization, and the density of their distribution. In order to understand these complex behaviors both the structure of the nucleosome core particles and the informational rules governing their interaction with defined DNA sequences are here taken into consideration. The fact that nucleosomes solve the problem of how to locate a specific interaction site on a potentially infinite combination of sequences, with interactions recurring to a controlled level of informational ambiguity and stochasticity, is discussed. Nucleosomes have been shown to slide along DNA. This novel facet of their behavior and its implications in chromatin remodeling are reviewed.     

Gingival recession and exposure of barrier membrane: effect on guided tissue regeneration of Class II furcation defects

The purpose of the present study was to evaluate the effect of barrier membrane exposure on the success of guided tissue regeneration in Class II furcation defects. Twenty-six subjects with mandibular Class II furcation defects received initial periodontal therapy followed by guided tissue regeneration surgery. The membrane was placed and the flaps were repositioned so that the membrane was totally submerged. Membranes were removed 4 to 6 weeks later, at which time the extent of their exposure was recorded. An overall improvement in all clinical parameters was observed for all subjects 1 year after surgery. Half of the patients had experienced no membrane exposure, while the other 13 subjects had experienced mild to pronounced exposure; both groups showed similar improvement in all clinical and surgical parameters. In light of the comparable results obtained in exposed sites, and the anatomic difficulties sometimes encountered in covering a membrane completely, in some of these cases the membrane may be left only partially submerged. This approach will allow for tighter occlusal "seal" of the tooth-membrane interface and preservation of the keratinized gingiva.     

Survey on using constraints in data mining

This paper provides an overview of the current state-of-the-art on using constraints in knowledge discovery and data mining. The use of constraints in a data mining task requires specific definition and satisfaction tools during knowledge extraction. This survey proposes three groups of studies based on classification, clustering and pattern mining, whether the constraints are on the data, the models or the measures, respectively. We consider the distinctions between hard and soft constraint satisfaction, and between the knowledge extraction phases where constraints are considered. In addition to discussing how constraints can be used in data mining, we show how constraint-based languages can be used throughout the data mining process.     

A quick tour on suffix arrays and compressed suffix arrays

Suffix arrays are a key data structure for solving a run of problems on texts and sequences, from data compression and information retrieval to biological sequence analysis and pattern discovery. In their simplest version, they can just be seen as a permutation of the elements in {1,2,…,n}, encoding the sorted sequence of suffixes from a given text of length n, under the lexicographic order. Yet, they are on a par with ubiquitous and sophisticated suffix trees. Over the years, many interesting combinatorial properties have been devised for this special class of permutations: for instance, they can implicitly encode extra information, and they are a well characterized subset of the n! permutations. This paper gives a short tutorial on suffix arrays and their compressed version to explore and review some of their algorithmic features, discussing the space issues related to their usage in text indexing, combinatorial pattern matching, and data compression.     

Light on! Real world evaluation of a P300-based brain-computer interface (BCI) for environment control in a smart home

Brain-computer interface (BCI) systems aim to enable interaction with other people and the environment without muscular activation by the exploitation of changes in brain signals due to the execution of cognitive tasks. In this context, the visual P300 potential appears suited to control smart homes through BCI spellers. The aim of this work is to evaluate whether the widely used character-speller is more sustainable than an icon-based one, designed to operate smart home environment or to communicate moods and needs. Nine subjects with neurodegenerative diseases and no BCI experience used both speller types in a real smart home environment. User experience during BCI tasks was evaluated recording concurrent physiological signals. Usability was assessed for each speller type immediately after use. Classification accuracy was lower for the icon-speller, which was also more attention demanding. However, in subjective evaluations, the effect of a real feedback partially counterbalanced the difficulty in BCI use. PRACTITIONER SUMMARY: Since inclusive BCIs require to consider interface sustainability, we evaluated different ergonomic aspects of the interaction of disabled users with a character-speller (goal: word spelling) and an icon-speller (goal: operating a real smart home). We found the first one as more sustainable in terms of accuracy and cognitive effort.     

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine

The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.     

On the Construction of Classes of Suffix Trees for Square Matrices: Algorithms and Applications

We provide a uniform framework for the study of index data structures for a two-dimensional matrixTEXT[1:n, 1:n] whose entries are drawn from an ordered alphabetΣ. An index forTEXTcan be informally seen as the two-dimensional analog of the suffix tree for a string. It allows on-line searches and statistics to be performed onTEXTby representing compactly theΘ(n³) square submatrices ofTEXTin optimalO(n²) space. We identify 4ⁿ⁻¹families of indices forTEXT, each containing ∏ⁿ_i=1 (2i−1)! isomorphic data structures. We also develop techniques leading to a single algorithm that efficiently builds any index in any family inO(n² log n) time andO(n²) space. Such an algorithm improves in various respects the algorithms for the construction of the PAT tree and the Lsuffix tree. The framework and the algorithm easily generalize tod>2 dimensions. Moreover, as part of our algorithm, we provide new algorithmic tools that yield a space-efficient implementation of the “naming scheme” of R. Karpet al.(in“Proceedings, Fourth Symposium on Theory of Computing,” pp. 125–136) for strings and matrices.