Tumor-infiltrating lymphocytes in patients receiving trastuzumab/pertuzumab-based chemotherapy : a TRYPHAENA Substudy

Background: There is an urgent requirement to identify biomarkers to tailor treatment in human epidermal growth factor receptor 2 (HER2)-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Methods: Among the 225 patients randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 patients, of which 126 demonstrated a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) events. We investigated associations between baseline TIL percentage and either pCR or EFS after adjusting for clinicopathological characteristics using logistic and Cox regression models, respectively. To understand TIL biology, we evaluated associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 patients. All statistical tests were two-sided. Results: Among the patients with measurable TILs at baseline, the median level was 14.1% (interquartile range = 7.1%-32.4%). After adjusting for clinicopathological characteristics, baseline percentage TIL was not associated with pCR (adjusted odds ratio [aOR] for every 10-percentage unit increase in TILs = 1.12, 95% confidence interval [CI] = 0.95 to 1.31, P = .17). At a median follow-up of 4.7 years, for every increase in baseline TILs of 10%, there was a 25% reduction in the hazard for an EFS event (aOR = 0.75, 95% CI = 0.56 to 1.00, P = .05) after adjusting for baseline clinicopathological characteristics and pCR. Additionally, genes associated with epithelial-mesenchymal transition, angiogenesis, and T-cell inhibition such as SNAIL1, ZEB1, NOTCH3, and B7-H3 were statistically significantly inversely correlated with percentage TIL. Conclusions: Baseline TIL percentage provides independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. However, further validation is required

Extreme and long-term drought in the La Plata Basin: event evolution and impact assessment until September 2022

The current drought conditions across the Parana-La Plata Basin (LPB) in Brazil-Argentina have been the worst since 1944. While this area is characterized by a rainy season with a peak from October to April, the hydrological year 2020-2021 was very deficient in rainfall, and the situation extended into the 2021-2022 hydrological year. Below-normal rainfall was dominant in south-eastern Brazil, northern Argentina, Paraguay, and Uruguay, suggesting a late onset and weaker South American Monsoon and the continuation of drier conditions since 2021. In fact, in 2021 Brazilian south and south-east regions faced their worst droughts in nine decades, raising the spectre of possible power rationing given the grid dependence on hydroelectric plants. The Paraná-La Plata Basin drought induced damages to agriculture and reduced crop production, including soybeans and maize, with effects on global crop markets. The drought situation continued in 2022 in the Pantanal region. Dry meteorological conditions are still present in the region at the end of September 2022 with below-average precipitation anomalies. Soil moisture anomaly and vegetation conditions are worst in the lower part of the La Plata Basin, in the southern regions. Conversely, upper and central part of the basin show partial and temporary recovery

Sediment source fingerprinting: benchmarking recent outputs, remaining challenges and emerging themes

Abstract: Purpose: This review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science. Methods: Web of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017. Scope: Areas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing. Conclusions: The popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach

Synthesis and NMR Spectra of Substituted 1,4,5,8‐Tetraazaphenanthrenes(TAP)

The synthesis of ring A substituted TAP'S starts from 5,6‐diaminoquinoxaline (II), which is condensed with n‐butylglyoxylate to give a mixture of 2‐ and 3‐hydroxy‐TAP, which reacted with POCl3/PCl5 to afford the corresponding monochlorocompound. Similarly, the condensation of II and ethyl oxalate produces 2,3‐dihydroxy‐TAP; this gives 2,3‐dichloro‐TAP with the same chlorinating agents. Nucleophilic substitution of the chlorine atom(s) (sodium methoxide, piperidine, hydrazine) occurs with high yields. The monohydrazino‐TAP's were oxidized into the corresponding monodeuterated derivatives, which allow an unambiguous assignment of the 1H NMR spectrum of TAP itself. Copyright © 1979 Wiley‐VCH Verlag GmbH & Co. KGaA, WeinheimSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Group vib carbonyl complexes of pyrazino[2.3-f]quinoxaline or 1,4,5,8-tetraazaphenanthrene (tap)

1,4,5,8-Tetraazaphenanthrenemetal tetracarbonyl complexes (metal = Cr, Mo, W) have been synthesized. The CO force constants show that there is more backbonding in these complexes than in the analogous 1,10-phenanthroline complexes, because of the two additional electron-withdrawing nitrogen atoms. The M→ L CT transitions show a strong bathochromic shift relative to the corresponding o-phenanthroline complexes. © 1979.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Synthesis of 9‐substituted‐1,4,5,8‐tetraazaphenanthrenes

The synthesis of 9‐substituted‐1,4,5,8‐tetraazaphenanthrenes was undertaken in the course of a study aimed at the preparation of organometallic complexing agents. Copyright © 1980 Journal of Heterocyclic ChemistrySCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

13C NMR spectra of chromium tetracarbonyl complexes of 1,4,5,8-tetraazaphenanthrene and 1,4,5,8,9,12-hexaazatriphenylene

The 13C NMR spectra of the chromium tetracarbonyl complexes (TAP)Cr(CO)4 and (HAT)Cr(CO)4 in both the carbonyl and the ligand region are assigned on the basis of substituent effects and 1H single frequency 13C spectra. © 1983.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A new heterocyclic ligand for transition metals: 1,4,5,8,9,12-hexaazatriphenylene and its chromium carbonyl complexes

The synthesis of 1,4,5,8,9,12-hexaazatriphenylene (HAT), a new ligand for low-valent transition metals, is described; it gives mono-, bis- and tris-chromium tetracarbonyl complexes. The CO stretching frequencies in (HAT)Cr(CO)4 show that HAT is a stronger electron acceptor than 1,10-phenanthroline. © 1981.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Photoelectrochemistry of a new ruthenium complex, the Ru(II)-tris-(1,4,5,8- tetra-aza phenanthrene)dication

info:eu-repo/semantics/publishe

Synthesis and spectroscopic and electrochemical properties of a new ruthenium complex: the tris(1,4,5,8-tetraazaphenanthrene-ruthenium(II)dication

SCOPUS: no.jinfo:eu-repo/semantics/publishe