Results

PaperS7685

Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging

Xavier Rovira-Clavé, Sizun Jiang, Yunhao Bai, Bokai Zhu, Graham Barlow, Salil Bhate, Ahmet F Coskun, Guojun Han, Chin-Min Kimmy Ho, Chuck Hitzman, Shih-Yu Chen, Felice-Alessio Bava, Garry P Nolan. ebi.ac.uk. July 30, 2021.

This cultured-cell imaging study maps biomolecules and drug distribution at fine spatial scales, with limited skin-tissue validation. Small cell samples and nested voxels limit generalization; 33 fields/cells across treatment groups came from one experiment. The proposed nuclear-pore pumping mechanism is an interpretation, without a demonstrated causal intervention or clinical outcome. Acknowledged NIH, Army and foundation support does not establish a secret approach or UAP programme. Nolan is a corresponding author and joint supervisor. The paper declares no competing interests; native graphics, supplements and underlying data remain unreviewed.

Complete specialist supplied XML text; native graphics unreviewed
PaperS7550

Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images

Yunhao Bai, Bokai Zhu, Xavier Rovira-Clave, Han Chen, Maxim Markovic, Chi Ngai Chan, Tung-Hung Su, David R. McIlwain, Jacob D. Estes, Leeat Keren, Garry P. Nolan, Sizun Jiang. ebi.ac.uk. July 5, 2021.

REDSEA compensates signal leakage between adjacent segmented cells. Published tests compare correction choices against a fallible manual reference and reused imaging data. Retaining signal and removing ambiguous classifications involve tradeoffs; poor segmentation and several other contamination mechanisms remain unresolved. Source counts, caption panels, equation notation and channel lists conflict. Nolan’s declared instrument-company financial interest and funding disclaimer remain part of the evidence.

Supplied article and published supplements read
PaperS7677

Virtual and augmented reality for biomedical applications

Mythreye Venkatesan, Harini Mohan, Justin R Ryan, Christian M Schürch, Garry P Nolan, David H Frakes, Ahmet F Coskun. ebi.ac.uk. July 2021.

This Nolan-coauthored review surveys biomedical virtual and augmented reality and presents illustrative case studies. It retains practical limitations: some training performs worse than hands-on instruction, a surgical comparison found no significant improvement in several broader outcomes, and image quality, tracking, cost, privacy and discomfort constrain use. Demonstrations and reported funding are distinct from proven clinical benefit or classified UAP access.

Complete supplied XML text; original figures and supplements unreviewed
PaperS7561

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging

Darci Phillips, Christian M Schürch, Michael S Khodadoust, Youn H Kim, Garry P Nolan, Sizun Jiang. ebi.ac.uk. May 19, 2021.

The authors develop a multiplexed imaging panel using eight previously treated tumor specimens. The 25,456 analyzed cells are nested within eight sampled cores, rather than independent patients. Cell types combine clustering with manual refinement; spatial marker patterns do not establish functional causation or clinical treatment prediction. Nolan supervised and revised the study, while Jiang is corresponding author. Channel labels, figure pointers and plotted units remain inconsistent in the supplied source.

Complete supplied text and received apparatus read
PaperS7560

Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction

Julia Kennedy‐Darling, Salil S Bhate, John W Hickey, Sarah Black, Graham L Barlow, Gustavo Vazquez, Vishal G Venkataraaman, Nikolay Samusik, Yury Goltsev, Christian M Schürch, Garry P Nolan. ebi.ac.uk. March 10, 2021.

The authors demonstrate repeated three-color imaging of DNA-tagged antibodies on five human tissue sections from five donors. Millions of segmented cells do not become independent human subjects. Barcode and repeated-cycle validation experiments each have one experimental replicate. Cell-type assignment and spatial associations depend on segmentation, markers and manual annotation. Barcode counts, omitted sequences, reagent labels, geometry and timing remain inconsistent in the supplied material. Nolan is a cosenior and corresponding coauthor.

Complete supplied text and received apparatus read
PaperS7627

Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study

David R McIlwain, Han Chen, Maria Apkarian, Melton Affrime, Bonnie Bock, Kenneth Kim, Nilanjan Mukherjee, Garry P Nolan, Monica M McNeal. ebi.ac.uk. February 25, 2021.

The authors compare BioFire and QuickVue tests with a study-specific qPCR comparator in selected influenza-challenge samples. Repeated matched swabs come from143 volunteers, and the two comparisons use different specimen sets. A linked correction changes the rapid-test table denominator from351 to299. These results do not establish performance in community infections, current product versions or UAP research.

Complete supplied main, correction, native tables and offered static figures
PaperS7620

Nanoscopic subcellular imaging enabled by ion beam tomography

Ahmet F Coskun, Guojun Han, Shambavi Ganesh, Shih-Yu Chen, Xavier Rovira Clavé, Stefan Harmsen, Sizun Jiang, Christian M Schürch, Yunhao Bai, Chuck Hitzman, Garry P Nolan. ebi.ac.uk. February 4, 2021.

The authors demonstrate destructive ion-beam imaging and computational reconstruction in fixed cells and selected tissue. Calibration resolution, localization precision and theoretical capability remain distinct. Nested depth slices and reconstruction-derived ground truth limit independence. The method is a research demonstration, with no clinical efficacy or UAP finding established.

Complete supplied main, mathematics and figures; supplements unreceived
PaperS7617

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

Ivan T. Lee et al.. ebi.ac.uk. October 28, 2020.

The authors localize ACE2 staining to respiratory cilia and compare receptor expression across medication groups. Small subgroups, treatment indication, age imbalance and retrospective confounding qualify the comparisons. Negative or nonsignificant results do not establish equivalence, infection protection or clinical benefit. The study reports localization and expression rather than a treatment trial.

Complete supplied main, figures and two supplements; peer review unreviewed
PaperS7624

Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front

Christian M Schürch, Salil S Bhate, Graham L Barlow, Darci J Phillips, Luca Noti, Inti Zlobec, Pauline Chu, Sarah Black, Janos Demeter, David R McIlwain, Shigemi Kinoshita, Nikolay Samusik, Yury Goltsev, Garry P Nolan. ebi.ac.uk. September 3, 2020.

The authors analyze spatial immune patterns in selected colorectal-cancer tissue. Thirty-five patients supply140 dependent tissue cores; repeated cells, regions and holdouts do not create new cohorts. Survival findings and correlation-based “communication” are exploratory. A linked correction adds Shigemi Kinoshita to the author list. No clinical efficacy or UAP finding is established.

Complete supplied main, figures and correction; bounded supplementary review
PaperS7625

Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

Andrew L Ji, Adam J Rubin, Kim Thrane, Sizun Jiang, David L Reynolds, Robin M Meyers, Margaret G Guo, Benson M George, Annelie Mollbrink, Joseph Bergenstråhle, Ludvig Larsson, Yunhao Bai, Bokai Zhu, Aparna Bhaduri, Jordan M Meyers, Xavier Rovira-Clavé, S Tyler Hollmig, Sumaira Z Aasi, Garry P Nolan, Joakim Lundeberg, Paul A Khavari. ebi.ac.uk. July 23, 2020.

The authors combine sequencing and imaging to describe selected squamous-cancer tissue, including a tumour-specific keratinocyte population. Cells, spots and fields depend on small patient subsets. Predicted interactions and proximity do not establish causal immune suppression. A linked correction repairs duplicated and mislabeled figure material; its unchanged-conclusions statement is attributed to the authors.

Complete supplied main, correction, S5 cells and S3 signature cells; remaining gaps
PaperS7610

Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity

Lu Cui, Shih-Yu Chen, Tristan Lerbs, Jin-Wook Lee, Pablo Domizi, Sydney Gordon, Yong-hun Kim, Garry Nolan, Paola Betancur, Gerlinde Wernig. ebi.ac.uk. June 3, 2020.

The authors report JUN-associated changes in lung fibroblasts and test mechanisms and interventions in engineered cultures and mouse models. Eleven end-stage cases and three cancer-resection controls define the human comparison. Preclinical findings, sampling biases and explicit toxicity cautions prevent claims of proven treatment benefit or safety in patients.

Complete supplied main text; bounded supplemental visuals
PaperS7603

Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line

Yapeng Su, Melissa E Ko, Hanjun Cheng, Ronghui Zhu, Min Xue, Jessica Wang, Jihoon W Lee, Luke Frankiw, Alexander Xu, Stephanie Wong, Lidia Robert, Kaitlyn Takata, Dan Yuan, Yue Lu, Sui Huang, Antoni Ribas, Raphael Levine, Garry P Nolan, Wei Wei, Sylvia K Plevritis, Guideng Li, David Baltimore, James R Heath. ebi.ac.uk. May 11, 2020.

The authors infer different routes to early drug tolerance within one cultured melanoma cell line and test selected drug combinations. The inferred barrier was not measured. Negative inhibitor assays, dependence among cell snapshots and possible normal-tissue toxicity qualify the results; clinical efficacy was not established.

Complete supplied main text; partial supplemental visuals

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