Search

Aim: To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico‐ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses. Methods: We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided. Results: Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch‐up growth. The remaining six patients exhibited spontaneous catch‐up growth. Conclusion: FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases. [ABSTRACT FROM AUTHOR]

Summary: Background: The diagnosis of monogenic obesity is burdened by frequent variants of uncertain significance (VUS). We describe our real‐life approach of variant reassessment over time and we assess whether inconclusive variants are decreasing in monogenic obesity. Methods: We tested for monogenic obesity (genes: LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in 101 children/adolescents (11.7 [7.3–13.7] years, 3.6 [3.3–4.0] z‐BMI) in Verona and 183 (11.3 [8.4–12.2] years, 3.2 [2.7–3.9] z‐BMI) in Naples from January 2020 to February 2023. In March–July 2024 we reassessed the baseline variants by updated software interpretation and literature renavigation. Results: We initially found 20 VUS, 4 Likely Pathogenic (LP), 5 Likely Benign (LB) and 1 benign variant in 33 individuals. At follow‐up, 6 VUS were reclassified as benign/LB, one LP as pathogenic and 3 LB as benign. Overall, 10/30 variants (6/18 in Verona, 3/11 in Naples and a variant found in both centres) were reclassified, leading to a less uncertain report for 13 of 33 variant‐carrying patients. Monogenic obesity was diagnosed in 3 probands in Verona and 4 in Naples, carrying variants at MC4R or NTRK2. Conclusion: Our variant reassessment was effective to improve classification certainty for the 39% of patients and suggested that the molecular diagnosis of monogenic obesity is becoming more accurate over time. [ABSTRACT FROM AUTHOR]

Background Study Design Endpoints Patients and Methods Trial Registration A second transurethral resection of bladder tumour (Re‐TURBT) is recommended by European Association of Urology (EAU) Guidelines on non‐muscle‐invasive bladder cancers (NMIBCs) due to the risk of understaging and/or persistent disease following the primary resection. However, in many cases this may be unnecessary, potentially harmful, and significantly expensive constituting overtreatment. The CUT‐less trial aims to combine the preoperative staging accuracy of Vesical Imaging‐Reporting and Data System (VI‐RADS) and the intraoperative enhanced ability of photodynamic diagnosis (PDD) to overcome the primary TURBT pitfalls thus potentially re‐defining criteria for Re‐TURBT indications.Single‐centre, non‐inferiority, phase IV, open‐label, randomised controlled trial with 1:1 ratio.The primary endpoint is short‐term BC recurrence between the study arms to assess whether patients preoperatively categorised as VI‐RADS Score 1 and/or Score 2 (i.e., very‐low and low likelihood of MIBC) could safely avoid Re‐TURBT by undergoing primary PDD‐TURBT. Secondary endpoints include mid‐ and long‐term BC recurrences and progression (i–ii). Also, health‐related quality of life (HRQoL) outcomes (iii) and health‐economic cost–benefit analysis (iv) will be performed.All patients will undergo preoperative Multiparametric Magnetic Resonance Imaging of the bladder with VI‐RADS score determination. A total of 327 patients with intermediate‐/high‐risk NMIBCs, candidate for Re‐TURBT according to EAU Guidelines, will be enrolled over a 3‐year period. Participants will be randomised (1:1 ratio) to either standard of care (SoC), comprising primary white‐light (WL) TURBT followed by second WL Re‐TURBT; or the Experimental arm, comprising primary PDD‐TURBT and omitting Re‐TURBT. Both groups will receive adjuvant intravesical therapy and surveillance according to risk‐adjusted schedules. Measure of the primary outcome will be the relative proportion of BC recurrences between the SoC and Experimental arms within 4.5 months (i.e., any ‘early’ recurrence detected at first follow‐up cystoscopy). Secondary outcomes measures will be the relative proportion of late BC recurrences and/or BC progression detected after 4.5 months follow‐up. Additionally, we will compute the HRQoL variation from NMIBC questionnaires modelled over a patient lifetime horizon and the health‐economic analyses including a short‐term cost–benefit assessment of incremental costs per Re‐TURBT avoided and a longer‐term cost‐utility per quality‐adjusted life year gained using 2‐year clinical outcomes to drive a lifetime model across the two arms of treatment.ClinicalTrial.gov identifier (ID): NCT05962541; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) ID: 2023‐507307‐64‐00. [ABSTRACT FROM AUTHOR]

The article discusses the use of [18F]‐florbetaben PET/CT imaging as a sensitive diagnostic tool for cardiac AL amyloidosis, a haematological disease characterized by amyloid insoluble fibrils deposition in various organs. The study aimed to explore the sensitivity of this imaging technique compared to traditional diagnostic methods in a cohort of 33 patients. Results showed that [18F]‐florbetaben PET/CT was effective in detecting amyloid deposits in various tissues, suggesting its potential as a non-invasive tool for diagnosing AL amyloidosis. The study highlights the importance of early detection in improving patient outcomes and suggests further research to confirm the efficacy of this imaging technique. [Extracted from the article]

Senescent cells produce a Senescence‐Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin‐6 (IL‐6), has the potential to amplify cellular senescence in the SASP‐producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear. We found that the senescence action does not involve IL‐6 secretion nor the interaction with the receptor expressed in the membrane but is amplified through an intracrine mechanism. IL‐6 sustains intracrine senescence interacting with the intracellular IL‐6 receptor located in anterograde traffic specialized structures, with cytosolic DNA, cGAS‐STING, and NFκB activation. This pathway triggered by intracellular IL‐6 significantly contributes to cell‐autonomous induction of senescence and impacts in tumor growth control. Inactivation of IL‐6 in somatotrophic senescent cells transforms them into strongly tumorigenic in NOD/SCID mice, while re‐expression of IL‐6 restores senescence control of tumor growth. The intracrine senescent IL‐6 pathway is further evidenced in three human cellular models of therapy‐induced senescence. The compartmentalization of the intracellular signaling, in contrast to the paracrine tumorigenic action, provides a pathway for IL‐6 to sustain cell‐autonomous senescent cells, driving the SASP, and opens new avenues for clinical consideration to senescence‐based therapies. [ABSTRACT FROM AUTHOR]

This study provides a comprehensive understanding of the factors influencing Italian consumers' choice of biodegradable and compostable packaging by using a hybrid framework that integrates the theory of planned behaviour with a discrete choice experiment. By analysing the interplay between internal and external factors and rational consumer evaluations, the research clarifies that consumers' choices can be explained by a combination of economic and psychological models, offering a more accurate representation of the driving forces behind consumer decisions. Applying latent class analysis, we identify consumer segments based on packaging preferences for packaged salad, knowledge of waste disposal rules and the psychological characteristics of a statistically representative sample of Italian consumers. The integration of a comprehensive behavioural model allows for the identification of psychological determinants that influence consumer behaviour, outlining detailed profiles of both early adopters and those most opposed to this technology. This research contributes to the literature on sustainable packaging and offers insights to marketers and policymakers for promoting the adoption of sustainable packaging. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders. [ABSTRACT FROM AUTHOR]

Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network‐based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network‐based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data‐driven approaches for the hazard assessment of nanomaterials and other advanced materials. [ABSTRACT FROM AUTHOR]

Aim: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. Methods: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Results: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8–15.2; p = 9.4e‐09) and neutrophils levels (OR = 1.13; 95%CI: 1.08–1.2; p = 6.8e‐07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7–6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. Conclusion: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR. [ABSTRACT FROM AUTHOR]

Aim: Paediatric eosinophilia is a common clinical dilemma, often leading to resource‐ and time‐consuming assessments. We aim to evaluate the main aetiologies of eosinophilia in children from different socioeconomic settings and propose a diagnostic algorithm. Methods: A systematic literature review was conducted through PubMed, Embase and the Cochrane Library. Studies published from January 2012 to June 2023 reporting the incidence and aetiology of peripheral eosinophilia in children were included. Evidence from studies on children originating from low‐ or high‐income countries was compared. Results: A total of 15 observational studies, encompassing 3409 children, were included. The causes of eosinophilia varied based on the children's origin and the eosinophilia severity. In children from high‐income countries, allergic diseases were the leading cause, with a prevalence of 7.7%–78.2%, while parasitosis ranged from 1.0% to 9.1%. In children from low‐income countries, parasitosis was predominant, ranging from 17.7% to 88.3%, although allergic diseases were found in 2.5%–4.8% of cases. Concerning severity, allergic diseases were the leading cause of mild‐to‐moderate eosinophilia; parasitosis was associated with moderate‐to‐severe eosinophilia, while immunological disorders were mostly found in severe cases. Conclusion: We developed a step‐up diagnostic algorithm that considers the child's origin and eosinophilia severity and could optimise resource allocation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti‐inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long‐term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL‐4 receptor α‐subunit (IL‐4Rα), antagonizing both IL‐4 and IL‐13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life. [ABSTRACT FROM AUTHOR]

Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti‐amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment. [ABSTRACT FROM AUTHOR]

The relationship between agriculture and wildlife can be both synergetic and challenging, as the increased surface of agricultural land makes it increasingly important for agriculture and wildlife to coexist. This study aims to describe the use of freshly drilled dry bean fields by birds and mammals in Brazilian Cerrado and Atlantic Forest sites and their diversity and abundance within in‐crop and off‐crop areas (with native permanent vegetation and other surrounding crop fields) at four different farms. A comprehensive survey was conducted, using various sampling methods, including point counts, foraging counts, trail cameras, and occasional encounters. In all, contacts for 12 518 birds across 306 species and 313 mammals across 34 species were registered. The off‐crop areas exhibited greater species richness, abundance, and diversity than the in‐crop areas on all farms. For birds, 47 species were recorded in‐crop, of which 15 were classified as insectivores, 15 as granivores, seven as omnivores, seven as carnivores, and three as frugivores. The number of in‐crop observations per species was small. The abundance off‐crop was greater for 31 species observed in‐crop, indicating that dry bean fields are probably not a preferred habitat for those species. Species classified as granivorous are most likely to feed on dry bean seeds. However, almost all granivorous species observed in‐crop areas are too small to be able to feed on dry bean seeds. For mammals, nine species were recorded in‐crop, of which four were classified as carnivores, three as omnivores, one as insectivore, and one as granivore. Additionally, despite the considerable effort in this study, no evidence was found that birds and mammals feed on dry bean seeds. The results highlight the importance of off‐crop areas in dry bean fields, characterized by a more diverse and abundant bird community than in‐crop. Integr Environ Assess Manag 2024;20:864–874. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: Off‐crop areas exhibited greater species richness, abundance, and diversity than the in‐crop areas.Dry bean fields are generally unattractive habitats for birds and mammals.Almost all species observed in dry bean fields were either not granivorous or too small to feed on dry bean seeds.Studies such as this can be used as refinements for risk assessment of plant protection products for birds and mammals. [ABSTRACT FROM AUTHOR]

High‐density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A‐I (ApoA‐I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA‐I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA‐I proteins with functional/structural features similar to those of amyloidogenic variants hold potential as a promising therapeutic approach. Here we explored the effect of protein cargo and lipid composition on the function of rHDL containing one of the ApoA‐I amyloidogenic variants G26R or L174S by Fourier transformed infrared spectroscopy and neutron reflectometry. Moreover, small‐angle x‐ray scattering uncovered the structural and functional differences between rHDL particles, which could help to comprehend higher cholesterol efflux activity and apparent lower phospholipid (PL) affinity. Our findings indicate distinct trends in lipid exchange (removal vs. deposition) capacities of various rHDL particles, with the rHDL containing the ApoA‐I amyloidogenic variants showing a markedly lower ability to remove lipids from artificial membranes compared to the rHDL containing the native protein. This effect strongly depends on the level of PL unsaturation and on the particles' ultrastructure. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid–protein interactions and their behavior. [ABSTRACT FROM AUTHOR]

Considering the ongoing, record‐setting migration in the Global South, this paper explores the values, principles and ethical tensions of Venezuelan migrants in the informal economy of Colombia. We found that migrants frequently prefer to stay within the informal economy as a way of preserving their identities, values and principles, rather than adopting those of their new country. This choice sets up ethical tensions for the migrants and their host countries. Our analysis challenges the current policy goals of transitioning migrants from informal to formal economies as a mark of success and inclusion. Instead, we attempt to recognize the migrant voice and their agency capacity through our research using focus groups and applied thematic analysis (ATA) of popular music and narratives. Our findings broaden the understanding of why migrants choose to stay in the informal economy and challenge policy goals that focus on inclusion and integration of migrants into formal economy. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have shown that lung ultrasound‐assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). Methods and results: All patients referred for suspicion of PAH in a tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work‐up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B‐lines using an 8‐site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53 ± 13 years; 71% female). World Health Organization functional classes I, II, and III were found in 2%, 52%, and 46% of them, respectively. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was 377 pg/ml (interquartile range [IQR] 218–906). B‐lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR 1–5]. At univariable analysis, B‐lines were positively correlated with male sex, age, NT‐proBNP, systolic pulmonary artery pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end‐diastolic volume and tricuspid annular plane systolic excursion (TAPSE), and negatively with cardiac output and stroke volume. At multivariable analysis, RAP (p < 0.001), TAPSE/sPAP (p = 0.001), and NT‐proBNP (p = 0.04) were independent predictors of B‐lines. Conclusion: Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricular to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow. [ABSTRACT FROM AUTHOR]

Summary: First‐line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long‐lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression‐free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine. [ABSTRACT FROM AUTHOR]

Background: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri‐operative safety and efficacy profile, but scarce data exist on long‐term follow‐up. Objectives: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5‐year follow‐up. Materials and methods: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan–Meier method was used to analyze IPP survival (defined as a working IPP). Results: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61−70) were included. The median (IQR) follow‐up duration was 71 months (63−80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4−96.6), 92.5% (95% CI, 89.7−95.3), and 92.5% (95% CI, 89.7−95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow‐up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19−23), personal 16 (15−18), relational 14 (12−15), and social 12 (11−14). Discussion and conclusion: This study represents the longest follow‐up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid‐term evaluation. [ABSTRACT FROM AUTHOR]

Objective: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node‐positive (cN+) bladder cancer (BCa). Patients and Methods: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin‐based peri‐operative chemotherapy for cTany N1‐3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence‐free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity‐score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. Results: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4–16) months, and median (IQR) follow‐up of alive patients was 30 (13–51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70–1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60–1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. Conclusion: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach. [ABSTRACT FROM AUTHOR]

Background: IgE antibodies to cross‐reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen‐specific IgE tests in vitro. Their prevalence and levels have been so far cross‐sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. Methods: We examined CCD with a cross‐sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN‐PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin‐coated paramagnetic microparticles (NOVEOS, HYCOR, USA). Results: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre‐school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. Conclusions: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD‐sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen‐specific, T‐B cell cognate interaction. [ABSTRACT FROM AUTHOR]

The present study seeks to shed further light on what favors the conversion of inventions into innovations in for‐profit firms and to advance our understanding of how to tackle cancer grand challenges (CGCs). Specifically, following the literature on knowledge search and recombination, we analyze whether and how cancer‐related inventions developed through an intense adoption of scientific knowledge (scientific search intensity) result in (i) a higher number of approved drugs and (ii) a shorter approval time for new drugs. Notably, while the role of science with regard to technological development has been widely studied, the extent to which science‐based solutions relate to new product introduction, especially in terms of coping with grand challenges such as approved cancer drugs, is less known. Furthermore, considering the digitization of (health) R&D and the role of information and communication technologies (i.e., digital technologies) to address grand challenges, we examine whether and how cancer‐related inventions developed through an intense adoption of digital knowledge (digital search intensity) directly affect the extent and speed of cancer drug approval, as well as whether interaction effects between scientific and digital search intensity exist. We develop hypotheses that we test on a sample of 65,861 cancer‐related patents owned by 139 for‐profit firms, collected from the USPTO Cancer Moonshot Patent Data. These have a priority date between 1990 and 2010, and have led to 1035 approved drugs. Results reveal that scientific search intensity is not associated with the number of different drugs developed from a single cancer‐related invention but is associated with the speed at which the invention leads to a newly approved drug. Digital search intensity appears not to directly affect cancer drug approval, but it lessens the effects of scientific search intensity, thus pointing to a limit of digitization in cancer R&D and innovation processes. [ABSTRACT FROM AUTHOR]

This article discusses the evaluation of routine molecular biology for the diagnosis of primary syphilis by assessing the serological status of patients with PCR-confirmed syphilitic ulcers. The study found that PCR analysis on lesions led to the diagnosis of primary syphilis in 64% of patients when serology was defective. This highlights the usefulness of PCR in detecting primary syphilis, especially in populations at risk of multiple reinfections or where follow-up is challenging. The article provides detailed clinical and epidemiological characteristics of patients with primary syphilis and emphasizes the importance of early detection for appropriate treatment and reducing transmission. [Extracted from the article]

The article discusses recent legislative amendments in Brazil regarding pesticide registration. The new law now requires the inclusion of pesticide risk assessments, encompassing both human and environmental assessments, in the dossier submission process. This regulatory update brings Brazil closer to the regulatory frameworks of more established systems, such as those in Europe and the United States. The article highlights the challenges and efforts involved in implementing new environmental risk assessment guidelines for various ecological compartments. It emphasizes the need for collaboration between regulatory agencies, academia, and the agricultural sector to address knowledge gaps and develop a tiered approach to risk assessment that considers the local reality while protecting the environment and supporting Brazilian agriculture. [Extracted from the article]

Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta‐analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease‐free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta‐analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub‐analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits. [ABSTRACT FROM AUTHOR]

A round‐robin study has been carried out to estimate the impact of the human element in small‐angle scattering data analysis. Four corrected datasets were provided to participants ready for analysis. All datasets were measured on samples containing spherical scatterers, with two datasets in dilute dispersions and two from powders. Most of the 46 participants correctly identified the number of populations in the dilute dispersions, with half of the population mean entries within 1.5% and half of the population width entries within 40%. Due to the added complexity of the structure factor, far fewer people submitted answers on the powder datasets. For those that did, half of the entries for the means and widths were within 44 and 86%, respectively. This round‐robin experiment highlights several causes for the discrepancies, for which solutions are proposed. [ABSTRACT FROM AUTHOR]

Summary: Here we evaluated the epigenomic and transcriptomic profile of XPO1 mutant chronic lymphocytic leukaemia (CLL) and their clinical phenotype. By ATAC‐seq, chromatin regions that were more accessible in XPO1 mutated CLL were enriched of binding sites for transcription factors regulated by pathways emanating from the B‐cell receptor (BCR), including NF‐κB signalling, p38‐JNK and RAS‐RAF‐MEK‐ERK. XPO1 mutant CLL, consistent with the chromatin accessibility changes, were enriched with transcriptomic features associated with BCR and cytokine signalling. By combining epigenomic and transcriptomic data, MIR155HG, the host gene of miR‐155, and MYB, the transcription factor that positively regulates MIR155HG, were upregulated by RNA‐seq and their promoters were more accessible by ATAC‐seq. To evaluate the clinical impact of XPO1 mutations, we investigated a total of 957 early‐stage CLL subdivided into 3 independent cohorts (N = 276, N = 286 and N = 395). Next‐generation sequencing analysis identified XPO1 mutations as a novel predictor of shorter time to first treatment (TTFT) in all cohorts. Notably, XPO1 mutations maintained their prognostic value independent of the immunoglobulin heavy chain variable status and early‐stage prognostic models. These data suggest that XPO1 mutations, conceivably through increased miR‐155 levels, may enhance BCR signalling leading to higher proliferation and shorter TTFT in early‐stage CLL. [ABSTRACT FROM AUTHOR]

The article discusses the identification of salivary immunoinflammatory proteins that can help diagnose children with eosinophilic esophagitis (EoE). The study found that inflammatory cytokines, including interleukin-17, correlated with the severity of esophageal mucosal involvement, but not with peak eosinophil count. The research suggests that EoE pathophysiology involves more than just eosinophils, highlighting the need for a multidimensional assessment in disease monitoring and management. Additionally, IL-17 may play a role in EoE pathogenesis, but further studies are needed to confirm its utility as a noninvasive biomarker. [Extracted from the article]

Objective: Leptin plays a key role in the regulation of body weight and other endocrine systems. Recently, impairment of leptin gene transcription due to genetic variations in a long noncoding RNA (lncOb) has been described. This retrospective study aims to characterize the clinical and metabolic phenotype of children and adolescents with obesity who were homozygous for the lncOb rs10487505 leptin lowering allele. Methods: Enrolled children underwent an anthropometrical evaluation, biochemical assessment, and genotyping for lncOb rs10487505. Plasma leptin levels were assessed in 150 participants. A total of 434 patients were included and divided into two groups according to rs10487505 recessive inheritance (CC vs. GG/GC). Results: Children who were homozygous for the C allele showed higher fasting insulin (p = 0.01), homeostasis model assessment of insulin resistance (p = 0.01), lower whole‐body insulin sensitivity index (p = 0.02), and lower disposition index (p = 0.03). Moreover, CC patients presented with a higher prevalence of prediabetes (9.3% vs. 3.4%, p = 0.04) and a 2.9‐fold (95% CI: 1.1–7.9, p = 0.04) higher risk of prediabetes compared with G‐carriers independently from confounders. Leptin plasma levels were significantly lower in the CC group (p = 0.002). Hormone levels correlated with BMI z score (r = 0.19, p = 0.04), fasting insulin (r = −0.34, p < 0.0001), homeostasis model assessment of insulin resistance (r = −0.33, p < 0.0001), and disposition index (r = 0.20, p = 0.04). Conclusions: The lncOb rs10487505 polymorphism affects leptin circulating levels, worsens insulin resistance, and heightens the risk of prediabetes in children and adolescents with obesity. [ABSTRACT FROM AUTHOR]

Summary: We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low‐risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%). The concordance rate between FISH and GM was 87.4%. Discordant results between cytogenetic banding analysis (CBA) and GM were observed in 45/119 cases (37.8%) and were mainly due to the intrinsic characteristics of each technique. The presence of additional lesions by GM was associated with age > 65 years (p = 0.047), advanced Binet stage (p = 0.001), CLL‐IPI score (p < 0.001), a complex karyotype (p = 0.004) and a worse time‐to‐first treatment in multivariate analysis (p = 0.009). Additional lesions by GM were also significantly associated with a worse time‐to‐first treatment in the subset of patients with wild‐type TP53 and mutated IGHV (p = 0.025). In CLL patients with low‐risk features, the presence of additional lesions identified by GM helps to identify a subset of patients with a worse outcome that could be proposed for a risk‐adapted follow‐up and for early treatment including targeted agents within clinical trials. [ABSTRACT FROM AUTHOR]

The operation of a dissipative network composed of two or three different crown‐ether receptors and an alkali metal cation can be temporally driven by the use (combined or not) of two orthogonal stimuli of a different nature. More specifically, irradiation with light at a proper wavelength and/or addition of an activated carboxylic acid, are used to modulate the binding capability of the above crown‐ethers towards the metal ion, allowing to control over time the occupancy of the metal cation in the crown‐ether moiety of a given ligand. Thus, application of either or both of the stimuli to an initially equilibrated system, where the metal cation is distributed among the crown‐ether receptors depending on the different affinities, causes a programmable change in the receptor occupancies. Consequently, the system is induced to evolve to one or more out‐of‐equilibrium states with different distributions of the metal cation among the different receptors. When the fuel is exhausted or/and the irradiation interrupted, the system reversibly and autonomously goes back to the initial equilibrium state. Such results may contribute to the achievement of new dissipative systems that, taking advantage of multiple and orthogonal stimuli, are featured with more sophisticated operating mechanisms and time programmability. [ABSTRACT FROM AUTHOR]

COVID19 in patients affected by lymphoma represents an important challenge because of the higher mortality rate. Anti‐SARS‐CoV‐2 monoclonal antibodies (anti‐S MoAbs) appear promising in this setting. We report a monocentric retrospective study including 176 patients affected by lymphoma which developed SARS‐CoV‐2 infection since the start of COVID19 pandemic. Overall, mortality was 13.1%, with a decreasing trend between first waves to the last wave of pandemic (18.5% vs. 9.4%, p 0.076). Patients receiving anti‐S MoAbs (41.3%) showed inferior mortality rate (overall survival, OS 93.2% vs. 82.7%, p 0.025) with no serious toxicity, reduced documented pneumonia (26% vs. 33%, p 0.005), and reduced need of oxygen support (14.5% vs. 35.7%, p 0.003). Among patients who received 3 doses of vaccine, the employment of anti‐COVID MoAbs showed a trend of superior survival versus those who did not receive Anti‐S MoAbs (OS rates 97.3% vs. 84.2%, p 0.064). On multivariate analysis, active haematological disease (OS 72% (HR 2.49 CI 1.00–6.41), bendamustine exposure (OS 60% HR 4.2 CI 1.69–10.45) and at least one comorbidity (HR 6.53 CI 1.88–22.60) were independent prognostic factors for death. Our study confirms the adverse prognostic role of COVID‐19 in lymphoma patients in presence of active disease, comorbidities and previous exposure to bendamustine. In our experience, anti‐S MoAbs represented a therapeutic option in vaccinated patients. [ABSTRACT FROM AUTHOR]

The I EGR2 i gene, coding for a transcription factor that also mediates the I TP53 i dependent apoptotic pathway, was found to be mutated in 3 patients (8.6%), and further stratifies the outcome of low-risk patients. Long-term benefit of IGHV mutated patients in a real-life multicenter cohort of FCR-treated chronic lymphocytic leukemia Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. [Extracted from the article]

Background. Allergy toward the dust mite is steadily increasing on the European continent. This sensitization may be a risk factor for developing sensitization to other mite molecules such as tropomyosin Der p 10. This molecule often correlates with food allergy and the risk of anaphylaxis after ingesting mollusks and shrimps. Materials and Methods. We analyzed the sensitization profiles by ImmunoCAP ISAC of pediatric patients from 2017 to 2021. The patients under investigation were being followed for atopic disorders such as allergic asthma and food allergies. The study aimed to analyze the prevalence of sensitization toward Der p 10 in our pediatric population and assess the related clinical symptoms and reactions after ingestion of foods containing tropomyosins. Results. This study included 253 patients; 53% were sensitized toward Der p 1 and Der p 2; 10.4% were also sensitized to Der p 10. Assessing patients sensitized to Der p 1 or Der p 2, and Der p 10, we observed that 78.6% were affected by asthma (p < 0.005) and had a history of prior anaphylaxis after ingestion of shrimp or shellfish (p < 0.0001). Conclusion. The component-resolved diagnosis gave us a deeper understanding of patients' molecular sensitization profiles. Our study showed that a fair proportion of children sensitive to Der p 1 or Der p 2 are also sensitive to Der p 10. However, many patients sensitized to all three molecules had a high risk of asthma and anaphylaxis. Therefore, the assessment of Der p 10 sensitization should be considered in atopic patients with sensitization to Der p 1 and Der p 2 to avoid encountering possible adverse reactions after ingesting foods containing tropomyosins. [ABSTRACT FROM AUTHOR]

Objectives To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. Patients and Methods We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). Results A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. Conclusion Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted. [ABSTRACT FROM AUTHOR]

The data that support the findings of this study are available from the corresponding author upon reasonable request. Given median ferritin at week 12 was only 27 g/L, patients may require longer oral iron supplementation, particularly those with ongoing menorrhagia or GI bleeding (Table S3). Imbalances may have favoured the daily group (more blood donors) whereas the EOD group had more patients with menorrhagia with lower baseline haemoglobins. Iron deficiency anaemia (IDA) is the most common anaemia worldwide.[1] IDA impacts physical[[2]] and cognitive function,[[4], [6]] and health-related quality of life.[7] Oral iron is associated with gastrointestinal effects in 30%-70% of patients[8] leading to non-adherence. [Extracted from the article]

Background. Food allergy is common in the Mediterranean, especially concerning lipid transfer proteins (LTPs) allergy. LTPs are widespread plant food allergens in fruits, vegetables, nuts, pollen, and latex. Also, LTPs are prevalent food allergens in the Mediterranean area. They can sensitize via the gastrointestinal tract and cause a wide range of conditions: from mild reactions, such as oral allergy syndrome, to severe reactions, such as anaphylaxis. LTP allergy in the adult population is well described in the literature, concerning both the prevalence and clinical characteristics. However, there is poor knowledge about its prevalence and clinical manifestation in children living in the Mediterranean. Materials and Methods. This study, including 800 children aged from 1 to 18 years, investigated the prevalence of 8 different molecules of nonspecific LTP over time in an Italian pediatric population visited over the last 11 years. Results. About 52% of the test population was sensitized to at least one LTP molecule. For all the LTPs analyzed, sensitization increased over time. In particular, using the years 2010 through 2020 as a comparison, the major increases were observed for the LTPs of the English walnut Jug r 3, the peanut Ara h 9, and the plane tree Pla a 3 (about 50%); the increase of the LTP of the Hazelnut Cor a 8 was about 36%, and that of the LTP of the artemisia Art v 3 was approximately 30%. Conclusions. The latest evidence in the literature indicates an increase in food allergy prevalence in the general population, including children. Therefore, the present survey represents an interesting perspective about the pediatric population of the Mediterranean area, exploring the trend of LTP allergy. [ABSTRACT FROM AUTHOR]

Background and objectives: Genetic variants in the gene TARDBP, encoding TDP‐43 protein, are associated with amyotrophic lateral sclerosis (ALS) in familial (fALS) and sporadic (sALS) cases. Objectives of this study were to assess the contribution of TARDBP in a large cohort of Italian ALS patients, to determine the TARDBP‐associated clinical features and to look for genotype–phenotype correlation and penetrance of the mutations. Methods: A total of 1992 Italian ALS patients (193 fALS and 1799 sALS) were enrolled in this study. Sanger sequencing of TARDBP gene was performed in patients and, when available, in patients' relatives. Results: In total, 13 different rare variants were identified in 43 index cases (10 fALS and 33 sALS) with a cumulative mutational frequency of 2.2% (5.2% of fALS, 1.8% of sALS). The most prevalent variant was the p.A382T followed by the p.G294V. Cognitive impairment was detected in almost 30% of patients. While some variants, including the p.G294V and the p.G376D, were associated with restricted phenotypes, the p.A382T showed a marked clinical heterogeneity regarding age of onset, survival and association with cognitive impairment. Investigations in parents, when possible, showed that the variants were inherited from healthy carriers and never occurred de novo. Conclusions: In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated with cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype–phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism. [ABSTRACT FROM AUTHOR]

Thirty-seven patients were alive at the last follow-up, 13 had died (two dementia-related causes, one pneumonia, one warfarin-related bleeding, one ovarian cancer, eight because of unknown causes); no patient died due to CLL progression. Of the five patients initially categorized as in partial SR, three have subsequently converted to SR, one remains in partial SR and in one patient who achieved a partial SR after 19 years from diagnosis the lymphocyte count started to increase five years later. Of the four patients in stage B/II at diagnosis, two converted to A/0 and one to A/I. In the five patients with a partial SR, the median lymphocyte count at regression was 6.3 × 10 SP 9 sp /L, with a median lymphocyte decrease of 75.1% (69-89%), and at the last follow-up a median lymphocyte count of 5.6 × 10 SP 9 sp /L (5.3-11.8) (Figure 1). [Extracted from the article]

Live cells act as biological lenses and can be employed as real‐world optical components in bio‐hybrid systems. Imaging at nanoscale, optical tweezers, lithography and also photonic waveguiding are some of the already proven functionalities, boosted by the advantage that cells are fully biocompatible for intra‐body applications. So far, various cell types have been studied for this purpose, such as red blood cells, bacterial cells, stem cells and yeast cells. White Blood Cells (WBCs) play a very important role in the regulation of the human body activities and are usually monitored for assessing its health. WBCs can be considered bio‐lenses but, to the best of our knowledge, characterization of their optical properties have not been investigated yet. Here, we report for the first time an accurate study of two model classes of WBCs (i.e., monocytes and lymphocytes) by means of a digital holographic microscope coupled with a microfluidic system, assuming WBCs bio‐lens characteristics. Thus, quantitative phase maps for many WBCs have been retrieved in flow‐cytometry (FC) by achieving a significant statistical analysis to prove the enhancement in differentiation among sphere‐like bio‐lenses according to their sizes (i.e., diameter d) exploiting intensity parameters of the modulated light in proximity of the cell optical axis. We show that the measure of the low intensity area (S: Iz

Mechanistic toxicology provides a powerful approach to inform on the safety of chemicals and the development of safe‐by‐design compounds. Although toxicogenomics supports mechanistic evaluation of chemical exposures, its implementation into the regulatory framework is hindered by uncertainties in the analysis and interpretation of such data. The use of mechanistic evidence through the adverse outcome pathway (AOP) concept is promoted for the development of new approach methodologies (NAMs) that can reduce animal experimentation. However, to unleash the full potential of AOPs and build confidence into toxicogenomics, robust associations between AOPs and patterns of molecular alteration need to be established. Systematic curation of molecular events to AOPs will create the much‐needed link between toxicogenomics and systemic mechanisms depicted by the AOPs. This, in turn, will introduce novel ways of benefitting from the AOPs, including predictive models and targeted assays, while also reducing the need for multiple testing strategies. Hence, a multi‐step strategy to annotate AOPs is developed, and the resulting associations are applied to successfully highlight relevant adverse outcomes for chemical exposures with strong in vitro and in vivo convergence, supporting chemical grouping and other data‐driven approaches. Finally, a panel of AOP‐derived in vitro biomarkers for pulmonary fibrosis (PF) is identified and experimentally validated. [ABSTRACT FROM AUTHOR]

This Concept is focused on the key features of dissipative dynamic combinatorial chemistry (DDCC). DDCC deals with transient libraries of compounds, maintained out‐of‐equilibrium by the consumption of a fuel, whose composition changes upon the selection pressure of kinetic and/or thermodynamic processes. Concepts and definitions of kinetic and thermodynamic dissipative dynamic libraries ("KDDL" and "TDDL"), are introduced and illustrated by a number of actual cases, thus showing the consistency of the present approach. Such concepts and definitions can help establish a common language for this emerging field, which, in our view, has the potential to become highly relevant to supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Oxygenic phototrophs perform carbon fixation through the Calvin–Benson cycle. Different mechanisms adjust the cycle and the light‐harvesting reactions to rapid environmental changes. Photosynthetic glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) is a key enzyme in the cycle. In land plants, different photosynthetic GAPDHs exist: the most abundant isoform is formed by A2B2 heterotetramers and the least abundant by A4 homotetramers. Regardless of the subunit composition, GAPDH is the major consumer of photosynthetic NADPH and its activity is strictly regulated. While A4‐GAPDH is regulated by CP12, AB‐GAPDH is autonomously regulated through the C‐terminal extension (CTE) of its B subunits. Reversible inhibition of AB‐GAPDH occurs via the oxidation of a cysteine pair located in the CTE and the substitution of NADP(H) with NAD(H) in the cofactor‐binding site. These combined conditions lead to a change in the oligomerization state and enzyme inhibition. SEC–SAXS and single‐particle cryo‐EM analysis were applied to reveal the structural basis of this regulatory mechanism. Both approaches revealed that spinach (A2B2)n‐GAPDH oligomers with n = 1, 2, 4 and 5 co‐exist in a dynamic system. B subunits mediate the contacts between adjacent tetramers in A4B4 and A8B8 oligomers. The CTE of each B subunit penetrates into the active site of a B subunit of the adjacent tetramer, which in turn moves its CTE in the opposite direction, effectively preventing the binding of the substrate 1,3‐bisphosphoglycerate in the B subunits. The whole mechanism is made possible, and eventually controlled, by pyridine nucleotides. In fact, NAD(H), by removing NADP(H) from A subunits, allows the entrance of the CTE into the active site of the B subunit, hence stabilizing inhibited oligomers. [ABSTRACT FROM AUTHOR]

In recent years, corporate social responsibility has become the most outstanding challenges for firms and circular economy has emerged as an innovative business model able to transform corporate social responsibility into actions. Even if by adopting such a strategic model firms could enhance their performance, results continue to be mixed and unclear. The aim of the paper is twofold. First, the study investigates the effect of three circular economy practices (waste treatment, reduction and recycling), on brand reputation and financial performance. Second, the study tests the role of brand reputation in mediating the relationship between circular economy practices and financial performance. The findings highlight the crucial role of 3Rs practices and of brand reputation in enhancing firm performance. This paper contributes to a better understanding on the relationship between circular economy practices, as sustainable strategic and managerial practices, and firm performance, in both marketing and financial terms. Moreover, it sheds light on circular economy implementation and its effect at the firm level, by analyzing managers perceptions on how firms and policy makers have to incorporate the circular economy concept in their sustainability agenda. [ABSTRACT FROM AUTHOR]

In particular, the results show that corporate social responsibility strengthens the relationship between corporations and employees due to employees' positive perception toward their organizations for the implementation of CSR initiatives. When corporate social responsibility (CSR) increases performance: Exploring the role of intrinsic and extrinsic CSR attribution. The results indicate that cross-cultural legitimacy is significantly associated with responsible innovation practices and firm performance within the Asia-Pacific CBM, while the cross-cultural legitimacy-firm performance association is partially mediated by the responsible innovation practice. This editorial of corporate social responsibility and environmental management summarizes the papers included in the Special Issue "The managerial implications of assessing corporate social performance.". [Extracted from the article]