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RNA datasets to derive predictors for immune checkpoint inhibitor therapy of non-small cell lung cancer
<p>Nanostring nCounter datasets and corresponding clinical data of tumor samples of patients with advanced NSCLC who received anti-PD-1 immuntherapy. Prospectively divided into a discovery and a validation cohort.</p> <p>Please cite the corresponding publication in Annals of Oncology (10.1093/annonc/mdz049)</p>
Spatial immunophenotyping of the tumor microenvironment in non-small cell lung cancer
<p>A dataset with spatial immune cell information on a lung cancer cohort from Uppsala University Hospital, Sweden, with anonymized clinical data. For more information please refer to the 'readme' file and the original study (https://doi.org/10.1016/j.ejca.2023.02.012).</p>
Identification of biomarkers for the early detection of non-small cell lung cancer: a systematic review and meta-analysis
<p>We sought to identify the best biomarkers for the early diagnosis of LC, using a systematic review of seven databases. We identified 79 articles that focused on the identification and assessment of diagnostic biomarkers and then performed a meta-analysis. This work has been submitted for publication.</p>
Flow cytometry of mesenteric lymph nodes, small and large intestinal lamina propria, and spinal cord cells from fibre-rich and fiber-free diet-fed gnotobiotic mice at baseline and after experimental autoimmune encephalomyelitis (EAE) induction
<p>We perform profiling of different immune cell populations in the small (SILP) and large intestine lamina propria (CLP), mesenteric lymph nodes (MLN) and spinal cords (SC). We are specifically interested to evaluate the impact of dietary fiber deprivation followed by mucus erosion on the immune cell profiles of T helper cells (Th cells, T cell population) of gnotobiotic mice fed a fiber-rich (FR) or fiber-free (FF) diet. This dataset aims to assess the impact of microbiome and diet on disease course in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) via T cell populations. Mice are either germ-free or colonized by intragastric gavage with a defined variation of a 14-member synthetic human gut microbiome (doi: 10.1016/j.cell.2016.10.043 and 10.1016/j.xpro.2021.100607): SM01 (Akkermansia muciniphila monocolonisation), SM03 (Bacteroides caccae, Bacteroides thetaiotaomicron, Barnesiella intestinihominis), SM04 (B. caccae, B. thetaiotaomicron, B. intestinihominis, A. muciniphila), SM12 (full community except mucin-specialists B. intestinihominis and A. muciniphila), SM13 (full community except mucin specialist A. muciniphila), or SM14 (full community: Roseburia intestinalis, Faecalibacterium prausnitzii, Marvinbryantia formatexigens, Collinsella aerofaciens, Desulfovibrio piger, B. caccae, B. thetaiotaomicron, Bacteroides ovatus, Bacteroides uniformis, B. intestinihominis, Eubacterium rectale, Clostridium symbiosum, Escherichia coli, and A. muciniphila). At age 5 to 8 weeks, mice were colonized with SM combinations while fed an FR diet. Mice were either maintained on an FR diet or switched to an FF diet at 5 days after initial colonization, until the end of experiment. Baseline samples were collected 20 days following the diet switch. Otherwise, EAE induction was performed 15 days after the diet switch and samples were collected 30 days after the induction.</p>
Data and scripts for SCLC_CellMiner: Integrated Genomics and Therapeutics Predictors of Small Cell Lung Cancer Cell Lines based on their genomic signatures
<p>This is the repository of data and scripts for the analysis of the CellminerCDB-SCLC manuscript and website (<a href="https://discover.nci.nih.gov/SclcCellMinerCDB/">https://discover.nci.nih.gov/SclcCellMinerCDB/</a>)</p> <p> </p> <p>CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB) integrates 118 patient-derived cell lines with drug sensitivity and genomic datasets, including high resolution methylome and RNAseq data. CellMiner-SCLC provides a new resource for SCLC research for this “recalcitrant cancer”. Of fundamental importance, we demonstrate the reproducibility and stability of the cell line datasets from different institutions (CCLE, GDSC, CTRP, NCI and UTSW). We validate the classification based on four master transcription factors: NEUROD1, ASCL1, POU2F3 and YAP1 and show transcription networks connecting them with the MYC genes (MYC, MYCL1 and MYCN) and the NOTCH and HIPPO pathways. We find that the 4 subsets express specific surface markers for antibody-targeted therapies. The YAP1-driven (SCLC-Y) cell lines differ from the other subsets by expressing the NOTCH pathway, epithelial-mesenchymal-transition (EMT) and antigen-presenting machinery (APM) genes, and by responding to mTOR and AKT inhibitors, suggesting the potential of NOTCH modulators, YAP1 inhibitors and immune checkpoint inhibitors for SCLC-Y tumors.</p>
Metabolomics Analysis for the Identification of Biomarkers in Small Cell Lung Cancer
<p>Small cell lung cancer (SCLC), a highly aggressive malignancy with a poor prognosis is usually detected at the extensive stage of the disease. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as NSE and NCAM have already been utilized in clinics. Here, we conducted untargeted metabolomics in 54 plasma samples from 34 patients with SCLC and 20 healthy controls.</p>
Bevacizumab plus erlotinib versus erlotinib alone as first line treatment of patients with EGFR-mutated advanced nonsquamous non-small cell lung cancer. BEVacizumab plus ERLotinib studY (BEVERLY): an academic, multicenter, randomised phase III trial.
<p>Background. Adding bevacizumab to erlotinib prolonged PFS of patients with EGFR-mutated advanced NSCLC in the Japanese NEJ026 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized phase III trial of bevacizumab plus erlotinib versus erlotinib alone as first-line treatment of advanced EGFR-mutated NSCLC.</p> <p>Methods. Eligible patients were randomized 1:1 to erlotinib (150mg daily) plus bevacizumab (15mg/kg iv q3w) or erlotinib alone, until disease progression or unacceptable toxicity. Center, ECOG PS and type of mutation (ex19 deletion vs ex21 L858R vs others) were stratification variables. Investigator-assessed PFS (IA-PFS) and blinded-independent centrally-reviewed PFS (BICR-PFS) were co-primary endpoints. With 80% power in detecting a 0·60 HR and 2–sided α error 0·05, 126 events out of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.</p> <p>Findings. From Apr 11, 2016 to Feb 27, 2019, 160 pts were randomized to erlotinib pus bevacizumab (80) or erlotinib alone (80). Baseline characteristics were balanced between arms; 34 (42·5%) patients in erlotinib plus bevacizumab arm and 43 (53·8%) in erlotinib arm were former or current smokers. At a median follow-up of 36·3 months, 140 PFS events (87·5%) were reported, 68 with erlotinib plus bevacizumab and 72 with erlotinib. Median IA-PFS was 15·4 months (95% CI 12·2–18·6) with erlotinib plus bevacizumab and 9·6 months (95% CI 8·2–10·6) with erlotinib (HR 0·66; 95%CI: 0·47–0·92). BICR-PFS analysis confirmed this result. A significant interaction with treatment effect was found for smoking habit (P=0·0323): former or current smokers receiving erlotinib plus bevacizumab had a longer PFS (16·9 months [95% CI 10·2–21·8] versus 8·8 months [95% CI 5·6–9·6]) than those receiving erlotinib alone.</p> <p>Hypertension (grade≥3: 24% vs 5%), skin rash (grade≥3: 31% vs 14%), thromboembolic events (any grade: 11% vs 4%), and proteinuria (any grade: 23% vs 6%) were more frequent with the combination treatment.</p> <p>Interpretation. The addition of bevacizumab to first-line erlotinib significantly prolonged PFS in Italian patients with EGFR-mutated NSCLC, without unexpected safety issues.</p>
Text-fig. 7. Scanning electron micrographs (a, b, d, e, g–k), X-ray microtomographic orthoslices (c) and synchrotron radiation X-ray tomographic microscopy orthoslices (f) of fruits and endocarps of uncertain affinity from Zliv-Řídká Blana locality. a–c: Trebecenia sarcocalis, a – tricarpellate fruit, no. NM-F 3637, b – fruits supported by pentamerous and persistent calyx, no. NMF 3637, c – fruit almost circular in transverse section, no. NM-F 3637; d: Taxon 17, small fruit with slightly sunken stylar region, no. NM-F 3201; e: Taxon 19, spherical fruit, the fruit wall composed of large isodiametric, thick walled cells, no. NM-F 3181; f: Taxon 19, single-seeded fruit, no. NM-F 3621; g: Taxon 20, syncarpous, multicarpellate fruit of ten carpels, no. NM-F 3200; h: Taxon 22, syncarpous, multicarpellate fruit of seven carpels, no. NM-F 3159; i: cf. Sabia menispermoides, endocarp of drupaceous fruits, no. NM-F 4624; j: Taxon 25, endocarp triangular in cross-section, no. NM-F 3218; k: Taxon 24, endocarp spherical in cross-section with a distinctly ribbed and foveolate surface, no. NM-F 3217. in Plant Mesofossils From The Late Cretaceous Klikov Formation, The Czech Republic
Text-fig. 7. Scanning electron micrographs (a, b, d, e, g–k), X-ray microtomographic orthoslices (c) and synchrotron radiation X-ray tomographic microscopy orthoslices (f) of fruits and endocarps of uncertain affinity from Zliv-Řídká Blana locality. a–c: Trebecenia sarcocalis, a – tricarpellate fruit, no. NM-F 3637, b – fruits supported by pentamerous and persistent calyx, no. NMF 3637, c – fruit almost circular in transverse section, no. NM-F 3637; d: Taxon 17, small fruit with slightly sunken stylar region, no. NM-F 3201; e: Taxon 19, spherical fruit, the fruit wall composed of large isodiametric, thick walled cells, no. NM-F 3181; f: Taxon 19, single-seeded fruit, no. NM-F 3621; g: Taxon 20, syncarpous, multicarpellate fruit of ten carpels, no. NM-F 3200; h: Taxon 22, syncarpous, multicarpellate fruit of seven carpels, no. NM-F 3159; i: cf. Sabia menispermoides, endocarp of drupaceous fruits, no. NM-F 4624; j: Taxon 25, endocarp triangular in cross-section, no. NM-F 3218; k: Taxon 24, endocarp spherical in cross-section with a distinctly ribbed and foveolate surface, no. NM-F 3217.
Text-fig. 2. Scanning electron micrographs of non-angiosperm remains (a–d) and insect remains (e–f) from Zliv-Řídká Blana locality. a: Eopolytrichium sp. small leafy shoot, no. NM-F 3631; b: Taxon 1, single tip of a young fern frond with circinate vernation, no. NM-F 4130; c: Taxon 2, fern with simple leaves and circinate vernation, no. NM-F 3459; d: Pagiophyllum sp., small needle-like leaf, no. NM-F 4132; e: Microcarpolithes hexagonalis, a faecal pellet/coprolite with subcylindrical shape, no. NMF 4520; f: Palaeoaldrovanda splendens, pieces of compact walls formed by rectangular cells, no. NM-F 3237. in Plant Mesofossils From The Late Cretaceous Klikov Formation, The Czech Republic
Text-fig. 2. Scanning electron micrographs of non-angiosperm remains (a–d) and insect remains (e–f) from Zliv-Řídká Blana locality. a: Eopolytrichium sp. small leafy shoot, no. NM-F 3631; b: Taxon 1, single tip of a young fern frond with circinate vernation, no. NM-F 4130; c: Taxon 2, fern with simple leaves and circinate vernation, no. NM-F 3459; d: Pagiophyllum sp., small needle-like leaf, no. NM-F 4132; e: Microcarpolithes hexagonalis, a faecal pellet/coprolite with subcylindrical shape, no. NMF 4520; f: Palaeoaldrovanda splendens, pieces of compact walls formed by rectangular cells, no. NM-F 3237.
Text-fig. 10. Platanoxylon cf. haydenii, a, e, h: UF 279-34470; b, c, d, f g: UF 279-34469. a, b: Diffuse porous wood with vessels solitary and in small multiples, which are mostly tangential or oblique, diffuse and diffuse-in-aggregates axial parenchyma., TS. c–e: Scalariform perforation plates. f, g: Opposite intervessel pits, TLS. h: Two size classes of rays, TLS. Platanus sp., UF 279- 24552. i: Predominantly solitary vessels, diffuse and diffuse-in-aggregates parenchyma, growth ring boundary distinct, noded rays, TS. j: Simple perforation plates (PP), RLS. k: Body of ray with procumbent ray cells, RLS. l: Scalariform perforation plate, RLS. m: Rays of two sizes, wide rays>10-seriate, TLS. Scale bars: 200 µm in a, b, h, i, m; 100 µm in j, k: 50 µm in c, d, e, f, l. in A Diverse Assemblage Of Late Eocene Woods From Oregon, Western Usa
Text-fig. 10. Platanoxylon cf. haydenii, a, e, h: UF 279-34470; b, c, d, f g: UF 279-34469. a, b: Diffuse porous wood with vessels solitary and in small multiples, which are mostly tangential or oblique, diffuse and diffuse-in-aggregates axial parenchyma., TS. c–e: Scalariform perforation plates. f, g: Opposite intervessel pits, TLS. h: Two size classes of rays, TLS. Platanus sp., UF 279- 24552. i: Predominantly solitary vessels, diffuse and diffuse-in-aggregates parenchyma, growth ring boundary distinct, noded rays, TS. j: Simple perforation plates (PP), RLS. k: Body of ray with procumbent ray cells, RLS. l: Scalariform perforation plate, RLS. m: Rays of two sizes, wide rays>10-seriate, TLS. Scale bars: 200 µm in a, b, h, i, m; 100 µm in j, k: 50 µm in c, d, e, f, l.
Text-fig. 7. SEM (a) and SRXTM (b–e) images of Miranthus kvacekii sp. nov.; Mira locality, Portugal. a: Lateral view of flower bud showing corolla lobes extending beyond calyx; note surface of pedicel, calyx and corolla with small equiaxial epidermal cells and indumentum of densely spaced, short stiff trichomes. b, c: Longitudinal sections through floral bud in two directions perpendicular to each other (a, orthoslice yz1024; b, orthoslice xz0950) showing corolla (co), calyx (ca), stamens (st) and semi-inferior ovary with thin ovary wall (ow) and central mushroom-shaped globose placenta (pl) bearing numerous ovules (ov). d, e: Transverse sections through floral bud above placenta (d, orthoslice xy0915; e, orthoslice xy1095) showing calyx (ca), corolla (co), ovary wall (ow) and ovules (ov); yellow outlines indicate the positions of anthers (d) and filaments (e); orange outlines indicate the position of three of the possible staminodes. Specimen, Mira 100-S170157 (a–e, holotype). Scale bars = 600 µm (a–c), 300 µm (d, e). in Early Flowers Of Primuloid Ericales From The Late Cretaceous Of Portugal And Their Ecological And Phytogeographic Implications
Text-fig. 7. SEM (a) and SRXTM (b–e) images of Miranthus kvacekii sp. nov.; Mira locality, Portugal. a: Lateral view of flower bud showing corolla lobes extending beyond calyx; note surface of pedicel, calyx and corolla with small equiaxial epidermal cells and indumentum of densely spaced, short stiff trichomes. b, c: Longitudinal sections through floral bud in two directions perpendicular to each other (a, orthoslice yz1024; b, orthoslice xz0950) showing corolla (co), calyx (ca), stamens (st) and semi-inferior ovary with thin ovary wall (ow) and central mushroom-shaped globose placenta (pl) bearing numerous ovules (ov). d, e: Transverse sections through floral bud above placenta (d, orthoslice xy0915; e, orthoslice xy1095) showing calyx (ca), corolla (co), ovary wall (ow) and ovules (ov); yellow outlines indicate the positions of anthers (d) and filaments (e); orange outlines indicate the position of three of the possible staminodes. Specimen, Mira 100-S170157 (a–e, holotype). Scale bars = 600 µm (a–c), 300 µm (d, e).
Text-fig. 16. Photomicrographs of thin sections of specimen BP/16/1734, Terminalioxylon mozambicense sp. nov. from Mhengere Hill, Gorongosa, Mozambique. a: TS with round vessels, scanty paratracheal to vasicentric parenchyma, diffuse and narrow terminal or initial bands; b: TS at higher magnification, note the very narrow rays; c: TLS, vessels with small alternate pits, and partly tylosed; d–g: TLS with crystals (small white arrows) in the parenchyma cells, medium to thick-walled fibres and uniseriate, low rays; h: TLS, rays up to 20 cells high; i: RLS rays with procumbent body cells and 1–2 rows of marginal upright cells. in Stratigraphy, Chronology And Palaeontology Of The Tertiary Rocks Of The Cheringoma Plateau, Mozambique
Text-fig. 16. Photomicrographs of thin sections of specimen BP/16/1734, Terminalioxylon mozambicense sp. nov. from Mhengere Hill, Gorongosa, Mozambique. a: TS with round vessels, scanty paratracheal to vasicentric parenchyma, diffuse and narrow terminal or initial bands; b: TS at higher magnification, note the very narrow rays; c: TLS, vessels with small alternate pits, and partly tylosed; d–g: TLS with crystals (small white arrows) in the parenchyma cells, medium to thick-walled fibres and uniseriate, low rays; h: TLS, rays up to 20 cells high; i: RLS rays with procumbent body cells and 1–2 rows of marginal upright cells.
Text-fig. 15. Photomicrographs of thin sections of holotype BP/16/1738, Sorindeioxylon gorongosense gen. et sp. nov. from Muaredzi site 5, Gorongosa, Mozambique. a: TS, note the irregularly spaced and very narrow bands of parenchyma and mostly solitary vessel elements; b: TS at higher magnification with narrow rays; c: radial longitudinal section (RLS), rather oblique but shows the alternate, small-to-medium inter-vessel pits; d: tangential longitudinal section (TLS), rays are 1–3 cells wide but maintain the same width. Small arrow towards the right hand ray indicates a prismatic crystal in the ray cell; e: TLS rays with fibres in between; f: RLS showing mixed ray cells (upright, square and procumbent) poorly preserved. in Stratigraphy, Chronology And Palaeontology Of The Tertiary Rocks Of The Cheringoma Plateau, Mozambique
Text-fig. 15. Photomicrographs of thin sections of holotype BP/16/1738, Sorindeioxylon gorongosense gen. et sp. nov. from Muaredzi site 5, Gorongosa, Mozambique. a: TS, note the irregularly spaced and very narrow bands of parenchyma and mostly solitary vessel elements; b: TS at higher magnification with narrow rays; c: radial longitudinal section (RLS), rather oblique but shows the alternate, small-to-medium inter-vessel pits; d: tangential longitudinal section (TLS), rays are 1–3 cells wide but maintain the same width. Small arrow towards the right hand ray indicates a prismatic crystal in the ray cell; e: TLS rays with fibres in between; f: RLS showing mixed ray cells (upright, square and procumbent) poorly preserved.
Text-fig. 5. Mastixiopsis nyssoides KIRCHH. a, b, g–n: Organic preservation. a, b: Lignitic, unpermineralized, early Eocene Dorset Pipe clays at Arne, V. 40762. a: Ventral view (original illustration from pl. 18, fig. 1 of Chandler 1962). b: Transverse fracture, somewhat distorted by compression. c–f: Pyrite permineralization. c: Ventral view, V. 22963(1) from Sheppey, originally listed as Mastixia cantiensis. d: Lateral view, V. 22969 from Sheppey (identified as Mastixia grandis by Reid and Chandler 1933: pl. 25, fig. 8). e: Equatorial transverse physical section from (c). f: Equatorial transverse physical section from (d). g: Detail of pericarp from (e), showing endocarp formed of dense fibrous tissue, surrounded by mesocarp of anticlinally oriented larger cells. h: Detail of pericarp from (f). i–n: Type material from Eocene of Riestadt, Germany, MNB. i: Ventral view. j, k: Ventral and apical views of holotype. l: View of the transversely fractured surface from (j) showing horseshoe shaped locule. m: Equatorial transverse physical cut of the specimen in (i); note yellow resin cavity (arrow). n: Scanning electron microscopy of pericarp from (l) with locule lining at lower edge of image. Note dense endocarp tissue composed of small cells (fibres and sclereids), extending about 3/5 of distance to periphery, surrounded by mesocarp of larger, anticlinally oriented cells. Scale bars 1 cm in (a–f), (i–k), 1 mm in (g), 2 mm in (h), 3 mm in (l), m, 250 Μm in (n). Bar in (d) applies also to (c). Bar in (l) also applies to (m). Bar in (i) also applies to (j) and (k). in Mastixioid Fruits (Cornales) From The Early Eocene London Clay Flora: Morphology, Anatomy And Nomenclatural Revision
Text-fig. 5. Mastixiopsis nyssoides KIRCHH. a, b, g–n: Organic preservation. a, b: Lignitic, unpermineralized, early Eocene Dorset Pipe clays at Arne, V. 40762. a: Ventral view (original illustration from pl. 18, fig. 1 of Chandler 1962). b: Transverse fracture, somewhat distorted by compression. c–f: Pyrite permineralization. c: Ventral view, V. 22963(1) from Sheppey, originally listed as Mastixia cantiensis. d: Lateral view, V. 22969 from Sheppey (identified as Mastixia grandis by Reid and Chandler 1933: pl. 25, fig. 8). e: Equatorial transverse physical section from (c). f: Equatorial transverse physical section from (d). g: Detail of pericarp from (e), showing endocarp formed of dense fibrous tissue, surrounded by mesocarp of anticlinally oriented larger cells. h: Detail of pericarp from (f). i–n: Type material from Eocene of Riestadt, Germany, MNB. i: Ventral view. j, k: Ventral and apical views of holotype. l: View of the transversely fractured surface from (j) showing horseshoe shaped locule. m: Equatorial transverse physical cut of the specimen in (i); note yellow resin cavity (arrow). n: Scanning electron microscopy of pericarp from (l) with locule lining at lower edge of image. Note dense endocarp tissue composed of small cells (fibres and sclereids), extending about 3/5 of distance to periphery, surrounded by mesocarp of larger, anticlinally oriented cells. Scale bars 1 cm in (a–f), (i–k), 1 mm in (g), 2 mm in (h), 3 mm in (l), m, 250 Μm in (n). Bar in (d) applies also to (c). Bar in (l) also applies to (m). Bar in (i) also applies to (j) and (k).
Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer
<p>Wallen ZD, Ko H, Nesline MK, Hastings SB, Strickland KC, Previs RA, Zhang S, Pabla S, Conroy J, Jackson JB, Saini KS, Jensen TJ, Eisenberg M, Caveney B, Sathyan P, Severson EA, Ramkissoon SH. <strong>Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer.</strong> <em>Front Immunol.</em> 2024 Jun 21;15:1413956. doi: <a href="https://doi.org/10.3389/fimmu.2024.1413956">10.3389/fimmu.2024.1413956</a>. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/38975340/">38975340</a>; PMCID: <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11224431/">PMC11224431</a>.</p> <p><strong>ABSTRACT</strong></p> <p>Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking. We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients. We defined older patients as those ≥65 years and used a 5-year sliding threshold from <45 to <65 years to define various groups of younger patients. Additionally, in an independent cohort of patients with NSCLC, we use our observations to inform testing of the combinatorial effect of age and sex on survival of patients given immunotherapy with or without chemotherapy. We observed distinct genomic and immune microenvironment profiles for tumors of younger patients compared to tumors of older patients. Younger patient tumors were enriched in clinically relevant genomic alterations and had gene expression patterns indicative of reduced immune system activation, which was most evident when analyzing male patients. Further, we found younger male patients treated with immunotherapy alone had significantly worse survival compared to male patients ≥65 years, while the addition of chemotherapy reduced this disparity. Contrarily, we found younger female patients had significantly better survival compared to female patients ≥65 years when treated with immunotherapy plus chemotherapy, while treatment with immunotherapy alone resulted in similar outcomes. These results show the value of comprehensive genomic and immune profiling (CGIP) for informing clinical treatment of younger patients with NSCLC and provides support for broader coverage of CGIP for younger patients with advanced NSCLC.</p> <p><strong>DATA AVAILABILITY: </strong></p> <p>De-identified, individual-level patient data, genomic variants, and individual immune gene expression data used in the manuscript can be found in this repository (https://zenodo.org/record/11396552). An R markdown file with R code used to perform the analyses and generate figures is also provided in the repository along with the data. All versions of software used are provided in the Methods section of the manuscript. Raw sequencing data were derived from routine clinical testing of real-world patients and cannot be shared publicly. Data for immune gene expression signatures are not publicly available due to a non‑provisional patent filing covering the methods used to generate and analyze these data but are available from the corresponding author on reasonable request.</p>
Text-fig. 18. Scanning electron microscope (SEM) images of a fruit of Canrightia sp. with associated pollen; Torres Vedras locality, Portugal. a) Fruit in lateral view showing prominent cavities in the fruit wall formed by the scattered oil bodies and the broad hypanthium fused to the base of the fruit (arrowhead); b) Fruit surface showing epidermal cells and the scattered oil cells embedded in the fruit wall (arrowheads); c) Cluster of monocolpate pollen grains in the probable stigmatic region of the fruit; d) Pollen grains showing the long colpus and semitectate-reticulate pollen wall; e) Pollen wall showing the reticulum with large and small lumina, and scattered, compressed columellae supporting the smooth muri. Specimen, TV142-S170213. Scale bars 300 Μm (a), 100 Μm (b), 30 Μm (c), 6 Μm (d), 1 Μm (e). in The Early Cretaceous Mesofossil Flora Of Torres Vedras (Ne Of Forte Da Forca), Portugal: A Palaeofloristic Analysis Of An Early Angiosperm Community
Text-fig. 18. Scanning electron microscope (SEM) images of a fruit of Canrightia sp. with associated pollen; Torres Vedras locality, Portugal. a) Fruit in lateral view showing prominent cavities in the fruit wall formed by the scattered oil bodies and the broad hypanthium fused to the base of the fruit (arrowhead); b) Fruit surface showing epidermal cells and the scattered oil cells embedded in the fruit wall (arrowheads); c) Cluster of monocolpate pollen grains in the probable stigmatic region of the fruit; d) Pollen grains showing the long colpus and semitectate-reticulate pollen wall; e) Pollen wall showing the reticulum with large and small lumina, and scattered, compressed columellae supporting the smooth muri. Specimen, TV142-S170213. Scale bars 300 Μm (a), 100 Μm (b), 30 Μm (c), 6 Μm (d), 1 Μm (e).
Text-fig. 8. Lusitanispermum choffatii gen. et sp. nov. seeds from the Early Cretaceous Famalicão locality (sample 025) (a, b, d, e), and the Vale de Água locality (sample 333) (c, f, g), Portugal; Synchrotron radiation X-ray tomographic microscopy (SRXTM, volume renderings). a) Smaller seed in lateral view showing the bulging region (arrow head) close to hilum (S174467). b) Cut volume rending (cut at yz1032) of seed in (8a) showing the expanded cells of exotesta immediately adjacent to the lower edge of the hilum (hi), micropyle (mi) and the well preserved nutritive tissue. c) Small seed in lateral view showing the bulging exotesta (arrow head) close to hilum (S175046). d, e) Larger seed in lateral (d) and raphal (e) view (S174035). f) Detail of seed in (8c) showing the micropylar slit (mi) above the hilum (hi) and bulging exotestal tissue (arrow head) in which the walls of the exotestal cells have straight anticlinal walls. g) Surface of seed in (8c) showing the raised undulate anticlinal walls of the exotestal cells. Scale bars = 500 µm (a–e); 250 µm (f); 125 µm (g). in Extinct Taxa Of Exotestal Seeds Close To Austrobaileyales And Nymphaeales From The Early Cretaceous Of Portugal
Text-fig. 8. Lusitanispermum choffatii gen. et sp. nov. seeds from the Early Cretaceous Famalicão locality (sample 025) (a, b, d, e), and the Vale de Água locality (sample 333) (c, f, g), Portugal; Synchrotron radiation X-ray tomographic microscopy (SRXTM, volume renderings). a) Smaller seed in lateral view showing the bulging region (arrow head) close to hilum (S174467). b) Cut volume rending (cut at yz1032) of seed in (8a) showing the expanded cells of exotesta immediately adjacent to the lower edge of the hilum (hi), micropyle (mi) and the well preserved nutritive tissue. c) Small seed in lateral view showing the bulging exotesta (arrow head) close to hilum (S175046). d, e) Larger seed in lateral (d) and raphal (e) view (S174035). f) Detail of seed in (8c) showing the micropylar slit (mi) above the hilum (hi) and bulging exotestal tissue (arrow head) in which the walls of the exotestal cells have straight anticlinal walls. g) Surface of seed in (8c) showing the raised undulate anticlinal walls of the exotestal cells. Scale bars = 500 µm (a–e); 250 µm (f); 125 µm (g).
Text-fig. 50. Scanning electron microscope (SEM, a, b) and synchrotron radiation X-ray tomographic microscopy (SRXTM, c–f) images of "Foveolate seed sp. 2"; Catefica locality, Portugal. a, b) Lateral (a) and apical (b) views of seed showing the coarsely foveolate surface; note the truncate apex and the slightly depressed hilar-micropylar region; c) Longitudinal section (volume rendering cut between orthoslices xz0740 and xz0840) through the middle of seed showing the truncate apex with slightly depressed hilar-micropylar region and basal rounded chalazal region; note thick outer integument (oi) composed of an exotesta of thickwalled palisade-like cells and a thin inner integument (ii); d, e, f) Transverse (d, orthoslice xy0800) and longitudinal sections (e, orthoslice xz1100, f, orthoslice yz0800) through seed hilar-micropylar region, showing the exotesta comprised of the thick-walled palisade-like cells of the outer integument (oi), small, thin-walled meso- endotestal cells of the outer integument (arrows) and thin inner integument (ii). Specimen, Catefica 153-S172332 (a–f). Scale bars = 300 Μm (a–f). in The Early Cretaceous Mesofossil Flora Of Catefica, Portugal: Angiosperms
Text-fig. 50. Scanning electron microscope (SEM, a, b) and synchrotron radiation X-ray tomographic microscopy (SRXTM, c–f) images of "Foveolate seed sp. 2"; Catefica locality, Portugal. a, b) Lateral (a) and apical (b) views of seed showing the coarsely foveolate surface; note the truncate apex and the slightly depressed hilar-micropylar region; c) Longitudinal section (volume rendering cut between orthoslices xz0740 and xz0840) through the middle of seed showing the truncate apex with slightly depressed hilar-micropylar region and basal rounded chalazal region; note thick outer integument (oi) composed of an exotesta of thickwalled palisade-like cells and a thin inner integument (ii); d, e, f) Transverse (d, orthoslice xy0800) and longitudinal sections (e, orthoslice xz1100, f, orthoslice yz0800) through seed hilar-micropylar region, showing the exotesta comprised of the thick-walled palisade-like cells of the outer integument (oi), small, thin-walled meso- endotestal cells of the outer integument (arrows) and thin inner integument (ii). Specimen, Catefica 153-S172332 (a–f). Scale bars = 300 Μm (a–f).
Processed counts data of cfMeDIP-seq profiles of small cell lung cancer patients
<p>R objects of cfMeDIP-seq profiles of small cell lung cancer patient cfDNA, peripheral blood leukocytes, non-cancer control patients cfDNA, and CDX tumour tissue. The data are whole-genome across 300bp windows after removing ENCODE-blacklisted regions. The data also includes MeDEStrand-converted MeDIP data for peripheral blood leukocytes</p>
ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
ClinicalTrials.gov study NCT02737501. IPD Sharing: YES. Countries: 19. Publications: 5.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.