Histologic diversity in chromophobe renal cell carcinoma does not impact survival outcome: A comparative international multi-institutional study.

Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome. This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched. Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation. Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.

SARS-CoV-2 placentitis - report of two cases and review of the literature.

Covid-19 disease caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) continues to be a global public health problem. Since the pandemic outbreak in early 2020, a number of cases have been reported in pregnant women whose infection has led to severe complications including preterm birth, miscarriage, intrauterine growth restriction or intrauterine fetal demise. The results of the current studies suggest that the transplacental transmission of infection from mother to fetus is a rare event and that the complications listed above are more likely due to damage of placental tissue. In this article, we describe two cases of SARS-CoV-2 placentitis with special consideration to the morphology and differential dia-gnosis of this newly defined entity.

The changing global distribution and prevalence of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer that is naturally transmitted between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT first arose several thousand years ago and has been reported in dog populations worldwide; however, its precise distribution patterns and prevalence remain unclear. RESULTS: We analysed historical literature and obtained CTVT prevalence information from 645 veterinarians and animal health workers in 109 countries in order to estimate CTVT's former and current global distribution and prevalence. This analysis confirmed that CTVT is endemic in at least 90 countries worldwide across all inhabited continents. CTVT is estimated to be present at a prevalence of one percent or more in dogs in at least 13 countries in South and Central America as well as in at least 11 countries in Africa and 8 countries in Asia. In the United States and Australia, CTVT was reported to be endemic only in remote indigenous communities. Comparison of current and historical reports of CTVT indicated that its prevalence has declined in Northern Europe, possibly due to changes in dog control laws during the nineteenth and twentieth centuries. Analysis of factors influencing CTVT prevalence showed that presence of free-roaming dogs was associated with increased CTVT prevalence, while dog spaying and neutering were associated with reduced CTVT prevalence. Our analysis indicated no gender bias for CTVT and we found no evidence that animals with CTVT frequently harbour concurrent infectious diseases. Vincristine was widely reported to be the most effective therapy for CTVT. CONCLUSIONS: Our results provide a survey of the current global distribution of CTVT, confirming that CTVT is endemic in at least 90 countries worldwide. Additionally, our analysis highlights factors that continue to modify CTVT's prevalence around the world and implicates free-roaming dogs as a reservoir for the disease. Our analysis also documents the disappearance of the disease from the United Kingdom during the twentieth century, which appears to have been an unintentional result of the introduction of dog control policies.

Sex disparity in oronasal presentations of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer spread by the direct transfer of living cancer cells. CTVT usually spreads during mating, manifesting as genital tumours. However, oronasal CTVT is also occasionally observed, and presumably arises through oronasal contact with genital CTVT tumours during sniffing and licking. METHODS: Given that sniffing and licking transmission behaviours may differ between sexes, we investigated whether oronasal CTVT shows sex disparity. RESULTS: Twenty-seven of 32 (84%) primary oronasal tumours in a CTVT tumour database occurred in males. In addition, 53 of 65 (82%) primary oronasal CTVT tumours reported in the published literature involved male hosts. These findings suggest that male dogs are at four to five times greater risk of developing primary oronasal CTVT than females. This disparity may be due to sex differences in licking and sniffing activity, perhaps also influenced by sex differences in CTVT accessibility for these behaviours. CONCLUSION: Although oronasal CTVT is rare, it should be considered as a possible diagnosis for oronasal tumours, particularly in male dogs.

Carrageenan as an Ecological Alternative of Polyvinylidene Difluoride Binder for Li-S Batteries.

Lithium-sulfur batteries are one of the most promising battery systems nowadays. However, this system is still not suitable for practical application because of the number of shortcomings that limit its cycle life. One of the main problems related to this system is the volumetric change during cycling. This deficiency can be compensated by using the appropriate binder. In this article, we present the influence of a water-soluble binder carrageenan on the electrochemical properties of the Li-S battery. The electrode with a carrageenan binder provides good stability during cycling and at high C-rates. Electrochemical testing was also carried out with a small prototype pouch cell with a capacity of 16 mAh. This prototype pouch cell with the water-based carrageenan binder showed lower self-discharge and low capacity drop. Capacity decreased by 7% after 70 cycles.

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer.

Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.

Somatic evolution and global expansion of an ancient transmissible cancer lineage.

The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

The evolutionary history of dogs in the Americas.

Dogs were present in the Americas before the arrival of European colonists, but the origin and fate of these precontact dogs are largely unknown. We sequenced 71 mitochondrial and 7 nuclear genomes from ancient North American and Siberian dogs from time frames spanning ~9000 years. Our analysis indicates that American dogs were not derived from North American wolves. Instead, American dogs form a monophyletic lineage that likely originated in Siberia and dispersed into the Americas alongside people. After the arrival of Europeans, native American dogs almost completely disappeared, leaving a minimal genetic legacy in modern dog populations. The closest detectable extant lineage to precontact American dogs is the canine transmissible venereal tumor, a contagious cancer clone derived from an individual dog that lived up to 8000 years ago.

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

The cancer which survived: insights from the genome of an 11000 year-old cancer.

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT affects dogs around the world and is the oldest and most divergent cancer lineage known in nature. CTVT first emerged as a cancer about 11000 years ago from the somatic cells of an individual dog, and has subsequently acquired adaptations for cell transmission between hosts and for survival as an allogeneic graft. Furthermore, it has achieved a genome configuration which is compatible with long-term survival. Here, we discuss and speculate on the evolutionary processes and adaptions which underlie the success of this remarkable lineage.