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Oral hygiene is an important self‐care skill that some children may lack, especially children with autism spectrum disorder (ASD). Although some studies have evaluated procedures for teaching toothbrushing, no previous studies have demonstrated procedures for teaching flossing, which is essential for oral hygiene. This study evaluated an intervention for teaching water flossing to two children with ASD and two children without an ASD diagnosis. The intervention package included backward chaining, video modeling, and reinforcement, with some components implemented by a caregiver and some components implemented by an experimenter via telehealth. Behavioral skills training was used to train caregivers prior to implementation of the study. Results indicated that the intervention package was effective in teaching all participants to independently floss their teeth with a water flosser. Effects maintained for all participants 1‐week after completion of teaching. Questionnaires given to caregivers, participants, and dental professionals indicated high social validity. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Nusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark‐based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period. Methods: Fifty‐one adult patients received 507 consecutive interlaminar nusinersen administrations. Patients presented with both 'uncomplicated spines' or 'complicated spines'; two patients had previous back surgery. Technical success and AEs were recorded using either technique. A generalised linear mixed model was applied to evaluate predictors of technical success and complications. Results: An overall success rate of 99.6%, with only two procedures failing to reach the intrathecal space, and an overall optimal procedure rate of 90.3% have been reported. A total of 455 procedures (89.7%) were uneventfully performed. One (0.2%) case of severe AE (puncture of a bulky abdominal annexal cyst) was recorded. Twenty‐seven episodes (5.3%) of post‐dural puncture headache (PDPH) and 24 episodes (4.7%) of radicular or back pain, both successfully treated with medical therapy, have also been reported. Technical success was significantly associated with 'complicated spines' (P = 0.022) and the use of ultrasound assistance (P = 0.01), and the use of ultrasound was the only independent predictor of uncomplicated procedures (P = 0.007). Discussion: In adult patients with SMA both landmark‐based and ultrasound‐assisted techniques are safe and effective even in the long term. The use of assistance is associated with technical success and can predict uncomplicated procedures. Conclusion: Our results support the use of ultrasonography in order to improve the success and reduce the burden of nusinersen intrathecal administration. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)‐assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients. Methods: Fifty‐eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US‐assisted technique) or Group 2 (nusinersen infusion with landmark‐based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t‐test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi‐square test or Fisher's exact test in case of expected frequencies <5. The p‐values <.05 were considered statistically significant. Results: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark‐based group (p <.05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US‐group versus landmark‐based group (p <.05). Discussion: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion. [ABSTRACT FROM AUTHOR]

Precise spatiotemporal regulation of gene expression is of paramount importance for eukaryotic development. The maternal-to-zygotic transition (MZT) during early embryogenesis in Drosophila involves the gradual replacement of maternally contributed mRNAs and proteins by zygotic gene products. The zygotic genome is transcriptionally activated during the first 3 hours of development, in a process known as "zygotic genome activation" (ZGA), by the orchestrated activities of a few pioneer factors. Their decisive role during ZGA has been characterized in detail, whereas the contribution of chromatin factors to this process has been historically overlooked. In this review, we aim to summarize the current knowledge of how chromatin regulation impacts the first stages of Drosophila embryonic development. In particular, we will address the following questions: how chromatin factors affect ZGA and transcriptional silencing, and how genome architecture promotes the integration of these processes early during development. Remarkably, certain chromatin marks can be intergenerationally inherited, and their presence in the early embryo becomes critical for the regulation of gene expression at later stages. Finally, we speculate on the possible roles of these chromatin marks as carriers of epialleles during transgenerational epigenetic inheritance (TEI). This review discusses the contribution of chromatin factors and genome architecture to zygotic genome activation in Drosophila embryos, and how chromatin marks might be carriers of epialleles during transgenerational epigenetic inheritance. [ABSTRACT FROM AUTHOR]

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte (CAR‐T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI‐related myocarditis with cardiogenic shock to more common complications including less severe ICI‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR‐T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus. [ABSTRACT FROM AUTHOR]

Previous research has supported selecting development‐matched targets rather than age‐matched targets to teach play skills to children with autism spectrum disorder. However, few studies have been conducted, and replications and extensions of this research are needed. The current study replicated Pane et al. (2022) by comparing the acquisition of development‐matched and age‐matched play targets when teaching play skills to four children with autism. No contrived prompts or consequences were used to teach play skills in either condition. Extensions included identifying targets via a newer version of the Developmental Play Assessment, targeting different play categories, assessing additional imitation skills, and conducting a caregiver assessment to identify socially valid toys, play actions, and vocalizations based on each participant's common experiences and preferences as well as their caregiver's values and preferences. As in Pane et al., participants demonstrated a higher level of scripted play actions in the development‐matched condition. [ABSTRACT FROM AUTHOR]

Introduction: To facilitate the implementation of controlled donation after circulatory death (cDCD) programs even in hospitals not equipped with a local extracorporeal membrane oxygenation (ECMO) team, some countries have launched a local cDCD network with an ECMO mobile team for normothermic regional perfusion (NRP). In the Tuscany region, in 2021, the Regional Transplant Authority launched a cDCD program to make the cDCD pathway feasible even in peripheral hospitals with NRP mobile teams, which were "converted" existing ECMO mobile teams, composed of highly skilled and experienced personnel. Methods: We describe the Tuscany cDCD program, (2021–2023), for cDCD from peripheral hospitals with NRP mobile teams. Results: Twenty‐six cDCDs (26/40, 65%) came from peripheral hospitals. Following the launch of the cDCD program, cDCDs from peripheral hospitals increased, from 33% (2021) to 75% (2022 and 2023) of the overall cDCDs. The mean age was 63 years, with older donors (>75 years) in half the cases. The median warm ischemia time was 45 min (20 min are required by the Italian law for death certification), ranging from 35 to 59 min. Among the 20 livers retrieved and 18 kidneys retrieved, 16 livers, and 11 kidneys (single kidney transplantation) were transplanted, after ex vivo reperfusion, respectively. Conclusions: The use of NRP mobile teams proved to be feasible and safe in the management of cDCD in peripheral hospitals. No complications were reported with NRP despite the advanced age of most cDCDs. [ABSTRACT FROM AUTHOR]

Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. Methods: The study employed two distinct methods. MDC was calculated using distribution‐based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor‐based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12‐month HFMSE could be anchored to a caregiver‐reported clinical perception questionnaire. Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution‐based methods uncovered varying values across age and functional status subgroups within each SMA type. Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies. [ABSTRACT FROM AUTHOR]

Objective: The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex. [ABSTRACT FROM AUTHOR]

Introduction: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. Purpose: To identify clinical and molecular factors associated with control of cervical disease with EBRT. Methods: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. Results: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression‐free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). Conclusion: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT. [ABSTRACT FROM AUTHOR]

Background: The Pediatric Eating Assessment Tool (PEDI‐EAT‐10) is a reliable and valid tool for rapid identification of dysphagia in patients aged 18 months to 18 years. Aims: To translate and adapt the PEDI‐EAT‐10 into the Italian language and evaluate its validity and reliability. Methods & Procedures: The translation and cross‐cultural adaptation of the tool consisted of five stages: initial translation, synthesis of the translations, back translation, expert committee evaluation and test of the prefinal version. The internal consistency of the translated tool was analysed in a clinical group composed of 200 patients with special healthcare needs aged between 18 months and 18 years. They were consecutively enrolled at the Rare Disease Unit, Paediatrics Department, Fondazione Policlinico Agostino Gemelli‐IRCCS, Rome. For test–retest reliability, 50 caregivers filled in the PEDI‐EAT‐10 questionnaire for a second time after a 2‐week period. Construct validity was established by comparing data obtained from patients with data from healthy participants (n = 200). The study was approved by the local ethics committee. Outcomes & Results: Psychometric data obtained from patients (104 M; mean age = 8.08 ± 4.85 years; median age = 7 years) showed satisfactory internal consistency (Cronbach's α = 0.89) and test–retest reliability (Pearson r = 0.99; Spearman r = 0.96). A total of 30% of children were classified as having a high risk of penetration/aspiration. The Italian PEDI‐EAT‐10 mean total score of the clinical group was significantly different from that resulting from healthy participants. Conclusions & Implications: The PEDI‐EAT‐10 was successfully translated into Italian, validated and found to be a reliable one‐page rapid screening tool to identify dysphagia in children and adolescents with special needs. What this paper adds: What is already known on the subject: The PEDI‐EAT‐10 is a valid and reliable quick discriminative paediatric tool for identifying penetration/aspiration risks. What this paper adds to the existing knowledge: In the present study we successfully translated and adapted the PEDI‐EAT‐10 into the Italian language. What are the potential or actual clinical implications of this work?: This translation and adaptation increase access to valid feeding and swallowing assessment for children of Italian‐speaking families. In addition, the I‐PEDI‐EAT‐10 can suggest further assessment of patients' swallowing abilities. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (cHL) consists of a heterogeneous group of haematological disorders that covers undifferentiated B cell neoplasms originating from germinal centre B cells. The HL molecular characterization still represents an ongoing challenge due to the low fraction of tumour Hodgkin and Reed–Sternberg cells mixed with a plethora of non‐tumour haematological cells. In this scenario, next generation sequencing of liquid biopsy samples is emerging as a useful tool in HL patients' management. In this review, we aimed to overview the clinical and methodological topics regarding the implementation of molecular analysis in cHL, focusing on the role of liquid biopsy in diagnosis, follow‐up, and response prediction. [ABSTRACT FROM AUTHOR]

This article discusses the seroprevalence of anti-human T-cell leukemia virus I/II (HTLV-I/II) antibodies among brain-dead donors in the Tuscany region of Italy. The study found that the seroprevalence of HTLV-I/II antibodies was very low (0.06%) with no documented transmission to recipients. The authors suggest that HTLV testing should only be performed in donors with a high epidemiological risk of infection in the Tuscany region. They emphasize the importance of accurate donor history and evaluation by an infection disease expert. The study provides valuable information for organ transplantation practices in areas with low seroprevalence of HTLV. [Extracted from the article]

The employment of chemical agents in the food industry is raising several concerns by consumers and is leading to an increasing interest in natural food preservatives. Among alternatives, host defense peptides (HDPs) have attracted great interest for their ability to preserve food samples from contamination without altering their quality, taste, and organoleptic properties. Recently, we evaluated the applicability of ApoB‐derived peptides as novel food bio‐preservatives and demonstrated their ability to prevent chicken meat sample contamination when immobilized on chitosan films. To perform a further step towards the applicability of these peptides in the food field, here we evaluated peptides biosafety and digestibility. To do this, we used a multidisciplinary approach including the evaluation of the peptides' toxicity and antimicrobial activity, the analysis of resistance phenotype development, an in silico prediction of the peptides' susceptibility to proteases and the evaluation of the peptides' stability in simulated gastric and intestinal fluids. ApoB‐derived peptides were found to be nontoxic when tested on human gastric carcinoma cells SNU‐1 and on human colon‐rectal adenocarcinoma cells HT‐29, and not to induce resistance phenotype in Salmonella strains. Bioinformatic analyses showed that the peptides are susceptible to several proteases, as also confirmed by experiments in simulated gastric and intestinal fluids. Altogether these findings open interesting perspectives to the future applicability of ApoB‐derived peptides as novel food biopreservatives. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the use of liposomal-encapsulated doxorubicin in the treatment of primary mediastinal large B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma (MGZL). The study examined the efficacy and safety of a new treatment regimen called R-COMP-DIx6, which included a higher dose of the medication. The study found that the treatment resulted in a high rate of complete metabolic response and was well-tolerated with minimal side effects. However, the study had limitations, including a small sample size and a long duration of data collection. Further research is needed to validate these findings in a larger clinical trial. [Extracted from the article]

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio‐demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W&W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health‐related quality of life was assessed with the EQ‐5D‐5L, EORTC QLQ‐C30 and QLQ CLL‐16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high‐risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health‐related quality of life scores were similar between groups. In the DCE, W&W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression‐free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID‐19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options. [ABSTRACT FROM AUTHOR]

Bio‐inspired and biodegradable quantum optics scenarios constitute a pathway toward environmentally friendly front‐end technologies. Such an inspiring perspective necessitates the replacement of classic gain materials with a biological counterpart like photoluminescent bacteria. It is easy to imagine that, in this case, a planar and cell‐viable substitute of classic bulk solid‐states resonators can be highly beneficial. In this paper a micro‐ and nano‐photonic structuration of both a standard and a functionalized version of a typical bacterial growth medium (Luria‐Bertani Agar – LBA) is successfully realized. Three structures belonging to the categories of photonic crystals are replicated, such as quasi‐crystals and meta‐surfaces, demonstrating how the proposed media can be used as templates for high‐end photonic applications. The optical quality of the replicated structures is confirmed by far‐field diffraction measurements. The structured growth media allow for a broad control of the surface wettability by accessing a so‐called Wenzel state, in which the original hydrophilicity of a material is increased due to the photonic structuration. Finally, the suitability of the nano‐structured LBA as a plasmonic platform is evidenced. The proposed micro‐and nano‐structured photonic growth media constitute the first, fundamental step toward quantum optical frameworks from biological media. [ABSTRACT FROM AUTHOR]

Objectives: The American Heartworm Society medical protocol represents the current standard of therapy for canine heartworm disease without caval syndrome. However, data on the tolerability of this protocol are limited. This study aimed to describe efficacy and prevalence of possible treatment‐related side effects in dogs with heartworm disease treated using the American Heartworm Society protocol. Materials and Methods: For this retrospective multi‐centre cohort study, dogs diagnosed with classes 1 to 3 heartworm disease that completed the American Heartworm Society medical protocol were searched in four medical databases. Demographic, clinical, diagnostic, therapeutic and outcome data, including the number and type of possible treatment‐related side effects, were retrieved. Results: Thirty‐five dogs were included. The median age and bodyweight were 6 years (1 to 13 years) and 17.3 kg (4.9 to 50 kg), respectively. Heartworm disease was classified as classes 1, 2 and 3 in 20 of 35, 11 of 35 and four of 35 dogs, respectively. In addition to the therapeutic recommendations of the American Heartworm Society, eight of 35 dogs underwent sedation to favour melarsomine administration, and 30 of 35 received ice at the injection site. After adulticide therapy, all dogs were hospitalised with cage rest [median time 12 hours (6 to 48 hours)]. All dogs survived the treatment. All dogs with long‐term follow‐up (32/35) became negative. Furthermore, treatment‐related side effects were rare, mild and rapidly recovered without the need for supporting therapies; these included depression/lethargy (4/35 dogs), cough (2/35 dogs) and lameness, pain and gastrointestinal signs (1/35 dog each). Clinical Significance: The American Heartworm Society medical protocol is efficient and safe in dogs with classes 1 to 3 heartworm disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. The aim of this study was to perform a meta‐analysis and network meta‐analysis of randomized and placebo‐controlled trials of innovative therapies in MG with available efficacy data. Methods: We assessed statistical heterogeneity across trials based on the Cochrane Q test and I2 values, and mean differences were pooled using the random‐effects model. Treatment efficacy was assessed after 26 weeks of eculizumab and ravulizumab, 28 days of efgartigimod, 43 days of rozanolixizumab, 12 weeks of zilucoplan, and 16, 24 or 52 weeks of rituximab treatment. Results: We observed an overall mean Myasthenia Gravis‐Activities of Daily Living scale (MG‐ADL) score change of −2.17 points (95% confidence interval [CI] −2.67, −1.67; p < 0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti‐FcRn treatment (p = 0.16). The change in Quantitative Myasthenia Gravis scale (QMG) score was −3.46 (95% CI −4.53, −2.39; p < 0.001), with a higher reduction with FcRns (−4.78 vs. −2.60; p < 0.001). Rituximab did not significantly improve the MG‐ADL (−0.92 [95% CI −2.24, 0.39]; p = 0.17) or QMG scores (−1.9 [95% CI −3.97, 0.18]; p = 0.07). In the network meta‐analysis, efgartigimod had the highest probability of being the best treatment, followed by rozanolixizumab. Conclusion: Anti‐complement and FcRn treatments both proved to be effective in MG patients, whereas rituximab did not show a significant benefit for patients. Within the limitations of this meta‐analysis, including efficacy time points, FcRn treatments showed a greater effect on QMG score in the short term. Real‐life studies with long‐term measurements are needed to confirm our results. [ABSTRACT FROM AUTHOR]

The reliability and safety of front‐line ultrasonography guided core needle biopsy (UG‐CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG‐CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG‐CNB from four Italian clinical units that routinely utilized 16‐gauge diameter modified Menghini needle under power‐Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG‐CNB in untreated patients over a 12‐year period. Overall, 1000 (superficial target, n = 750; deep‐seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B‐cell non‐Hodgkin lymphoma [aBc‐NHL], 309 cases; indolent B‐cell [iBc]‐NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T‐cell [NPTC]‐NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non‐malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro‐histological sampling was 97% (95% confidence interval: 95%–98%) for the series. The sensitivity of UG‐CNB for the detection of aBc‐NHL was 100%, for iBc‐NHL 95%, for HL 93%, and for NPTC‐NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy‐related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG‐CNB as mini‐invasive diagnostic procedure is effective with minimal risk for the patient. [ABSTRACT FROM AUTHOR]

Over the past several decades, forests worldwide have experienced increases in biotic disturbances caused by insects and plant pathogens – a trend that is expected to continue with climate warming. Whereas the causes and effects of individual biotic disturbances are well studied, spatiotemporal interactions among multiple biotic disturbances are less so, despite their importance to ecosystem function and resilience. Here, we highlight an emerging phenomenon of "hotspots" of biotic disturbances (that is, two or more biotic disturbances that overlap in space and time), documenting trends in recent decades in temperate conifer forests of the western US. We also explore potential mechanisms behind and effects of biotic disturbance hotspots, with particular focus on how altered post‐disturbance recovery (successional pathways) can have profound consequences for ecosystem resilience and biodiversity conservation. Finally, we propose research directions that can elucidate drivers of biotic disturbance hotspots and their ecological effects at various spatial scales, and provide insight into this new knowledge frontier. [ABSTRACT FROM AUTHOR]

Background: This study aimed to estimate if the altered sphygmic wave transmission may affect the left ventricular (LV) contractile function in patients undergoing endovascular aortic repair (EVAR). Methods: A prospective single‐centre study was carried out on consecutive patients undergoing EVAR for abdominal aortic aneurysm. A preoperative and 6‐month single photon emission computed tomography (SPECT) with arterial stiffness measurement were performed to evaluate variations in pressure wave curve and myocardial perfusion parameters. Results: From 2018 to 2020 a total of 16 patients were included in the study. Among the parameters evaluated, we found a measurable reduction of the reflected wave transit time from pre‐ to postoperative period, for both stress (115.13 ± 7.2 ms–111.1 ± 7.0 ms, p =.08) and rest SPECT acquisitions (115.3 ± 6.2 ms–112.2 ± 5.6 ms, p =.1). Unidirectional increase of both LV end‐systolic volume (34 ± 9 mL–39 ± 8 mL, p =.02) and end‐diastolic volume (85 ± 34 mL–89 ± 29 mL, p =.6) was also observed. Lastly, the ratio between the end‐systolic pressure and the end‐systolic volume (maximal systolic myocardial stiffness) decreased from 3.6 ± 1.5 mmHg/mL to 2.66 ±.74 mmHg/mL (p =.03). Conclusions: Our data showed that EVAR induced an altered transmission of the sphygmic wave associated with an early LV contractile impairment. [ABSTRACT FROM AUTHOR]

There has been a steady increase in people with symptoms of depression over the past several years (since 2011). The further increase in stress and depression in the early part of the COVID‐19 pandemic was accompanied by an increase in unmet mental health needs. Many have turned to complementary and alternative medicine (CAM) therapies such as bright‐light therapy, yoga, meditation, and dietary supplements like St. John's wort or folic acid. The reliability of evidence for use of CAM therapies for depression has remained low. There are few randomized controlled trials (RCTs) in the current literature and poor methodology in many of the trials that are available. This state of the science review examines current published guidelines, meta‐analyses, systematic reviews, and RCTs regarding use of CAM therapies in the management of depression. [ABSTRACT FROM AUTHOR]

Background: We report the 4‐year follow‐up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. Methods: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE‐II). Results: Forty‐eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE‐II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE‐2 increased significantly in patients younger than 2 years at treatment. In a mixed‐model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. Conclusions: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time. [ABSTRACT FROM AUTHOR]

Soft magnetic structures having a non‐uniform magnetization profile can achieve multimodal locomotion that is helpful to operate in confined spaces. However, incorporating such magnetic anisotropy into their body is not straightforward. Existing methods are either limited in the anisotropic profiles they can achieve or too cumbersome and time‐consuming to produce. Herein, a 3D printing method allowing to incorporate magnetic anisotropy directly into the printed soft structure is demonstrated. This offers at the same time a simple and time‐efficient magnetic soft robot prototyping strategy. The proposed process involves orienting the magnetized particles in the magnetic ink used in the 3D printer by a custom electromagnetic coil system acting onto the particles while printing. The resulting structures are extensively characterized to confirm the validity of the process. The extent of orientation is determined to be between 92% and 99%. A few examples of remotely actuated small‐scale soft robots that are printed through this method are also demonstrated. Just like 3D printing gives the freedom to print a large number of variations in shapes, the proposed method also gives the freedom to incorporate an extensive range of magnetic anisotropies. [ABSTRACT FROM AUTHOR]

Background: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. Aims: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24‐month period. Methods: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture‐related adverse events. Results: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). Conclusion: In this single‐center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration. [ABSTRACT FROM AUTHOR]

Although response interruption and redirection (RIRD) and multiple schedule arrangements have sometimes been shown to be effective in reducing stereotypy for individuals with autism spectrum disorder (ASD), important questions remain about optimal methods for facilitating generalization and social validity. In the current study, we sought to extend the literature on stereotypy treatment and MSAs in several ways. First, we programmed for generalization by conducting sessions with two exemplars of two different categories of activities (i.e., school work, toy play) and assessing generalization with novel exemplars and activities and during the participant's typical instructional program. Second, we used RIRD instructions that were contextual models of appropriate behavior relevant to each activity. Third, during the free access component of the multiple schedule, we used a child's play tent as a first step toward teaching participants to engage in stereotypy during private free time. For all three participants with ASD, stereotypy decreased quickly and substantially, with reductions generalizing to novel activities and contexts. An extensive social validity assessment with board‐certified behavior analysts indicated high social acceptability of the goals, procedures, and outcomes. [ABSTRACT FROM AUTHOR]

Background. Currently, conventional radiography is still widely used to diagnose knee osteoarthritis and assess the grade according to Kallgren and Lawrence's criteria. Ultrasound is a simple, inexpensive, noninvasive, and dynamic modality for evaluating femoral cartilage (FC) thickness. This study aims to measure the FC thickness in knee osteoarthritis (OA) patients and compare it to healthy adults using ultrasound assessment. Methods. An observational study with a cross-sectional design was conducted at the Department of Physical Medicine and Rehabilitation of Hajj General Hospital, Surabaya, Indonesia, from May to July 2022. Participants radiologically diagnosed with OA were included in the study and assigned to the OA group. Meanwhile, healthy adults without knee symptoms were included in the control group. FC thickness was measured using ultrasound scans at three sites: medial condyle (MC), intercondylar (IC), and lateral condyle (LC) on both sides of the knee. Results. The mean age in the OA and control groups was 61.03 ± 8.6 and 33.93 ± 14.7 years, respectively. Most participants in both groups were female. The OA group exhibited a thinner FC (1.49–1.63 mm) than the control group (1.68–1.87 mm). There was a significant difference in the mean of the right and left MC in both groups (p < 0.05) but no significant difference in the IC and LC. Conclusion. OA patients exhibited a thinner FC than healthy adults in the control group. There was a significant difference in the mean thickness of the MC between groups. [ABSTRACT FROM AUTHOR]

Fruit anthracnose caused by Colletotrichum species is a major disease of olive (Olea europaea) worldwide. In this study, we tested in vitro the susceptibility of eight widely grown Italian olive cultivars and one Spanish cultivar to five Colletotrichum species. The Italian cultivars were Carolea, Cassanese, Coratina, Dolce Agogia, Frantoio, Leccino, Ottobratica and Sant'Agostino. The Spanish cultivar, included as a reference, was Picual. The five Colletotrichum species, included in pathogenicity tests, were C. acutatum, C. gloeosporioides, C. godetiae, C. karsti and C. nymphaeae. Olive drupes at comparable ripening stage were wound‐inoculated with a conidial suspension and the severity of infections was rated at various time intervals after inoculation using a scale of 0 to 6. The results were expressed in terms of relative area under disease progress curve (rAUDPC). C. acutatum was the most aggressive while C. karsti was the least aggressive among the Colletotrichum species tested. Frantoio and Leccino were the least susceptible cultivars while Ottobratica, Coratina and Carolea were the most susceptible to all Colletotrichum species. Separate experiments aimed to evaluate the effect of both inoculation method and drupe ripening stage on the interaction between Colletotrichum species and olive cultivars. Only C. acutatum and C. nymphaeae induced symptoms in nonwounded drupes. In general, the disease severity in green drupes was significantly lower than in mature drupes; however, the rankings of olive cultivars for their susceptibility to Colletotrichum species on both green and mature drupes showed similar trends. [ABSTRACT FROM AUTHOR]

Background: The regulatory functions of microRNAs (miRNAs) in anti‐tumour immunity have been mainly described in immune effector cells. Since little is known about miRNA effects on the susceptibility of target cells during T cell—target cell interaction, this study focused on the identification of miRNAs expressed in tumour cells controlling their susceptibility to CD8+ T cell‐mediated cytotoxicity. Methods: Luciferase expressing B16F10 melanoma (B16F10 Luci+) cells transfected with individual miRNAs covering a comprehensive murine miRNA library were screened for their susceptibility to lysis by an established cytotoxic T lymphocyte (CTL) line (5a, clone Nβ) specific for the melanoma‐associated antigen tyrosinase‐related protein 2. miRNAs with the most pronounced effects on T cell‐mediated lysis were validated and stably expressed in B16F10 cells. In silico analyses identified common targets of miRNA sets determined by the screen, which were further confirmed by small interfering RNA (siRNA)‐mediated silencing experiments modulating immune surveillance. The Ingenuity Pathway Analysis (IPA) software and RNA sequencing (RNA‐seq) data from miRNA‐overexpressing cell lines were applied to investigate the underlying mechanisms. The Cancer Genome Atlas (TCGA)‐derived miRNA sequencing data were used to assess the correlation of miRNA expression with melanoma patients' survival. Results: The miRNA screen resulted in the selection of seven miRNAs enhancing CTL‐mediated melanoma cell killing in vitro. Upon stable overexpression of selected miRNAs, hsa‐miR‐320a‐3p, mmu‐miR‐7037‐5p and mmu‐miR‐666‐3p were determined as most effective in enhancing susceptibility to CTL lysis. In silico analyses and subsequent siRNA‐mediated silencing experiments identified Psmc3 and Ndufa1 as common miRNA targets possibly involved in the functional effects observed. The analyses of RNA‐seq data with IPA showed pathways, networks, biological functions and key molecules potentially involved in the miRNA‐mediated functional effects. Finally, based on TCGA data analysis, a positive correlation of the conserved miRNAs among the panel of the seven identified miRNAs with overall survival of melanoma patients was determined. Conclusions: For the first time, this study uncovered miRNA species that affect the susceptibility of melanoma cells to T cell‐mediated killing. These miRNAs might represent attractive candidates for novel therapy approaches against melanoma and other tumour entities. [ABSTRACT FROM AUTHOR]

Background: Emergence of dysplastic haematopoietic precursor/s, cytopenia and variable leukaemia risk characterise myelodysplastic syndromes (MDS). Impaired immune‐regulation, preferentially affecting cytotoxic T cells (CTL), has been largely observed in MDS. Recently, we described the TR3−56 T cell subset, characterised by the co‐expression of CD3 and CD56, as a novel immune‐regulatory population, able to modulate cytotoxic functions. Here, we address the involvement of TR3−56 cells in MDS pathogenesis/progression. Objectives: To analyse the relationship between TR3−56 and CTL activation/expansion in bone marrow (BM) of very‐low/low‐risk MDS subjects. Methods: Peripheral blood and BM specimens, obtained at disease onset in a cohort of 58 subjects, were analysed by immune‐fluorescence and flow cytometry, to preserve the complexity of the biological sample. Results: We observed that a trend‐increase of BM TR3−56 in high/very‐high MDS stage, as compared with very‐low/low group, associates with a decreased activation of BM resident CTL; significant correlation of TR3−56 with BM blasts has been also revealed. In addition, in very‐low/low‐risk subjects the TR3−56 amount in BM inversely correlates with the presence of activated BM CTL showing a skewed Vβ T‐cell repertoire. Conclusions: These data add TR3−56 to the immune‐regulatory network involved in MDS pathogenesis/progression. Better knowledge of the immune‐mediated processes associated with the disease might improve MDS clinical management. [ABSTRACT FROM AUTHOR]

Summary: Real‐world data on daily practice management, treatment modifications and outcome of a large cohort of chronic myeloid leukaemia (CML) patients treated with ponatinib was performed through monitoring Registries of the Italian Medicines Agency (AIFA). Overall, 666 CML subjects were included in the ponatinib registry from February 2015 to December 2020 and were eligible for analysis: 515 in chronic phase (CP), 50 in accelerated phase (AP) and 101 in blast crisis (BC). Median age at baseline was 58.7 years with a predominance of male subjects (57.1%). The median time from diagnosis to start of ponatinib was 2.35 years: 259 (38.9%) subjects had received two previous lines of treatment, 260 (39.0%) three lines and 147 (22.1%) four or more lines. A molecular response [from major molecular response (MMR) to a score of ≤0.01% on the international reporting scale (IS)] was reported for 59% of patients out of 593 patients analysed. With a median follow‐up of 14.4 months, 136 subjects (20.4%) required at least one dose reduction due to adverse events (AEs), whereas 309 patients (46.4%) required dose reduction in the absence of any evidence of side effects. Treatment discontinuation occurred in 261 patients (39%). This real‐life analysis shows that dose reductions were made primarily as a precaution rather than due to the occurrence of adverse reactions. [ABSTRACT FROM AUTHOR]

Phytoplanktonic organisms are particularly sensitive to environmental change, and, as they represent a direct link between abiotic and biotic compartments within the marine food web, changes in the functional structure of phytoplankton communities can result in profound impacts on ecosystem functioning. Using a trait‐based approach, we examined changes in the functional structure of the southern North Sea phytoplankton over the past five decades in relation to environmental conditions. We identified a shift in functional structure between 1998 and 2004 which coincides with a pronounced increase in diatom and decrease in dinoflagellate abundances, and we provide a mechanistic explanation for this taxonomic change. Early in the 2000s, the phytoplankton functional structure shifted from slow growing, autumn blooming, mixotrophic organisms, towards earlier blooming and faster‐growing microalgae. Warming and decreasing dissolved phosphorus concentrations were linked to this rapid reorganization of the functional structure. We identified a potential link between this shift and dissolved nutrient concentrations, and we hypothesise that organisms blooming early and displaying high growth rates efficiently take up nutrients which then are no longer available to late bloomers. Moreover, we identified that the above‐mentioned functional change may have bottom‐up consequences, through a food quality‐driven negative influence on copepod abundances. Overall, our study highlights that, by altering the phytoplankton functional composition, global and regional changes may have profound long‐term impacts on coastal ecosystems, impacting both food‐web structure and biogeochemical cycles. [ABSTRACT FROM AUTHOR]

The study reports real world data in type 2 and 3 SMA patients treated for at least 2 years with nusinersen. Increase in motor function was observed after 12 months and during the second year. The magnitude of change was variable across age and functional subgroup, with the largest changes observed in young patients with higher function at baseline. When compared to natural history data, the difference between study cohort and untreated patients swas significant on both Hammersmith Functional Motor Scale and Revised Upper Limb Module both at 12 months and at 24 months. [ABSTRACT FROM AUTHOR]

Background: Vitiligo management is challenging and requires long‐term adherence of patients who often complain of the burden associated with treatment. Objective: To develop and validate a patient reported measurement of the burden of treatment in vitiligo. Methods: The study was nested within the ComPaRe Vitiligo e‐cohort, an online e‐cohort of vitiligo patients in France. Items were derived from a literature review and from the qualitative analysis of a survey using open‐ended questions of 204 patients with Vitiligo. Construct validity of the resulting instrument was assessed by comparing the instrument's score to the Dermatology Life Quality Index (DLQI), Vitiligo Impact Patient score (VIPs) and Treatment Burden Questionnaire (TBQ) scores. Reliability was assessed by test‐retest with 15 ± 10 days of interval between both assessments. Results: In total, 343 adult participants participated in the validation of the Vitiligo Treatment Impact score (VITs). The VITs is a 19‐item questionnaire assessing the burden of treatment in patients with vitiligo with results suggesting four domains ('Finding a doctor', 'Phototherapy', 'Topical treatment' and 'Impact on outdoor activities and photoprotection'). The VITs total score was well correlated with the DLQI, VIP and TBQ scores. Agreement between test and retest was good (ICC 0.705, 95% CI 0.491–0.818). Conclusions: We developed a patient reported measurement of the burden of treatment in vitiligo with good psychometric properties. [ABSTRACT FROM AUTHOR]

Background: Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting.Methods: The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1 × 109 live cells and Bifidobacterium breve B632 1 × 109 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety.Results: The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations (OR = 3.17). In addition, the number of children with two exacerbations was less than a third in the active group (OR = 3.65).Conclusions: This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies. [ABSTRACT FROM AUTHOR]

Although neurotypical children often spend the majority of their time engaged in play activities, children with autism spectrum disorder (ASD) can present with substantial delays in the development of play skills, requiring intensive intervention. Although targets for language and basic learning skills are often selected based on the development of neurotypical children (e.g., Sundberg, 2008), little research has been conducted on methods for selecting play skill targets. The current study compared acquisition of play skills that were development‐matched (DM) and age‐matched (AM) with 4 children diagnosed with ASD. Targets were selected based on the results of the Developmental Play Assessment (DPA; Lifter, 2008). No contrived prompts or consequences were used to teach play skills in either condition. Generalization was programmed for by teaching with 3 sets of toys in both conditions. All participants demonstrated acquisition of DM play targets and generalization to novel toys; none of the participants acquired AM play targets. [ABSTRACT FROM AUTHOR]

Late blight caused by the oomycete Phytophthora infestans is a disease of potato and tomato of worldwide relevance and is widespread throughout Europe and the Mediterranean region. While pathogen populations in northern Europe have been sampled and characterized for many years, the genetic structure of populations from southern Europe, including Italy, has been less studied. Between 2018 and 2019, we collected 91 samples of P. infestans from potato and tomato crops in Italy, Algeria, and Tunisia on FTA cards and genotyped them using 12‐plex microsatellites. These samples were compared to genotypes of P. infestans previously collected within the framework of the EuroBlight network and from published sources. Four clonal lineages were identified: 13_A2 (Blue 13), 2_A1, 23_A1, and 36_A2. Two other isolates collected could not be matched to any currently known clonal lineage. The 13_A2 and 36_A2 lineages were found exclusively in southern Italy and Algeria, while 2_A1 was only found in Algeria. This is the first report of the 36_A2 lineage in Italy. Two isolates from Solanum nigrum were 13_A2, suggesting this weed host could be a reservoir of inoculum. The 23_A1 lineage was found widely on infected tomato crops in Italy and is the same as the lineage US‐23 that is widespread in North America. Differences in genotypes across the country suggests that there may be different sources of introduction into Italy, possibly via infected seed tubers from other countries in Europe, tubers for consumption from North Africa, or tomatoes. [ABSTRACT FROM AUTHOR]