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Although Gallium Nitride (GaN) Field Effect Transistor (FET) devices have found extensive application in DC-DC converters, their utilization in inverter motor drives remains an evolving area of study. In particular, the intricacies of reverse conduction operation during the dead time, specific to GaN FETs, require in-depth exploration for inverters supplying AC currents to electrical motors. Therefore, this paper undertakes an assessment of reverse conduction during the dead time intervals in low-voltage GaN FETs employed in motor drives applications. This analysis provides correlations between device technology attributes and the variations in AC phase current. To facilitate this investigation, a dedicated numerical tool is developed to evaluate the reverse conduction characteristics of GaN FET and associated power losses. Furthermore, this study includes a comparative analysis of the reverse conduction behavior of GaN FET devices with their low-voltage MOSFET counterparts, taking into account their differing static and dynamic characteristics. As a result, the main contribution of this work is to provide to the inverter designers a comprehensive understanding of dead-time effects in GaN-based inverters, along with guidance on selecting and optimizing dead time intervals within inverter legs for motor control applications employing the latest generation of GaN FET devices.

Purpose of the research: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. Methods: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. Principal results: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. Conclusions: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Demanding attention in order to keep postural balance increases with aging and with the presence of concurrent tasks that require information processing. Several studies have demonstrated that motor performance can be related to the complexity of the task and aging process, presenting a possible interaction between these factors. The aim of this review was to identify and analyze published papers about the effects of cognitive tasks on the postural control of elderly individuals. A systematic search in the Web of Science, SportDiscus, CINAHL, Science Direct on line, Biological Abstracts, PsycINFO, and Medline databases was made and 444 articles were found. Eight were selected that studied the variables of interest. These studies showed that postural control seems to be influenced by the individual's attention processes and that deficits in such ability may be associated to an increased risk of falls.

Thyrotoxic hypokalemic periodic paralysis (THPP) is an endocrine emergency with sudden onset of acute muscle hypo-asthenia associated with severe hypokalemia and normal acid-base balance, due to thyrotoxicosis. It may develop in patients of Asian and Native American descent, but it is very rare and undiagnosed in Western countries. Standard treatment includes β-blockers and thyrostatic drugs, but hypokalemia should not be treated with high potassium doses due to the risk of hyperkalemic rebound. Since early diagnosis and correct treatment can prevent life-threatening cardio-pulmonary complications, the emergency physician should keep in mind this rare possibility. We report a case of a 43 year old Caucasian man presenting at ED with tetraparesis as the first symptom of thyrotoxicosis with no other remarkable symptoms or signs.

This work studies the stability of wild-type frataxin and some of its variants found in cancer tissues upon Co2+ binding. Although the physiologically involved metal ion in the frataxin enzymatic activity is Fe2+, as it is customarily done, Co2+ is most often used in experiments because Fe2+ is extremely unstable owing to the fast oxidation reaction Fe2+ → Fe3+. Protein stability is monitored following the conformational changes induced by Co2+ binding as measured by circular dichroism, fluorescence spectroscopy, and melting temperature measurements. The stability ranking among the wild-type frataxin and its variants obtained in this way is confirmed by a detailed comparative analysis of the XAS spectra of the metal-protein complex at the Co K-edge. In particular, a fit to the EXAFS region of the spectrum allows positively identifying the frataxin acidic ridge as the most likely location of the metal-binding sites. Furthermore, we can explain the surprising feature emerging from a detailed analysis of the XANES region of the spectrum, showing that the longer 81-210 frataxin fragment has a smaller propensity for Co2+ binding than the shorter 90-210 one. This fact is explained by the peculiar role of the N-terminal disordered tail in modulating the protein ability to interact with the metal.

Trypanosoma brucei inosine-5′-monophosphate dehydrogenase (IMPDH) is an enzyme in the guanine nucleotide biosynthesis pathway and of interest as a drug target. Here the authors present the 2.8 Å room temperature structure of TbIMPDH determined by utilizing X-ray free-electron laser radiation and crystals that were grown in insect cells and find that ATP and GMP are bound at the canonical sites of the Bateman domains.

We have prepared new polyesters containing quadratic, nonlinear optical (NLO) active chromophores covalently incorporated into the main chain. In these polymers, the sequence of the chromophore units along the main chain is rigorously head to tail. All the polyesters are processable, both in the melt and in solution. For one polyester, a full second‐order NLO characterization has been performed. An out‐of‐resonance d33 coefficient of 21 pm/V at 1368 nm has been measured. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2719–2725, 2007 [ABSTRACT FROM AUTHOR]

Current hard X-ray free-electron laser (XFEL) sources can deliver doses to biological macromolecules well exceeding 1 GGy, in timescales of a few tens of femtoseconds. During the pulse, photoionization can reach the point of saturation in which certain atomic species in the sample lose most of their electrons. This electronic radiation damage causes the atomic scattering factors to change, affecting, in particular, the heavy atoms, due to their higher photoabsorption cross sections. Here, it is shown that experimental serial femtosecond crystallography data collected with an extremely bright XFEL source exhibit a reduction of the effective scattering power of the sulfur atoms in a native protein. Quantitative methods are developed to retrieve information on the effective ionization of the damaged atomic species from experimental data, and the implications of utilizing new phasing methods which can take advantage of this localized radiation damage are discussed.

Rationale & Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. Progressive increase in cyst number and size leads to kidney failure in a majority of patients. Large kidney cysts, although few, can be especially deleterious by impeding kidney blood flow and obstructing urine flow over a large region. Foam sclerotherapy is a minimally invasive procedure that may be used to ablate large cysts. We examined the effectiveness and safety of foam sclerotherapy for kidney volume reduction in patients with ADPKD. Study Design: Prospective cohort study. Setting & Participants: Adults with ADPKD at a tertiary referral center in Toronto. Predictor: Foam sclerotherapy. Outcomes: Volume of treated kidneys and adverse events. Analytical Approach: Treated and nontreated kidney volume, kidney function, tolerability, and symptoms were analyzed within each patient. Results: We performed 77 foam sclerotherapy treatment sessions in 66 patients. Foam sclerotherapy was associated with a 21.8% volume reduction of the treated kidneys (n = 95; median, 1,138 [IQR, 801-1,582] mL before vs 891 [IQR, 548-1,450] mL after; P

Objective: To estimate the economic consequences of the current Brazilian government policy for attention-deficit/hyperactivity disorder (ADHD) treatment and how much the country would save if treatment with immediate-release methylphenidate (MPH-IR), as suggested by the World Health Organization (WHO), was offered to patients with ADHD. Method: Based on conservative previous analyses, we assumed that 257,662 patients aged 5 to 19 years are not receiving ADHD treatment in Brazil. We estimated the direct costs and savings of treating and not treating ADHD on the basis of the following data: a) spending on ADHD patients directly attributable to grade retention and emergency department visits; and b) savings due to impact of ADHD treatment on these outcomes. Results: Considering outcomes for which data on the impact of MPH-IR treatment are available, Brazil is probably wasting approximately R$ 1.841 billion/year on the direct consequences of not treating ADHD in this age range alone. On the other hand, treating ADHD in accordance with WHO recommendations would save approximately R$ 1.163 billion/year. Conclusions: By increasing investments on MPH-IR treatment for ADHD to around R$ 377 million/year, the country would save approximately 3.1 times more than is currently spent on the consequences of not treating ADHD in patients aged 5 to 19 years.

Objective:To perform a cost-utility analysis on the treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate immediate-release (MPH-IR) in children and adolescents from Brazil.Method:A Markov model was constructed to compare MPH-IR vs. no treatment. A 24-week naturalistic study was conducted to collect transition probabilities and utility data. Effectiveness was expressed as quality-adjusted life-years (QALY), and costs reported in 2014 international dollars (I$). The perspective was the Brazilian Unified Health System as payer, and the time horizon was 6 years.Results:Of 171 patients, 73 provided information at baseline, and 56 at week 24. Considering the MPH-IR monthly cost of I$ 38, the incremental cost-effectiveness ratio (ICER) of treatment was I$ 9,103/QALY for children and I$ 11,883/QALY for adolescents. In two-way sensitivity analysis, considering one Gross National Product per capita (I$ 11,530) as willingness-to-pay, a cost of no-treatment lower than I$ 45/month would render MPH-IR a cost-saving strategy.Discussion:MPH-IR treatment of children and adolescents is cost-effective for ADHD patients from the Brazilian public health system perspective. Both patients and the healthcare system might benefit from such a strategy.Trial registration number:NCT01705613.

Background: Anti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in non-relapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell-associated hematotoxicity (ICAHT)., Aims: To validate the ability of the HT score to predict ICAHT and survival., Methods: The CART-SIE is an ongoing multicenter prospective observational study collecting data on patients affected by B-cell lymphoma treated with commercial anti-CD19 CAR T-cells (ClinicalTrials.gov ID: NCT06339255)., Results: Since 2019 to 2024, 1002 consecutive patients were enrolled. Out of 746 patients infused, the HT score at infusion was evaluable in 389. Median age was 59 years (48-66). Patients with high HT score had greater disease burden and a greater need for bridge therapy. Patients with a HT HIGH score had a 4-fold higher risk of experiencing late ICAHT of grade≥3 (OR=3.99, 95% CI=1.16-13.77, p=0.03). Patients with a HT HIGH score also showed lower overall response rates (ORR) and complete response rates (CRR) at 90 days (CRR at 90 days: 59% HT LOW vs 38% HT HIGH , OR=0.42, 95% CI=0.27-0.66, p=0.0002; ORR at 90 days: 67% HT LOW vs 49% HT HIGH , OR=0.47, 95% CI=0.29-0.74, p=0.001). Adjusted logistic models confirmed that the effect of HT score was independent from baseline characteristics. With a median follow-up of 18 months, patients with a HT HIGH score have lower OS and PFS (1-year OS: 78% HT LOW versus 62% HT HIGH , p=0.0002; 1-year PFS: 49% versus 39%, p=0.003). Adjusted Cox models confirmed that HT was an independent prognostic factor for OS. A high HT-score was found to be associated with higher risk of secondary primary malignancy (HR=2.8, 95% CI=1.03-7.8, p=0.04). A simplified version of HT (simpleHT), based solely on the platelet count and C-reactive protein at infusion, was calculated for 560 patients and proved significant in predicting both OS and PFS (1-year was 72% simpleHT LOW vs 37% simpleHT HIGH , p<0.0001, 1-year PFS was 48% simpleHT LOW vs 22% simpleHT HIGH , p<0.0001)., Conclusion: In our prospective real-world study, we validated the ability of the HT score to predict ICAHT and survival. SimpleHT identified a population at very high risk with an impaired progression free and overall survival., Competing Interests: Declaration of competing interest FS –nothing to disclose., MP –nothing to disclose, AC - Advisory boards: Gilead-Sciences, Ideogen, Roche, SecuraBIO, Takeda; honoraria for lectures/educational events: Abbvie, Eli Lilly, Gilead-Sciences, Incyte, Janssen-Cilag, Novartis, Takeda., BC –Advisory boards and honoraria for lectures/educational events: Kite Gilead, Novartis.., SB - Speaker bureau: BMS; GILEAD, NOVARTIS, ADVISORY BOARD NOVARTIS, TRAVEL ACCOMODATION NOVARTIS, ROCHE, SL –nothing to disclose, PC –nothing to disclose, ADR –consulting fees: Roche, Takeda, Incyte, Kite-Gilead, Novartis, Abbvie; speakers bureaus: Roche, Kite-Gilead, Janssen, Abbvie, Eli-Lilly, Sobi, Incyte, Recordati, Rare Disease; advisory board: Takeda, Kite-Gilead, Roche, Abbvie, Novartis., MCT –personal fees from Novartis, Gilead, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Sanofi, and Incyte., PA –to disclose ., IC –nothing to disclose, MM - advisory board Kite/Gilead; Novartis; BMS. Speakers bureau: Kite/Gilead; Novartis; BMS, AB –nothing to disclose., FB - Advisory boards and honoraria for lectures/educational events: Kite Gilead, Novartis, AS –Advisory Board: Bms (Bristol-Myers-Squibb) / Servier / Gilead / Pfizer / Eisai / Bayer / Msd (Merck Sharp & Dohme). Consultancy: Sanofi/ Incyte. Speaker's Bureau: Takeda / Bms / Roche / Abb-Vie / Amgen / Celgene / Servier / Gilead / Astrazeneca / Pfizer / Lilly / Sandoz / Eisai / Novartis / Bayer / Msd/ Beigene, FSo –nothing to disclose., MN –nothing to disclose., AMB –nothing to disclose., DR –nothing to disclose., MMu –nothing to disclose., GG –nothing to disclose., MK –Advisory boards and honoraria for lectures/educational events: Kite Gilead, Novartis, Janssen-Cilag, Incyte, AbbVie, BeiGene, Menarini StemLine, Roche., JO –personal fees from AbbVie and Incyte., BL –nothing to disclose., FCa –other support from Incyte, Eli Lilly and Company, and AstraZeneca, grants and other support from Roche, and nonfinancial support from BeiGene, Takeda, and GSK outside the submitted work., MMa –nothing to disclose., LA - Honoraria: EUSA Pharma, Novartis. Advisory boards for Roche, Janssen-Cilag, Verastem, Incyte, EUSA Pharma, Celgene/Bristol Myers Squibb, Kite/Gilead, ADC Therapeutics, Novartis., LF –AbbVie, Biotest, AstraZeneca, Beigene, AbbVie, Janssen., PLZ –Consultant: MSD, Eusapharma, Novartis; Advisory boards: ADC Therapeutics, Astrazeneca, BeiGene, BMS, Celltrion, Eusapharma, Gilead, Incyte, Janssen-Cilag, KyowaKirin, MSD, Novartis, Roche, Sandoz, SecuraBio, Servier, Takeda; speakers bureau: Astrazeneca, Beigene, BMS, Celltrion, Eusapharma, Gilead, Incyte, Janssen-Cilag, Kyowa-Kirin, MSD, Novartis, Roche, Servier, Takeda., RM –nothing to disclose ., PCo - Advisory boards: AbbVie, ADC Therapeutics, Amgen, BeiGene, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda; honoraria for lectures: AbbVie, Amgen, Celgene, Gilead/Kite, Janssen, Novartis, Roche, Sanofi, Takeda., (Copyright © 2025. Published by Elsevier Inc.)

B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and possible interactions with T cells in the context of NSCLC. In this study, using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics we explored the intricate landscape of B cell phenotypes, bioenergetics, and their interaction with T cells in NSCLC. Our analysis revealed that TME contains diverse B cell clusters, including VISTA + Bregs, with distinct metabolic and functional profiles. Target liquid chromatography-tandem mass spectrometry confirmed the expression of VISTA on B cells. VISTA + Bregs displayed high metabolic demand and were able to produce different cytokines, including interleukin (IL)-10, transforming growth factor (TGF)-β, IL-6, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Spatial analysis showed colocalization of B cells with CD4 + /CD8 + T lymphocytes in TME. The computational analysis of intercellular communications that links ligands to target genes, performed by NicheNet, predicted B-T interactions via VISTA-PSGL-1 axis. Colocalization analyses revealed that PSGL-1 T cells and VISTA + B cells are adjacent in the TME. Notably, tumor infiltrating CD8 + T cells expressing PSGL-1 exhibited enhanced metabolism and cytotoxicity. In NSCLC patients, prediction analysis performed by PENCIL revealed the presence of an association between PSGL-1 + CD8 + T cells and VISTA + Bregs with lung recurrence. Our findings suggest a potential interaction between Bregs and T cells through the VISTA-PSGL-1 axis, that could influence NSCLC recurrence., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the local Ethical Committes (“Area Vasta Emilia Nord”, protocol number 0018007/21; “Comitato Etico della Romagna”, protocol number 7043/2021). All participants involved in this study provided written informed consent for both sample collection and data analyses. Detailed clinical information and the analysis methods employed for each sample are reported in Supplementary Table 1. Competing interests: All authors declare no competing interests., (© 2025. The Author(s).)

Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu-cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real-world evidence studies. Notably, beyond established poor prognostic factors-such as blastoid variant and elevated lactate dehydrogenase-Bruton tyrosine-kinase inhibitors (BTKi) refractoriness and platelet count emerged as significant predictors of survival. Specifically, the 1-year overall survival was 56% in BTKi-refractory patients compared to 92% in BTKi-relapsed patients (p = 0.0001). Our study also demonstrated that in-vivo monitoring of brexu-cel expansion is feasible and correlates with progression-free survival and toxicities. Progression-free survival at 1 year was 74% in patients categorized as strong expanders, based on brexu-cel peak concentration, versus 54% in poor expanders (p = 0.02). Furthermore, in-vivo expansion helped identify a high-risk group of non-responders, those with progressive or stable disease at the 90-day post-infusion evaluation (OR = 4.7, 95% CI = 1.1-34, p = 0.04) characterized by dismal outcomes. When integrated with other clinical factors, monitoring brexu-cel expansion could assist in recognizing patients at high risk of early relapse., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Cancer stem cells (CSCs) may be dedifferentiated somatic cells following oncogenic processes, representing a subpopulation of cells able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which may be a main cause of resistance to therapies. It has been shown that the "less differentiated process" may have an impact on tumor plasticity, particularly when non-CSCs may dedifferentiate and become CSC-like. Bidirectional interconversion between CSCs and non-CSCs has been reported in other solid tumors, where the inflammatory stroma promotes cell reprogramming by enhancing Wnt signaling through nuclear factor kappa B activation in association with intracellular signaling, which may induce cells' pluripotency, the oncogenic transformation can be considered another important aspect in the acquisition of "new" development programs with oncogenic features. During cell reprogramming, mutations represent an initial step toward dedifferentiation, in which tumor cells switch from a partially or terminally differentiated stage to a less differentiated stage that is mainly manifested by re-entry into the cell cycle, acquisition of a stem cell-like phenotype, and expression of stem cell markers. This phenomenon typically shows up as a change in the form, function, and pattern of gene and protein expression, and more specifically, in CSCs. This review would highlight the main epigenetic alterations, major signaling pathways and driver mutations in which CSCs, in tumors and specifically, in lung cancer, could be involved, acting as key elements in the differentiation/dedifferentiation process. This would highlight the main molecular mechanisms which need to be considered for more tailored therapies., Competing Interests: Conflict of interest The authors declare that have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to develop a machine learning model to infer OCEAN traits from text., Background: The psycholexical approach allows retrieving information about personality traits from human language. However, it has rarely been applied because of methodological and practical issues that current computational advancements could overcome., Method: Classical taxonomies and a large Yelp corpus were leveraged to learn an embedding for each personality trait. These embeddings were used to train a feedforward neural network for predicting trait values. Their generalization performances have been evaluated through two external validation studies involving experts (N = 11) and laypeople (N = 100) in a discrimination task about the best markers of each trait and polarity., Results: Intrinsic validation of the model yielded excellent results, with R 2 values greater than 0.78. The validation studies showed a high proportion of matches between participants' choices and model predictions, confirming its efficacy in identifying new terms related to the OCEAN traits. The best performance was observed for agreeableness and extraversion, especially for their positive polarities. The model was less efficient in identifying the negative polarity of openness and conscientiousness., Conclusions: This innovative methodology can be considered a "psycholexical approach 2.0," contributing to research in personality and its practical applications in many fields., (© 2024 Wiley Periodicals LLC.)

Background:  Respiratory muscle strength affects pulmonary function after lung resection; however, the role of diaphragm density, an emerging index of muscle quality, remains unexplored. We investigated the role of crural diaphragm density (CDD) in respiratory complications (RC) after video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer., Methods:  A total of 118 patients were retrospectively enrolled between 2015 and 2022. Exclusion criteria were neoadjuvant therapy, thoracic trauma, and previous cardiothoracic and abdominal surgery. Demographic, functional, and radiological data were collected. The CDD in Hounsfield Unit (HU) was defined as the average of the density of the right and left crural diaphragm at the level of the median arcuate ligament on computed tomography axial images. RC included sputum retention, respiratory infections, atelectasis, pneumonia, respiratory failure, and acute respiratory distress syndrome., Results:  The prevalence of postoperative RC was 41% (48 of 118). RC occurred mostly in males (64.6 vs. 44.3%, p  = 0.04), current smokers (41.7 vs. 21.4%, p  = 0.02), a longer surgical procedure (210 vs. 180 minutes, p  = 0.04), and a lower CDD (42.5 vs. 48 HU, p  = 0.05). The optimal cutoff of CDD was 39.75 HU (sensitivity 43%, specificity 82%, accuracy 65%, area under the curve: 0.62, p  = 0.05), slightly above the threshold for reduced muscle mass (<30 HU). By multivariable logistic regression a CDD ≤ 39.75 HU (hazard ratio [HR]: 3.134 [95% confidence interval, CI: 1.111-8.844], p  = 0.03) and current smoking (HR: 2.733 [95% CI: 1.012-7.380], p  = 0.05) were both independent risk factors of postoperative RC., Conclusion:  The CDD seems to be a simple and useful tool for predicting RC after VATS lobectomy, especially among current smokers. Such patients, identified early, could benefit from preoperative functional and nutritional rehabilitation., Competing Interests: None declared., (Thieme. All rights reserved.)

Hippocampal-dependent memory is known to emerge late in ontogeny, and its full development is protracted. Yet the changes in hippocampal neuronal function that underlie this delayed and gradual maturation remain relatively unexplored. To address this gap, we recorded ensembles of CA1 neurons while charting the development of hippocampal-dependent spatial working memory (WM) in rat pups (∼2-4 weeks of age). We found a sharp transition in WM development, with age of inflection varying considerably between individual animals. In parallel with the sudden emergence of WM, hippocampal spatial representations became abruptly task specific, remapping between encoding and retrieval phases of the task. Further, we show how the development of task-phase remapping could partly be explained by changes in place-field size during this developmental period as well as the onset of precise temporal coordination of CA1 excitatory input. Together, these results suggest that a hallmark of hippocampal memory development may be the emergence of contextually specific CA1 representations driven by the maturation of CA1 micro-circuits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : In the last decades, the increasing number of adolescent and young adult (AYA) survivors of breast cancer (BC) has highlighted the cardiotoxic role of cancer therapies, making cardiovascular diseases (CVDs) among the most frequent, although rare, long-term sequalae. Leveraging innovative artificial intelligence (AI) tools and real-world data (RWD), we aimed to develop a causally interpretable model to identify young BC survivors at risk of developing CVDs. Methods : We designed and trained a Bayesian network (BN), an AI model, making use of expert knowledge and data from population-based (1036 patients) and clinical (339 patient) cohorts of female AYA (i.e., aged 18 to 39 years) 1-year survivors of BC, diagnosed in 2009-2019. The performance achieved by the BN model was validated against standard classification metrics, and two clinical applications were proposed. Results: The model showed a very good classification performance and a clear causal semantic. According to the predictions made by the model, focusing on the 25% of AYA BC survivors at higher risk of developing CVDs, we could identify 81% of the patients who would actually develop it. Moreover, a desktop-based app was implemented to calculate the individual patient's risk. Conclusions: In this study, we developed the first causal model for predicting the CVD risk in AYA survivors of BC, also proposing an innovative AI approach that could be useful for all researchers dealing with RWD. The model could be pivotal for clinicians who aim to plan personalized follow-up strategies for AYA BC survivors.

This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs. 89.3%, P = 0.0017) and neurotoxicity (9.9% vs. 32.2%, P < 0.0001) but also superior progression-free survival (PFS) at 1 year (46.5% vs. 34.1%, P = 0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs. 22.7%, P = 0.0059). Differences in overall survival and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, P < 0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients. Significance: The findings of this study on 485 patients with relapsed/refractory large B-cell lymphoma treated with commercial axi-cel and tisa-cel indicate axi-cel's superior PFS after propensity score weighting. The predictive utility of CAR-HEMATOTOX in assessing not only toxicity but also outcomes across both CAR T-cell products may guide future risk-stratified management strategies., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Type-2 Diabetes Mellitus (T2D) is a growing concern worldwide, and family doctors are called to help diabetic patients manage this chronic disease, also with Medical Nutrition Therapy (MNT). However, MNT for Diabetes is usually standardized, while it would be much more effective if tailored to the patient. There is a gap in patient-tailored MNT which, if addressed, could support family doctors in delivering effective recommendations. In this context, decision support systems (DSSs) are valuable tools for physicians to support MNT for T2D patients - as long as DSSs are transparent to humans in their decision-making process. Indeed, the lack of transparency in data-driven DSS might hinder their adoption in clinical practice, thus leaving family physicians to adopt general nutrition guidelines provided by the national healthcare systems., Method: This work presents a prototypical ontology-based clinical Decision Support System (OnT2D- DSS) aimed at assisting general practice doctors in managing T2D patients, specifically in creating a tailored dietary plan, leveraging clinical expert knowledge. OnT2D-DSS exploits clinical expert knowledge formalized as a domain ontology to identify a patient's phenotype and potential comorbidities, providing personalized MNT recommendations for macro- and micro-nutrient intake. The system can be accessed via a prototypical interface., Results: Two preliminary experiments are conducted to assess both the quality and correctness of the inferences provided by the system and the usability and acceptance of the OnT2D-DSS (conducted with nutrition experts and family doctors, respectively)., Conclusions: Overall, the system is deemed accurate by the nutrition experts and valuable by the family doctors, with minor suggestions for future improvements collected during the experiments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)