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Abstract Vitality Forms (VFs) constitute the dynamic essence of human actions, providing insights into how individuals engage in activities. The ability to perceive and express VFs during interpersonal interactions is pivotal for understanding others’ intentions, behaviors, and fostering effective social communication. Despite their ubiquity in all actions, research exploring the role of VFs in neurodivergent conditions related to social and communicative skills, particularly in autism, remains limited. This study aims to investigate the expression of different VFs during the execution of both social and non-social actions in children with an Autism Spectrum Condition (ASC) in comparison to neurotypical children (NT). ASC children and NT children were asked to move a small bottle either towards a target point (non-social context) or moving it towards a receiver (social context) with different VFs specifically neutral, gentle, or rude. Videotaped tasks were subsequently analyzed to study kinematic parameters characterizing VFs. Our results highlighted three main findings: (1) overall, ASC children are able to tune the motor profile of their actions, effectively conveying both gentle and rude VFs; (2) distinct kinematic parameters in the execution of VFs are able to distinguish autistic children from NT children; (3) the social context significantly influences the child’s ability to express positive and negative VFs in autism. Taken together, these findings provide new insights to understand how VFs contribute to the complex dynamics of social communication in neurodivergent autistic children, providing a valuable contribution for future interventions and support strategies.

Atherosclerosis is an inflammatory disease wherein neutrophils play a key role in plaque evolution. We observed that neutrophil CD11b was associated with a higher necrotic core volume in coronary plaques. Since platelets modulate neutrophil function, we explored the influence of neutrophil–platelet conjugates on the cytokine-modulated neutrophil complex CD11b/CD18 and CCR5 receptor expression. In 55 patients [68.53 ± 7.95 years old (mean ± SD); 71% male], neutrophil positivity for CD11b, CD18 and CCR5 was expressed as Relative Fluorescence Intensity (RFI) and taken as a dependent variable. Cytokines and chemokines were assessed by ELISA. Following log-10-based logarithmic transformation, they were used as independent variables in Model 1 of multiple regression together with Body Mass Index and albumin. Model 1 was expanded with the RFI of neutrophil CD41a+ (model 2). The RFI of neutrophil CD41a+ correlated positively and significantly with CD11b, CD18, and CCR5. In Model 2, CCR5 correlated positively only with the RFI of neutrophil CD41a+. Albumin maintained its positive effect on CD11b in both models. These observations indicate the complexity of neutrophil phenotypic modulation in stable CAD. Despite limitations, these findings suggest there is a role played by neutrophil–platelet interaction on the neutrophil cytokine-modulated expression of adhesive and chemotactic receptors.

Abstract Background Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. Methods Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. Results Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. Conclusions In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis.

Purpose: The Instagram site, teacherwhispers, was created as part of a qualitative research project that chronicled the stories and lived experience of preservice and graduate teachers. Since 2020, the purpose of the study was to identify themes connected to the participants' experiences of current trends in education. The intent was to situate the research as a critical interruption into the bigger political discourses surrounding education. The study sought to question why pedagogical practices are increasingly being positioned and located for political and economic reasons and to frame the questions of how we emerge as teachers in specific moments in time. Design/methodology/approach: The methodology employed in the project was ethnographic and narrative-based, representing stories of teachers and teaching. Ethnography as embodiment contributes to an evocative portrayal of the participants' experiences. Teacher stories can be used to progress understandings of schools and schooling and play an important role in reflecting upon and learning from experience. Findings: The selection of posts from teacherwhispers have brought into sharp focus the broad range of difficulties and rewards that are inherent in teaching. The site has been a microcosm of current issues in education. As a problematic and uncomfortable site of public pedagogy, it has been a site for sharing the realities, specificities and challenges of situatedness. The places where teachers work within their respective communities are highly diverse and can be a source of pressure both professionally and personally. Consequently, in the analysis of teacherwhispers, generalisations have been avoided. Research limitations/implications: As a repository of data for research, a public online site has its challenges; research is meant to be generalisable but in teaching each setting is unique and generalisations can be problematic. Sites of public pedagogy for teachers tend to be kaleidoscopic representations: diverse locations, groups, interests and disciplines. They are a stark reminder to be sceptical of accepting the statement, "research tells us" without questioning the positioning and biases that are inherently at play. Practical implications: Practical elements of the project have included navigating a public online space for the dissemination of data. Social implications: Created in the spirit of problematising the methodology of public pedagogy, the online space at the centre of this project eventuated into something of a definition of what can be problematic in defining teachers' spaces of connection. The site was a place where opinions were expressed in confidentiality and that problematised methodology by putting into question what that methodology may be in a public sphere. What came forth as a result of putting methodology at the centre, rather than a definite answer, was unpredictability. Originality/value: The online space has been an original place to display unanalysed data. The willingness to tell stories through an intermediary was juxtaposed by the public readership's unwillingness to engage with the stories, which would have meant exposing their identity. The online space is one that is increasingly relevant in public sharing and communications relating to communities of practice. This research is a critical interruption to the bigger political discourses in education. It questions why pedagogical practices are increasingly politicised. The project has been significant in mapping the stories of emerging educators at a time of unprecedented pedagogical change.

Inductive and capacitive end couplings in the design of combline microwave filters are compared. For instance, a combline microwave cavity filter for the E1 Galileo band (1559–1591 MHz, 2 % fractional bandwidth) is considered. The inductive end coupling is composed of an L-shaped pin in galvanic contact with the end resonator, while the capacitive end coupling is realized by a straight pin parallel to the end resonator's axis. Although both end couplings can realize the desired external quality factor, the capacitive end coupling is easier to manufacture, while the inductive end coupling is less sensitive to the design parameter. An excellent agreement between synthesized (5th-order Chebyshev mask with 0.05 dB ripple) and measured responses is observed for the realized prototype of the filter. The insertion losses at the center frequency are 1.72 and 1.53 dB for the inductive and capacitive end couplings, respectively. The spurious-free ranges are up to 8.23 and 8.92 GHz for inductive and capacitive end couplings, respectively.

Abstract Musculoskeletal disorders challenge significantly the performance of many daily life activities, thus impacting the quality of life. The efficiency of the traditional physical therapy programs is limited by ecological parameters such as intervention duration and frequency, number of caregivers, geographic accessibility, as well as by subjective factors such as patient’s motivation and perseverance in training. The implementation of VR rehabilitation systems may address these limitations, but the technology still needs to be improved and clinically validated. Furthermore, current applications generally lack flexibility and personalization. A VR rehabilitation game simulation is developed, which focuses on the upper-limb movement of reaching, an essential movement involved in numerous daily life activities. Its novelty consists in the integration of a machine learning algorithm, enabling highly adaptive and patient-customized therapeutic intervention. An immersive VR system for the rehabilitation of reaching movement using a bubble popping game is proposed. In the virtual space, the patient is presented with bubbles appearing at different locations and is asked to reach the bubble with the injured limb and pop it. The implementation of a Q-learning algorithm enables the game to adjust the location of the next bubble according to the performance of the patient, represented by his kinematic characteristics. Two test cases simulate the performance of the patient during a training program of 10 days/sessions, in order to validate the effectiveness of the algorithm, demonstrated by the spatial and temporal distribution of the bubbles in each evolving scenario. The results show that the algorithm learns the patient’s capabilities and successfully adapts to them, following the reward policy dictated by the therapist; moreover, the algorithm is highly responsive to kinematic features’ variation, while demanding a reasonable number of iterations. A novel approach for upper limb rehabilitation is presented, making use of immersive VR and reinforcement learning. The simulation suggests that the algorithm offers adaptive capabilities and high flexibility, needed in the comprehensive personalization of a rehabilitation process. Future work will demonstrate the concept in clinical trials.

Copper contamination stemming from copper-based pesticides poses a grave concern in vineyards and orchards, causing toxicity to soil organisms. Here, we present a comprehensive review of global data encompassing copper levels in these soils, coupled with variables such as the age of agricultural establishments, climate, soil organic matter content, soil pH, and farming practices (organic vs. conventional). The results suggest that there are three pivotal determinants driving copper content in vineyard and orchard soils: climate, the age of agricultural establishments, and soil organic matter content. It was impossible to estimate soil pH's effect on soil copper content because of its dependence on precipitation. Copper content in vineyard and orchard soils worldwide follows a direct correlation with precipitation while inversely correlating with aridity (i.e. potential evapotranspiration divided by precipitation). Furthermore, a clear linkage emerges between farm age and increased copper content in soils globally. Intriguingly, the increased soil organic matter content has shown inverse impacts on soil copper levels. These effects of soil properties on soil copper contents were discussed in terms of copper losses from soil via surface runoff. However, no discernible disparities in soil copper content between organic and conventional farming systems were found. This worldwide survey not only underscores the established influence of climate on European vineyards but also sheds novel light on the historical legacy of copper contamination in these landscapes.

Japanese art tradition, contrary to the case of China, is characterized by an efficient and continued, although mostly undocumented, use of smalt from the late 16th century onward. Recent studies have successfully identified this pigment, the cobalt-colored glass that spread throughout the Old Continent during the Renaissance period, as the coloring agent employed for overglaze-blue enameling on Japanese porcelains produced at the kilns of Arita (the porcelain production center of Japan) from the early 1640s until the 20th century. Fragmentary evidence of the use of smalt in Japanese sacred art has also been reported, yet its earliest incorporation into such a type of traditional art form could not be identified. In order to resolve this crucial issue, portable EDXRF was employed for the non-destructive analyses of Japanese porcelains and sacred images bearing blue decoration. Scientific analysis allowed, for the first time ever, to establish a clear timeline of smalt use. Furthermore, this evidence and the literature data both agree, leading to the identification of the origin of the blue material used on both art productions.

In the construction and analysis of a planar Pythagorean–hodograph (PH) quintic curve r(t), t∈[0,1] using the complex representation, it is convenient to invoke a translation/rotation/scaling transformation so r(t) is in canonical form with r(0)=0, r(1)=1 and possesses just two complex degrees of freedom. By choosing two of the five control–polygon legs of a quintic PH curve as these free complex parameters, the remaining three control–polygon legs can be expressed in terms of them and the roots of a quadratic or quartic equation. Consequently, depending on the chosen two control–polygon legs, there exist either two or four distinct quintic PH curves that are consistent with them. A comprehensive analysis of all possible pairs of chosen control polygon legs is developed, and examples are provided to illustrate this control–polygon paradigm for the construction of planar quintic PH curves.

Multiple myeloma (MM), characterized by abnormal proliferation of clonal plasma cells, is an incurable hematological malignancy. Various immunotherapy strategies have emerged as an efficacious approach for the treatment of MM, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cells. Anti-B-cell maturation antigen (BCMA) CAR-T cells have revolutionized the treatment of MM patients with relapsed/refractory disease and their clinical use was approved for the treatment of these patients. Despite this progress, the efficacy of CAR-T cells in MM is limited by the responsiveness of only a part of the treated patients, the relapse of other patients, the cost of the treatment and the diminished response in patients with prior exposure to anti-BCMA targeting agents. Ongoing clinical trials are evaluating the use of CAR-T cells at an earlier stage of MM disease and the use of CAR-T cells targeting other membrane antigens expressed on malignant plasma cells.

IntroductionColorectal cancer (CRC) is the third most incident and the second most lethal malignant tumor. Despite the recognized association between obesity and CRC, further clarification is necessary regarding the lipids that are overexpressed during the development of CRC. In this scenario, the combination of metabolomics and a three-dimensional (3D) co-culture model involving CRC tumor cells and lipids can enhance the knowledge of energy metabolism modifications at the cross-talk between colorectal cancer and adipocytes. This study aimed to screen potential metabolites in the three dimensional (3D) co-culture of CRC and adipocytes by investigating the metabolome composition of this co-culture released into the extracellular space, which is known as the secretome.MethodsPre-adipocyte cells (3T3-L1), human colon carcinoma (HT-29), and the 3D co-culture (3T3-L1 + HT-29) were cultured for the secretome obtention. Then, ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was employed to analyze the metabolomics of each secretome.ResultsOverall, 3.731 molecules were detected independent of the cell culture. When comparing the three cultures, 105 molecules presented a statistically significant difference in abundance between groups. Among these molecules, 16 were identified, with a particular emphasis on six lipids (PG 20:0, octadecenal, 3-Hydroxytetracosanoyl-CoA, 9,10-dihydroxy-octadecenoic acid, palmitoleic acid, and PA 18:4) and one amino acid derivative (acetylglutamic acid), which presented significant scores during the partial least-squares discriminant analysis (PLS-DA).DiscussionAlthough it is too early to determine the possible impact of such molecules in a CRC microenvironment, these results open new avenues for further studies on the energy metabolism at the cross-talk of colorectal cancer adipocytes.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Background: Sports are associated with numerous physiological and psychological benefits. However, it is unclear to what extent adults with congenital heart disease(CHD) participate in sports and whether this is safe. Furthermore, little is known about lifestyle habits in this group. Methods: Consecutive patients diagnosed with atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot and transposition of the great arteries who underwent open-heart surgery during childhood between 1968 and 1980 were included in a longitudinal follow-up study. Patients underwent cardiological investigations every 10 years and completed a questionnaire regarding sports participation in 2011 and in 2021. Results: Of the 2021 cohort(n = 204, mean age:50 years, 46%female), 49% participated in sports. Compared to the general Dutch population they invested less time in sport(female: p = 0.03, male: p = 0.03). Patients participating in sports had better exercise capacity (p

Abstract Background Non-invasive respiratory support (conventional oxygen therapy [COT], non-invasive ventilation [NIV], high-flow nasal oxygen [HFNO], and NIV alternated with HFNO [NIV + HFNO] may reduce the need for invasive mechanical ventilation (IMV) in patients with COVID-19. The outcome of patients treated non-invasively depends on clinical severity at admission. We assessed the need for IMV according to NIV, HFNO, and NIV + HFNO in patients with COVID-19 according to disease severity and evaluated in-hospital survival rates and hospital and intensive care unit (ICU) lengths of stay. Methods This cohort study was conducted using data collected between March 2020 and July 2021. Patients ≥ 18 years admitted to the ICU with a diagnosis of COVID-19 were included. Patients hospitalized for 50% lung damage on chest computed tomography (CT): NIV (13.3%), HFNO (15%), NIV + HFNO (71.6%) (p = 0.038); SpO2/FiO2: NIV (271 [118–365] mmHg), HFNO (317 [254–420] mmHg), NIV + HFNO (229 [102–317] mmHg) (p = 0.001); rate of IMV: NIV (26.1%, p = 0.002), HFNO (22.6%, p = 0.023), NIV + HFNO (46.8%); survival rate: HFNO (83.9%), NIV + HFNO (63.6%) (p = 0.027); ICU length of stay: NIV (8.5 [5–14] days), NIV + HFNO (15 [10–25] days (p

ABSTRACTIL-37 is a member of the IL-1 superfamily exerting anti-inflammatory functions in a number of diseases. Extracellular IL-37 triggers the inhibitory receptor IL-1R8 that is known to regulate different NK cell pathways and functional activities including their anti-tumor effect. However, the effect of IL-37 on human NK cell functions is still to be unveiled. This study aimed to investigate the functional effect of IL-37 in human NK cells activated with IL-15. We found that IL-37 enhanced both NK cell cytotoxic activity against different tumor cell lines and cytokines production. These effects were associated with increased phosphorylation of ERK and NF-Kb. The improved NK cell activity was also strictly related to a time-dependent GSK3β-mediated degradation of IL-1R8. The enhanced activation profile of IL-37 treated NK cells possibly due to IL-1R8 degradation was confirmed by the results with IL-1R8-silenced NK cells. Lastly, in line with these data, through the analysis of the TNM plot database of a large group of patients, IL-37 mRNA expression was found to be significantly lower in colon and skin cancers than in normal tissues. Colon adenocarcinoma and neuroblastoma patients with higher IL-37 mRNA levels had significantly higher overall survival, suggesting that the presence of IL-37 might be considered an independent positive prognostic factor for this tumor. Our results provide novel information on the mechanisms regulating IL-1R8 function in human NK cells, highlighting the IL-37-IL-1R8 axis as a potential new target to improve the anti-tumor immune response.

Blinatumomab, a CD19-CD3 bispecific T cell engager (BiTE), has two recombinant single-chain variable fragments that temporarily link CD3+ T cells and CD19+ B cells, leading to the T cell-mediated lysis of neoplastic B cells. Improved minimal residual disease (MRD)-negative response rates and long-term overall survival have been observed in B-ALL patients who received this drug. These therapeutic successes have led to FDA approval for refractory/relapsed and MRD-positive B-ALL patients. Furthermore, recent studies in newly diagnosed B-ALL patients have led in Philadelphia chromosome-positive patients to the development of chemotherapy-free regimens based on tyrosine kinase inhibitors plus Blinatumomab and in Philadelphia chromosome-negative patients to improvement in outcomes using chemotherapy regimens that have incorporated Blinatumomab in the consolidation phase of treatment.

Multiple myeloma (MM) is a disorder of the monoclonal plasma cells and is the second most common hematologic malignancy. MM initiation and progression are dependent upon complex genomic abnormalities. The current pathogenic model of MM includes two types of primary events, represented by chromosome translocations or chromosome number alterations resulting in hyperdiploidy. These primary molecular events are observed both in MM and in monoclonal gammopathy, its premalignant precursor. Subsequent genetic events allow the progression of monoclonal gammopathy to MM and, together with primary events, contribute to the genetic complexity and heterogeneity of MM. Newer therapies have considerably improved patient outcomes; however, MM remains an incurable disease and most patients experience multiple relapses. The dramatic progresses achieved in the analysis of the heterogeneous molecular features of different MM patients allowed a comprehensive molecular classification of MM and the definition of an individualized prognostic model to predict an individual MM patient’s response to different therapeutic options. Despite these progresses, prognostic models fail to identify a significant proportion of patients destined to early relapse. Treatment strategies are increasingly. Based on disease biology, trials are enriched for high-risk MMs, whose careful definition and categorization requires DNA sequencing studies. Keywords: Multiple Myeloma; Chromosome Abnormalities; Molecular Events; Mutations.

Abstract The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3–6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life. Clinical trial registration: Clinicaltrial.gov (NCT01899352).

Abstract The transcription factors TTF1/NKX2-1 and ΔNp63/p40 are the counterposed molecular markers associated with the main Non-Small Cell Lung Cancer subtypes: TTF1 for adenocarcinoma, p40 for squamous cell carcinoma. Although they generally display a mutually exclusive expression, some exceptions exist simultaneously lacking or (very rarely) expressing both markers, either pattern being associated to poor prognosis. Hence, we quantitatively analyzed the relationship between their coordinated activity and prognosis. By analyzing the respective downstream transcriptional programs of the two genes, we defined a simple quantitative index summarizing the amount of mutual exclusivity between their activities, called Mean Absolute Activity (MAA). Systematic analysis of the MAA index in a dataset of 1018 NSCLC samples replicated on a validation dataset of 275 showed that the loss of imbalance between TTF-1 and p40 corresponds to a steady, progressive reduction in both overall and recurrence-free survival. Coherently, samples correspondent to more balanced activities were enriched for pathways related to increased malignancy and invasiveness. Importantly, multivariate analysis showed that the prognostic significance of the proposed index MAA is independent of other clinical variables including stage, sex, age and smoke exposure. These results hold irrespectively of tumor morphology across NSCLC subtypes, providing a unifying description of different expression patterns.

Fluorene-benzothiadiazole (PFBT), commercially known as F8BT, and fluorene-thiophene (PFT) copolymers were synthesized by the Suzuki-Miyaura coupling polycondensation technique in the presence of a phase transfer catalyst (Aliquat 336). These novel copolymers showed higher molar masses, lower dispersivity, and thermal stability above 400 °C when synthesized under the modified (M) action of Aliquat 336 (F8BT-M). Polymer Light-emitting diodes (PLEDs) were assembled with the novel synthesized copolymers as the emitter layer. For F8BT-M, a maximum luminance of 327 cd/m2 was achieved, while a diode containing just the commercial F8BT resulted in only 210 cd/m2. As for the PFT copolymers, it was observed that for the Aliquat 336 sample synthesized in a 60h extended (E) (PFT-ME), the luminance of the PLED was much higher than that where the reaction time was 48 h (PFT-M), with a luminance of 168 cd/m2 and 54 cd/m2, respectively. Without Aliquat 336, the PFT copolymer did not show an electroluminescent signal. The improved electroluminescence in the copolymers with Aliquat 336 was attributed to the improved synthesis conditions, i.e., reaction time and catalytic system employed. The results suggest that copolymers with luminescent and morphological properties, more suitable for light-emitting devices, might be obtained with simple modifications during synthetic polycondensation reactions.

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). Methods Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. Results The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. Conclusion LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).