Longitudinal assessment of tumor-infiltrating lymphocytes in primary breast cancer following neoadjuvant radiotherapy.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast. Despite interest in combining radiotherapy with immunotherapy, little is known about the effect of radiotherapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of tumor-infiltrating and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiotherapy (NART), from XXX and XXX breast clinical trials. METHODS: We manually scored stromal TILs (sTILs) from longitudinal tumor samples using standardized guidelines, as well as deep learning-based scores at cell-level (cTIL) and cell- and tissue-level combination analysis (SuperTIL). In parallel, we interrogated absolute lymphocyte counts from routine blood tests at corresponding timepoints during treatment. Exploratory analyses studied the relationship between TILs and pathological complete response (pCR) and long-term outcomes. RESULTS: Patients receiving NART experienced a significant and uniform decrease in sTILs that did not recover at the time of surgery (P < 0.0001). This lymphodepletive effect was also mirrored in peripheral blood. Our "SuperTIL" deep learning score showed good concordance with manual sTILs, and importantly performed comparably to manual scores in predicting pCR from diagnostic biopsies. Analysis suggested an association between baseline sTILs and pCR, as well as sTILs at surgery and relapse, in patients receiving NART. CONCLUSIONS: This study provides novel insights into TIL dynamics in the context of NART in breast cancer, and demonstrates the potential for artificial intelligence to assist routine pathology. We have identified trends which warrant further interrogation and have a bearing on future radio-immunotherapy trials.

An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript.

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. The paternal UBE3A allele is imprinted in neurons of the central nervous system (CNS) by the UBE3A antisense (UBE3A-AS) transcript, which represents the distal end of the small nucleolar host gene 14 (SNHG14) transcription unit. Reactivating the expression of the paternal UBE3A allele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we described the development of an antisense oligonucleotide (ASO) therapy for Angelman syndrome that targets an evolutionarily conserved region demarcating the start of the UBE3A-AS transcript. We designed and chemically optimized gapmer ASOs targeting specific sequences at the start of the human UBE3A-AS transcript. We showed that ASOs targeting this region precisely and efficiently repress the transcription of UBE3A-AS, reactivating the expression of the paternal UBE3A allele in neurotypical and Angelman syndrome induced pluripotent stem cell-derived neurons. We further showed that human-targeted ASOs administered to the CNS of cynomolgus macaques by lumbar intrathecal injection repress UBE3A-AS and reactivate the expression of the paternal UBE3A allele throughout the CNS. These findings support the advancement of this investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov, NCT04259281).

Artificial intelligence and digital pathology: Opportunities and implications for immuno-oncology.

The field of immuno-oncology has expanded rapidly over the past decade, but key questions remain. How does tumour-immune interaction regulate disease progression? How can we prospectively identify patients who will benefit from immunotherapy? Identifying measurable features of the tumour immune-microenvironment which have prognostic or predictive value will be key to making meaningful gains in these areas. Recent developments in deep learning enable big-data analysis of pathological samples. Digital approaches allow data to be acquired, integrated and analysed far beyond what is possible with conventional techniques, and to do so efficiently and at scale. This has the potential to reshape what can be achieved in terms of volume, precision and reliability of output, enabling data for large cohorts to be summarised and compared. This review examines applications of artificial intelligence (AI) to important questions in immuno-oncology (IO). We discuss general considerations that need to be taken into account before AI can be applied in any clinical setting. We describe AI methods that have been applied to the field of IO to date and present several examples of their use.

Artists on the edge of the world: An integrated approach to the study of Magdalenian engraved stone plaquettes from Jersey (Channel Islands).

The Upper Palaeolithic is characterised by the appearance of iconographic expressions most often depicting animals, including anthropomorphic forms, and geometric signs. The Late Upper Palaeolithic Magdalenian saw a flourishing of such depictions, encompassing cave art, engraving of stone, bone and antler blanks and decoration of tools and weapons. Though Magdalenian settlement exists as far northwest as Britain, there is a limited range of art known from this region, possibly associated with only fleeting occupation of Britain during this period. Stone plaquettes, flat fragments of stone engraved on at least one surface, have been found in large quantities at numerous sites spanning the temporal and geographical spread of the Magdalenian, but they have been absent so far from the archaeological record of the British Isles. Between 2015 and 2018, ten fragments of stone plaquettes extensively engraved with abstract designs were uncovered at the Magdalenian site of Les Varines, Jersey, Channel Islands. In this paper, we report detailed analyses of these finds, which provide new evidence for technologies of abstract mark-making, and their significance within the lives of people on the edge of the Magdalenian world. These engraved stone fragments represent important, rare evidence of artistic expression in what is the far northern and western range of the Magdalenian and add new insight to the wider significance of dynamic practices of artistic expression during the Upper Palaeolithic.

La medicina tradicional herbolaria en los sistemas de salud convencionales / The traditional herbalist medicine in the conventional health systems

RESUMEN La medicina tradicional herbolaria desde su evolución hasta la contemporaneidad ha sido objeto de uso para la medicina convencional. Por eso el objetivo del trabajo es describir el comportamiento de la medicina tradicional herbolaria en los sistemas de salud convencionales. Se realizó la búsqueda y análisis documental de numerosas fuentes sobre la temática pertenecientes a las bases de datos SciELO Cuba, SciELO Regional, Science Direct, Clinical Key, Cumed, Lilacslo. Se concluye que la actualidad social registra manifestaciones alentadoras en el campo de la aceptación de la herbolaria como medicina complementaria por el equipo de salud y un renovado interés en el ámbito mundial por estudiar los efectos que tienen las plantas sobre la salud.

ABSTRACT The traditional herbalist medicine from its evolution to the contemporaneity has been an object use for the conventional medicine. That's why the objective of the work is to describe the behavior of the traditional herbalist medicine in the conventional health systems. A search and documentary analysis of numerous sources on the subject-matter belonging to the databases SciELO Cuba, SciELO Regional, Science Direct, Clinical Key, Cumed, Lilacslo was carried out. It is concluded that the social actuality registers encouraging declarations in the field of the acceptance of the herbalist as complementary medicine for the team of health and a renewed interest in the world ambience to study the effects that have the plants on the health.

La medicina tradicional herbolaria en los sistemas de salud convencionales / The traditional herbalist medicine in the conventional health systems

La medicina tradicional herbolaria desde su evolución hasta la contemporaneidad ha sido objeto de uso para la medicina convencional. Por eso el objetivo del trabajo es describir el comportamiento de la medicina tradicional herbolaria en los sistemas de salud convencionales. Se realizó la búsqueda y análisis documental de numerosas fuentes sobre la temática pertenecientes a las bases de datos SciELO Cuba, SciELO Regional, Science Direct, Clinical Key, Cumed, Lilacs. Se concluye que la actualidad social registra manifestaciones alentadoras en el campo de la aceptación de la herbolaria como medicina complementaria por el equipo de salud y un renovado interés en el ámbito mundial por estudiar los efectos que tienen las plantas sobre la salud(AU)

The traditional herbalist medicine from its evolution to the contemporaneity has been an object use for the conventional medicine. That's why the objective of the work is to describe the behavior of the traditional herbalist medicine in the conventional health systems. A search and documentary analysis of numerous sources on the subject-matter belonging to the databases SciELO Cuba, SciELO Regional, Science Direct, Clinical Key, Cumed, Lilacs was carried out. It is concluded that the social actuality registers encouraging declarations in the field of the acceptance of the herbalist as complementary medicine for the team of health and a renewed interest in the world ambience to study the effects that have the plants on the health(AU)

Material complementario para desarrollar la competencia sociocultural a través de las clases de Inglés e Historia de Cuba / Complementary material to develop the sociocultural competence through the classes of English and History of Cuba

Introducción: en los programas de Idioma Inglés e Historia de Cuba no existe información sobre aspectos socioculturales ni de la historia local, lo cual causa serias dificultades al profesor por no disponer de algún material para su autoprepación.Objetivo: diseñar un material complementario que permita la preparación de los profesores para desarrollar la competencia sociocultural a través de las clases de Idioma Inglés e Historia de Cuba.Métodos: se realizó un análisis documental para acopiar información teórica para la fundamentación del trabajo y la elaboración del folleto correspondiente; se revisaron los programas de las asignaturas Idioma Inglés e Historia de Cuba y se encuestó a los docentes de los Departamentos de Inglés y Filosofía e Historia, así como a los estudiantes.Resultados: se elaboró un folleto titulado English through Culture con los temas Who are the Cuban five?, Museums in Ciego de Ávila, Personalities in Medicine and Dentistry from Ciego de Ávila, Cuban painters from Ciego de Ávila, General Culture, English speaking countries where health care professionals from Ciego de Ávila have fulfilled international missions.Conclusiones: los profesores de las asignaturas Idioma Inglés e Historia de Cuba que cuentan con el folleto propuesto para el desarrollo de la competencia sociocultural tienen a mano un valioso instrumento de trabajo que les posibilita realizar debates en sus clases a la par que les facilita la autopreparación con vistas a incrementar su acervo cultural(AU)

Introduction: there is no information in programs of English Language and History of Cuba about-cultural aspects of local history, causing serious difficulties to the teacher for not having a material for self study.Objective: to design a complementary material that allows the preparation of teachers to develop cultural competence through English Language and History of Cuba classes.Methods: a documentary analysis was carried out to gather information for the theoretical foundation of the work and preparation of the corresponding brochure; programs of English Language and History of Cuba subjects were reviewed and the teachers of the Department of English and Philosophy and History were surveyed, as well the students.Results: a brochure appointed English through Culture was elaborated with the tracks Who are the Cuban Five , Museums in Ciego de Ávila, Personalities in Medicine and Dentistry from Ciego de Ávila , Cuban painters from Ciego de Ávila , General Culture , English speaking countries where health care professionals from Ciego de Ávila have fulfilled international missions".Conclusions: the teachers of the subjects English Language and History of Cuba who have the brochure proposed for the development of cultural competence have at hand a valuable working tool that enables them to conduct discussions in their classes and, at the same time, it provides them self-preparation in order to increase their cultural heritage(AU)