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1.
Sci Total Environ ; 931: 172913, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38697521

ABSTRACT

This study examines the influence of meteorological factors and air pollutants on the performance of automatic pollen monitoring devices, as part of the EUMETNET Autopollen COST ADOPT-intercomparison campaign held in Munich, Germany, during the 2021 pollen season. The campaign offered a unique opportunity to compare all automatic monitors available at the time, a Plair Rapid-E, a Hund-Wetzlar BAA500, an OPC Alphasense, a KH-3000 Yamatronics, three Swisens Polenos, a PollenSense APS, a FLIR IBAC2, a DMT WIBS-5, an Aerotape Sextant, to the average of four manual Hirst traps, under the same environmental conditions. The investigation aimed to elucidate how meteorological factors and air pollution impact particle capture and identification efficiency. The analysis showed coherent results for most devices regarding the correlation between environmental conditions and pollen concentrations. This reflects on one hand, a significant correlation between weather and airborne pollen concentration, and on the other hand the capability of devices to provide meaningful data under the conditions under which measurements were taken. However, correlation strength varied among devices, reflecting differences in design, algorithms, or sensors used. Additionally, it was observed that different algorithms applied to the same dataset resulted in different concentration outputs, highlighting the role of algorithm design in these systems (monitor + algorithm). Notably, no significant influence from air pollutants on the pollen concentrations was observed, suggesting that any potential difference in effect on the systems might require higher air pollution concentrations or more complex interactions. However, results from some monitors were affected to a minor degree by specific weather variables. Our findings suggest that the application of real-time devices in urban environments should focus on the associated algorithm that classifies pollen taxa. The impact of air pollution, although not to be excluded, is of secondary concern as long as the pollution levels are similar to a large European city like Munich.


Subject(s)
Air Pollutants , Air Pollution , Environmental Monitoring , Pollen , Environmental Monitoring/methods , Air Pollutants/analysis , Germany , Air Pollution/statistics & numerical data , Air Pollution/analysis , Weather
2.
ACS Cent Sci ; 9(8): 1525-1537, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37637738

ABSTRACT

Before leveraging big data methods like machine learning and artificial intelligence (AI) in chemistry, there is an imperative need for an affordable, universal digitization standard. This mirrors the foundational requisites of the digital revolution, which demanded standard architectures with precise specifications. Recently, we have developed automated platforms tailored for chemical AI-driven exploration, including the synthesis of molecules, materials, nanomaterials, and formulations. Our focus has been on designing and constructing affordable standard hardware and software modules that serve as a blueprint for chemistry digitization across varied fields. Our platforms can be categorized into four types based on their applications: (i) discovery systems for the exploration of chemical space and novel reactivity, (ii) systems for the synthesis and manufacture of fine chemicals, (iii) platforms for formulation discovery and exploration, and (iv) systems for materials discovery and synthesis. We also highlight the convergent evolution of these platforms through shared hardware, firmware, and software alongside the creation of a unique programming language for chemical and material systems. This programming approach is essential for reliable synthesis, designing experiments, discovery, optimization, and establishing new collaboration standards. Furthermore, it is crucial for verifying literature findings, enhancing experimental outcome reliability, and fostering collaboration and sharing of unsuccessful experiments across different research labs.

3.
Nat Commun ; 14(1): 2973, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221181

ABSTRACT

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.


Subject(s)
Carcinoid Tumor , Neuroendocrine Tumors , Humans , B7-H1 Antigen , Lung
4.
Environ Impact Assess Rev ; 99: 107013, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36532697

ABSTRACT

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy.

5.
Nat Chem ; 14(11): 1311-1318, 2022 11.
Article in English | MEDLINE | ID: mdl-36202987

ABSTRACT

Robotic systems for synthetic chemistry are becoming more common, but they are expensive, fixed to a narrow set of reactions, and must be used within a complex laboratory environment. A portable system that could synthesize known molecules anywhere, on demand, and in a fully automated way, could revolutionize access to important molecules. Here we present a portable suitcase-sized chemical synthesis platform containing all the modules required for synthesis and purification. The system uses a chemical programming language coupled to a digital reactor generator to produce reactors and executable protocols based on text-based literature syntheses. Simultaneously, the platform generates a reaction pressure fingerprint, used to monitor processes within the reactors and remotely perform a protocol quality control. We demonstrate the system by synthesizing five small organic molecules, four oligopeptides and four oligonucleotides, in good yields and purities, with a total of 24,936 base steps executed over 329 h of platform runtime.


Subject(s)
Oligonucleotides
7.
Clin. transl. oncol. (Print) ; 23(5): 948-960, mayo 2021. tab, ilus
Article in English | IBECS | ID: ibc-221235

ABSTRACT

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available (AU)


Subject(s)
Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Melanoma/diagnosis , Melanoma/therapy , Neoplasm Staging , Societies, Medical , Spain
8.
ACS Cent Sci ; 7(2): 212-218, 2021 Feb 24.
Article in English | MEDLINE | ID: mdl-33655058

ABSTRACT

We describe a system, ChemSCAD, for the creation of digital reactors based on the chemical operations, physical parameters, and synthetic sequence to produce a given target compound, to show that the system can translate the gram-scale batch synthesis of the antiviral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anticancer agent Lomustine (batch yield 65% over two steps) in purities greater than or equal to 96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a database repository, with the information necessary to critically evaluate and improve upon reactionware syntheses being easily shared and versioned.

9.
Clin Transl Oncol ; 23(5): 948-960, 2021 May.
Article in English | MEDLINE | ID: mdl-33651321

ABSTRACT

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.


Subject(s)
Melanoma/pathology , Melanoma/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Biopsy , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Chemotherapy, Adjuvant/methods , Follow-Up Studies , Humans , Immunotherapy/methods , Lymph Node Excision , Medical Oncology , Melanoma/diagnosis , Melanoma/genetics , Molecular Targeted Therapy/methods , Neoplasm Staging , Proto-Oncogene Proteins B-raf/analysis , Proto-Oncogene Proteins B-raf/genetics , Radiotherapy, Adjuvant , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Societies, Medical , Spain
10.
Sci Rep ; 10(1): 13234, 2020 08 06.
Article in English | MEDLINE | ID: mdl-32764560

ABSTRACT

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.


Subject(s)
Antigens, Bacterial/immunology , Latent Tuberculosis/diagnosis , Mycobacterium tuberculosis/immunology , Tuberculosis/diagnosis , Adult , Case-Control Studies , Early Diagnosis , Female , Humans , Interferon-gamma Release Tests , Male , Middle Aged , Sensitivity and Specificity , Spain , Tuberculin Test , Tuberculosis/immunology
11.
J Am Chem Soc ; 142(6): 2935-2947, 2020 02 12.
Article in English | MEDLINE | ID: mdl-31927883

ABSTRACT

Single-site organolanthanum complexes supported on mesoporous silica nanoparticles, La{C(SiHMe2)3}n@MSNs, catalyze the ring-opening hydroboration reaction of aliphatic and styrenic epoxides with pinacolborane (HBpin). The surface-bound complexes, synthesized by reaction of the homoleptic tris(alkyl)lanthanum La{C(SiHMe2)3}3 and SBA-type MSN treated at 700 °C (MSN700), are mostly monopodal ≡SiO-La{C(SiHMe2)3}2 and contain an average of one bridging La↼H-Si per alkyl ligand. This structure was established through a combination of solid-state NMR (SSNMR) experiments, including J-resolved SiH coupling and quantitative 29Si measurements, diffuse reflectance IR, and elemental analysis. These rigorous analyses also established that grafting reactions in pentane provide a preponderance of ≡SiO-La{C(SiHMe2)3}2 sites and are superior to those in benzene and THF, and that grafting onto MSN treated at 550 °C (MSN550) results in a mixture of surface species. The single-site supported catalysts are more selective and in most cases more active than the homogeneous analogue, allow easy purification of products from the catalyst, are strongly resistant to leaching into solution phase, and may be recycled for reuse at least five times. After reaction of La{C(SiHMe2)3}n@MSN and HBpin, species including ≡SiO-La{C(SiHMe2)3}(H2Bpin) and ≡SiO-La{C(SiHMe2)3}{κ2-pinB-O(CMe2)2OBH3} are identified by detailed 1D and 2D 11B SSNMR experiments.

12.
Clin Transl Oncol ; 22(3): 411-419, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31144211

ABSTRACT

PURPOSE: We performed a cross-sectional study of neurocognitive function in non-brain cancer patients treated with long-term bevacizumab. METHODS/PATIENTS: From 2015 to 2017, we included patients with different types of cancer treated with bevacizumab with or without chemotherapy (BEV; N = 20) or only chemotherapy (ChT; N = 19) for at least 34 weeks, patients who received non-brain radiotherapy (RxT; N = 19), and healthy controls (HC; N = 19) were assessed once at week 34 of treatment (BEV and ChT) or at completion of radiotherapy. Neurocognition was evaluated with the Hopkins Verbal Learning Test-Revised (HVLT-R) total and delayed recall, the Trail Making Test A and B, and the Controlled Oral Word Association Test in the four groups. Non-parametric tests were used to assess differences between groups. RESULTS: The BEV, ChT, and RxT groups scored significantly lower than the HC group on all tests and especially on the HVLT-R total recall. In no case were the mean scores of the BEV group significantly lower than those of the ChT or RxT groups. CONCLUSIONS: Neurocognitive impairment was seen even in patients treated with local non-brain radiotherapy. Treatment with bevacizumab for a long period of time does not seem to worsen neurocognitive function to a greater extent than chemotherapy.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Bevacizumab/therapeutic use , Neoplasms/drug therapy , Neurocognitive Disorders/diagnosis , Antineoplastic Agents, Immunological/adverse effects , Bevacizumab/adverse effects , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Neoplasms/radiotherapy , Neurocognitive Disorders/etiology , Neuropsychological Tests
13.
Sci Total Environ ; 673: 821-830, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31005018

ABSTRACT

Solar photovoltaic systems have become one of the most popular topics in the water management industry. Moreover, irrigation networks are water- and energy-hungry, and utility managers are likely to adapt water consumption (and consequently energy demand) to the hours in which there is energy availability. In countries such as Spain (with high irradiance values), solar energy is an available green alternative characterised by zero electricity costs and significantly lower environmental impact. In this work, several types of irrigation scheduled programmes (according to different irrigation sectors) that minimise the number of photovoltaic solar panels to be installed are studied; moreover, the effects of the variable costs linked to energy (energy and emissions costs) are presented. Finally, the effect of incorporating batteries for storing energy to protect the system against emergencies, such as unfavourable weather, is proposed. The irrigation hours available to satisfy water demands are limited by sunlight; they are also limited by the condition that the irrigation schedule type has to be rigid (predetermined rotation) and that the pressure at any node has to be above minimum pressure required by standards. A real case study is performed, and the results obtained demonstrate that there is no universal solution; this is because the portfolio of alternatives is based on investments for purchasing equipment at present and also on future energy savings (revenues). Apart from these two values, there is an economic value (equivalent discontinuous discount rate), which also influences the final results.

14.
Sci Rep ; 9(1): 3943, 2019 03 08.
Article in English | MEDLINE | ID: mdl-30850687

ABSTRACT

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.


Subject(s)
Dried Blood Spot Testing/methods , Latent Tuberculosis/diagnosis , Adult , Chemokine CXCL10/blood , Contact Tracing , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interferon-gamma Release Tests/methods , Latent Tuberculosis/blood , Male , Postal Service , ROC Curve , Sensitivity and Specificity
15.
Ann Oncol ; 30(3): 439-446, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30689692

ABSTRACT

BACKGROUND: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. PATIENTS AND METHODS: Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. RESULTS: After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples. CONCLUSIONS: No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours.


Subject(s)
Colorectal Neoplasms/drug therapy , GTP Phosphohydrolases/genetics , Membrane Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cetuximab/administration & dosage , Class I Phosphatidylinositol 3-Kinases/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Germany , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation/genetics , Neoplasm Metastasis , Protein Kinase Inhibitors/administration & dosage , Treatment Outcome
16.
Eur J Cancer ; 101: 263-272, 2018 09.
Article in English | MEDLINE | ID: mdl-30054049

ABSTRACT

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab/administration & dosage , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease-Free Survival , Exanthema/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm Metastasis , Neutropenia/chemically induced , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Proto-Oncogene Proteins p21(ras)/genetics
17.
Sci Total Environ ; 618: 870-880, 2018 Mar 15.
Article in English | MEDLINE | ID: mdl-29108696

ABSTRACT

The application of next-generation sequencing (NGS) techniques for the identification of viruses present in urban sewage has not been fully explored. This is partially due to a lack of reliable and sensitive protocols for studying viral diversity and to the highly complex analysis required for NGS data processing. One important step towards this goal is finding methods that can efficiently concentrate viruses from sewage samples. Here the application of a virus concentration method based on skimmed milk organic flocculation (SMF) using 10L of sewage collected in different seasons enabled the detection of many viruses. However, some viruses, such as human adenoviruses, could not always be detected using metagenomics, even when quantitative PCR (qPCR) assessments were positive. A targeted metagenomic assay for adenoviruses was conducted and 59.41% of the obtained reads were assigned to murine adenoviruses. However, up to 20 different human adenoviruses (HAdV) were detected by this targeted assay being the most abundant HAdV-41 (29.24%) and HAdV-51 (1.63%). To improve metagenomics' sensitivity, two different protocols for virus concentration were comparatively analysed: an ultracentrifugation protocol and a lower-volume SMF protocol. The sewage virome contained 41 viral families, including pathogenic viral species from families Caliciviridae, Adenoviridae, Astroviridae, Picornaviridae, Polyomaviridae, Papillomaviridae and Hepeviridae. The contribution of urine to sewage metavirome seems to be restricted to a few specific DNA viral families, including the polyomavirus and papillomavirus species. In experimental infections with sewage in a rhesus macaque model, infective human hepatitis E and JC polyomavirus were identified. Urban raw sewage consists of the excreta of thousands of inhabitants; therefore, it is a representative sample for epidemiological surveillance purposes. The knowledge of the metavirome is of significance to public health, highlighting the presence of viral strains that are circulating within a population while acting as a complex matrix for viral discovery.


Subject(s)
Metagenomics , Public Health Surveillance , Sewage/virology , Viruses/isolation & purification , Animals , Humans , Macaca mulatta , Spain , Viruses/genetics
18.
Ann Oncol ; 29(2): 439-444, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29145602

ABSTRACT

Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.


Subject(s)
Colorectal Neoplasms/drug therapy , DNA-Binding Proteins/genetics , Endonucleases/genetics , Pharmacogenomic Testing/methods , Pharmacogenomic Variants/genetics , Thymidylate Synthase/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Female , Genotype , Humans , Male , Middle Aged , Patient Selection , Precision Medicine/methods , Progression-Free Survival , Treatment Outcome
19.
Cytopathology ; 29(1): 35-40, 2018 02.
Article in English | MEDLINE | ID: mdl-29119620

ABSTRACT

BACKGROUND: In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer. PATIENTS AND METHODS: The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS-TBNA in our institution were retrospectively analysed. The ability of EBUS-TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated. RESULTS: Twenty-four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS-TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients. CONCLUSION: In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS-TBNA whenever a sufficient tissue sample is collected.


Subject(s)
Biomarkers, Tumor/analysis , Biopsy, Fine-Needle/methods , Breast Neoplasms/pathology , Mediastinal Neoplasms/secondary , Neoplasm Metastasis/pathology , Female , Humans , Mediastinal Neoplasms/pathology , Receptor, ErbB-2/analysis , Receptor, ErbB-2/biosynthesis , Receptors, Estrogen/analysis , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/analysis , Receptors, Progesterone/biosynthesis , Retrospective Studies , Ultrasonography, Interventional/methods
20.
Sci Rep ; 7(1): 6777, 2017 07 28.
Article in English | MEDLINE | ID: mdl-28754991

ABSTRACT

We developed a novel method, PyroTyping, for discrimination of Mycobacterium tuberculosis isolates combining pyrosequencing and IS6110 polymorphism. A total of 100 isolates were analysed with IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, mycobacterial interspersed repetitive units - variable number tandem repeats (MIRU-VNTR), and PyroTyping. PyroTyping results regarding clustering or discrimination of the isolates were highly concordant with the other typing methods performed. PyroTyping is more rapid than RFLP and presents the same discriminatory power, thus, it may be useful for taking timely decisions for tuberculosis control.


Subject(s)
High-Throughput Nucleotide Sequencing/methods , Mycobacterium tuberculosis/genetics , Bacterial Typing Techniques , Genotype , Minisatellite Repeats/genetics , Mycobacterium tuberculosis/classification , Polymorphism, Restriction Fragment Length/genetics
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