MALINC1 an Immune-Related Long Non-Coding RNA Associated with Early-Stage Breast Cancer Progression.

Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding MALINC1 intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this study was to characterize MALINC1 expression, localization, and phenotypic and molecular effects in non-invasive and invasive breast cancer cells. We determined that MALINC1 is an estrogen-estrogen receptor-modulated lncRNA enriched in the cytoplasmic fraction of luminal A/B breast cancer cells that is associated with worse overall survival in patients with primary invasive breast carcinomas. Transcriptomic studies in normal and DCIS cells identified the main signaling pathways modulated by MALINC1, which mainly involve bioprocesses related to innate and adaptive immune responses, extracellular matrix remodeling, cell adhesion, and activation of AP-1 signaling pathway. We determined that MALINC1 induces premalignant phenotypic changes by increasing cell migration in normal breast cells. Moreover, high MALINC1 expression in invasive carcinomas was associated with a pro-tumorigenic immune environment and a favorable predicted response to immunotherapy both in luminal and basal-like subtypes compared with low-MALINC1-expression tumors. We conclude that MALINC1 behaves as an oncogenic and immune-related lncRNA involved with early-stage breast cancer progression.

Six asymmetric bilateral additional heads of biceps brachii muscle observed in a cadaver / Seis cabezas adicionales bilaterales asimétricas del músculo bíceps braquial observadas en un cadáver

SUMMARY: Anatomic variation of the biceps brachii muscle (BBM) is frequently observed; its pattern is diverse and clinically important. During the educational dissection of a 78-year-old Korean male cadaver, six additional asymmetrical heads of the biceps brachii muscle (BBM) were found on both sides. On the right side, two additional heads originated from the humerus; the musculocutaneous nerve passed between these heads and the short head of the BBM. Four additional heads were found on the left side, anterior to the BBM, one of which originated from the pectoralis major muscle. Posterior to the BBM, two heads of tendons originated from the coracobrachialis muscle and one head of the muscle belly originated from the humerus. The left musculocutaneous nerve pierced the coracobrachialis muscle and continued distally passing between the short head of the BBM and the additional heads located posterior to the BBM. It then gave off the variant musculocutaneous nerve to the median nerve. On both sides, the short and long heads of the BBM had normal origins, insertions, and courses. This novel variation has various clinical and embryological implications.

RESUMEN: Con frecuencia se observa una variación anatómica del músculo bíceps braquial (MBB); su patrón es diverso y clínicamente importante. Durante la disección de un cadáver masculino coreano de 78 años, se encontraron seis cabezas asimétricas adicionales del músculo bíceps braquial en ambos lados. En el lado derecho, dos cabezas adicionales se originaban en el húmero; el nervio musculocutáneo atravesaba entre estas cabezas y la cabeza corta del MBB. Se encontraron cuatro cabezas adicionales en el lado izquierdo, anterior al MBB, una de las cuales se originaba en el músculo pectoral mayor. Posterior al MBB, dos cabezas tendinosas se originaban en el músculo coracobraquial y una cabeza de vientre muscular se originaba en el húmero. El nervio musculocutáneo izquierdo perforaba el músculo coracobraquial y continuaba distalmente pasando entre la cabeza corta del MBB y las cabezas adicionales ubicadas por detrás del MBB. Luego emitía la variante el nervio musculocutáneo al nervio mediano. En ambos lados, las cabezas corta y larga del MBB tenían orígenes, inserciones y trayectos normales. Esta nueva variación tiene varias implicaciones clínicas y embriológicas.

Effects of open board lecture videos on anatomy / Efectos de los videos de conferencias de tablero abierto sobre anatomía

SUMMARY: COVID-19 has forced anatomists to perform non-face-to-face education using lecture videos. A Korean anatomist has given (white and black) board lectures and distributed lecture videos to the public for many years. This study was to verify the effects of open board lecture videos in the anatomy field. A questionnaire survey was carried out with the help of medical students who were exposed to the board lecture videos. The video provider uploaded the lecture videos on YouTube, where the viewing numbers were counted. At a medical school where the video provider belonged, the students mainly watched the lecture videos before the anatomy class. The watching hours of the lecture videos were related to the written examination scores. Students gave positive and negative comments on the board lectures. At the other two medical schools, students partly watched the lecture videos regardless of the teacher who delivered the lectures. The results suggested that students understood the board lectures themselves. On YouTube, the lecture videos were viewed by approximately 1,000 students. This paper introduces the desirable aspects of open board lecture videos on anatomy. The videos could enhance the quality of both students and teacher.

RESUMEN: COVID-19 ha obligado a los anatomistas a realizar una enseñanza no presencial mediante videos de conferencias. Un anatomista coreano ha impartido conferencias (en blanco y negro) y ha distribuido videos de conferencias al público durante muchos años. El objetivo de este estudio fue verificar los efectos de los videos de conferencias de pizarra abierta en el campo de la anatomía. Se llevó a cabo una encuesta con la ayuda de estudiantes de medicina que habían sido expuestos a los videos de conferencias de la pizarra. El proveedor de videos subió los videos de las conferencias a YouTube, donde se contabilizó el número de visualizaciones. En una facultad de medicina a la que pertenecía el proveedor de videos, los estudiantes vieron principalmente los videos de conferencias antes de la clase de anatomía. Las horas de revisión de los vídeos de las conferencias se relacionaron con las puntuaciones de los exámenes escritos. Los estudiantes dieron comentarios positivos y negativos sobre las conferencias de la pizarra. En las otras dos facultades de medicina, los estudiantes vieron parcialmente los videos de las clases, independientemente del profesor que las impartiera. Los resultados sugerían que los estudiantes entendieron las conferencias de la pizarra por sí mismos. En YouTube, los videos de las conferencias fueron vistos por aproximadamente 1000 estudiantes. Este artículo presenta los aspectos deseables de los videos de conferencias abiertas sobre anatomía. Los videos podrían mejorar la calidad tanto de los estudiantes como del profesor.

Variation of serratus anterior muscle originated from the clavipectoral fascia: a case report / Variación del músculo serrato anterior originado en la fascia clavipectoral: reporte de un caso

SUMMARY: The variations in the serratus anterior (SA) muscle are common. Here, we report a rare variation of the muscle origin with a potentially great clinical implication. We found an aberrant SA variation in an 81-year-old Korean male cadaver during a routine dissection for medical students. Additional slip (AS) of the SA originated from the clavipectoral fascia and the pectoralis minor. It traveled inferiorly and merged to the typical SA part. Precise knowledge about SA variations is clinically valuable; therefore, clinicians should be aware of the possible variation.

RESUMEN: Las variaciones en el músculo serrato anterior (MSA) son comunes. En este trabajo informamos una variación rara del origen muscular con una implicación clínica potencialmente importante. Encontramos una variación aberrante del MSA en un cadáver masculino, coreano de 81 años, durante una disección de rutina para estudiantes de medicina, con un fascículo adicional del MSA originado en la fascia clavipectoral y el músculo pectoral menor. Este fascículo se dirigió inferiormente y se fu- sionó con la parte común de MSA. El conocimiento preciso sobre las variaciones de MSA es útil clínicamente; por lo tanto, los médicos deben ser conscientes de esta posible variación.

HOTAIR Modulated Pathways in Early-Stage Breast Cancer Progression.

The long-non-coding HOX transcript antisense intergenic RNA (HOTAIR) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by HOTAIR in early-stage breast cancer progression. We determined that HOTAIR induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and in vivo growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by HOTAIR which include bioprocesses related to epithelial to mesenchymal transition, cell migration, extracellular matrix remodeling and activation of several signaling pathways (HIF1A, AP1 and FGFR). Similar pathways were identified as activated in primary invasive breast carcinomas with HOTAIR over-expression. We conclude that HOTAIR over-expression behaves as a positive regulator of cell growth and migration both in normal and DCIS breast cells involved with early-stage breast cancer progression.

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression.

Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

The axillary arch inserted to the coracoid process compressing the brachial plexus / El arco axilar insertado en el proceso coracoideo comprimiendo el plexo braquial

The axillary arch is a variant slip extending between the latissimus dorsi muscle and the pectoralis major. During educational dissection, a variant muscle was found in left arm of 70-year-old female cadaver. A slip muscle originated from the lateral margin of the latissimus dorsi and crossed the axilla obliquely. Therefore, we defined this muscular variation as axillary arch. It ran anterior (superficial) to the medial and lateral cords of the brachial plexus, and then it inserted to coracoid process. We reported this variant muscle and discussed its clinical significances.

El arco axilar es una variante que se extiende entre el músculo dorsal ancho y el pectoral mayor. Durante la disección educativa, se encontró una variante muscular en el brazo izquierdo de un cadáver de una mujer de 70 años. El músculo deslizante se originó en el borde lateral del dorsal ancho y cruzó la axila oblicuamente. Por lo tanto, definimos esta variación muscular como el arco axilar. Se extendió anterior (superficial) a los cordones medial y lateral del plexo braquial, y luego se insertó en el proceso coracoideo. Reportamos esta variante muscular y discutimos sus significados clínicas.

Third head of the biceps brachii muscle originated from the greater tubercle connecting long and short heads: a case report / Tercera cabeza del músculo bíceps braquial originada en la tubrosidad mayor del húmero conectando las cabezas larga y corta: informe de un caso

Variation in the biceps brachii muscle is extremely frequent and has a clinical significance. During an educational dissection, third head of the biceps brachii muscle was found on the left side in a Korean cadaver. The short and long heads showed normal morphology and course: however, additional head originated from the greater tubercle connected to long head of biceps brachii muscle and crossed the musculocutaneous nerve perpendicularly. And then, it was inserted into short head of the biceps brachii muscle. The author describes this previously novel case report and discusses the clinical implications of such a variant.

La variación en el músculo bíceps braquial es extremadamente frecuente y tiene un significado clínico. Durante una disección educativa, se encontró la tercera cabeza del músculo bíceps braquial en el lado izquierdo de un cadáver coreano. Las cabezas cortas y largas mostraron una morfología y curso normales: sin embargo, la cabeza adicional se originó de la tuberosidad mayor conectado a la cabeza larga del músculo bíceps braquial y cruzaba el nervio musculocutáneo perpendicularmente, insertándose en la cabeza corta del músculo bíceps braquial. El autor describe este informe de un caso novedoso y discute las implicaciones clínicas de tal variante.

Infrared optical and thermal properties of microstructures in butterfly wings.

While surface microstructures of butterfly wings have been extensively studied for their structural coloration or optical properties within the visible spectrum, their properties in infrared wavelengths with potential ties to thermoregulation are relatively unknown. The midinfrared wavelengths of 7.5 to 14 µm are particularly important for radiative heat transfer in the ambient environment, because of the overlap with the atmospheric transmission window. For instance, a high midinfrared emissivity can facilitate surface cooling, whereas a low midinfrared emissivity can minimize heat loss to surroundings. Here we find that the midinfrared emissivity of butterfly wings from warmer climates such as Archaeoprepona demophoon (Oaxaca, Mexico) and Heliconius sara (Pichincha, Ecuador) is up to 2 times higher than that of butterfly wings from cooler climates such as Celastrina echo (Colorado) and Limenitis arthemis (Florida), using Fourier-transform infrared (FTIR) spectroscopy and infrared thermography. Our optical computations using a unit cell approach reproduce the spectroscopy data and explain how periodic microstructures play a critical role in the midinfrared. The emissivity spectrum governs the temperature of butterfly wings, and we demonstrate that C. echo wings heat up to 8 °C more than A. demophoon wings under the same sunlight in the clear sky of Irvine, CA. Furthermore, our thermal computations show that butterfly wings in their respective habitats can maintain a moderate temperature range through a balance of solar absorption and infrared emission. These findings suggest that the surface microstructures of butterfly wings potentially contribute to thermoregulation and provide an insight into butterflies' survival.

The third head of the biceps brachii muscle perforated by the musculocutaneous nerve / La tercera cabeza del músculo bíceps braquial perforada por el nervio musculocutáneo

During an educational dissection, the third head of the biceps brachii muscle was found on the left side in a 63-yearold female Korean cadaver. The short and long heads showed normal morphology, and their courses were as follows: The third head was originated from the middle level of the humerus under the short head and inserted in the conjoined tendon of the long and short heads of the biceps brachii muscle. The musculocutaneous nerve penetrated the third head of the biceps brachii muscle and became the lateral cutaneous nerve of the forearm. The authors describe this novel case and discuss the clinical implications of such a variation.

Durante una disección educativa, la tercera cabeza del músculo bíceps braquial se encontró en el lado izquierdo en un cadáver coreano de 63 años de edad. La cabeza corta y la cabeza larga mostraron una morfología normal, y se presentaron de la siguiente forma: La tercera cabeza se originó en el nivel medio del húmero, inferior a la cabeza corta, y se insertó en el tendón unido de las cabezas larga y corta del músculo bíceps braquial. El nervio musculocutáneo penetró en la tercera cabeza del músculo bíceps braquial para transformarse en el nervio cutáneo lateral del antebrazo. Los autores describen este nuevo caso y discuten las implicaciones clínicas de esta variación.

Description of the chondroepitroclearis muscle and its relationship to the median nerve in a Korean corpse / Descripción del músculo condroepincondilar medial y su relación con el nervio mediano en un cadáver coreano

SUMMARY: Anomalous muscle slips of pectoralis major have been reported on several cases in the literature. Among these, chondroepitroclearis muscle is an extremely rare aberrant muscular slip originating from the pectoral region. During an educational dissection, chondroepitroclearis muscle was found on the right side in a Korean cadaver. Tendinous muscular slip originated from pectoralis major muscle, crossing the neurovascular bundle in the arm, and inserted onto medial epicondyle of the humerus. Clinical significance of these anomalous slip can cause median nerve entrapment and functionally limited movement of the humerus. We report a case of tendinous chondroepitroclearis muscle and discuss its clinical and embryological significance.

RESUMEN: En la literatura se han reportado fascículos anómalos del músculo pectoral mayor. Entre estos, el condroepicondilar medial es un fascículo muscular aberrante extremadamente raro que se origina en la región pectoral. Durante una disección educativa, se encontró esta variación en el lado derecho de un cadáver coreano. El fascículo muscular tendinoso se originó a partir del músculo pectoral mayor, cruzando el paquete neurovascular en el brazo, y se insertó en el epicóndilo medial del húmero. La importancia clínica de estos fascículos anómalos radica en la posibilidad de causar el atrapamiento del nervio mediano, causando un movimiento funcionalmente limitado del húmero. Divulgamos un caso de músculo condroepicondilar medial tendinoso y discutimos su significado clínico y embriológico.

Topography of the middle genicular artery is associated with the superior and inferior genicular arteries / La topografía de la arteria genicular media está asociada con las arterias geniculares superiores e inferiores

Total knee arthroplasty has increased substantially, however anatomical studies of the genicular arteries (GAs) in this region are rare. The aim of this study was to identify the pattern and branching points of GAs and their relationship. In 42 lower limbs, the pattern and branching points of GAs were confirmed. The horizontal line which extends between the most prominent point of the lateral and medial margins of patella was defined as a reference line. The distance of branching point of the GAs from the reference line was measured, and the correlations between these points were analyzed. The superior lateral and medial genicular arteries (SLGA and SMGA) were located at + 38.17 ± 3.10 mm and + 32.68 ± 3.83 mm from the reference line, respectively. The middle genicular artery (MGA) was originated from + 7.57 ± 3.98 mm. The inferior lateral and medial genicular arteries (ILGA and IMGA) were located at - 18.46 ± 2.63 mm and - 24.09 ± 3.52 mm, respectively. The branching points of the SLGA changed significantly according to the arterial branching pattern with the MGA. In addition, the branching point of the MGA had positive relationships with that of the IMGA (r = 0.385, p <0.05) and that of the ILGA (r = 0.348, p <0.05), respectively. In this study, topography of the GAs and its anatomical association were demonstrated for the first time in Korean cadavers. Knowledge of the topography about frequent variation would be useful for safe surgery and clinical procedures.

La artroplastía total de rodilla ha aumentado sustancialmente, sin embargo los estudios anatómicos de las arterias geniculares (AGs) en esta región son escasos. El objetivo de este estudio fue identificar los patrones y puntos de ramificación de las AGs y sus relaciones. En 42 miembros inferiores, se identificaron el patrón y los puntos de ramificación de las AGs. La línea horizontal que se extiende entre el punto más prominente de los márgenes lateral y medial de la patela se definió como una línea de referencia. Se midió la distancia entre el punto de ramificación de las AGs y la línea de referencia, y se analizaron las correlaciones entre estos puntos. Las arterias geniculares superiores lateral y medial (AGSL y AGSM, respectivamente) se situaron a + 38,17 ± 3,10 mm y + 32,68 ± 3,83 mm de la línea de referencia, respectivamente, y la arteria genicular media (AGM) se originó a partir de + 7,57 ± 3,98 mm. Las arterias geniculares inferiores lateral y medial (AGIL e AGIM, respectivamente) se localizaron a - 18,46 ± 2,63 mm y - 24,09 ± 3,52 mm, respectivamente. Los puntos de ramificación de la AGSL cambiaron significativamente de acuerdo con el patrón de ramificación arterial con respecto a la AGSM. Además, el punto de ramificación de la AGSM tuvo relaciones positivas con el de la AGIM (r = 0.385, p <0.05) y el de la AGIL (r = 0.348, p <0.05). En este estudio, la topografía de las AGs y su asociación anatómica se demostraron por primera vez en cadáveres coreanos. El conocimiento de la topografía sobre la variación frecuente sería útil para su aplicación en el desarrollo de cirugías y procedimientos clínicos seguros.

Tracheal compression by aberrant brachiocephalic trunk accompanying variant origin of the vertebral artery / Compresión traqueal por un tronco braquiocefálico aberrante acompañado de una variación en el origen de la arteria vertebral

The aorta is the main arterial trunk in the human body, however, its variation was extremely variable. During an educational dissection, aberrant branching pattern of aortic arch was found in a Korean cadaver. The brachiocephalic trunk (innominate artery) originated from the aortic arch at the left side of the trachea. It crossed the trachea and divided into the right common carotid and subclavian arteries. The left vertebral artery originated from the aortic arch between the origins of the left common carotid artery and the left subclavian artery, then the left vertebral artery coursed upward to the transverse foramen of the C7. The author describes this previously novel case report with aberrant brachiocephalic trunk and left vertebral arteries and discusses the clinical implications of such a variant.

La aorta es el tronco arterial principal del cuerpo humano, sin embargo, su variación es extremadamente variable. Durante una disección de rutina de un cadáver coreano, se encontró un patrón de ramificación aberrante del arco aórtico. El tronco braquiocefálico se originaba del arco aórtico en el lado izquierdo de la tráquea. Cruzaba la tráquea y se dividía en las arterias carótida común y subclavia derecha. La arteria vertebral izquierda se originó a partir del arco aórtico entre los orígenes de la arteria carótida común izquierda y la arteria subclavia izquierda, luego la arteria vertebral izquierda ascendió hacia el foramen transversal de la séptima vértebra cervical. Se describe un caso de tronco braquiocefálico aberrante y la correspondiente arteria vertebral izquierda y se discuten las implicaciones clínicas de tal variante.

DMBA induced mouse mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations.

Controversy always existed on the utility of chemically induced mouse mammary carcinogenesis models as valid equivalents for the study of human breast cancer. Here, we performed whole exome and RNA sequencing on long latency mammary tumors (218 ± 27 days) induced by the carcinogen 7,12-Dimethylbenzathracene (DMBA) and short latency tumors (65 ± 11 days) induced by the progestin Medroxyprogesterone Acetate (MPA) plus DMBA in CD2F1 mice. Long latency tumors displayed a high frequency of Pi3kca and/or Pten mutations detected in 11 of 13 (85%) long latency cases (14/22, 64% overall). Eighty-two percent (9/11) of tumors carried the Pik3ca H1047L/R hot-spot mutation, as frequently found in human breast cancer. These tumors were luminal-like and mostly ER/PR+, as in humans. Transcriptome profiling indicated a significant activation of the PI3K-Akt pathway (p=3.82e-6). On the other hand MPA+DMBA induced short latency tumors displayed mutations in cancer drivers not commonly found mutated in human breast cancer (e.g. Hras and Apc). These tumors were mostly basal-like and MPA exposure led to Rankl overexpression (60 fold induction) and immunosuppressive gene expression signatures. In summary, long latency DMBA induced mouse mammary tumors reproduce the molecular profile of human luminal breast carcinomas representing an excellent preclinical model for the testing of PIK3CA/Akt/mTOR pathway inhibitory therapies and a good platform for the developing of additional preclinical tools such as syngeneic transplants in immunocompetent hosts.

A Molecular Portrait of High-Grade Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2(+)) displayed signatures characteristic of activated Treg cells (CD4(+)/CD25(+)/FOXP3(+)) and CTLA4(+)/CD86(+) complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer.