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Objective: The aim of this work was to better understand the role of personality as it relates to psychopathology, with satisfaction as a mediating variable. Background: Personality is an important determinant of many life outcomes including relationship satisfaction and psychopathology. Previous work has demonstrated that broad domains of normal personality have low‐to‐moderate associations with various forms of psychopathology. Research has primarily focused on mechanisms that might explain how common personality traits put one at risk for common forms of psychopathology; this work builds upon existing work in examining relationship satisfaction as one possible mechanism. No study to date has examined whether relationship satisfaction mediates the connection between personality and psychopathology. Method: We utilized multilevel modeling in a longitudinal sample of 100 newlywed couples to test the hypothesis that major domains of personality (positive temperament, negative temperament, disinhibition) have a significant effect on relationship satisfaction which, in turn, is significantly associated with internalizing and externalizing forms of psychopathology. Results: We found no evidence for the mediating role of relationship satisfaction; however, in exploratory analyses, we did find evidence for both between‐person and within‐person effects of personality on psychopathology. Conclusions: This study confirms the role of personality as an important factor in consideration of dyadic processes, though not entirely deterministic for downstream functioning. Thus, separate factors in addition to personality may be worth examining in consideration of how low relationship satisfaction may be associated with psychopathology. [ABSTRACT FROM AUTHOR]

Background: To meet the population's needs, community care should be customized and continuous, adequately equipped, and monitored. Introduction: Considering their fragmented and heterogeneous nature, a summary of community healthcare services described in European literature is needed. The aim of this study was to summarize their organizational models, outcomes, nursing contribution to care, and nursing‐related determinants of outcomes. Methods: A systematic review was performed by searching PubMed, CINAHL, Scopus, and Embase in October 2022 and October 2023 (for updated results). Quantitative studies investigating the effects of community care, including nursing contribution, on patient outcomes were included and summarized. Reporting followed the PRISMA checklist. The review protocol was registered on PROSPERO (CRD42022383856). Results: Twenty‐three studies describing six types of community care services were included, which are heterogeneous in terms of target population, country, interventions, organizational characteristics, and investigated outcomes. Heterogeneous services' effects were observed for access to emergency services, satisfaction, and compliance with treatment. Services revealed a potential to reduce rehospitalizations of people with long‐term conditions, frail or older persons, children, and heart failure patients. Models are mainly multidisciplinary and, although staffing and workload may also have an impact on provided care, this was not enough investigated. Discussion: Community health services described in European literature in the last decade are in line with population needs and suggest different suitable models and settings according to different care needs. Community care should be strengthened in health systems, although the influence of staffing, workload, and work environment on nursing care should be investigated by developing new management models. Conclusions and implications for health policy: Community care models are heterogeneous across Europe, and the optimum organizational structure is not clear yet. Future policies should consider the impact of community care on both health and economic outcomes and enhance nursing contributions to care. [ABSTRACT FROM AUTHOR]

Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well‐functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)‐vaccination were retrieved from Staten's Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non‐normal cell samples without timely follow‐up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%–90%. By 2020–2022, the cervical cancer incidence rate in women aged 20–29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one‐time HPV screening, and by 2020–2022, the old‐age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non‐normal cell samples without timely follow‐up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid‐based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30–59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one‐time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion Accurate time perception is crucial to daily life but vulnerable to interference, particularly through negative affect, which dilates individuals' sense of time passing. Regulation strategies like rumination, and disorders like borderline personality disorder (BPD), are linked to time distortion, yet their interrelationships remain untested. We investigated whether rumination and BPD symptoms increase time dilation in negative affective states to understand the clinical implications of time distortion.In an online pilot study, we tested whether negative affect (NA) predicts subjective time perception and explored how rumination, BPD symptoms, and their interaction predicted time perception using a between‐subjects online experimental mood induction. Adult participants (Ncombined = 760) were recruited from Prolific Academic and a large, Midwestern U.S. university.State NA and increased BPD features predicted increased time dilation. The role of trait‐level rumination was nuanced, with individuals low in BPD symptoms and elevated trait rumination exhibiting reduced time dilation in response to NA. Conversely, those with elevated rumination and BPD symptoms reported increased time dilation in the neutral condition.Findings offer foundational evidence of NA and rumination's roles in time dilation for individuals across levels of BPD symptom endorsement. Subsequent replication and extension could flesh out these relationships and inform psychotherapeutic treatment targets. [ABSTRACT FROM AUTHOR]

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen to and carbon dioxide from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow set of parameters that determine gas exchange efficiency and blood flow resistance, principally: fiber packing density, path length, and frontal area. These same parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro‐rods (380 μm diameter) arranged with three packing densities (40%, 50%, and 60%) and two path lengths (2 and 4 cm). Blood was pumped through these devices corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of the fiber bundle enhances deposition upstream, and consequently (3) greater path length provides greater clot‐free fiber surface area for gas exchange than a shorter path length. These results can help guide the design of less thrombogenic, more efficient artificial lung designs. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a questionnaire to evaluate missed nursing care (MNC) in a home care setting. Design: A new instrument was developed and tested performing a preliminary analysis of a multicenter cross‐sectional study in Italy. Reporting was performed according to COnsensus‐based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines. Sample: Eight hundred out of a total of 2549 home care nurses enrolled in AIDOMUS‐IT were considered for the validation of the Missed Nursing Care in Home Care (MNC_HC). Measurements: The MNC_HC instrument was developed by a panel of experts and underwent content and face validation. Exploratory (EFA) and confirmatory factor analyses (CFA) were conducted. Results: EFA revealed a one‐factor solution, explaining 56% of the total variance for MNC_HC. CFA confirmed excellent structural validity, with a one‐factor model showing an exceptional fit (χ2 (27) = 141.39, p <.001, RMSEA = 0.04, SRMR = 0.04, CFI = 0.99, TLI = 0.99, factor loadings > 0.5). MNC_HC also demonstrated high reliability (Cronbach's α = 0.92). The activity with the highest rate of missed care was the documentation of nursing care (77%), while activities related to nursing techniques (e.g., injections, dressings, etc.) were reported to be missed less (33.63%). Conclusions: MNC_HC is a quick‐filling, valid, reliable, and psychometrically sound instrument for measuring MNC in home care useful for future research. [ABSTRACT FROM AUTHOR]

We study the estimation problem of the spectral density function for harmonizable non‐stationary processes. More precisely, we consider spectrally correlated processes whose spectral measure has the support contained in the union of unknown lines with possibly non‐unit slopes. We propose the frequency‐smoothed periodogram along the estimated support line as an estimator of the spectral density function. We show the mean‐square consistency of the proposed estimator. Additionally, we discuss the estimation of the support line in a specific model with its applications in locating a moving source. Finally, we present simulations confirming the proven results. [ABSTRACT FROM AUTHOR]

Therapeutic development for skeletal muscle diseases is challenged by a lack of ex vivo models that recapitulate human muscle physiology. Here, we engineered 3D human skeletal muscle tissue in the Biowire II platform that could be maintained and electrically stimulated long‐term. Increasing differentiation time enhanced myotube formation, modulated myogenic gene expression, and increased twitch and tetanic forces. When we mimicked exercise training by applying chronic electrical stimulation, the "exercised" skeletal muscle tissues showed increased myotube size and a contractility profile, fatigue resistance, and gene expression changes comparable to in vivo models of exercise training. Additionally, tissues also responded with expected physiological changes to known pharmacological treatment. To our knowledge, this is the first evidence of a human engineered 3D skeletal muscle tissue that recapitulates in vivo models of exercise. By recapitulating key features of human skeletal muscle, we demonstrated that the Biowire II platform may be used by the pharmaceutical industry as a model for identifying and optimizing therapeutic drug candidates that modulate skeletal muscle function. [ABSTRACT FROM AUTHOR]

Objective: New indices of dyslipidemia, such as the Atherogenic Index of Plasma (AIP) or Castelli Risk Index I and II (CR‐I/II), have been tested to predict erectile dysfunction (ED). The aim of this study was to assess the role of these lipidic scores in predicting severe ED and erectile function (EF) worsening in patients who underwent robot‐assisted radical prostatectomy (RARP). Methods: Data from 1249 prostate cancer patients who underwent RARP at our single tertiary academic referral center from September 2021 to April 2023 were reviewed. RARP patients with a complete lipid panel were included in the final analysis. Two independent multivariable logistic regression models (LRMs) were fitted to identify predictors of ED severity and worsening in RARP patients. Results: Among the 357 RARP patients, the median age was 70 (interquartile range [IQR]: 65–74), and the median BMI was 28.4 (IQR: 26–30.4). According to the preoperative IIEF5, 115 (32.2%), 86 (24.5%), 26 (7.3%), and 40 (11.2%) were mild, mild‐moderate, moderate, and severe ED patients, respectively. After multivariable LRMs predicting severe ED, only the nerve‐sparing (NS) approach (odds ratio [OR]: 0.09) as well as the preoperative IIEF5 score (OR: 0.32) were independent predictors (p < 0.001). After LRMs predicting EF worsening, only preoperative IIEF5 was an independent predictor (OR: 1.42, p < 0.001). Conclusion: The power of novel lipidic scores in predicting severe ED and EF worsening in RARP patients was low, and they should not be routinely applied as a screening method in this patient subgroup. Only preoperative IIEF5 and nerve‐sparing approaches are relevant in EF prediction after RARP. [ABSTRACT FROM AUTHOR]

Evans syndrome (ES) is rare and mostly treated on a "case‐by‐case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP‐NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work‐up and management. Thirty clinicians who had followed a median of 5 patients (1–45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p <.001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti‐platelets and anti‐neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess COVID‐19‐related gray matter (GM) structural alterations in two distinct groups of patients presenting with the prevailing and distinctive COVID‐19‐related neurological symptoms – isolated olfactory disorders as sole neurological manifestation (COVID‐OD) and cognitive disorders (COVID‐CD) – as compared to a control group of unaffected individuals. Methods: The study included 61 COVID‐CD patients (57 [60–63] years, 62% females), 84 COVID‐OD patients (49 [35–57] years, 60% females), and 17 controls (51 [41–52] years, 41% females). Region‐based morphometry (RBM) and voxel‐based morphometry (VBM) were performed on T1‐weighted MRI scans to assess GM regional volume and voxel‐wise density differences between COVID‐19 patients and controls. Surface‐based morphometry (SBM) was applied to investigate cortical thickness alterations. The statistical models built to assess GM structural differences among groups included total intracranial volume and age as nuisance variables. Results: The multi‐morphometric analysis revealed statistically significant (p < 0.05 corrected for multiple comparisons) reduction in GM regional volumes, in voxel‐wise GM density and in cortical thickness in both COVID‐CD and COVID‐OD patient groups as compared to controls. Across all three analyses, COVID‐CD patients showed more distributed and severe GM loss than COVID‐OD patients. The most prominently affected GM regions in the COVID‐CD group included the hippocampus, putamen, cingulate gyrus, precuneus, precentral and postcentral gyri, amygdala, lingual gyrus, and caudate nucleus. Interpretation: Our MRI findings show that COVID‐19‐related olfactory and cognitive disorders both induce GM atrophy, although at different degrees of severity, likely indicative of neurodegeneration and neuroinflammation. [ABSTRACT FROM AUTHOR]

RTEL1 is an essential DNA helicase which plays an important role in various aspects of genome stability, from telomere metabolism to DNA replication, repair and recombination. RTEL1 has been implicated in a number of genetic diseases and cancer development, including glioma, breast, lung and gastrointestinal tumors. RTEL1 is a FeS helicase but, in addition to the helicase core, it comprises a long C‐terminal region which includes a number of folded domains connected by intrinsically disordered loops and mediates RTEL1 interaction with factors involved in pivotal cellular pathways. However, information on the architecture and the function of this region is still limited. We expressed and purified a variety of fragments encompassing the folded domains and the unstructured regions. We determined the crystal structure of the second repeat, confirming that it has a fold similar to the harmonin homology domains. SAXS data provide low‐resolution information on all the fragments and suggest that the presence of the RING domain affects the overall architecture of the C‐terminal region, making the structure significantly more compact. NMR data provide experimental information on the interaction between PCNA and the RTEL1 C‐terminal region, revealing a putative low‐affinity additional site of interaction. A biochemical analysis shows that the C‐terminal region, in addition to a preference for telomeric RNA and DNA G‐quadruplexes, has a high affinity for R‐loops and D‐loops, consistent with the role played by the RTEL1 helicase in homologous recombination, telomere maintenance and preventing replication‐transcription conflicts. We further dissected the contribution of each domain in binding different substrates. [ABSTRACT FROM AUTHOR]

A retrospective study conducted in Italy analyzed data from 116 patients with severe atopic dermatitis (AD) to determine if the drug upadacitinib could improve symptoms of concomitant allergic rhinitis (AR) or allergic asthma (AA). The study found that after 16 weeks of treatment with upadacitinib, 81.9% of patients achieved a reduction of at least 75% in their AD symptoms, and 56.03% achieved a reduction of at least 90%. Upadacitinib also showed a slight improvement in symptoms of AA and AR. The study suggests that upadacitinib may have a beneficial impact on AA and AR symptoms in patients with severe AD, but further research is needed. [Extracted from the article]

Background: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post‐partum outcomes. Methods: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18–49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. Results: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3–118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2–24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug‐associated risk for adverse pregnancy, congenital, neonatal or post‐partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. Conclusions: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Hand eczema (HE) is a common skin disease with a negative impact on patients' quality of life in occupational and non‐occupational settings. Up‐to‐date, data on HE in Italian patients referred for patch testing are lacking.To characterise the profile in terms of demographics, aetiology and patch test results of Italian patients affected by HE referred for patch testing.A retrospective descriptive study on consecutive patients affected by HE who underwent patch testing from 2016 to 2023 in eight dermatology clinics was performed. HE patients were divided into two groups according to the exclusive (HE‐only group) and not‐exclusive (HE+ group) hand involvement, and compared to patients with eczema localised in body areas other than hands (NHE group).One thousand five hundred and ninety‐seven patients were affected by HE (35.3% males; mean age 42.7 years), 60.2% belonging to the HE‐only group and 39.8% to the HE+ group. Occupational dermatitis was diagnosed in 33.2% of HE‐only patients, 25.0% of HE+ patients and 5.2% of NHE patients (p < 0.001). HE‐only patients presented: Allergic Contact Dermatitis (ACD), Irritant Contact Dermatitis (ICD), atopic HE in 48.1%, 47.5% and 7.1%, respectively; hyperkeratotic palmar, acute recurrent vesicular and nummular clinical subtypes in 52.2%, 43.9% and 11.9%, respectively; relevant positive patch test reactions in 48.1% (nickel sulphate 18.9%, methylchloroisothiazolinone/methylisothiazolinone 10.6%, methylisothiazolinone 8.6%, p‐phenylenediamine 6.0% and potassium dichromate 4.7%).HE patients, and particularly those with exclusive hand involvement, show a particular profile in terms of demographic and clinical characteristics, etiologies and relevant positive patch test reactions. [ABSTRACT FROM AUTHOR]

We described an unusual combination of fibroblastic connective nevus (FCTN) already present at birth with underlying vascular anomalies. Overall, the lesion appeared as a large purplish‐brown mass in the groin region up to the third of the right thigh, with partial spontaneous regression during the first three months of life. The FCTN observed exhibited several unusual characteristics: it was congenital, large in size, and located in the lower limbs. Finally, it represented the first case described in which an FCTN arose in association with vascular anomalies. [ABSTRACT FROM AUTHOR]

Dermatologists' burnout is a growing phenomenon. During the last years, an important role on medical stress is played by the ever‐increasing use of common technological devices (smartphones, smartwatches, PCs and tablets). The aim of the study was to investigate whether digital technology use causes burnout among Italian dermatologists, using a survey conducted among a group of Italian dermatologists. The final sample contained 194 responses valid for analysis. A positive and significant relationship between technostress, assessed through Technostress Inventory and burnout, assessed through Maslach Burnout Inventory, among Italian dermatologists was found. Our data seems suggesting a close relationship between technostress and dermatologist burnout. [ABSTRACT FROM AUTHOR]

The article discusses a case of allergic contact dermatitis in a 14-year-old male patient with Brugada syndrome following the insertion of a subcutaneous implantable cardioverter-defibrillator (ICD). The patient experienced dehiscence of the surgical scar and eczema at the implantation site, leading to the replacement of the ICD with a defibrillator vest. Patch testing revealed a positive reaction to cobalt chloride, prompting the implantation of a new ICD composed of titanium oxide. The authors highlight the importance of considering cardiac device allergy in cases of suspected infection or negative culture results. [Extracted from the article]

INTRODUCTION: We examined the association of long‐term exposure to air pollution and road traffic noise with dementia incidence in the Danish Nurse Cohort. METHODS: Female nurses were followed for dementia incidence (hospital contact or medication prescription) from 1993/1999 to 2020. Air pollution and road traffic noise levels were estimated at nurses' residences, and their associations with dementia were examined using Cox regression models. RESULTS: Of 25,233 nurses 1409 developed dementia. Particulate matter with a diameter of ≤2.5 µm (PM2.5) was associated with dementia incidence, after adjusting for lifestyle, socioeconomic status, and road traffic noise (hazard ratio [95% confidence interval] 1.35 [1.15–1.59] per interquartile range of 2.6 µg/m3). There was no association of PM2.5 with dementia in physically active nurses. Association with road traffic noise diminished after adjusting for PM₂.₅ (1.02 [0.93–1.11] per 7.6 dB). DISCUSSION: Long‐term exposure to air pollution increases risk of dementia, and physical activity may moderate this risk. Highlights: Long‐term exposure to air pollution was associated with increased risk of dementia among female nurses from the Danish Nurse Cohort.Association of air pollution with dementia was independent of road traffic noise.Association of road traffic noise with dementia diminished after adjusting for air pollution.Physical activity moderated adverse effects of air pollution on dementia. [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]

Introduction: Consensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half‐life (SHL) or extended half‐life (EHL); despite this, no universally accepted definition currently exists. One proposed definition includes half‐life, area under the curve, and technology designed to extend half‐life; however, the International Society on Thrombosis and Haemostasis defines activity over time as the most intuitive information for building treatment regimens and the World Federation of Hemophilia describes rFVIII product classification in terms of infusion frequency. Aim: To summarise published data on the clinical and pharmacokinetic criteria used to define rFVIII product classification. Methods: PubMed and EMBASE database searches of English‐language articles (2002–2022) were conducted using search strings to identify the relevant population, intervention, and outcomes (e.g., clinical and pharmacokinetic parameters). Articles then underwent title/abstract and full‐text screens. Results: Among 1147 identified articles, 62 were included. Half‐life was the most widely reported outcome with no clear trends or product groupings observed. No clear groupings emerged among other outcomes, including infusion frequency, consumption, and efficacy. As activity over time was reported in few articles, further investigation of its relevance to rFVIII product classification is warranted. Conclusion: The findings of this systematic literature review suggest that parameters other than half‐life might be important for the development of a comprehensive and clinically relevant rFVIII product classification definition. There seems to be an opportunity to consider parameters that are clinically meaningful and useful for shared decision‐making in haemophilia A treatment. [ABSTRACT FROM AUTHOR]

Background: Eyelid dermatitis is a frequent reason of dermatological consultation. Its aetiology is not univocal, being contact dermatitis, both allergic and irritant, the most frequent. The primary sources of allergen exposure include cosmetics, metals, and topical medications, from direct, indirect, or airborne contact. Objectives: To define the frequency of positive patch test reactions to SIDAPA baseline series allergens, to document positive allergens, and to precise the final diagnosis in patients with eyelid involvement. Methods: A total of 8557 consecutive patients from 12 Italian Dermatology Clinics underwent patch testing with SIDAPA baseline series in 2018 and 2019. Patients were divided into two groups: (i) with eyelid involvement with or without other involved sites (E‐Group) and (ii) without eyelid involvement (NE‐Group). The final diagnosis and the frequency of positive relevant patch test reactions were evaluated. Results: E‐Group consisted of 688 patients (females 78.6%, mean age 45.3 years), 8.0% of 8557 consecutively patch‐tested patients. The final diagnosis in E‐Group was ADC in 42.4%, ICD in 34.2%, and AD in 30.5%. The highest reaction rates were elicited by nickel sulphate and methylchloroisothiazolinone/methylisothiazolinone in both E‐Group and NE‐Group, even if these allergens were significantly more frequently positive in NE‐Group patients than in E‐Group ones. Positive patch test reactions to fragrance Mix II, dimethylaminopropylamine, and sorbitan sesquiolate were significantly more frequent in E‐Group patients than in NE‐Group ones. Conclusions: Eyelid dermatitis is a frequent dermatological complaint. Allergic contact dermatitis is the most frequent diagnosis commonly caused by nickel sulphate, isothiazolinones, and fragrances. The surfactants dimethylaminopropylamine and sorbitan sesquioleate are emerging causes of eyelid allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

In the search for novel, effective inhibitors of High‐Mobility Group Box1 (HMGB1)—a protein involved in various inflammatory and autoimmune diseases as well as in cancer—we herein discovered a set of anti‐HMGB1 G‐quadruplex(G4)‐forming aptamers by using an in vitro selection procedure applied to a doped library of guanine‐rich oligonucleotides. The selected DNA sequences were then studied in a pseudo‐physiological buffer mimicking the extracellular medium, where HMGB1 exerts its pathological activity, using spectroscopic, electrophoretic, and chromatographic techniques. All the oligonucleotides proved to fold into monomeric G4s and in some cases also dimeric species, stable at physiological temperature. Remarkably, the protein preferentially recognized the sequences forming dimeric parallel G4 structures, as evidenced by a properly designed chemiluminescent binding assay which also highlighted a good selectivity of these aptamers for HMGB1. Moreover, all aptamers showed anti‐HMGB1 activity, inhibiting protein‐induced cell migration. The acquired data allowed identifying L12 as the best anti‐HMGB1 aptamer, featured by high thermal and enzymatic stability, no toxicity at least up to 5 μM concentration on healthy cells, along with potent anti‐HMGB1 activity (IC50 ca. 28 nM) and good binding affinity for the protein, thus indicating it as a very promising lead candidate for in vivo studies. [ABSTRACT FROM AUTHOR]

The ability for nuclear magnetic resonance (NMR) spectroscopy to provide quantitative, structurally rich information makes this spectroscopic technique an attractive reaction monitoring tool. The practicality of NMR for this type of analysis has only increased in the recent years with the influx of commercially available benchtop NMR instruments and compatible flow systems. In this study, we aim to compare 19F NMR reaction profiles acquired under both on‐line continuous‐flow and stopped‐flow sampling methods, with modern benchtop NMR instrumentation, and two reaction systems: a homogeneous imination reaction and a biphasic activation of a carboxylic acid to acyl fluoride. Reaction trends with higher data density can be acquired with on‐line continuous‐flow analyses, and this work highlights that representative reaction trends can be acquired without any correction when monitoring resonances with a shorter spin–lattice relaxation time (T1), and with the used flow conditions. On‐line stopped‐flow analyses resulted in representative reaction trends in all cases, including the monitoring of resonances with a long T1, without the need of any correction factors. The benefit of easier data analysis, however, comes with the cost of time, as the fresh reaction solution must be flowed into the NMR system, halted, and time must be provided for spins to become polarized in the instrument's external magnetic field prior to spectral measurement. Results for one of the reactions were additionally compared with the use of a high‐field NMR. [ABSTRACT FROM AUTHOR]

Research exists to support the efficacy of the Interview‐Informed Synthesized Contingency Analysis (IISCA) and skill‐based treatment (SBT) to address problem behavior within a clinical setting. However, limited research is available to support their use in a classroom setting and especially as a tool to avoid the display of problem behavior altogether. In the current study, the IISCA, informed by an open‐ended interview, was conducted with a single participant in the classroom after a prolonged absence from school due to COVID‐19. Results of the IISCA were used to determine the multiple contingencies that were likely to evoke problem behavior upon re‐introduction of academic task demands. A skill‐based treatment was then developed based on these contingencies, which involved teaching the participant functional communication, delay tolerance, and following academic instruction in relevant contexts. After 25 treatment sessions, the participant had acquired and maintained all of these skills, including the ability to functionally communicate, tolerate removal of preferred items, and follow educational instructions within the typical classroom routine. This study shows the applicability of the IISCA and SBT when implemented within the classroom setting and when used to reintroduce educational instruction to an individual with autism after a prolonged break from school. [ABSTRACT FROM AUTHOR]

Northwestward‐propagating North Brazil Current (NBC) Rings are often destroyed upon reaching the Caribbean islands, carrying South Atlantic waters into the North Atlantic gyre and connecting the two branches of the Atlantic Meridional Overturning Circulation. Recent observations of NBC rings reported surface and subsurface cores separated by strong stratification. As independent structures, the subsurface eddies often appeared below—even if not aligned with—the surface rings. Motivated by these findings, this paper investigates the occurrence and consequences of vertical coupling between surface and subsurface NBC rings by applying a simplified theoretical model to a realistic numerical simulation. Eddy tracking in this complex simulation reveals around 1,600 instantaneous observations where eddies overlap. At each observation, we assess the eddies' vertical interaction with a 21 /2‐layer quasi‐geostrophic framework. This interaction boils down to either coupling between the layers or a vertical splitting of the system, depending on eddy strength versus background shear. The effects of coupling include long‐lived eddies that can travel longer distances. These effects are particularly important for the lower layer, where differences between coupled and non‐coupled eddies are striking: about 40% of eddies with coupling travel 500 km, with ∼10% carrying South Atlantic Water up to the Caribbean sea. Without coupling, eddies propagate less than 150 km. During coupling, lower‐layer eddies could be driven by their surface counterparts to move offshore and bypass a topographic choke point, thus leaving the NBC retroflection region. Although still speculative, this idea explains the link between coupling and the increase in both lifetime and distance traveled for these eddies. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique with the ability to acquire both quantitative and structurally insightful data for multiple components in a test sample. This makes NMR spectroscopy a desirable tool to understand, monitor, and optimize chemical transformations. While quantitative NMR (qNMR) approaches relying on internal standards are well‐established, using an absolute external calibration scheme is beneficial for reaction monitoring as resonance overlap complications from an added reference material to the sample can be avoided. Particularly, this type of qNMR technique is of interest with benchtop NMR spectrometers as the likelihood of resonance overlap is only enhanced with the lower magnetic field strengths of the used permanent magnets. The included study describes a simple yet robust methodology to determine concentration conversion factors for NMR systems using single‐ and multi‐analyte linear regression models. This approach is leveraged to investigate a pharmaceutically relevant amide coupling batch reaction. An on‐line stopped‐flow (i.e., interrupted‐flow or paused‐flow) benchtop NMR system was used to monitor both the 1,1′‐carbonyldiimidazole (CDI) promoted acid activation and the amide coupling. The results highlight how quantitative measurements in benchtop NMR systems can provide valuable information and enable analysts to make decisions in real time. [ABSTRACT FROM AUTHOR]

FANCJ, a DNA helicase linked to Fanconi anemia and frequently mutated in cancers, counteracts replication stress by dismantling unconventional DNA secondary structures (such as G-quadruplexes) that occur at the DNA replication fork in certain sequence contexts. However, how FANCJ is recruited to the replisome is unknown. Here, we report that FANCJ directly binds to AND-1 (the vertebrate ortholog of budding yeast Ctf4), a homo-trimeric protein adaptor that connects the CDC45/MCM2-7/GINS replicative DNA helicase with DNA polymerase α and several other factors at DNA replication forks. The interaction between FANCJ and AND-1 requires the integrity of an evolutionarily conserved Ctf4-interacting protein (CIP) box located between the FANCJ helicase motifs IV and V. Disruption of the CIP box significantly reduces FANCJ association with the replisome, causing enhanced DNA damage, decreased replication fork recovery and fork asymmetry in cells unchallenged or treated with Pyridostatin, a G-quadruplex-binder, or Mitomycin C, a DNA inter-strand cross-linking agent. Cancer-relevant FANCJ CIP box variants display reduced AND-1-binding and enhanced DNA damage, a finding that suggests their potential role in cancer predisposition. Synopsis: FANCJ/BRIP1, a DNA helicase counteracting replication stress, is recruited to the DNA replication machinery by directly binding to AND-1. Disruption of the FANCJ/AND-1 interaction causes enhanced DNA damage, replication fork stalling and asymmetry in either unperturbed or stressful conditions. Human FANCJ associates with the DNA replication machinery through an interaction with AND-1 that is mediated by a Ctf4-interacting protein (CIP) box. The FANCJ/AND-1 interaction is important for promoting replication fork progression and suppressing DNA damage. Previously uncharacterized FANCJ CIP box missense mutations, found in cancer patients, reduce AND-1-binding and enhance DNA damage. FANCJ/BRIP1, a DNA helicase counteracting replication stress, is recruited to the DNA replication machinery by directly binding to AND-1. Disruption of the FANCJ/AND-1 interaction causes enhanced DNA damage, replication fork stalling and asymmetry in either unperturbed or stressful conditions. [ABSTRACT FROM AUTHOR]

The cis/trans isomerization of peptidyl‐prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4‐substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4‐thiaproline (Thp) has been shown to bias the ring pucker of Pro, to increase the cis population percentage of model peptides in comparison to Pro, and to diminish the activation energy barrier for the cis/trans isomerization reaction. Despite its intriguing properties, Thp has been seldom incorporated into proteins. Moreover, the impact of Thp on the folding kinetics of globular proteins has never been reported. In this study, we show that upon incorporation of Thp at cisPro76 into the thioredoxin variant Trx1P the half‐life of the refolding reaction decreased from ~2 h to ~35 s. A dramatic acceleration of the refolding rate could be observed also for the protein pseudo wild‐type barstar upon replacement of cisPro48 with Thp. Quantum chemical calculations suggested that the replacement of the CγH2 group by a sulfur atom in the pyrrolidine ring, might lower the barrier for cis/trans rotation due to a weakened peptide bond. The protein variants retained their thermodynamic stability upon incorporation of Thp, while the catalytic and enzymatic activities of the modified Trx1P remained unchanged. Our results show that the Pro isostere Thp might accelerate the rate of the slow refolding reaction for proteins containing cis proline residues in the native state, independent from the local structural environment. [ABSTRACT FROM AUTHOR]

Radar‐based human activity recognition is considered as a competitive solution for the elderly care health monitoring problem, compared to alternative techniques such as cameras and wearable devices. However, raw radar signals are often contaminated with noise, clutter, and other artifacts that significantly impact recognition performance, which highlights the importance of prepossessing techniques that enhance radar data quality and improve classification model accuracy. In this study, two different human activity classification models incorporated with pre‐processing techniques have been proposed. The authors introduce wavelet denoising methods into a cyclostationarity‐based classification model, resulting in a substantial improvement in classification accuracy. To address the limitations of conventional pre‐processing techniques, a deep neural network model called Double Phase Cascaded Denoising and Classification Network (DPDCNet) is proposed, which performs end‐to‐end signal‐level classification and achieves state‐of‐the‐art accuracy. The proposed models significantly reduce false detections and would enable robust activity monitoring for older individuals with radar signals, thereby bringing the system closer to a practical implementation for deployment. [ABSTRACT FROM AUTHOR]

Objective: To assess the reproducibility of ultrasound measurements of fetal biometry using a 'focus point' to assist the acquisition of the relevant plane. Methods: This was a study of 80 women with a singleton non‐anomalous pregnancy who attended University College London Hospital, London, UK, between 18 and 37 weeks' gestation. Planes to measure head circumference (HC), abdominal circumference (AC) and femur length (FL) were obtained four times by two different sonographers with different levels of experience, who were blinded to one another; the first set of images was obtained with reference to a standard image, and the second set of images was obtained using the focus point technique. The focus point was defined as a unique fetal anatomical landmark in each plane (cavum septi pellucidi for HC, two‐thirds of the umbilical vein for AC and one of the two extremities of the diaphysis for FL). Once identified, the focus point was maintained in view while the sonographer rotated the probe along three axes (x, y, z) to acquire the relevant plane. Sonographers were either in training or had > 3000 scans worth of experience. Intra‐ and interobserver reproducibility were assessed using Bland–Altman plots, and absolute values and percentages for mean difference and 95% limits of agreement (LoA) were reported. Results: Overall reproducibility was good, with all 95% LoA < 8%. Reproducibility was improved by use of the focus point compared with the standard technique for both intraobserver comparison (95% LoA, < 4% vs < 6%) and interobserver comparison (95% LoA, < 7% vs < 8%). These findings were independent of sonographer seniority and plane acquired. Conclusions: Reproducibility of fetal biometry assessment is improved with use of the focus point for plane acquisition, regardless of sonographer experience. We propose that this method should be implemented in clinical practice and training programs in fetal biometry. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Investigate cost‐effectiveness of first trimester pre‐eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. Design: Retrospective observational study. Setting: London tertiary hospital. Population: 5957 pregnancies screened for pre‐eclampsia using the National Institute for Health and Care Excellence (NICE) method. Methods: Differences in pregnancy outcomes between those who developed pre‐eclampsia, term pre‐eclampsia and preterm pre‐eclampsia were compared by the Kruskal–Wallis and Chi‐square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. Main outcome measures: Incremental healthcare costs and QALY gained per pregnancy screened. Results: Of 5957 pregnancies, 12.8% and 15.9% were screen‐positive for development of pre‐eclampsia using the NICE and FMF methods, respectively. Of those who were screen‐positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre‐eclampsia, term pre‐eclampsia and preterm pre‐eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre‐eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. Conclusions: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving. [ABSTRACT FROM AUTHOR]

Design and implementation of functional coatings is a topic of active research in a variety of health‐related applications, most of which require wet adhesion. The powerful wet adhesion of mussel byssus proteins rich in DOPA and lysine residues provided a clue to realize that the combination of a catechol and an amine component has a specific role in the interfacial adhesion. From this natural model, polydopamine (PDA)‐based coatings have been developed that result from the oxidative polymerization of dopamine combining the catechol and amine functionalities in the same molecule. Covalent interactions resulting from Michael‐type addition or Schiff‐base formation of the polymeric products from dopamine oxidation as well as non‐covalent π‐stacking and cation‐π interactions exemplify the diverse mode of catechol/amine interplay that have been identified as responsible of the adhesion and cohesion properties of PDA. In the last decade coatings inspired to the same chemistry but using different starting materials have been explored particularly catechols of natural origin and different amine components, while mechanistic studies with model compounds have allowed to rationalize the structural requirements for adhesion and to expand the potential of these functional coatings. [ABSTRACT FROM AUTHOR]

Externally calibrated quantitative nuclear magnetic resonance (NMR) approaches offer practical means to simultaneously evaluate chemical identity and content without the addition of calibrants to the test sample. Despite continuous advances in external calibration over the last few decades, adoption of these approaches has been slower than expected. Variations in NMR tube geometry are a commonly overlooked factor that can have a substantial effect on externally calibrated quantitation methods. In this report, we investigate the extent to which tube‐to‐tube volume variability can affect quantitative NMR outcomes. The results highlight the importance of considering tube quality during the development stages of externally calibrated quantitative methods. In addition, we propose a simple, yet effective volume correction strategy using the residual protonated solvent signal that, based on experiments with mixed NMR tubes of varying quality, alleviates the effect of tube‐to‐tube variability. [ABSTRACT FROM AUTHOR]

Adjuvant immunotherapy (IO) and targeted therapy (TT) have improved relapse‐free survival (RFS) in patients with stage III melanoma, although about 25% of them relapse within a year. However, real‐world data on treatment efficacy and safety as well as management of treatment recurrences are still limited. We retrospectively analyzed 113 patients with stage III melanoma who received at least one cycle of anti‐PD‐1 (nivolumab or pembrolizumab) or dabrafenib + trametinib as adjuvant therapy. Most of patients included into the analyses harbor BRAV600E mutation (66.4%) and had a stage IIIC melanoma (63.7%). Immunotherapy was administered in 48.7% of patients, whereas targeted therapy in 51.3% At data cut‐off, median RFS was not reached with 12‐ and 24‐months RFS of 81% and 64%, respectively. No new adverse events were registered. Thirty patients (26.5%) relapsed, mainly at distant sites. Patient treated with IO recurred mostly during adjuvant treatment (ON‐treatment) while patients treated with TT relapsed at the end of treatment (OFF‐treatment). At relapse, surgery, radiotherapy and systemic therapy were used alone or in combination. Among patients who started a first‐line therapy, an excellent response switching to a different treatment was observed. Real‐world outcomes and safety of adjuvant treatment for resected stage III melanoma appear comparable to clinical trials data. Moreover, management of recurrences depends on type of relapse (loco‐regional vs distant) and timing (during vs OFF treatment). Furthermore, patients who relapse after adjuvant TT respond well to subsequent anti‐PD1 based therapy. [ABSTRACT FROM AUTHOR]

Objective: Extant literature has seldom examined the naturalistic role of reaction to threat on downstream emotional distress while also considering buffers, such as perceived social support, to acute negative mental health outcomes. The present study examined how trauma symptoms, in reaction to a global stressor, predicted increased psychological distress via elevated emotional hostility and whether perceived social support modified such effects. We predicted a priori that increased exposure to trauma would be associated with increased hostility and global psychological distress, but that this path would be attenuated by greater levels of perceived social support, as individuals who report greater support exhibit greater emotional coping. Methods: We recruited 408 adults from a large university in the Midwestern United States to participate in a survey assessing past‐week trauma, hostility, distress, and perceived social support following the initial COVID‐19 lockdown. The survey was conducted in March 2020, directly after strict shelter‐in‐place orders were locally mandated. To test our hypotheses, we employed a moderated mediation analysis approach. Results: Results demonstrate that higher trauma predicted increased hostility, which in turn predicted increased distress, and trauma predicted distress via hostility (an indirect effect). As hypothesized, higher perceived social support attenuated the association between trauma and hostility. Conclusion: Results support a hostile emotional pathway that may increase distress in the context of increased traumatic impact; however, social support likely buffers these effects, particularly in the face of new or novel threats and stressors. Findings suggest broad application for understanding the relation between the introduction of stressors, psychological distress, and social support. [ABSTRACT FROM AUTHOR]

To fulfill their function, pancreatic beta cells require precise nutrient‐sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta‐cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene expression in response to amino acid deprivation. Interestingly, ChIP‐seq analysis showed binding of TFEB to super‐enhancer regions that regulate insulin transcription. Conditional, beta‐cell‐specific, Tfeb‐overexpressing, and Tfeb/Tfe3 double‐KO mice showed severe alteration of insulin transcription, secretion, and glucose tolerance, indicating that TFEB and TFE3 are important physiological mediators of pancreatic function. Our findings reveal a nutrient‐controlled transcriptional mechanism that regulates insulin production, thus playing a key role in glucose homeostasis at both cellular and organismal levels. Synopsis: Pancreatic beta‐cells require precise nutrient‐sensing mechanisms to control insulin production, yet the molecular pathways involved remain poorly understood. Here, genetic work identifies transcription factors TFEB and its homologue TFE3 as novel regulators of beta‐cells and pancreas function in mice, controlling their adaptive response to environmental cues. The subcellular localization and activity of TFEB and TFE3 are modulated by nutrient availability in pancreatic beta cells.TFEB and TFE3 negatively regulate insulin gene expression in response to nutrient deprivation in pancreatic beta cells.Genetic manipulation of TFEB and TFE3 in beta cells affects body weight and glucose tolerance in mice. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x‐ray‐based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic–therapeutic pathways of cancer, cardiology and surgery patients. Objectives: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. Methods: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. Results: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria‐like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. Conclusions: In at least half of patients, delayed‐type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost‐effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative. [ABSTRACT FROM AUTHOR]

Single‐walled carbon nanotubes (SWCNTs) were functionalized with a dopamine derivative in which the amine group was converted to azide (dopamine azide). The direct reaction of SWCNTs and dopamine azide in o‐dichlorobenzene at high temperature (160 °C) led to very highly functionalized CNTs (≈60 wt.%). Surprisingly, despite this high degree of functionalization, Raman spectroscopy detected a low disruption of the π‐network of the carbonaceous support. This finding was justified by the rehybridization from sp3 to sp2 of the sidewall carbon atoms of CNTs involved in the functionalization process. Further characterization by means of different techniques such as X‐ray photoelectron spectroscopy (XPS) analysis and transmission electron microscopy (TEM) allowed to shed some light on the chemical composition and morphology of the obtained material. Moreover, the estimation of the total content of phenolic units and their reducing potential after CNTs functionalization was also assessed using Folin and Ciocalteu and 2,2‐diphenyl‐1‐picryl hydrazide (DPPH) assays. The functionalization of CNTs was exploited to immobilize palladium(II) species that were subsequently reduced with NaBH4 leading to the formation of Pd nanoparticles (NPs). The so obtained hybrid material was used as a recyclable heterogeneous catalyst for the reduction of nitro compounds and the Heck reaction. [ABSTRACT FROM AUTHOR]

The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression‐free survival (PFS) as compared to trifluridine/tipiracil in third‐line therapy in patients with refractory RAS wild‐type (WT) metastatic colorectal cancer (mCRC). With longer follow‐up, final overall survival results and posttreatment subgroup analysis are presented. Sixty‐two patients with refractory RAS WT mCRC were randomly assigned to receive, as third‐line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5‐16.7) in arm A compared to 11.6 months (95% CI 6.3‐17.0) in arm B (HR: 0.96, 95% CI 0.54‐1.71, P =.9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth‐line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44‐6.83) for 17 patients treated with anti‐EGFR rechallenge as compared to 3.0 months (95% CI 1.61‐4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10‐0.85, P =.024). Median OS from the start of fourth‐line treatment was 13.6 months (95% CI 7.2‐20), and 5.1 months (95% CI 1.8‐8.3) for patients treated with anti‐EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11‐0.81, P =.019). Final results of the VELO trial support the role of anti‐EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC. [ABSTRACT FROM AUTHOR]

Objective: This study aims to create a synthetic laryngeal microsurgery simulation model and training program; to assess its face, content, and construct validity; and to review the available phonomicrosurgery simulation models in the literature. Study Design: Nonrandomly assigned control study. Setting: Simulation training course for the otolaryngology residency program at Pontificia Universidad Católica de Chile. Methods: Resident (postgraduate year 1 [PGY1]/PGY2) and expert groups were recruited. A laryngeal microsurgery synthetic model was developed. Nine tasks were designed and assessed through a set of programmed exercises with increasing difficulty, to fulfill 5 surgical competencies. Imperial College Surgical Assessment Device sensors applied to the participants' hands measured time and movements. The activities were video‐recorded and blindly assessed by 2 laryngologists using a specific and global rating scale (SRS and GRS). A 5‐point Likert survey assessing validity was completed by experts. Results: Eighteen participants were recruited (14 residents and 4 experts). Experts performed significantly better than residents in the SRS (p =.003), and GRS (p =.004). Internal consistency was demonstrated for the SRS (α =.972, p <.001). Experts had a shorter execution time (p =.007), and path length with the right hand (p =.04). The left hand did not show significant differences. The survey assessing validity resulted in a median 36 out of 40 points score for face validity; and 43 out of 45 points score, for global content validity. The literature review revealed 20 available phonomicrosurgery simulation models, only 6 with construct validity. Conclusion: The face, content, and construct validity of the laryngeal microsurgery simulation training program were established. It could be replicated and incorporated into residents' curricula. [ABSTRACT FROM AUTHOR]

The article discusses the challenges of treating atopic dermatitis (AD) in patients with severe comorbidities, such as cancer, due to limitations with traditional systemic drugs and JAK inhibitors. It highlights a case study of a 47-year-old man with AD and metastatic renal cell carcinoma successfully treated with dupilumab, suggesting its safety in patients with malignancies. Real-life data from various studies confirm the efficacy and safety of dupilumab in patients with a history of cancer, although further research with larger cohorts is needed to validate these findings. [Extracted from the article]