Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in
...family members are biomarkers of poor prognosis for a large number of SCLC. In particular,
alterations define SCLC cases with immunotherapy failure.
has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to
inhibition by an
-specific antigene-PNA oligonucleotide (BGA002)-as a new precision medicine for
-related SCLC. We found that BGA002 profoundly and specifically inhibited
expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an
-related SCLC gene signature comprehending
,
and
, that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in
-amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in
-related SCLC.
Anthropometry and body composition were investigated in 43 female handball players from the Italian championships, grouped according to their competitive level (elite vs. sub-elite) or their playing ...position goalkeeper (n = 7), back (n = 14), wing (n = 18), or pivot (n = 4). The anthropometry consisted of several circumferences, lengths, widths, and skinfold measurement at six sites; the regional and total body compositions were assessed by means of dual-energy X-ray absorptiometry (DXA). One-way ANOVA was used for statistical analysis, with a Bonferroni post-hoc test where needed. The results showed that elite players have significantly lower percentages of fat and higher bone mineral content than sub-elite as well as a clear tendency to accrue more lean mass, especially in upper limbs. Overall, the physical characteristics and body composition of handball players in Italy compared unfavourably with those in other countries, suggesting a need for improved selection and training. When playing position was included in the analysis of the whole group of handball players (n = 43) significant differences were found between the stature, mass, body mass index (BMI), several skinfolds, circumferences and lengths, and total body mineral mass, lean mass and fat mass of players in different positions. Post-hoc analysis suggests that players on the wing and in goalkeeper positions differed most from one another. These findings confirm and expand on previous data about the presence of anthropometric differences within playing positions in handball.
The quantity and quality of environmental stimuli and contexts are crucial for children's development. Following the outbreak of SARS-CoV-2 (COVID-19), restrictive measures have been implemented, ...constraining children's social lives and changing their daily routines. To date, there is a lack of research assessing the long-lasting impacts that these changes have had on children's language and emotional-behavioral development. In a large sample of preschoolers (N = 677), we investigated (a) the long-lasting effects of changes in family and social life and in daily activities over the first Italian nationwide COVID-19-pandemic-related lockdown upon children's linguistic and emotional-behavioral profiles and (b) how children's demographic variables and lifelong family characteristics moderated these associations within a multiple-moderator framework. Our findings showed a relationship between the time spent watching TV/playing video games and affective problems that was moderated by the number of siblings. Our findings showed that children who could be at high risk in more normal circumstances, such as only children, have been particularly harmed. Therefore, assessing the long-term effects of lockdown-related measures and how these could have been moderated by potential risk/protective factors added significant information to the existing literature.
Resumo A partir da perspectiva das ciências sociais aplicadas, este artigo aborda o significado dos termos risco, desastre e vulnerabilidade, considerando sua compreensão e a necessidade de ...incorporá-los às diretrizes e às ações do planejamento na Macrometrópole Paulista (MMP) no contexto de variabilidade climática. Para garantir um entendimento aprofundado do que se denomina construção social do risco, urge considerar os aspectos físicos de dado espaço geográfico, pois nele são estabelecidas variadas formas de uso e de ocupação promovidas pela sociedade em dada conjuntura política e econômica. Dentre as diversas intervenções antropogênicas pelas quais a MMP tem passado, este artigo aborda o problema das inundações que atingem a área da MMP, mas especialmente daquelas ocupadas pelas populações em baixa renda, nas periferias urbanas.
Abstract Based on the perspective of the applied social sciences, this article addresses the meaning of risk, disaster and vulnerability, considering that they need to be understood and incorporated into the planning guidelines and actions for the São Paulo Macrometropolis in the context of climate variability. To ensure a deep understanding of what is called social construction of risk, it is necessary to consider the physical aspects of a given geographical space, since it is in this space that different forms of land use and occupation are promoted by society, within a given political and economic conjuncture. Among the several anthropogenic interventions the São Paulo Macrometropolis has undergone, this article addresses the problem of the floods that affect the region, focusing on areas occupied by low-income groups in urban peripheries.
Background: The Prenatal Attachment Inventory (PAI) is a widely used questionnaire to measure prenatal attachment. However, its internal structure is controversial. None of the previous studies have ...investigated the dimensions of the Italian version of the scale using both an exploratory and a confirmatory approach. There is also a need to explore extensively the external validity of the Italian PAI.
Objective: We designed a study aimed at shedding further light on the dimensionality of the questionnaire and expanding the evidence of its reliability and validity.
Method: Five-hundred and thirty-five Italian expectant mothers participated in the prenatal phase; a subsample of 100 women participated in the postnatal phase of the study. The PAI was administered together with other scales measuring maternal-fetal attachment, psychological wellbeing and relational variables.
Results: The hypothesised relationships with external criteria were substantiated overall. The five dimensions described in the Italian study by Barone, Lionetti, and Dellagiulia also emerged from our factor analyses, with the exception of two items. Internal consistency was adequate for the total scale and for four of the five subscales.
Conclusion: As the Fantasy subscale showed poor internal consistency, we advise against its use as an independent measure. However, when used as a global score, the PAI is a reliable and valid measure of prenatal attachment in Italian women. Thus, it can be used for research purposes. The use of the PAI could also be very helpful in clinical settings, in order to identify expectant mothers who have difficulty in establishing an affective bond with their unborn infants. To this end, further research should study the characteristics of the PAI on high-risk groups and clinical samples in order to obtain clinical cut-offs.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the ...occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO(2) hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO(2) through genetic control of sensitivity to the environment.
Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O(2)), CO(2)-enriched air (6% CO(2)), hypoxic air (10%O(2)), and avoidance of CO(2)-enriched environments.
Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO(2)-enriched air and heightened aversion towards CO(2)-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO(2) was present at 16-20, and 75-90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO(2) breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO(2) increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals.
A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO(2) sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Token Sliding on Split Graphs Belmonte, Rémy; Kim, Eun Jung; Lampis, Michael ...
Theory of computing systems,
05/2021, Letnik:
65, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We consider the complexity of the
Independent Set Reconfiguration
problem under the Token Sliding rule. In this problem we are given two independent sets of a graph and are asked if we can transform ...one to the other by repeatedly exchanging a vertex that is currently in the set with one of its neighbors, while maintaining the set independent. Our main result is to show that this problem is PSPACE-complete on split graphs (and hence also on chordal graphs), thus resolving an open problem in this area. We then go on to consider the
c
-
Colorable Reconfiguration
problem under the same rule, where the constraint is now to maintain the set
c
-colorable at all times. As one may expect, a simple modification of our reduction shows that this more general problem is PSPACE-complete for all fixed
c
≥ 1 on chordal graphs. Somewhat surprisingly, we show that the same cannot be said for split graphs: we give a polynomial time (
n
O
(
c
)
) algorithm for all fixed values of
c
, except
c
= 1, for which the problem is PSPACE-complete. We complement our algorithm with a lower bound showing that
c
-
Colorable Reconfiguration
is W2-hard on split graphs parameterized by
c
and the length of the solution, as well as a tight ETH-based lower bound for both parameters. Finally, we study
c
-
Colorable Reconfiguration
under a relaxed rule called Token Jumping, where exchanged vertices are not required to be adjacent. We show that the problem on chordal graphs is PSPACE-complete even if
c
is some fixed constant. We then show that the problem is polynomial-time solvable for strongly chordal graphs even if
c
is a part of the input.
Motivated by the importance of dynamic programming (DP) in parameterized complexity, we consider several fine-grained questions, such as the following examples: (i) can Dominating Set be solved in ...time \((3-\epsilon)^{pw}n^{O(1)}\)? (where \(pw\) is the pathwidth) (ii) can Coloring be solved in time \(pw^{(1-\epsilon)pw}n^{O(1)}\)? (iii) can a short reconfiguration between two size-\(k\) independent sets be found in time \(n^{(1-\epsilon)k}\)? Such questions are well-studied: in some cases the answer is No under the SETH, while in others coarse-grained lower bounds are known under the ETH. Even though questions such as the above seem "morally equivalent" as they all ask if a simple DP can be improved, the problems concerned have wildly varying time complexities, ranging from single-exponential FPT to XNLP-complete. This paper's main contribution is to show that, despite their varying complexities, these questions are not just morally equivalent, but in fact they are the same question in disguise. We achieve this by putting forth a natural complexity assumption which we call the Primal Pathwidth-Strong Exponential Time Hypothesis (PP-SETH) and which states that 3-SAT cannot be solved in time \((2-\epsilon)^{pw}n^{O(1)}\), for any \(\epsilon>0\), where \(pw\) is the pathwidth of the primal graph of the input. We then show that numerous fine-grained questions in parameterized complexity, including the ones above, are equivalent to the PP-SETH, and hence to each other. This allows us to obtain sharp fine-grained lower bounds for problems for which previous lower bounds left a constant in the exponent undetermined, but also to increase our confidence in bounds which were previously known under the SETH, because we show that breaking any one such bound requires breaking all (old and new) bounds; and because we show that the PP-SETH is more plausible than the SETH.
Transcribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/β-catenin pathway in ...liver cancer.
Hypomorphic Apc mice (
) and thiocetamide (TAA)-treated rats developed Wnt/β-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation.
Overexpression of the T-UCR uc.158- could differentiate Wnt/β-catenin dependent HCC from normal liver and from β-catenin negative diethylnitrosamine (DEN)-induced HCC. uc.158- was overexpressed in human HepG2 versus Huh7 cells in line with activation of the Wnt pathway. In vitro modulation of β-catenin altered uc.158- expression in human malignant hepatocytes. uc.158- expression was increased in
-mutated human HCCs compared with non-mutated human HCCs, and in human HCC with nuclear localisation of β-catenin. uc.158- was increased in TAA rat CCA and reduced after treatment with Wnt/β-catenin inhibitors. uc.158- expression was negative in human normal liver and biliary epithelia, while it was increased in human CCA in two different cohorts. Locked nucleic acid-mediated inhibition of uc.158- reduced anchorage cell growth, 3D-spheroid formation and spheroid-based cell migration, and increased apoptosis in HepG2 and SW1 cells. miR-193b was predicted to have binding sites within the uc.158- sequence. Modulation of uc.158- changed miR-193b expression in human malignant hepatocytes. Co-transfection of uc.158- inhibitor and anti-miR-193b rescued the effect of uc.158- inhibition on cell viability.
We showed that uc.158- is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics.
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