Human-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes.

Computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction. Still, lack of interpretability remains a significant barrier to clinical integration. We present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features (HIFs). Our method leverages >1.6 million annotations from board-certified pathologists across >5700 samples to train deep learning models for cell and tissue classification that can exhaustively map whole-slide images at two and four micron-resolution. Cell- and tissue-type model outputs are combined into 607 HIFs that quantify specific and biologically-relevant characteristics across five cancer types. We demonstrate that these HIFs correlate with well-known markers of the tumor microenvironment and can predict diverse molecular signatures (AUROC 0.601-0.864), including expression of four immune checkpoint proteins and homologous recombination deficiency, with performance comparable to 'black-box' methods. Our HIF-based approach provides a comprehensive, quantitative, and interpretable window into the composition and spatial architecture of the tumor microenvironment.

24.0 kyr cal BP stone artefact from Vale da Pedra Furada, Piauí, Brazil: Techno-functional analysis.

Current archaeological paradigm proposes that the first peopling of the Americas does not exceed the Last Glacial Maximum period. In this context, the acceptance of the anthropogenic character of the earliest stone artefacts generally rests on the presence of projectile points considered no more as typocentric but as typognomonic, since it allows, by itself, to certify the human character of the other associated artefacts. In other words, without this presence, nothing is certain. Archaeological research at Piauí (Brazil) attests to a Pleistocene human presence between 41 and 14 cal kyr BP, without any record of lithic projectile points. Here, we report the discovery and interpretation of an unusual stone artefact in the Vale da Pedra Furada site, in a context dating back to 24 cal kyr BP. The knapping stigmata and macroscopic use-wear traces reveal a conception centred on the configuration of double bevels and the production in the same specimen of at least two successive artefacts with probably different functions. This piece unambiguously presents an anthropic character and reveals a technical novelty during the Pleistocene occupation of South America.

Rare anatomic variation on a 10,000-year-old South American skeleton: the case of Iuzu, Toca dos Coqueiros, Piauí State, Brazil.

PURPOSE: A skeleton named Iuzu has been unearthed from an exceptional middle Holocene burial in Toca dos Coqueiros site, in Serra da Capivara National Park (UNESCO World Heritage Site, Piauí State, Brazil). During a bioarchaeological analysis of its remains, we discovered that Iuzu was suffering from rare vertebral malformations. A double foramen transversaria, the agenesis of a foramen on the atlas and the hypoplasia of the transverse process of the axis have been highlighted. We aimed to deduce the clinical consequences of the malformation on the patient's health. METHODS: We proceeded to macroscopic observation and radiography of the bones, then we search for other examples of such a pathology in archaeological litterature. RESULT: The malformation caused vascular insufficiency that may have led to neurological lesions leading to various pains and troubles. The very rare malformations Iuzu presented have not been found on a paleoindian skeleton from South America so far. CONCLUSION: This case allowed us to examine the conditions of selection of individuals buried in southern Piauí during the Middle Holocene, during which time this rite does not seem to predominate.

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group.

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation.

Micronutrients are essential components of the diet and are required to maintain fundamental bodily functions. Liver disease has a profound effect on nutrient intake, metabolism of nutrients, and nutrition status, often resulting in some degree of malnutrition, including micronutrient deficiency. Vitamin and mineral deficiencies can impair metabolic processes at the cellular and biochemical level even before clinical and physical alterations are seen. It is essential that micronutrient status is evaluated as part of a comprehensive nutrition assessment for all patients with chronic or advanced liver disease. Early intervention to correct suspected or confirmed deficiencies may minimize symptoms and improve clinical outcomes and quality of life. In this narrative review, different types of liver disease and associated micronutrient abnormalities are outlined, and methods of micronutrient assessment and supplementation are discussed.

A 1842 skull from Dupuytren's museum of Paris: an original artifact of Joseph Gensoul first maxillectomy technique.

Joseph Gensoul was a pioneer of ENT surgery. In 1827, he performed the first total maxillectomy on 17-year-old boy. His work inspired many surgeons, who were previously unwilling to remove maxillary tumours. A paleopathological study performed in the Dupuytren museum allowed us to identify a skull from the early 19th century, with a large maxillar tumour. There were indications that this skull was operated according to Gensoul's technique. The aim of this study is to confirm that this patient had, in fact, received this surgical treatment. This is a historical and descriptive paleopathological study of a skull of the early 19th century of Dupuytren Museum in Paris. The historical research was conducted in collaboration with the French Academy of Medicine and the Museum of Medicine History (Paris). Bones mark cut studies allowed us to confirm that the patient was operated according to the method described by Gensoul in his "Surgical letter" in 1833. Our historical research has allowed us to understand the perspectives of surgeons in the 19th century and the intellectual processes that led to this discovery. At a time when the robotization and industrialization dominate our art, it is interesting to look to our past, our origins, and our history. The study of ancient humans remains and allows us to understand the origin of our specialty and pay tribute to these pioneering surgeons. Their intellectual approach and boldness should be acknowledged and applauded, especially as it is also the key to our success.

Rhabdomyosarcoma arising in a giant congenital melanocytic nevus.

A number of lesions have been documented to arise within congenital melanocytic nevi (CMNs). Although the most frequent malignancy arising within a CMN is melanoma, the association between rhabdomyosarcoma and CMN has rarely been documented. We present a case arising in a 4-month-old girl with a giant CMN. She presented for evaluation of a pedunculated lesion at the superior gluteal crease that had been present since birth and exhibited rapid growth. Biopsy of the lesion revealed two distinct components: an expansile proliferation of pleomorphic cells with varying degrees of cellularity and a proliferation of banal-appearing melanocytic nevic cells. The cells of the expansile proliferation displayed a wide range of morphologic features, including nests of round cells, spindle-shaped cells, and more differentiated rhabdomyoblasts within a myxoid, highly vascularized stroma. Cross-striations, a marker of skeletal muscle differentiation, were present. These tumor cells were strongly immunoreactive with desmin, myo-D1, and myogenin. Fluorescence in situ hybridization analysis with PAX3/7-FKHR probes was negative. A diagnosis of embryonal rhabdomyosarcoma in association with CMN was made. Initial excision revealed tumor at the margins, and the patient underwent reexcision with subsequent chemotherapy with vincristine, actinomycin D, and cyclophosphamide. She was disease-free at the 6-year follow-up. It has been postulated that the combination of melanocytic and rhabdomyoblastic cells within the same lesion may imply derivation from a common pluripotent stem cell or neural crest cell. Clinicians following patients with giant CMN should consider rhabdomyosarcoma in the differential diagnosis of lesions arising within the nevus.