Combining Brentuximab Vedotin With Dexamethasone, High-dose Cytarabine, and Cisplatin as Salvage Treatment in Pediatric Relapsed or Refractory Classic Hodgkin Lymphoma: Two Case Reports.

Hodgkin lymphoma (HL) is among the most commonly occurring malignancies in adolescents. For relapsed/refractory disease, many regimens have been proposed. Novel agents are increasingly used, like brentuximab vedotin (BV), an antiCD30 antibody-drug conjugate, used as a single agent or in combination with classic regimens mainly in adults, while limited is the experience in pediatrics. We report here on 2 boys with aggressive and high-risk relapsed HL, successfully treated with the BV plus dexamethasone, high-dose cytarabine, cisplatin regimen as induction salvage treatment. Our experience provides real-world evidence on the use of BV-dexamethasone, high-dose cytarabine, cisplatin as first-line salvage therapy for relapsed/refractory HL and expands the current therapeutic choices.

PSYCHOACOUSTICS-WEB: A free online tool for the estimation of auditory thresholds.

PSYCHOACOUSTICS-WEB is an online tool written in JavaScript and PHP that enables the estimation of auditory sensory thresholds via adaptive threshold tracking. The toolbox implements the transformed up-down methods proposed by Levitt (Journal of the Acoustical Society of America, 49, 467-477, (1971) for a set of classic psychoacoustical tasks: frequency, intensity, and duration discrimination of pure tones; duration discrimination and gap detection of noise; and amplitude modulation detection with noise carriers. The toolbox can be used through a common web browser; it works with both fixed and mobile devices, and requires no programming skills. PSYCHOACOUSTICS-WEB is suitable for laboratory, classroom, and online testing and is designed for two main types of users: an occasional user and, above all, an experimenter using the toolbox for their own research. This latter user can create a personal account, customise existing experiments, and share them in the form of direct links to further users (e.g., the participants of a hypothetical experiment). Finally, because data storage is centralised, the toolbox offers the potential for creating a database of auditory skills.

Locally advanced breast cancer (LABC) and delayed care: a qualitative analysis of psychosocial factors.

The literature has extensively documented how delayed access to health care services in the context of cancer can result from subjective characteristics, dysfunctional coping styles, barriers to care, or procrastination. However, limited research has investigated the psychosocial experience of women diagnosed with Locally Advanced Breast Cancer (LABC). This qualitative study aimed at understanding cognitive, emotional and relational factors associated with delayed access to care and treatment decision-making. In-depth interviews with 14 Italian women were conducted. A thematic analysis of elementary contexts using T-LAB was used to identify the association between emerging clusters and participants' coping styles as measured by the Mini-MAC. Five clusters were identified: 'relationships', 'ineluctability', 'disease', 'surgery', and 'diagnosis'. The 'relationships' cluster was characterized by elevated rates of Fighting Spirit (p < 0.01) while Anxious Preoccupation was associated with 'surgery' (p < 0.01). Findings contribute to explain individual and relational variables related to delay seeking care of LABC patients by illustrating the interplay of personal motivations and social networks' characteristics. Evidence from this work expands current understanding of the interplay of factors contributing to delays in seeking medical attention and may be utilized to inform strategies to timely identify women at greater risk.

Face in collision: emotional looming stimuli modulate interpersonal space across development and gender.

Basic visual functions have evolved to allow for rapid detection of dynamic stimuli in our surrounding environment. In particular, looming stimuli are of relevance because they are expected to enter the individual's interpersonal space representing a potential threat. Different studies showed that emotions can modulate the perception of visual looming stimuli and the borders of interpersonal space, defined as the area around the body that individuals maintain between themselves and others during social interactions. Here, we investigated how emotions modulate the perception and the physiological correlates of interpersonal space and whether such indexes change across age and gender. Children and adults were asked to quickly react to emotional looming stimuli while measuring their skin conductance response (SCR). We found that emotional looming stimuli shrink the borders of interpersonal space of males more than females, and that this pattern does not change with age. In addition, adults reacted faster to angry than happy and neutral faces, which is in line with the notion that threatening stimuli capture attention more quickly than other types of emotional stimuli. However, this was not observed in children, suggesting that experience with negative stimuli, rather than the evolutionary meaning they possess, may influence the boundaries of interpersonal space. Overall, our study suggests that interpersonal space is modulated by emotions, but this appears to be modulated by gender and age: while behavioural responses to emotional looming stimuli refine with age, physiological responses are adult-like as early as 5 years of age.

Auditory and visual short-term memory: influence of material type, contour, and musical expertise.

Short-term memory has mostly been investigated with verbal or visuospatial stimuli and less so with other categories of stimuli. Moreover, the influence of sensory modality has been explored almost solely in the verbal domain. The present study compared visual and auditory short-term memory for different types of materials, aiming to understand whether sensory modality and material type can influence short-term memory performance. Furthermore, we aimed to assess if music expertise can modulate memory performance, as previous research has reported better auditory memory (and to some extent, visual memory), and better auditory contour recognition for musicians than non-musicians. To do so, we adapted the same recognition paradigm (delayed-matching to sample) across different types of stimuli. In each trial, participants (musicians and non-musicians) were presented with two sequences of events, separated by a silent delay, and had to indicate whether the two sequences were identical or different. The performance was compared for auditory and visual materials belonging to three different categories: (1) verbal (i.e., syllables); (2) nonverbal (i.e., that could not be easily denominated) with contour (based on loudness or luminance variations); and (3) nonverbal without contour (pink noise sequences or kanji letters sequences). Contour and no-contour conditions referred to whether the sequence can entail (or not) a contour (i.e., a pattern of up and down changes) based on non-pitch features. Results revealed a selective advantage of musicians for auditory no-contour stimuli and for contour stimuli (both visual and auditory), suggesting that musical expertise is associated with specific short-term memory advantages in domains close to the trained domain, also extending cross-modally when stimuli have contour information. Moreover, our results suggest a role of encoding strategies (i.e., how the material is represented mentally during the task) for short-term-memory performance.

A listening experiment comparing the timbre of two Stradivari with other violins.

The violins of Stradivari are recognized worldwide as an excellence in craftsmanship, a model for instrument makers, and an unachievable desire for collectors and players. However, despite the myth surrounding these instruments, blindfolded players tendentially prefer to play modern violins. Here, we present a double blind listening experiment aimed at analyzing and comparatively rating the sound timbre of violins. The mythic instruments were listened to among other well regarded and not so well regarded violins. 70 listeners (violin makers of the Cremona area) rated the timbre difference between the simple musical scales played on a test and a reference violin, and the results showed that their preference converged on one particular Stradivari. The acoustical measurements revealed some similarities between the subjective ratings and the physical characteristics of the violins. It is speculated that the myth of Stradivari could have been boosted, among other factors, by the specimens of tonal superior quality, which biased favourably the judgment on his instruments and spread on all of the maker's production. These results contribute to the understanding of the timbre of violins and suggest the characteristics that are in a relationship with the pleasantness of the timbre.

Auditory selective attention under working memory load.

Can cognitive load enhance concentration on task-relevant information and help filter out distractors? Most of the prior research in the area of selective attention has focused on visual attention or cross-modal distraction and has yielded controversial results. Here, we studied whether working memory load can facilitate selective attention when both target and distractor stimuli are auditory. We used a letter n-back task with four levels of working memory load and two levels of distraction: congruent and incongruent distractors. This combination of updating and inhibition tasks allowed us to manipulate working memory load within the selective attention task. Participants sat in front of three loudspeakers and were asked to attend to the letter presented from the central loudspeaker while ignoring that presented from the flanking ones (spoken by a different person), which could be the same letter as the central one (congruent) or a different (incongruent) letter. Their task was to respond whether or not the central letter matched the letter presented n (0, 1, 2, or 3) trials back. Distraction was measured in terms of the difference in reaction time and accuracy on trials with incongruent versus congruent flankers. We found reduced interference from incongruent flankers in 2- and 3-back conditions compared to 0- and 1-back conditions, whereby higher working memory load almost negated the effect of incongruent flankers. These results suggest that high load on verbal working memory can facilitate inhibition of distractors in the auditory domain rather than make it more difficult as sometimes claimed.

Pitch height and brightness both contribute to elicit the SMARC effect: a replication study with expert musicians.

Pitch-height can be represented in a spatial format. Reaction times (RTs) to lower pitch-heights are faster when responses are executed in the lower side of space, whereas RTs to higher pitch-heights are faster when responses are executed in the upper side of space. This effect is called the Spatial-Music Association of Response Codes (SMARC) effect. We investigated how pitch-height and the brightness of a tone's timbre might contribute in eliciting the SMARC effect as a function of music expertise by comparing the results of 24 musicians with the results we gathered previously (Pitteri et al., 2017) with 24 non-musicians. Three experimental conditions were used: pitch-height varied, brightness varied; pitch-height varied, brightness fixed; pitch-height fixed, brightness varied. We found that the coherent modulation of both pitch-height and brightness elicited the strongest SMARC effect, independently of music expertise. These results add evidence to the hypothesis that the strongest SMARC effect does not belong to pitch-height or brightness, but to pitch-height and brightness together.

Two replications of Raymond, Shapiro, and Arnell (1992), The Attentional Blink.

In order to improve the trustworthiness of our science, several new research practices have been suggested, including preregistration, large statistical power, availability of research data and materials, new statistical standards, and the replication of experiments. We conducted a replication project on an original phenomenon that was discovered more than 25 years ago, namely the attentional blink (Raymond, Shapiro, & Arnell, Human Perception and Performance, 18(3), 849-860, 1992), which has been conceptually replicated hundreds of times with major variations. Here, we ran two identical experiments, adopting the new practices and closely reproducing the original experiment. The two experiments were run by different research groups in different countries and laboratories with different participants. Experiment 1 shared remarkable similarities (in magnitude and duration of the effect) with the original study, but also some differences (the overall accuracy of participants, the timing of the effect, and lag-1 sparing). Experts interviewed to evaluate our results stressed the similarities rather than the differences. Experiment 2 replicated nearly identically the results observed in Experiment 1. These findings show that the adoption of new research practices improves the replicability of experimental research and opens the door for a quantitative and direct comparison of the results collected across different laboratories and countries.

Human Fibrinogen Concentrate and Fresh Frozen Plasma in the Management of Severe Acquired Hypofibrinogenemia in Children With Acute Lymphoblastic Leukemia: Results of a Retrospective Survey.

OBJECTIVE OF THE STUDY: In this study we aimed to retrospectively evaluate how centers, belonging to the Associazione Italiana Ematologia e Oncologia Pediatrica (AIEOP), manage severe acquired hypofibrinogenemia in children with acute lymphoblastic leukemia, particularly evaluating the therapeutic role of human fibrinogen concentrate (HFC) and fresh frozen plasma (FFP). METHODS: We conducted a survey among AIEOP centers; thereafter, we collected and analyzed data with regard to the treatment of episodes of severe acquired hypofibrinogenemia occurring during the induction and reinduction phases of the AIEOP-BFM ALL 2009 protocol. RESULTS: In total, 15 of the 37 AIEOP centers invited to join the survey agreed to collect the data, with 10 and 5 centers declaring to react to severe acquired hypofibrinogenemia (<70 mg/dL) by administering HFC or FFP, respectively. Of the 150 episodes of severe hypofibrinogenemia occurring in 101 patients, 47.3% were treated with HFC and 52.7% with FFP, with a normalization of fibrinogen levels achieved in greater proportion and in a shorter amount of time in the HFC group as compared with the FFP group. None of the patients presented with bleeding or thrombosis during the observation period. CONCLUSIONS: Even with the limitations of the retrospective nature of this study, HFC seems to be a safe and effective alternative to FFP for replacement therapy in case of severe hypofibrinogenemia in children with acute lymphoblastic leukemia.

Is working memory training in older adults sensitive to music?

Evidence in the literature suggests that listening to music can improve cognitive performance. The aim of the present study was to examine whether the short- and long-term gains of a working memory (WM) training in older adults could be enhanced by music listening-the Mozart's Sonata K448 and the Albinoni's Adagio in G minor-which differ in tempo and mode. Seventy-two healthy older adults (age range: 65-75 years) participated in the study. They were divided into four groups. At each training session, before starting the WM training activities, one group listened to Mozart (Mozart group, N = 19), one to Albinoni (Albinoni group, N = 19), one to white noise (White noise group, N = 16), while one served as an active control group involved in other activities and was not exposed to any music (active control group, N = 18). Specific training gains on a task like the one used in the training, and transfer effects on visuo-spatial abilities, executive function and reasoning measures were assessed. Irrespective of listening condition (Mozart, Albinoni, White noise), trained groups generally outperformed the control group. The White noise group never differed from the two music groups. However, the Albinoni group showed larger specific training gains in the criterion task at short-term and transfer effects in the reasoning task at both short-and long term compared to the Mozart group. Overall the present findings suggest caution when interpreting the effects of music before a WM training, and are discussed according to aging and music effect literature.

Naturally together: pitch-height and brightness as coupled factors for eliciting the SMARC effect in non-musicians.

Pitch-height is often labeled spatially (i.e., low or high) as a function of the fundamental frequency of the tone. This correspondence is highlighted by the so-called Spatial-Musical Association of Response Codes (SMARC) effect. However, the literature suggests that the brightness of the tone's timbre might contribute to this spatial association. We investigated the SMARC effect in a group of non-musicians by disentangling the role of pitch-height and the role of tone-brightness. In three experimental conditions, participants were asked to judge whether the tone they were listening to was (or was not) modulated in amplitude (i.e., vibrato). Participants were required to make their response in both the horizontal and the vertical axes. In a first condition, tones varied coherently in pitch (i.e., manipulation of the tone's F0) and brightness (i.e., manipulation of the tone's spectral centroid); in a second condition, pitch-height varied whereas brightness was fixed; in a third condition, pitch-height was fixed whereas brightness varied. We found the SMARC effect only in the first condition and only in the vertical axis. In contrast, we did not observe the effect in any of the remaining conditions. The present results suggest that, in non-musicians, the SMARC effect is not due to the manipulation of the pitch-height alone, but arises because of a coherent change of pitch-height and brightness; this effect emerges along the vertical axis only.

Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

Central venous catheters (CVC), used for the management of children with hemato-oncological disorders, are burdened by a significant incidence of mechanical, infective, or thrombotic complications. These complications favor an increasing risk in prolongation of hospitalization, extra costs of care, and sometimes severe life-threatening events. No guidelines for the management of CVC-related occlusion and CVC-related thrombosis are available for children. To this aim, members of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) reviewed the pediatric and adult literature to propose the first recommendations for the management of CVC-related occlusion and CVC-related thrombosis in children with hemato-oncological disorders.

Beauty Therapy to Support Psychosocial Recovery from Oncological Care: A Qualitative Research on the Lived Experience of Women with Breast Cancer Treated with Chemotherapy.

During the oncological care path, breast cancer patients treated with chemotherapy suffer from a number of psycho-physical changes, and appearance-related side effects are among the primary determinants of psychosocial impairment. Appropriate interventions are needed due to the fact that treatment-induced transformations have been associated with a decline in overall quality of life, interpersonal and sexual difficulties, and adverse effects on therapeutic adherence. In the framework of integrative oncology, beauty therapy is an affordable and straightforward intervention that could be used in the clinical management of breast cancer side effects. This study aims to comprehend the emotional and lived experiences of women undergoing chemotherapy after a brief beauty therapy intervention with licensed beauticians. The Interpretative Phenomenological Analysis was used as a methodological guideline. Sixteen women were purposefully recruited in a day hospital of a cancer unit, where the beauty therapy was implemented. At the end of the intervention, data were gathered using a semi-structured interview with open-ended questions. A thematic analysis was performed on verbatim transcriptions. Findings support the proposal of beauty therapy for patients undergoing chemotherapy. Assuming a relational viewpoint, beauty therapy could improve patients' feelings about themselves and the way they feel about others, even if they do not declare a specific interest in their outward appearance.

Pannonibacter anstelovis sp. nov. Isolated from Two Cases of Bloodstream Infections in Paediatric Patients.

This study describes two cases of bacteraemia sustained by a new putative Pannonibacter species isolated at the U.O.C. of Microbiology and Virology of the Policlinico of Bari (Bari, Italy) from the blood cultures of two patients admitted to the Paediatric Oncohaematology Unit. Pannonibacter spp. is an environmental Gram-negative bacterium not commonly associated with nosocomial infections. Species identification was performed using Sanger sequencing of the 16S rRNA gene and Whole-Genome Sequencing (WGS) for both strains. Genomic analyses for the two isolates, BLAST similarity search, and phylogeny for the 16S rDNA sequences lead to an assignment to the species Pannonibacter phragmitetus. However, by performing ANIb, ANIm, tetranucleotide correlation, and DNA-DNA digital hybridization, analyses of the two draft genomes showed that they were very different from those of the species P. phragmitetus. MALDI-TOF analysis, assessment of antimicrobial susceptibility by E-test method, and Analytical Profile Index (API) tests were also performed. This result highlights how environmental bacterial species can easily adapt to the human host and, especially in nosocomial environments, also gain pathogenic potential through antimicrobial resistance.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

Corrigendum: The new Italian registry of infantile thrombosis (RITI): a reflection on its journey, challenges and pitfalls.

[This corrects the article DOI: 10.3389/fped.2023.1094246.].

Screening for coagulopathy and identification of children with acute lymphoblastic leukemia at a higher risk of symptomatic venous thrombosis: an AIEOP experience.

INTRODUCTION: Venous thromboembolic events (VTEs) are frequent complications of childhood acute lymphoblastic leukemia (ALL) treatment. The aim of the study was to evaluate the rate of symptomatic VTEs in children with ALL and the predictive value of clinical and biological factors and routine monitoring of coagulation parameters in identifying children at a higher risk of this complication. MATERIALS AND METHODS: Between September 2000 and July 2006, 2042 children (≥1 and younger than 18 y) with newly diagnosed ALL were enrolled in Italy in the AIEOP (Italian Association of Pediatric Hematology and Oncology)-BFM (Berlin-Frankfurt-Muenster) ALL 2000 trial. Patients with symptomatic VTEs (deep venous thromboses or cerebral venous thromboses) were identified after a careful review of clinical records. The impact of coagulation derangement at the onset of VTEs was evaluated by a nested case-control study. RESULTS: Forty-eight (2.4%) children presented with a VTE. The rate of VTEs was higher in male patients (P=0.001); patients randomized to receive dexamethasone tended to have a higher rate of VTE compared with those who received prednisone (P=0.10). The coagulation derangement at the onset of VTE was not associated with VTE occurrence. The prevalence of a factor V Leiden G1691A mutation and the prothrombin G20210A variant was higher in children with VTE than that expected in the general population.

Evidence for a spatial bias in the perception of sequences of brief tones.

Listeners are unable to report the physical order of particular sequences of brief tones. This phenomenon of temporal dislocation depends on tone durations and frequencies. The current study empirically shows that it also depends on the spatial location of the tones. Dichotically testing a three-tone sequence showed that the central tone tends to be reported as the first or the last element when it is perceived as part of a left-to-right motion. Since the central-tone dislocation does not occur for right-to-left sequences of the same tones, this indicates that there is a spatial bias in the perception of sequences.