Search

Patients with triple-negative breast cancer (TNBC) have a relatively poor clinical outcome. The immune checkpoint inhibitor (ICI) pembrolizumab combined with chemotherapy is the current standard of care in TNBC patients with stage II and III. Monotherapy with ICIs has not been comprehensively assessed in the neoadjuvant setting in TNBC patients, given unfavorable results in metastatic trials. ICIs, however, have been tested in the window of opportunity (WOO) before surgery or standard chemotherapy-based neoadjuvant treatment. The WOO design is well suited to assess an ICI alone or in combination with other ICIs, targeted therapy, radiotherapy or cryotherapy, and measure their pharmacodynamic and clinical effect in this treatment-naive population. Some patients show a good response to ICIs in WOO studies. Biomarkers like tumor-infiltrating lymphocytes, programmed death ligand-1, and interferon-γ signature may predict activity and may identify patients likely to benefit from ICIs. Moreover, an increase in tumor-infiltrating lymphocytes, programmed death ligand-1 expression or T cell receptor expansion following administration of ICIs in the WOO setting could potentially inform of immunotherapy benefit, which would allow tailoring further treatment. This article reviews WOO trials that assessed immunotherapy in the early-stage TNBC population, and how these results could be translated to test de-escalation strategies of neoadjuvant chemotherapy and immunotherapy without compromising a patient's prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The current research aims to develop a new analytical method applying a dispersive liquid-liquid microextraction (DLLME) assisted by vortex and using an environmentally friendly extractant for the preconcentration of organochlorine and organophosphorus pesticides followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. The extractant (i.e., natural deep eutectic solvent (NADES)) is safe, cheap, biodegradable and can be prepared by simply mixing DL-menthol and decanoic acid (molar ratio 2:1). The main experimental factors affecting the extraction of all analytes evaluated (19 organochlorine and organophosphorus pesticides) have been optimised using a multivariate analysis consisting in two steps: a Plackett-Burman design followed by a central composite design (CCD). Seven experimental factors have been evaluated: (i) sample volume; (ii) NADES volume; (iii) sample pH; (iv) extraction time; (v) centrifugation time; (vi) centrifugation speed; and (vii) ionic strength (NaCl %, w v -1 ). For the significant variables, the optimum values were 10 mL sample and 45 μL NADES. No pH adjustment as well as addition of NaCl were needed. The other variables were set at 3 min extraction time, 5 min centrifugation time and 900×g centrifugation speed, respectively. Under the optimised extraction conditions, the limit of quantification (LOQ) values ranged between 0.2 and 78 ng L -1 for all analysed pesticides. Furthermore, the proposed analytical method has been successfully applied to drinking water (bottled spring water). The recovery study (n = 3) has been evaluated at 0.1, 1.0 and 5.0 μg L -1 spiking levels, obtaining relative recovery values within the range of 70 % and 117 % and RSD values between 1 % and 20 % for all the analytes studied, except for p,p-DDT (56-77 % in high conductivity water samples)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Secondary data sources are frequently used for characterizing physical access to food. Although several studies have reported that they tend to show a moderate agreement with field observation in WEIRD (Western Educated Industrialized Rich and Democratic) countries, little is known about their validity in non-WEIRD countries. The aim of the present research was to assess the validity of secondary data sources of the retail food environment in Montevideo, the capital of Uruguay, an emerging Latin American country. A random sample of 106 census tracts was obtained, covering 12% (62 km 2 ) of the city's total area. Two secondary data sources were considered: administrative records and Google Maps. An aggregate database was created by manually removing duplicates. A total of 1051 unique outlets were listed in the database within the census tracts included in the sample. Field validation was performed by six teams of two observers. A total of 1200 food outlets were identified on the ground, including 463 (38.6%) outlets not listed on any database. On the contrary, 297 outlets listed in the databases (28.3%) were not found or were closed at the time of field validation. At the aggregate level, sensitivity and concordance were moderate (0.614 and 0.487, respectively), whereas positive predictive value was substantial (0.701). However, large heterogeneity in the validity of the database across census tracts was found. Sensitivity, positive predictive value, and concordance were positively associated with the socio-economic status index of the census tract. These results suggest that secondary data sources must be used with caution, particularly for the characterization of areas with low socio-economic status., Competing Interests: Declaration of competing interest The authors declare no conflicting interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim of the present study was to critically analyze operational definitions of food deserts and food swamps included in empirical studies published in peer-reviewed journals. A scoping review was conducted following the recommendations of the Joanna Briggs Institute and PRISMA Extension for Scoping Reviews. A search of the scientific literature was performed on August 2023 to identify empirical studies including operational definitions of food deserts and/or food swamps in three databases: Scopus, PubMed, and Scielo. A total of 932 scientific articles were identified in the three databases, from which 157 articles, published between 2002 and 2023, were included in the review. The included studies were mainly conducted in WEIRD (Western, Educated, Industrilaized, Rich and Democractic) countries. They presented a total of 107 operational definitions of food deserts and 30 operational definitions of food swamps. Large heterogeneity in the operational definitions of food deserts and food swamps was found. Published studies differed in all the elements of the operational definitions analyzed in the present work. Results stress the need for standardization and the development of more objective and multivariate continuous measures of physical food accessibility that reflect the complexity of modern food environments globally. A series of recommendations to advance food environment research are derived., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A new simple, fast and environmentally friendly deep eutectic solvent based dispersive liquid-liquid microextraction (DES-based DLLME) methodology assisted by vortex is presented for the separation and preconcentration of three elements (i.e., Fe, Cu and Pb) from edible oil samples (i.e., soybean, sunflower, rapeseed, sesame, and olive oil) prior to the determination by microwave-induced plasma optical emission spectrometry (MIP-OES). The deep eutectic solvent selected as extractant (i.e., choline chloride and ethylene glycol, 1:2) is synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and differential scanning calorimetry (DSC), and the extraction conditions are optimized by a two steps experimental design. Under the optimum extraction conditions (i.e., diluted sample weight: 8.6 g; DES volume: 100 μL; extraction time: 1 min; centrifugation time and speed: 3 min and 3000 rpm; and dispersion system: vortex) the analytical method presents excellent linearity (i.e., R 2 values higher than 0.99) in the range 10-500 μg kg -1 , repeatability (i.e., CV values lower than 9.2%), and limits of detection (LOD) values of 3, 2 and 0.7 μg kg -1 for Pb, Fe and Cu, respectively. None of the analytes displayed amounts over the upper limit permitted by law, and recovery values of all analytes evaluated in the different samples using external standard calibration were close to 100%, which excludes significant matrix effects. Finally, AGREEprep metric has been used to evaluate the method greenness (final score of 0.47) and it has been compared successfully with previous publications for the same type of analytes and matrices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Problem: Midwifery led units are rare in Spain., Background: Midwife-Led Care (MLC) is a widely extended model of care and, within this, the alongside midwifery-led units (AMLU) are those hospital-based and located in close connection with obstetric units. In Spain, CL is the first center belonging to the National Health System of these characteristics., Aim: To evaluate the first year of activity of this pioneering unit., Methods: An observational cross-sectional study was carried out to assess maternal and neonatal outcomes of births facilitated at CL by comparing with those births that fulfilled the criteria to be admitted at the AMLU but were assisted at the standard obstetric care unit of the hospital., Findings: 174 (20,3%) women and birthing people decided to give birth at CL, whereas 684 (79,7%) gave birth at the Obstetric Unit of the Hospital. Women assisted at the AMLU had lower intervention rates (episiotomy, epidural analgesia) and a higher rate of breastfeeding practice. There were no statistical differences in maternal outcomes (postpartum hemorrhage, third-or-four-degree laceration) or neonatal outcomes (Apgar< 7 at 5 min; birth weight < 2500 gr; macrosomia; shoulder dystocia, neonatal care transfer)., Discussion: There were differences in transfers from MLU to OU between nulliparous and multiparous; the main reason for transfer is the request for analgesia. Epidural analgesia should be considered when analyzing maternal outcomes., Conclusion: An alongside midwifery-led unit is a safe option with a low incidence of complications. This model of care can be positively implemented at the Public Healthcare System., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The study aimed to evaluate and discuss the use of an innovative PSI made of porous hydroxyapatite, with interconnected porosity promoting osteointegration, called MyBone Custom® implant (MBCI), for maxillofacial bone reconstruction. A multicentric cohort of 13 patients underwent maxillofacial bone reconstruction surgery using MBCIs for various applications, from genioplasty to orbital floor reconstruction, including zygomatic and mandibular bone reconstruction, both for segmental defects and bone augmentation. The mean follow-up period was 9 months (1-22 months). No infections, displacements, or postoperative fractures were reported. Perioperative modifications of the MBCIs were possible when necessary. Additionally, surgeons reported significant time saved during surgery. For patients with postoperative CT scans, osteointegration signs were visible at the 6-month postoperative follow-up control, and continuous osteointegration was observed after 1 year. The advantages and disadvantages compared with current techniques used are discussed. MBCIs offer new bone reconstruction possibilities with long-term perspectives, while precluding the drawbacks of titanium and PEEK. The low level of postoperative complications associated with the high osteointegration potential of MBCIs paves the way to more extensive use of this new hydroxyapatite PSI in maxillofacial bone reconstruction., Competing Interests: Declaration of competing interest EC is a CERHUM employee. J-LN and GN have direct ownership in CERHUM. The other authors have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background Aims: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively degenerates, resulting in subsequent loss of photoreceptors and ultimately vision. There is currently no cure for AMD, but therapeutic strategies targeting the complement system are being developed to slow the progression of the disease., Methods: Replacement therapy with pluripotent stem cell-derived (hPSC) RPEs is an alternative treatment strategy. A cell therapy product must be produced in accordance with Good Manufacturing Practices at a sufficient scale to facilitate extensive pre-clinical and clinical testing. Cryopreservation of the final cell product is therefore highly beneficial, as the manufacturing, pre-clinical and clinical testing can be separated in time and location., Results: We found that mature hPSC-RPE cells do not survive conventional cryopreservation techniques. However, replating the cells 2-5 days before cryopreservation facilitates freezing. The replated and cryopreserved hPSC-RPE cells maintained their identity, purity and functionality as characteristic RPEs, shown by cobblestone morphology, pigmentation, transcriptional profile, RPE markers, transepithelial resistance and pigment epithelium-derived factor secretion. Finally, we showed that the optimal replating time window can be tracked noninvasively by following the change in cobblestone morphology., Conclusions: The possibility of cryopreserving the hPSC-RPE product has been instrumental in our efforts in manufacturing and performing pre-clinical testing with the aim for clinical translation., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making. In this review, we summarize the evidence supporting the choice of NACT vs NET in HR+/HER2- BC, discussing the issues surrounding clinical trial design and proper selection of patients for every treatment. It is time to question the binary paradigm of responder vs non-responders as well as the "one size fits all" approach in luminal BC, supporting the utilization of continuous endpoints and the adoption of tissue and plasma-based biomarkers at multiple timepoints. This will eventually unleash the full potential of neoadjuvant therapy which is to modulate patient treatment based on treatment sensitivity and surgical outcomes. We also reviewed the current landscape of neoadjuvant studies for HR+/HER2- BC, focusing on antibody-drug conjugates (ADCs) and immunotherapy combinations. Finally, we proposed a roadmap for future neoadjuvant approaches in HR+/HER2- BC, which should be based on a staggered biomarker-driven treatment selection aiming at impacting long-term relevant endpoints., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LC, MK, LV, and KSS are employees of Fortrea Inc.. KSS reports consulting fees from the European Commission, and stock and/or other ownership interests in Fortrea Inc. and Quantum Health Analytics (UK) Ltd, outside the submitted work. GC reports personal fees for consulting, advisory role and speakers’ bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, and Daichii-Sankyo; honoraria from Ellipses Pharma; fees for travel and accommodation from Roche/Genentech, and Pfizer outside the submitted work. The other authors do not report any conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Mollusc rearing is a relevant global socioeconomic activity. However, this activity has faced severe problems in the last years in southeast Brazil. The mariculture scallop production dropped from 51,2 tons in 2016 to 10,2 tons in 2022 in the Baia da Ilha Grande (BIG; Rio de Janeiro). However, the possible causes of this collapse are unknown. This study aimed to analyze decadal trends of water quality in Nodipecten nodosus spat and adult production in BIG. We also performed physical-chemical and biological water quality analyses of three scallop farms and two nearby locations at BIG in 2022 to evaluate possible environmental stressors and risks. Scallop spat production dropped drastically in the last five years (2018-2022: mean ± stdev: 0.47 ± 0.45 million). Spat production was higher in colder waters and during peaks of Chlorophyll a in the last 13 years. Reduction of Chlorophyll a coincided with decreasing spat production in the last five years. Warmer periods (>27 °C) of the year may hamper scallop development. Counts of potentially pathogenic bacteria (Vibrios) and Escherichia coli were significantly higher in warmer periods which may further reduce scallop productivity. Shotgun metagenomics of seawater samples from the five studied corroborated these culture-based counts. Vibrios and fecal indicator bacteria metagenomic sequences were abundant across the entire study area throughout 2022. The results of this study suggest the collapse of scallop mariculture is the result of a synergistic negative effect of global warming and poor seawater quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The fifteenth edition of the international workshop organized by the "Tumour Targeting and Radiotherapies network" of the Cancéropôle Grand-Ouest focused on the latest advances in internal and external radiotherapy from different disciplinary angles: chemistry, biology, physics, and medicine. The workshop covered several deliberately diverse topics: the role of artificial intelligence, new tools for imaging and external radiotherapy, theranostic aspects, molecules and contrast agents, vectors for innovative combined therapies, and the use of alpha particles in therapy., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The Colombian mining industry has witnessed significant growth. Depending on the scale and mineral extracted, complex chemical mixtures are generated, impacting the health of occupationally exposed populations and communities near mining projects. Increasing evidence suggests that chromosomal instability (CIN) is an important link between the development of certain diseases and exposure to complex mixtures. To better understand the effects of exposure to complex mixtures we performed a biomonitoring study on 407 healthy individuals from four areas: three located in municipalities exploiting different-scale mining systems and a reference area with no mining activity. Large, medium, and small-scale mining systems were analyzed in Montelibano (Córdoba), artisanal and small-scale mining (ASGM) in Nechí (Antioquia), and a closed mining system in Aranzazu (Caldas). The reference area with no mining activity was established in Montería (Córdoba). ICP-MS measured multi-elemental exposure in hair, and CIN was evaluated using the cytokinesis-block micronucleus technique (MNBN). Exposure to mixtures of chemical elements was comparable in workers and residents of the mining areas but significantly higher compared to reference individuals. In Montelibano, increased MNBN frequencies were associated with combined exposure to Se, Hg, Mn, Pb, and Mg. This distinct pattern significantly differed from other areas. Specifically, in Nechí, Cr, Ni, Hg, Se, and Mg emerged as the primary contributors to elevated frequencies of MNBN. In contrast, a combination of Hg and Ni played a role in increasing MNBN in Aranzazu. Interestingly, Se consistently correlated with increased MNBN frequencies across all active mining areas. Chemical elements in Montelibano exhibit a broader range compared to other mining zones, reflecting the characteristics of the high-impact and large-scale mining in the area. This research provides valuable insights into the effects of exposure to chemical mixtures, underscoring the importance of employing this approach in the risk assessment of communities, especially those from residential areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It has been hypothesised that manipulation during surgery releases tumoral components into circulation. We investigate the effect of surgery on plasma-borne DNA biomarkers and the oncological outcomes in resectable pancreatic ductal adenocarcinoma (PDAC). We also compare non-touch isolation techniques (NTIT) with standard techniques., Materials and Methods: We performed a systematic review and a meta-analysis of studies analysing liquid biopsy as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and messenger RNA (mRNA) in resectable PDAC patients who underwent surgery and its association with overall survival (OS) and disease-free survival (DFS). Research in EMBASE, Web of Science and PubMed was performed. The ctDNA shift negative-to-positive (ctDNA -/+) or ctDNA shift positive-to-negative (ctDNA +/-) before and after surgery was evaluated., Results: Twelve studies comprising 413 patients were included. Shorter OS and DFS were identified in patients with positive ctDNA status before (HR = 2.28, p = 0.005 and HR = 2.16, p = 0.006) or after surgery (HR = 3.88, p < 0.0001 and HR = 3.81, p = 0.03), respectively. Surgical resection increased the rate of ctDNA +/-. There were no differences in OS or DFS in the ctDNA +/- group compared with ctDNA +/+ or ctDNA -/+. However, there was a trend to shorter OS in the ctDNA -/+ group (HR = 5.00, p = 0.09). No differences between NTIT and standard techniques on liquid biopsy status were found., Conclusion: Positive ctDNA in the perioperative period is associated with a worse prognosis. Surgical resection has a role in the negativisation of liquid biopsy status. More studies are needed to assess the potential of minimally invasive techniques on ctDNA dynamics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Vidal reports article publishing charges was provided by Autonomous University of Barcelona., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Population-based fecal tests for colorectal cancer (CRC) screening have shown to reduce mortality thanks to the early detection of the disease. However, currently available fecal tests are limited in their sensitivity and specificity. Our aim is to look for volatile organic compounds in fecal samples as biomarkers for CRC detection., Material and Methods: Eighty participants were included; 24 had adenocarcinoma, 24 had adenomatous polyps and 32 presented no neoplasms. Fecal samples were collected 48 h preceding the colonoscopy from all participants, except CRC patient samples that were collected after 3-4 weeks from the colonoscopy. Magnetic headspace adsorptive extraction (Mag-HSAE) followed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) was performed on stool samples to identify volatile organic compounds as biomarkers., Results: p-Cresol was significantly more abundant in the cancer samples (P < 0.001) with an area under the curve (AUC) of 0.85 (CI 95%; 0.737-0.953), having a sensitivity and specificity of 83% and 82%, respectively. In addition, 3(4H)-dibenzofuranone,4a,9b-dihydro-8,9b-dimethyl- (3(4H)-DBZ) was also more abundant in the cancer samples (P < 0.001) with an AUC of 0.77 (CI 95%; 0.635-0.905), sensitivity of 78% and specificity of 75%. When combined (p-cresol and 3(4H)-DBZ), the AUC was 0.86, sensitivity 87% and specificity 79%. p-Cresol also appeared to be promising as a biomarker for pre-malignant lesions with an AUC of 0.69 (CI 95%; 0.534-0.862), sensitivity 83% and specificity 63%, P = 0.045., Conclusions: Volatile organic compounds emitted from feces and determined by a sensitive analytical methodology (Mag-HSAE-TD-GC-MS), employing a magnetic graphene oxide as extractant phase, could be used as a potential screening technology for CRC and pre-malignant lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m 3 s -1 ), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Advanced non-small cell lung cancer (aNSCLC) is an incurable disease. The effort to develop treatments with more effective systemic agents continues. This has led to the FDA approval of one antibody-drug conjugate (ADC) and eight immune checkpoint inhibitors (ICIs) for patients with aNSCLC., Areas Covered: Due to the demonstrated efficacy of ADCs and ICIs in aNSCLC, treatment combining both agents merits attention. This article, therefore, explores the use of ADCs and ICIs in patients with NSCLC, assesses the scientific rationale for combination treatment, and provides an overview of ongoing trials. It also presents some early efficacy and safety results of such combination use., Expert Opinion: It is not clear whether ADC-immunotherapy has a significant impact on those with a targetable oncogenic driver alteration since targeted therapies are effective. However, in aNSCLC without a targetable oncogenic driver alteration, the combination of ADCs and ICIs has potential and remains an area of active clinical research., Competing Interests: Declaration of Competing Interest Kamal S Saini reports consulting fees from the European Commission, and stock and/or other ownership interests in Labcorp Inc. and Quantum Health Analytics SPRL, outside the submitted work. Jordi Remon Participation in Advisory board: MSD, Boehringer Ingelheim, Janssen, Bayer, GenMab, BMS, Takeda. Speaker: Pfizer, Janssen. Honoraria: MSD Travel fees: OSE Immunotherapeutics, BMS, AstraZeneca, Roche. Role in International Organizations: Unpaid secretary of the EORTC Lung Cancer group. Institution grant: Merck Angela Quintana is currently an employee of AstraZeneca. The other authors do not report any conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Sponges have co-evolved with microbes for over 400 myr. Previous studies have demonstrated that sponges can be classified according to the abundance of microbes in their tissues as Low Microbial Abundance (LMA) and High Microbial Abundance (HMA). While LMA sponges rely mainly on water column microbes, HMA appear to rely much more on symbiotic fermentative and autotrophic microbes maintained in their tissues. However, it is unclear if this pattern holds when comparing different species of tropical sponges under extreme nutrient conditions and sediment loads in the water column, such as the Great Amazon Reef System (GARS), which covers an area of ~56,000 km 2 off the Amazon River mouth. Sponges are the major GARS benthic components. However, these sponges' microbiome across the GARS is still unknown. Here, we investigated water quality, isotopic values (δ 13 C and δ 15 N), metagenomic and lipidomic profiles of sponges obtained from different sectors throughout the GARS. >180 million shotgun metagenomic reads were annotated, covering 22 sponge species. Isotopic and lipidomic analyses suggested LMA sponges rely on the Amazon River Plume for nutrition. HMA sponges (N = 15) had higher Roseiflexus and Nitrospira abundance, whereas LMA sponges (N = 7) had higher Prochlorococcus and Pelagibacter abundance. Functional data revealed that the LMA sponge microbiomes had greater number of sequences related to phages and prophages as well as electron transport and photophosphorylation which may be related to photosynthetic processes associated with the Prochlorococcus and Synechococcus found in the LMA. The higher phages abundance in LMA sponges could be related to these holobionts' reduced defense towards phage infection. Meanwhile, HMA sponge microbiomes had higher Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR abundance, which may be involved in defense against phage infection. This study sheds light on the nutrient fluxes and microbes from the Amazon River plume into the sponge holobionts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown., Patients and Methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death., Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90)., Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research., Competing Interests: Disclosure JSF reports personal fees from Roche Genentech, personal fees and non-financial support from Seattle Genetics, Novartis, Pfizer, Lilly, Novartis, GSK, Clovis oncology, AstraZeneca, Daiichi Sankyo, Gilead, MSD, Pierre Fabre, and Amgen, outside the submitted work. PP reports non-financial support from GSK, AstraZeneca, Clovis Oncology outside the submitted work. JAL reports personal fees from Pfizer, AstraZeneca, GSK, MSD, Clovis Oncology, Eisai, Bristol Myers Squibb, Artios Pharma, VBL Therapeutics, Neopharm, outside the submitted work. RTP reports personal fees from AbbVie, AstraZeneca, Eisai, Genentech / Roche, GSK Inc., Merck & Co, Sutro Biopharma, Vascular Biogenics Ltd, outside the submitted work. SP reports personal fees from, AstraZeneca, MSD; ROCHE, Clovis, GSK, Pfizer, PharmaMar, outside the submitted work. NC reports personal fees from AstraZeneca, Esai, Genentech, GSK, Merck, Pfizer, Regeneron pharmaceutical, outside the submitted work. TWPS reports personal fee from AstraZeneca, Tesaro, GSK, outside the submitted work. GSS has received grant from Agendia, AstraZeneca, Merck, Novartis, Roche, Seagen, outside the submitted work. CKL reports personal fee from AstraZeneca, Amgen, Takeda, Boehringer Ingelheim, Pfizer, Yuhan, Merck KGA, Roche, MSD, outside the submitted work. EPL reports grants and personal fees from AstraZeneca, Merck, GSK, Roche, Incyte, ARCAGY Research, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To explore parents' accounts of the goals they seek when choosing foods for their young children through the lens of goal-systems theory., Design: In-depth interviews with parents of children aged from 6 months to 5 years., Setting: Montevideo, Uruguay., Participants: Forty-two parents (aged 19-44 years, 90% female)., Phenomenon of Interest: Parents' personal experiences, feelings, and opinions related to how they choose foods for their children., Analysis: Content analysis based on deductive-inductive coding., Results: Parents' accounts confirmed they intended to pursue different goals when choosing foods for their children. Health-related goals mainly motivated the selection of healthy foods, but they also drove the selection of some ultra-processed products because of misconceptions about their healthiness. Pleasure and enjoyment motivated the selection of ultra-processed products, whereas stress avoidance was associated with selecting convenient foods. The selection of unhealthy foods raised conflicts between goals, which were solved using goal shielding, changes in risk perception and/or compensatory health beliefs., Conclusions and Implications: Results point to the need for communication campaigns and community-based interventions to introduce changes in how ultra-processed products are conceptualized and increase the associations between healthy foods and children's pleasure and enjoyment to promote healthier eating patterns during infancy and early childhood., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity., Method: A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n = 152) was designed. PCT determination was tested on admission (first 72 h). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications., Results: PCT >0.68 mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT >0.68 mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis., Discussion: PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Few studies to date have explored the health-related quality of life (HRQoL) in patients with long COVID., Methods: The Anticipate Study is a prospective single-centre observational cohort study. Hospitalised and nonhospitalised patients were seen at a dedicated post-COVID clinic at a 2-4 month (Timepoint 1) and 7-14 month follow-up (Timepoint 2). The main objectives of this study are to assess the longitudinal impact of COVID-19 in patients using the 12-item Short Form Survey (SF-12) score, a health-related quality of life tool, and to identify predictors of developing post-COVID-19 syndrome (PoCS). In addition, we aimed to describe symptomatology and identify predictors of PoCS at 1-year., Results: A total of 155 patients were enrolled, 105 (68%) were female aged 43.3 (31-52) years. In total 149 (96%) and 94 (61%) patients completed follow-up at median 96 (76-118) days and 364 (303-398) days. The overall cohort had significantly reduced physical composite score (PCS) of the SF-12 (45.39 [10.58] vs 50 [10], p = 0.02). Participants with PoCS had significantly lower scores than those without symptoms at 1-year follow-up (37.2 [10.4] v 46.1 [10.9] p <0.001), and scores for these patients did not improve over the 2 Timepoints (PCS 34.95 [10.5] - 37.2 [10.4], p = 0.22). Fatigue was the most common symptom. Those with 5 or more symptoms at initial diagnosis had lower PCS and mental composite score (MCS) at 1-year. Predictors of PoCS at 1-year were lower PCS and higher baseline heart rate (HR) at clinic review median 3 months after COVID-19., Conclusion: Patients with PoCS have lower PCS scores during follow-up, which did not significantly improve up to a 1-year follow-up. Lower PCS scores and higher HR at rest can be used in the weeks after COVID-19 can help predict those at risk of PoCS at 1 year., Competing Interests: Competing interests The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A recent paper by Beretta-Blanco and Carrasco-Letelier (2021) claims that agricultural eutrophication is not one of the main causes for cyanobacterial blooms in rivers and artificial reservoirs. By combining rivers of markedly different hydrological characteristics e.g., presence/absence and number of dams, river discharge and geological setting, the study speculates about the role of nutrients for modulating phytoplankton chlorophyll-a. Here, we identified serious flaws, from erratic and inaccurate data manipulation. The study did not define how erroneous original dataset values were treated, how the variables below the detection/quantification limit were numerically introduced, lack of mandatory variables for river studies such as flow and rainfall, arbitrary removal of pH > 7.5 values (which were not outliers), and finally how extreme values of other environmental variables were included. In addition, we identified conceptual and procedural mistakes such as biased construction/evaluation of model prediction capability. The study trained the model using pooled data from a short restricted lotic section of the (large) Uruguay River and from both lotic and reservoir domains of the Negro River, but then tested predictability within the (small) Cuareim River. Besides these methodological considerations, the article shows misinterpretations of the statistical correlation of cause and effect neglecting basic limnological knowledge of the ecology of harmful algal blooms (HABs) and international research on land use effects on freshwater quality. The argument that pH is a predictor variable for HABs neglects overwhelming basic paradigms of carbon fluxes and change in pH because of primary productivity. As a result, the article introduces the notion that HABs formation are not related to agricultural land use and water residence time and generate a great risk for the management of surface waterbodies. This reply also emphasizes the need for good practices of open data management, especially for public databases in view of external reproducibility., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No competing financial interest. On behalf of all authors Ignacio Alcántara and Felipe García-Rodríguez., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel, simple, fast, sensitive and environmentally friendly approach is presented to determine cadmium in urine samples, combining magnetic dispersive solid-phase extraction (MDSPE) for sample preparation and screen-printed carbon electrodes (SPCEs) for square-wave anodic stripping voltammetry. This association involves the miniaturization of sample preparation and measurement process. Firstly, cadmium was extracted directly from urine samples employing a ZSM-5/Fe 2 O 3 , then, the composite enriched with cadmium was deposited onto the SPCE and finally covered with a suitable electrolyte for electrochemical detection. Thereby, the elution and detection of cadmium were carried out in a single step. To optimize experimental parameters affecting MDSPE, a two-step multivariate strategy has been employed. The method has been evaluated under optimized extraction/elution conditions (i.e., type of sorbent, ZSM-5/Fe 2 O 3; amount of sorbent, 10 mg; sample pH, 6.8; extraction time, 5.5 min; and HCl concentration, 0.5 M) using standard addition calibration. Standard addition calibration curves gave a good linearity in the range from 0 to 30 μg L -1 with correlation coefficients ranging from 0.997 to 0.998 (N = 7). The limit of detection, evaluated empirically and statistically, ranged from 0.5 to 1.0 μg L -1 and from 0.4 to 0.8 μg L -1 , respectively, which are lower than the threshold level established by the Ministry of Labour and Social Affairs (Spain) and World Health Organization for normal cadmium content in urine (i.e., 3.4 and 4.0 μg L -1 , respectively). The repeatability of the proposed method was evaluated at 5 and 20 μg L -1 spiking levels obtaining coefficients of variation ranged between 12 and 15% (n = 6). A certified reference material (REC-8848/Level II) was analyzed to assess method accuracy finding 92% and 1.3 μg L -1 as the recovery (trueness) and standard deviation values, respectively. Finally, the method was applied to spiked urine samples, obtaining good agreement between spiked and found concentrations (recovery ranged from 89 to 98% and CV values ranged from 7% to 14%). Therefore, this is a new and successful contribution to the portable total analytical systems., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To explore the specific type of messages people consider most appropriate for a mass communication campaign aimed to promote healthy eating in the context of the implementation of nutritional warnings., Design: Online study including multiple-choice and open-ended questions., Setting: Uruguay, 1 of the Latin American countries with the highest prevalence of overweight and obesity., Participants: A total of 859 participants were recruited using social media. They were diverse in terms of gender, age, educational level, socioeconomic status, and self-reported body mass index., Phenomenon of Interest: Participants were presented with 3 series of messages and were asked to select the 1 they perceived as the most appropriate and to provide a brief explanation for their selection., Analysis: Descriptive statistics for the multiple-choice questions and inductive coding for the responses to the open-ended questions., Results: Participants tended to prefer messages that conveyed a cue to action for achieving changes to their perceived ability to make healthful food choices. Although messages related to the promotion of informed food choices were the most frequently preferred, messages related to negative health consequences and health benefits were also selected repetitively., Conclusions and Implications: Communication campaigns aimed at promoting healthy eating through the use of nutritional warnings could include different contents to target specific segments with different motivations., (Copyright © 2020 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Reconstructing large bone defects caused by severe trauma or resection of tumors remains a challenge for surgeons. A fibula free flap and its vascularized bed can be transplanted to the reconstruction site to achieve healing. However, this technique adds morbidity, and requires microsurgery and sculpting of the bone tissue to adapt the graft to both the vasculature and the anatomy of the defect. The aim of the current study was to evaluate an alternative approach consisting of the in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a critical-sized bone defect. 3D printed chambers containing biphasic calcium phosphate (BCP) granules, perfused by a local vascular pedicle, with or without the addition of stromal vascular fraction (SVF), were subcutaneously implanted into New Zealand White female rabbits. SVF was prepared extemporaneously from autologous adipose tissue, the vascular pedicle was isolated from the inguinal site, while BCP granules alone served as a control group. After 8 weeks, the constructs containing a vascular pedicle exhibited abundant neovascularization with blood vessels sprouting from the pedicle, leading to significantly increased vascularization compared to BCP controls. Pre-vascularized synthetic bone grafts were then transplanted into 15 mm critical-sized segmental ulnar defects for a further 8 weeks. Micro-CT and decalcified histology revealed that pre-vascularization of synthetic bone grafts led to enhanced bone regeneration. This pre-clinical study demonstrates the feasibility and efficacy of the in situ production of pre-vascularized synthetic bone grafts for regenerating large bone defects, thereby addressing an important clinical need. STATEMENT OF SIGNIFICANCE: The current gold standard in large bone defect regeneration is vascularized fibula grafting. An alternative approach consisting of in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a bone defect is presented here. 3D printed chambers were filled with biphasic calcium phosphate granules, supplemented with autologous stromal vascular fraction and an axial vascular pedicle and subcutaneously implanted in inguinal sites. These pre-vascularized synthetic grafts were then transplanted into critical-sized segmental ulnar defects. Micro-CT and decalcified histology revealed that the pre-vascularized synthetic bone grafts led to higher bone regeneration than non-vascularized constructs. An alternative to vascularized fibula grafting is provided and may address an important clinical need for large bone defect reconstruction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Impaired multisensory integration in autism spectrum disorder (ASD) may arise from functional dysconnectivity among brain systems. Our study examines the functional connectivity integration between primary modal sensory regions and heteromodal processing cortex in ASD, and whether abnormalities in network integration relate to clinical severity., Method: We studied a sample of 55 high-functioning ASD and 64 healthy control (HC) male children and adolescents (total n = 119, age range 7-18 years). Stepwise functional connectivity analysis (SFC) was applied to resting state functional magnetic resonance images (rsfMRI) to characterize the connectivity paths that link primary sensory cortices to higher-order brain cognitive functional circuits and to relate alterations in functional connectivity integration with three clinical scales: Social Communication Questionnaire, Social Responsiveness Scale, and Vineland Adaptive Behavior Scales., Results: HC displayed typical functional connectivity transitions from primary sensory systems to association areas, but the ASD group showed altered patterns of multimodal sensory integration to heteromodal systems. Specifically, compared to the HC group, the ASD group showed the following: (1) hyperconnectivity in the visual cortex at initial link step distances; (2) hyperconnectivity between sensory unimodal regions and regions of the default mode network; and (3) hypoconnectivity between sensory unimodal regions and areas of the fronto-parietal and attentional networks. These patterns of hyper- and hypoconnectivity were associated with increased clinical severity in ASD., Conclusion: Networkwise reorganization in high-functioning ASD individuals affects strategic regions of unimodal-to-heteromodal cortical integration predicting clinical severity. In addition, SFC analysis appears to be a promising approach for studying the neural pathophysiology of multisensory integration deficits in ASD., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

This study is the first to use a new ZSM-5 zeolite-based composite decorated with iron oxide magnetic nanoparticles and modified with hexadecyltrimethylammonium bromide surfactant (i.e., HDTMA-ZSM-5/Fe 2 O 3 ) as an efficient sorbent for magnetic dispersive solid-phase extraction (MDSPE) of nonsteroidal anti-inflammatory drugs in water and urine samples with subsequent measurement by liquid chromatography diode array detection. Experimental factors affecting MDSPE were optimized using a multivariate optimization strategy. The optimum experimental conditions were: amount of sorbent, 40 mg; sample pH, 2.2; NaCl concentration, 2.5%; extraction time, 2 min; eluent solvent, methanol; eluent solvent volume, 424 μL; and elution time, 2 min. The linearity of the method was studied from 3.3 to 400 μg L -1 (N = 8) for ketoprofen, from 1.7 to 400 μg L -1 (N = 8) for felbinac, from 6.6 to 400 μg L -1 (N = 7) for diclofenac and from 9.9 to 400 μg L -1 (N = 6) for ibuprofen. Method repeatability was evaluated at 10 and 200 μg L -1 spiking levels, obtaining coefficients of variation between 2 and 5% (n = 6). Limits of detection, determined empirically, were 1.0 μg L -1 , 0.5 μg L -1 , 2.0 μg L -1 and 3.0 μg L -1 for ketoprofen, felbinac, diclofenac and ibuprofen, respectively. Tap water, reservoir water, wastewater and five urine samples were selected to assess method applicability. Recovery values ranged between 86-107% and 80-112% for water and urine samples, respectively, showing negligible matrix effects. Finally, this method was employed to monitor ibuprofen excretion in real urine samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

After the popularization of transcatheter aortic valve-in-valve replacement, mitral valve-in-valve is being increasingly performed for failing bioprostheses or annuloplasty rings. In the tricuspid position, despite smaller experience, valve-in-valve is also becoming an alternative to high-risk redo tricuspid surgery. We report the case of a patient with 2 failing mitral and tricuspid bioprostheses who was successfully treated with simultaneous transapical mitral and percutaneous transjugular tricuspid transcatheter valve-in-valve replacements., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Fluorine-18 fluorodeoxyglucose (FDG) avidity varies in peripheral T-cell lymphoma (PTCL). We evaluated FDG avidity of pretreatment positron emission tomography/computed tomography (P-PET/CT), to appraise the prognostic significance of interim PET/CT (I-PET/CT) and end of treatment PET/CT (E-PET/CT) in PTCL., Patients and Methods: We performed a retrospective cohort study of patients with newly diagnosed or relapsed PTCL who had received any chemotherapy regimen from 2008 to 2015 in a tertiary center. P-PET/CT, I-PET/CT, and E-PET/CT studies were centrally reviewed. The primary outcomes were the prognostic role of I-PET/CT and E-PET/CT on progression-free survival (PFS) and overall survival (OS). The secondary outcomes were P-PET/CT avidity, the prognostic role of other baseline characteristics, and the correlation between the PET/CT and bone marrow biopsy findings., Results: We included 40 patients in the present analysis. The median OS and PFS for the whole cohort was 39 and 16 months, respectively. Of the 40 patients, 36 had positive P-PET/CT findings. A total of 23 patients underwent I-PET/CT, with positive findings for 10. Of the 40 patients, 34 underwent E-PET/CT, 26 of which had positive findings. The sensitivity, specificity, and negative predictive value of P-PET/CT for bone marrow involvement was 40%, 83%, and 89%, respectively. The factors significantly associated with PFS and OS on univariate analysis included elevated lactate dehydrogenase, and low lymphocyte, hemoglobin, and albumin levels. On multivariate analysis, only lymphopenia remained prognostic for PFS and OS. The E-PET/CT and I-PET/CT results were not prognostic for PFS or OS., Conclusion: Our study has shown that 90% of PTCL cases will be FDG avid. However, PET/CT was not predictive for PFS or OS at any point. The only predictive factor was the presence of lymphopenia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: We aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT)., Methods: This is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre., Results: Febrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02)., Conclusion: According to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A novel approach is presented to determine hydrophilic phenols in olive oil samples, employing vortex-assisted reversed-phase dispersive liquid-liquid microextraction (RP-DLLME) for sample preparation and screen-printed carbon electrodes for voltammetric analysis. The oxidation of oleuropein, hydroxytyrosol, caffeic acid, ferulic acid and tyrosol was investigated, being caffeic acid and tyrosol selected for quantification. A matrix-matching calibration using sunflower oil as analyte-free sample diluted with hexane was employed to compensate matrix effects. Samples were analyzed under optimized RP-DLLME conditions, i.e., extractant phase, 1M HCl; extractant volume, 100µL; extraction time, 2min; centrifugation time, 10min; centrifugation speed, 4000rpm. The working range showed a good linearity between 0.075 and 2.5mgL -1 (r = 0.998, N = 7) for caffeic acid, and between 0.075 and 3mgL -1 (r = 0.999, N = 8) for tyrosol. The methodological limit of detection was empirically established at 0.022mgL -1 for both analytes, which is significantly lower than average contents found in olive oil samples. The repeatability was evaluated at two different spiking levels (i.e., 0.5mgL -1 and 2mgL -1 ) and coefficients of variation ranged from 8% to 11% (n = 5). The applicability of the proposed method was tested in olive oil samples of different quality (i.e., refined olive oil, virgin olive oil and extra virgin olive oil). Relative recoveries varied between 83% and 108% showing negligible matrix effects. Finally, fifteen samples were analyzed by the proposed method and a high correlation with the traditional Folin-Ciocalteu spectrophotometric method was obtained. Thereafter, the concentrations of the fifteen oil samples were employed as input variables in linear discriminant analysis in order to distinguish between olive oils of different quality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The adjunction of platelet-rich plasma with graft fat has been the subject of a few clinical trials which have demonstrated its value in adipocyte survival. The aim of this study was to assess the different efficacies between activated and non-activated PRP on adipose cells in vitro and for adipose tissue graft survival in vivo., Methods: The in vitro study assessed the effects of PRP on both the proliferation and adipocyte differentiation of adipose cells. For the in vivo study, 8 nude rats received 3 human fat injections as follows: 0.8 mL of fat + 0.2 mL of normal saline; 0.8 mL of fat + 0.2 mL of non-activated PRP; and 0.8 mL of fat + 0.2 mL of PRP activated with calcium chloride (CaCl 2 ). The quantitative assessment of adipocyte survival was implemented after 3 months using histomorphometric analysis. Histological and immunohistochemical analysis were also performed to evaluate angiogenesis, inflammation and quality of adipocytes in the grafted tissue., Results: We showed that activated PRP stimulated, in vitro, proliferation and differentiation of adipose cells. In vivo experiments indicated that CaCl 2 -activated PRP was more efficient than non-activated to prolong the survival of fat grafts in nude rats. The mean percentage areas occupied by viable adipocytes in the PRP-free group, non-activated PRP group and activated PRP group were 13%, 14% and 24% (p = 0.05%), respectively. Histological and immunohistochemical analysis revealed protective effect of activated PRP on inflammation and adipocyte death., Conclusion: This study showed that activation by CaCl 2 improves the beneficial effects of PRP for fat graft maintenance., (Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

NAD(P)H-dependent oxidoreductases catalyze the reduction or oxidation of a substrate coupled to the oxidation or reduction, respectively, of a nicotinamide adenine dinucleotide cofactor NAD(P)H or NAD(P) + . NAD(P)H-dependent oxidoreductases catalyze a large variety of reactions and play a pivotal role in many central metabolic pathways. Due to the high activity, regiospecificity and stereospecificity with which they catalyze redox reactions, they have been used as key components in a wide range of applications, including substrate utilization, the synthesis of chemicals, biodegradation and detoxification. There is great interest in tailoring NAD(P)H-dependent oxidoreductases to make them more suitable for particular applications. Here, we review the main properties and classes of NAD(P)H-dependent oxidoreductases, the types of reactions they catalyze, some of the main protein engineering techniques used to modify their properties and some interesting examples of their modification and application., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

This study presents a new, user-friendly, cost-effective and portable headspace solid-phase extraction technique based on graphene oxide decorated with iron oxide magnetic nanoparticles as sorbent, located on one end of a small neodymium magnet. Hence, the new headspace solid-phase extraction technique has been called Magnetic Headspace Adsorptive Extraction (Mag-HSAE). In order to assess Mag-HSAE technique applicability to model analytes, some chlorobenzenes were extracted from water samples prior to gas chromatography-mass spectrometry determination. A multivariate approach was employed to optimize the experimental parameters affecting Mag-HSAE. The method was evaluated under optimized extraction conditions (i.e., sample volume, 20 mL; extraction time, 30 min; sorbent amount, 10 mg; stirring speed, 1500 rpm, and ionic strength, non-significant), obtaining a linear response from 0.5 to 100 ng L -1 for 1,3-DCB, 1,4-DCB, 1,2-DCB, 1,3,5-TCB, 1,2,4-TCB and 1,2,3-TCB; from 0.5 to 75 ng L -1 for 1,2,4,5-TeCB, and PeCB; and from 1 to 75 ng L -1 for 1,2,3,4-TeCB. The repeatability of the proposed method was evaluated at 10 ng L -1 and 50 ng L -1 spiking levels, and coefficients of variation ranged between 1.5 and 9.5% (n = 5). Limits of detection values were found between 93 and 301 pg L -1 . Finally, tap, mineral and effluent water were selected as real water samples to assess method applicability. Relative recoveries varied between 86 and 110% showing negligible matrix effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To evaluate the influence of label design on children's perception of 2 popular snack foods across 3 income levels., Design: Labels of 2 snack products (yogurt and sponge cake) were designed using a fractional factorial design with 3 2-level variables: cartoon character, nutrition claims, and front-of-package nutritional information., Participants: A total of 221 children (aged 9-13 years) from Montevideo, Uruguay, with different income levels, participated in the study., Main Outcome Measures: Children's attitude toward and liking of 2 food products., Results: Low-income children showed a more positive attitude toward the products than did middle- and high-income children. The inclusion of a cartoon character in sponge cake labels significantly affected hedonic expectations regardless of income. Middle- and high-income children tended to use the term funny more frequently and the term boring less frequently to describe labels that included the cartoon character, compared with those that did not., Conclusions and Implications: Results showed that the inclusion of cartoon characters on food labels is associated with fun. Low-income children seem more susceptible to the marketing strategies of food companies than do middle- and high-income children., (Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Purpose: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound., Methods: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET) imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT). TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS)., Results: PET imaging with [ 18 F]ICF15002 evidenced tumoral uptake of 14.33±2.11%ID/g and 4.87±0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [ 131 I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT) of 2.9±0.5 days in treated vs 1.8±0.3 in controls] and a prolonged median survival (27 days vs 21 in controls). P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5±7.8 days vs 11.0±3.8 in controls) and improved median survival (111 days vs 74 in controls)., Conclusion: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

This study reports a new composite based on ZSM-5 zeolite decorated with iron oxide magnetic nanoparticles as a valuable sorbent for magnetic solid-phase extraction (MSPE). A proposal is made to determine benzene, toluene, ethylbenzene and xylenes (BTEX) as model analytes in water samples using gas chromatography-mass spectrometry. A two-step multivariate optimization strategy, using Plackett⬜Burman and circumscribed central composite designs, was employed to optimize experimental parameters affecting MSPE. The method was evaluated under optimized extraction conditions (i.e., amount of sorbent, 138mg; extraction time, 11min; sample pH, pH of water (i.e., 5.5⬜6.5); eluent solvent volume, 0.5mL; and elution time, 5min), obtaining a linear response from 1 to 100μgL(↙1) for benzene; from 10 to 100μgL(↙1) for toluene, ethylbenzene and o-xylene; and from 10 to 75μgL(↙1) for m,p-xylene. The repeatability of the proposed method was evaluated at a 40μgL(↙1) spiking level and coefficients of variation ranged between 8 and 11% (n=5). Limits of detection were found to be 0.3μgL(↙1) for benzene and 3μgL(↙1) for the other analytes. These values satisfy the current normative of the Environmental Protection Agency and European Union for BTEX content in waters for human consumption. Finally, drinking water, wastewater and river water were selected as real water samples to assess the applicability of the method. Relative recoveries varied between 85% and 114% showing negligible matrix effects., (Copyright © 2016 Elsevier B.V. All rights reserved.)