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Exercise is a common strategy for disease prevention or management, including for diabetes and cardiac dysfunction. However, exercise response varies immensely between individuals, and in humans, the same exercise treatment can lead both to positive and negative responses. Drosophila melanogaster is an established model for exercise research that can be leveraged to understand this variation in exercise response. Here, we investigated how two early life exercise treatments differing in duration (5 and 20 days) impact the animals' health- and lifespan in four genotypes. Specifically, we measured lifespan, activity level, body condition, physical ability, and reproductive output in this exploratory study to gain insights into potential trade-offs. For most measures, we found both immediate and long-term effects, with some effects persisting weeks past the cessation of exercise. The effect of the exercise treatment was context-dependent, with treatment, sex, and genotype interactions determining phenotypes. For example, the 20-day treatment did not exhibit a consistently larger effect than the 5-day treatment. Similarly, neither the 5-day nor the 20-day treatment impacted lifespan, but two specific genotype/sex combinations showed altered lifespan after exercise. The 20-day treatment decreased climbing performance compared to controls up to several weeks after treatment ended in some genotypes. Together, our results highlight the complex, interacting factors controlling exercise response and demonstrate that early life exercise can have long-lasting effects in the Drosophila exercise model even though most individual groups show no response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Schukow is an Ambassador for Knowledge In Knowledge Out but he does not receive financial compensation for this position. He has also published in Pathology Outlines and StatPearls, but does not acknowledge his specific chapters in this review as they are not pertinent or does he receive financial compensation. He does not receive financial compensation for his podcast titled “Bone and Soft Tissue Pathology Podcast” referenced in Table 2, nor is the intent to increase his audience. The authors’ X accounts are referenced in Table 2, but are done so to give readers more sources for authors who publish BSTpath-related materials and anonymized them for peer review. Riddle is an administrator for the Bone and Soft Tissue Pathology Facebook group referenced in Table 2, but she does not receive financial compensation for this position. Fitzhugh has no conflicts.

Context.—: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume, highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice., Objective.—: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology., Data Sources.—: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours., Conclusions.—: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice., (© 2024 College of American Pathologists.)

Primary peritoneal serous carcinoma (PPSC) is a rare tumor that develops in the peritoneum. PPSC originates from embryonic nests of Müllerian cells in the peritoneum, which are also present in the epithelium of the ovary. This similarity explains the histopathological resemblance between PPSC and low-grade serous ovarian carcinoma. While PPSC primarily affects women, it is an extremely rare occurrence in males, and it is believed that the significant difference in diagnosis rates between males and females is due to the inhibition of Müllerian system growth by substances produced by male Sertoli cells. These substances are present at higher levels in males, which may prevent the development of Müllerian system-derived tumors in men. We describe a 65-year-old male patient who presented for elective bariatric surgery and umbilical hernia repair, and an incidental finding of low-grade PPSC was made based on hernia sac pathology. The patient underwent further management, including tumor debulking and hyperthermic intraperitoneal chemotherapy (HIPEC), with positive outcomes. Long-term follow-up and oral letrozole treatment are planned., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Ganam et al.)

Comparative studies of aging are a promising approach to identifying general properties of and processes leading to aging. While to date, many comparative studies of aging in animals have focused on relatively narrow species groups, methodological innovations now allow for studies that include evolutionary distant species. However, comparative studies of aging across a wide range of species that have distinct life histories introduce additional challenges in experimental design. Here, we discuss these challenges, highlight the most pressing problems that need to be solved, and provide suggestions based on current approaches to successfully carry out comparative aging studies across the animal kingdom., (© 2023. The Author(s).)

Context.—: The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice., Objective.—: To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology., Data Sources.—: The 4th and 5th editions of the World Health Organization Classification of Tumours., Conclusions.—: The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice., (© 2023 College of American Pathologists.)

PitNETs are usually restricted in their cytodifferentiation to only one of 3 lineages dictated by expression of the pituitary transcription factors (TFs) PIT1, TPIT, or SF1. Tumors that show lineage infidelity and express multiple TFs are rare. We searched the pathology files of 4 institutions for PitNETs with coexpression of PIT1 and SF1. We identified 38 tumors in 21 women and 17 men, average age 53 (range 21-79) years. They represented 1.3 to 2.5% of PitNETs at each center. Acromegaly was the presentation in 26 patients; 2 had central hyperthyroidism associated with growth hormone (GH) excess and one had significantly elevated prolactin (PRL). The remainder had mass lesions with visual deficits, hypopituitarism, and/or headaches. Tumor size ranged from 0.9 to 5 cm; all 7 lesions smaller than 1 cm were associated with acromegaly. Larger lesions frequently invaded the cavernous sinuses. Four cases represented a second attempt at surgical resection. PIT1 was usually diffusely positive but 5 cases had variable (patchy or focal) staining. SF1 reactivity was variable in intensity but diffuse in all but 2 cases. GATA3 data, available in 14 cases, identified diffuse positivity in 5 and focal staining in 1. GH was expressed in all but 5 tumors, PRL and thyrotropin (TSH) were expressed in 14 and 13, respectively, follicle-stimulating hormone (FSH) in 11 of 18, and luteinizing hormone (LH) in 4 of 17. Keratin staining patterns were diffuse perinuclear/membranous in 27, variable perinuclear in 4, and negative in 3; scattered fibrous bodies were seen in 5 and diffuse fibrous bodies in 1. Ki67 labeling index ranged from < 1 to 7.9%. In 3 cases, these tumors represented one of multiple synchronous PitNETs; a separate corticotroph tumor was seen in 2 patients and one patient had 2 additional discrete lesions, a sparsely granulated lactotroph, and a pure gonadotroph tumor comprising a triple tumor. PitNETs expressing PIT1 and SF1 represent multilineage PitNETs. These rare tumors have variable clinical and morphological features, most often presenting as large tumors with GH excess and occasionally as one of multiple synchronous PitNETs of distinct lineages., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Syphilis is a resurging disease which can present itself in many ways, including lesions within the head and neck mucosa. Some of these lesions may clinically mimic oral malignancies. This literature review aims to better characterize the mucosal presentations of syphilis. Methods: PubMed, EMBASE, and clinicaltrials.gov were searched for full-text, English articles published from 1950 to 2022 that reported patients with head and neck mucosal manifestations of syphilis. Articles were screened according to PRISMA guidelines. Results: One hundred forty-three manuscripts documenting 236 individual patients were included in the review. Patients with secondary syphilis accounted for 62% of patients presenting with head and neck mucosal lesions. The most common lesions found in primary and secondary syphilis were ulcerations, primarily found on the tongue, lips, and palate. While serologic studies are the gold standard for diagnosing syphilis, biopsy of these lesions have characteristic syphilitic changes. Conclusions: Syphilis' nickname of "The great imitator" remains to be true, and the head and neck mucosal manifestations of this disease can resemble commonly seen malignancies. Awareness of this disease and its lesions is prudent given the rising incidence of syphilis within the United States., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions., Competing Interests: Declaration of interests Z.J.G. is an advisor and/or board member of Scribe Biosciences, Provenance Bio, and Serotiny. Z.J.G. is an author on patents related to the topic of this commentary. E.L. reports research grants from the American Cancer Society (RSG-22-022-01-CDP) 2022–2026, and the Minnesota Ovarian Cancer Alliance in 2019, 2021, and 2022; honorarium and travel expenses for a research talk at GlaxoSmithKline in 2016; honoraria and travel expenses for lab-based research talks 2018–21, and equipment for laboratory-based research 2018–present, Novocure, Ltd; honorarium for panel discussion organized by Antidote Education for a CME module on diagnostics and treatment of HER2+ gastric and colorectal cancers, funded by Daiichi-Sankyo, 2021 (honorarium donated to lab); compensation for scientific review of proposed printed content, Elsevier Publishing and Johns Hopkins Press; consultant, Nomocan Pharmaceuticals (no financial compensation); Scientific Advisory Board Member, Minnetronix, LLC, 2018–2019 (no financial compensation); consultant and speaker honorarium, Boston Scientific US, 2019; Institutional Principal Investigator for clinical trials sponsored by Celgene, Novocure, Intima Biosciences, and the National Cancer Institute, and University of Minnesota membership in the Caris Life Sciences Precision Oncology Alliance (no financial compensation). D.P. is a member of the advisory board of Insitro. G.L.S. is a current employee of Seagen and is an inventor on patents related to immunotherapies for treatment of cancer., (Published by Elsevier Inc.)

In eukaryotes, DNA is packaged into chromatin, which presents significant barriers to transcription. Non-histone chromatin proteins such as the Heterochromatin Protein 1 (HP1) proteins are critical regulators of transcription, contributing to gene regulation through a variety of molecular mechanisms. HP1 proteins are highly conserved, and many eukaryotic genomes contain multiple HP1 genes. Given the presence of multiple HP1 family members within a genome, HP1 proteins can have unique as well as shared functions. Here, we review the mechanisms by which HP1 proteins contribute to the regulation of transcription. Focusing on the Drosophila melanogaster HP1 proteins, we examine the role of these proteins in regulating the transcription of genes, transposable elements, and piRNA clusters. In D. melanogaster, as in other species, HP1 proteins can act as transcriptional repressors and activators. The available data reveal that the precise impact of HP1 proteins on gene expression is highly context dependent, on the specific HP1 protein involved, on its protein partners present, and on the specific chromatin context the interaction occurs in. As a group, HP1 proteins utilize a variety of mechanisms to contribute to transcriptional regulation, including both transcriptional (i.e. chromatin-based) and post-transcriptional (i.e. RNA-based) processes. Despite extensive studies of this important protein family, open questions regarding their functions in gene regulation remain, specifically regarding the role of hetero- versus homodimerization and post-translational modifications of HP1 proteins., (© 2022. The Author(s).)

Context.—: Multiple articles and surveys in the literature suggest that medical students find a career in pathology undesirable and believe it is disproportionately focused primarily on the autopsy., Objective.—: To measure the effect of applied interventions on medical student attitudes about the field of pathology., Design.—: This prospective study involving medical students from first through fourth year was conducted as a pilot study in 2 medical schools in the United States. A 2-part anonymous survey regarding interest in pathology as a career and familiarity with the specialty using a 10-point scale was given to first- and second-year medical students before and after they listened to a 10-minute pathology career presentation. The same survey was given to third- and fourth-year medical students before and after a 4-week pathology elective., Results.—: A total of 121 and 83 students responded to the survey before and after the intervention, respectively. Of the 121 students who responded to the survey before the intervention, 106 (87.6%) had not spent significant time in a pathology laboratory before the intervention. The majority of responses in interest in career, job responsibilities, and features of pathologists before and after the intervention demonstrated a statistically significant difference (P < .001). We compared survey scores of presentation versus 4-week rotation groups before and after the intervention. Students who experienced the presentation did not differ from students who experienced the rotation in the majority of questions related to interest in career, job responsibilities, and features of pathologists., Conclusions.—: Our study suggests that pathology exposure strategies can have a beneficial effect on student perceptions of the field and consideration of a career in pathology. Overall, the presentation intervention seemed to have the greatest effect on the first- and second-year students.

Evidence from across the tree of life suggests that epigenetic inheritance is more common than previously thought. If epigenetic inheritance is indeed as common as the data suggest, this finding has potentially important implications for evolutionary theory and our understanding of how evolution and adaptation progress. However, we currently lack an understanding of how common various epigenetic inheritance types are, and how they impact phenotypes. In this perspective, we review the open questions that need to be addressed to fully integrate epigenetic inheritance into evolutionary theory and to develop reliable predictive models for phenotypic evolution. We posit that addressing these challenges will require the collaboration of biologists from different disciplines and a focus on the exploration of data and phenomena without preconceived limits on potential mechanisms or outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age-associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer-lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well-characterized processes. In particular, understanding the role of sex-determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Exercise is recommended to promote health and prevent a range of diseases. However, how exercise precipitates these benefits is unclear, nor do we understand why exercise responses differ so widely between individuals. We investigate how climbing ability in Drosophila melanogaster changes in response to an exercise treatment. We find extensive variation in baseline climbing ability and exercise-induced changes ranging from -13% to +20% in climbing ability. Climbing ability, and its exercise-induced change, is sex- and genotype-dependent. GWASs implicate 'cell-cell signalling' genes in the control of climbing ability. We also find that animal activity does not predict climbing ability and that the exercise-induced climbing ability change cannot be predicted from the activity level induced by the exercise treatment. These results provide promising new avenues for further research into the molecular pathways controlling climbing activity and illustrate the complexities involved in trying to predict individual responses to exercise., (© 2021 The Authors.)

Drosophila Heterochromatin Protein 1a (HP1a) is essential for heterochromatin formation and is involved in transcriptional silencing. However, certain loci require HP1a to be transcribed. One model posits that HP1a acts as a transcriptional silencer within euchromatin while acting as an activator within heterochromatin. However, HP1a has been observed as an activator of a set of euchromatic genes. Therefore, it is not clear whether, or how, chromatin context informs the function of HP1 proteins. To understand the role of HP1 proteins in transcription, we examined the genome-wide binding profile of HP1a as well as two other Drosophila HP1 family members, HP1B and HP1C, to determine whether coordinated binding of these proteins is associated with specific transcriptional outcomes. We found that HP1 proteins share many of their endogenous binding targets. These genes are marked by active histone modifications and are expressed at higher levels than nontarget genes in both heterochromatin and euchromatin. In addition, HP1 binding targets displayed increased RNA polymerase pausing compared with nontarget genes. Specifically, colocalization of HP1B and HP1C was associated with the highest levels of polymerase pausing and gene expression. Analysis of HP1 null mutants suggests these proteins coordinate activity at transcription start sites to regulate transcription. Depletion of HP1B or HP1C alters expression of protein-coding genes bound by HP1 family members. Our data broaden understanding of the mechanism of transcriptional activation by HP1a and highlight the need to consider particular protein-protein interactions, rather than broader chromatin context, to predict impacts of HP1 at transcription start sites., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Body size and weight show considerable variation both within and between species. This variation is controlled in part by genetics, but also strongly influenced by environmental factors including diet and the level of activity experienced by the individual. Due to the increasing obesity epidemic in much of the world, there is considerable interest in the genetic factors that control body weight and how weight changes in response to exercise treatments. Here, we address this question in the Drosophila model system, utilizing 38 strains of the Drosophila Genetics Reference Panel. We use GWAS to identify the molecular pathways that control weight and weight changes in response to exercise. We find that there is a complex set of molecular pathways controlling weight, with many genes linked to the central nervous system (CNS). The CNS also plays a role in the weight change with exercise, in particular, signaling from the CNS. Additional analyses revealed that weight in Drosophila is driven by two factors, animal size, and body composition, as the amount of fat mass versus lean mass impacts the density. Thus, while the CNS appears to be important for weight and exercise-induced weight change, signaling pathways are particularly important for determining how exercise impacts weight.

Aims: To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma., Methods and Results: We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next-generation sequencing assay targeting recurrent gene fusions, and fluorescence in-situ hybridisation (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid carcinoma (n = 10), adenosquamous carcinoma (n = 7), and pleomorphic giant-cell carcinoma (n = 7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in nine (47%, seven via sequencing, showing TMPRSS2-ERG fusions and one GRHL2-ERG fusion, and two via FISH, showing rearrangement via deletion). ERG was immunohistochemically positive in the adenocarcinoma in eight of nine (89%) patients, but was immunohistochemically positive in the variant in only five of nine patients (56%, typically decreased). One patient had a false-positive ERG immunohistochemical result in the sarcomatoid component despite a negative FISH result. Two (11%) harboured BRAF fusions (FAM131A-BRAF and SND1-BRAF)., Conclusions: ERG fusions are present in these rare prostate cancer variants with a frequency close to that in conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma, but is less sensitive for the variant histology, with weak to negative staining. Adenosquamous and sarcomatoid variants can, particularly, occur together. Molecular assessment may be an additional tool in selected cases to confirm the prostatic origin of unusual tumours. The presence of two BRAF rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1-2% of prostate cancers., (© 2020 John Wiley & Sons Ltd.)

Animals' behaviors vary in response to their environment, both biotic and abiotic. These behavioral responses have significant impacts on animal survival and fitness, and thus, many behavioral responses are at least partially under genetic control. In Drosophila , for example, genes impacting aggression, courtship behavior, circadian rhythms and sleep have been identified. Animal activity also is influenced strongly by genetics. My lab previously has used the Drosophila melanogaster Genetics Reference Panel (DGRP) to investigate activity levels and identified over 100 genes linked to activity. Here, I re-examined these data to determine whether Drosophila strains differ in their response to rotational exercise stimulation, not simply in the amount of activity, but in activity patterns and timing of activity. Specifically, I asked whether there are fly strains exhibiting either a 'marathoner' pattern of activity, i.e. remaining active throughout the 2 h exercise period, or a 'sprinter' pattern, i.e. carrying out most of the activity early in the exercise period. The DGRP strains examined differ significantly in how much activity is carried out at the beginning of the exercise period, and this pattern is influenced by both sex and genotype. Interestingly, there was no clear link between the activity response pattern and lifespan of the animals. Using genome-wide association studies (GWAS), I identified 10 high confidence candidate genes that control the degree to which Drosophila exercise behaviors fit a marathoner or sprinter activity pattern. This finding suggests that, similar to other aspects of locomotor behavior, the timing of activity patterns in response to exercise stimulation is under genetic control., Competing Interests: Competing interestsThe author declares no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the social media committee reviews the strategies that were employed and the resultant outcome data. In addition, we categorize tweets by topic to identify the topics of greatest interest to meeting participants, and we discuss the differences between Twitter and other social media platforms. Lastly, we review the existing literature on this topic from 23 medical specialties and health care fields., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Maintaining genome stability is essential to an organism's health and survival. Breakdown of the mechanisms protecting the genome and the resulting genome instability are an important aspect of the aging process and have been linked to diseases such as cancer. Thus, a large network of interconnected pathways is responsible for ensuring genome integrity in the face of the continuous challenges that induce DNA damage. While these pathways are diverse, epigenetic mechanisms play a central role in many of them. DNA modifications, histone variants and modifications, chromatin structure, and non-coding RNAs all carry out a variety of functions to ensure that genome stability is maintained. Epigenetic mechanisms ensure the functions of centromeres and telomeres that are essential for genome stability. Epigenetic mechanisms also protect the genome from the invasion by transposable elements and contribute to various DNA repair pathways. In this review, we highlight the integral role of epigenetic mechanisms in the maintenance of genome stability and draw attention to issues in need of further study.

Exercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual's inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model system Drosophila melanogaster Activity levels were assayed in the Drosophila Genetics Reference Panel fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels in D. melanogaster and provides a resource for exercise biologists., (Copyright © 2020 Watanabe et al.)

Participants at academic conferences frequently use social media to disseminate educational content learned while at the meeting. Although most agree that this activity is harmless, some have expressed concern regarding the accuracy of the shared content and whether it truly reflects the intent and message of the speaker. As part of the goals of the APC 2018 social media committee to promote excellence through social media, a study was conducted to measure the perceived accuracy of tweets that represented an opinion or statement from a speaker and was shared during the annual meeting. Tweets shared on Twitter using the meeting hashtag (#APCPRODS2018) were collected and a survey unique to each speaker was created, to which 54% responded. The majority of speakers regarded the use of Twitter at the conference as beneficial in spreading their intended message in an accurate way. This study exemplifies the positive impact that social media use can have at academic meetings., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Because of the growing rates of obesity in much of the world, exercise as a treatment option for obesity and as part of a healthy lifestyle is of great interest to the general public, health policy makers, and scientists alike. Despite the long history of exercise promotion and exercise research, there are still significant gaps in our understanding of how exercise impacts individuals and what role genetics plays in determining an individual's response to exercise. Model organisms are positioned uniquely to help address these questions because of the challenges associated with carrying out large-scale, well-controlled studies in humans. The fruit fly model system, Drosophila melanogaster , has joined the models used for exercise research only recently but already has made significant contributions to the field. In this review, we highlight the opportunities for exercise research in Drosophila. We review the resources available to researchers interested in using Drosophila for exercise research, focusing on the existing systems to induce exercise in Drosophila, to measure the amount of exercise performed, and to assess physical fitness. We illustrate the potential of the Drosophila system by drawing attention to pioneering studies in Drosophila exercise research and emphasize the unique opportunities this model system represents.

The use of immunosuppressing agents can act as a catalyst for viral reactivation, promoting systemic infection with organ involvement. Current literature remains sparse on this topic but does provide individual case reports involving single viruses. We present the case of an immunocompromised patient with skin lesions, pancreatitis, colitis and hepatitis. Work-up revealed varicella zoster virus, which likely put the patient at risk for multi-organ involvement, as well as clinical suspicion of other implicated viruses, specifically herpes simplex virus and cytomegalovirus. A high clinical index of suspicion along with biopsy guidance for viral involvement in immunocompromised patients is crucial for early diagnosis and treatment of these conditions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Hamartomas are benign lesions composed of aberrant disorganized growth of mature tissues. Choristomas are similar, except that they are composed of tissues not normally found at the anatomic site in which the lesion is arising. A wide range of hamartomas and choristomas can arise in the skin and soft tissue. Some of these may cause diagnostic difficulty and potentially be mistaken for neoplasms. Some neoplasms may resemble hamaratomas. Here we review the current clinical and pathologic features of these lesions, both common and rare, and discuss how to distinguish them from other entities in the differential diagnosis., (Copyright © 2018. Published by Elsevier Inc.)

Extraskeletal mesenchymal chondrosarcoma is a rare soft tissue sarcoma arising from soft tissues, mainly of the lower extremities, meninges, and orbits. It usually presents during the second to third decades of life, and has a slight predominance in females. Histologically, it has a typical biphasic pattern comprising small cells and islands of hyaline cartilage. It can pose a diagnostic challenge in small biopsy specimens where 1 of the 2 components can be absent. The prognosis is extremely variable; survival varies depending on the location of the tumor.

The F element of the Drosophila karyotype (the fourth chromosome in Drosophila melanogaster ) is often referred to as the "dot chromosome" because of its appearance in a metaphase chromosome spread. This chromosome is distinct from other Drosophila autosomes in possessing both a high level of repetitious sequences (in particular, remnants of transposable elements) and a gene density similar to that found in the other chromosome arms, ∼80 genes distributed throughout its 1.3-Mb "long arm." The dot chromosome is notorious for its lack of recombination and is often neglected as a consequence. This and other features suggest that the F element is packaged as heterochromatin throughout. F element genes have distinct characteristics ( e.g , low codon bias, and larger size due both to larger introns and an increased number of exons), but exhibit expression levels comparable to genes found in euchromatin. Mapping experiments show the presence of appropriate chromatin modifications for the formation of DNaseI hypersensitive sites and transcript initiation at the 5' ends of active genes, but, in most cases, high levels of heterochromatin proteins are observed over the body of these genes. These various features raise many interesting questions about the relationships of chromatin structures with gene and chromosome function. The apparent evolution of the F element as an autosome from an ancestral sex chromosome also raises intriguing questions. The findings argue that the F element is a unique chromosome that occupies its own space in the nucleus. Further study of the F element should provide new insights into chromosome structure and function., (Copyright © 2018 by the Genetics Society of America.)

Heterochromatin Protein 1 (HP1) proteins are an important family of chromosomal proteins conserved among all major eukaryotic lineages. While HP1 proteins are best known for their role in heterochromatin, many HP1 proteins function in euchromatin as well. As a group, HP1 proteins carry out diverse functions, playing roles in the regulation of gene expression, genome stability, chromatin structure, and DNA repair. While the heterochromatic HP1 proteins are well studied, our knowledge of HP1 proteins with euchromatic distribution is lagging behind. We have created the first mutations in HP1B, a Drosophila HP1 protein with euchromatic function, and the Drosophila homolog most closely related to mammalian HP1α, HP1β, and HP1γ. We find that HP1B is a non-essential protein in Drosophila, with mutations affecting fertility and animal activity levels. In addition, animals lacking HP1B show altered food intake and higher body fat levels. Gene expression analysis of animals lacking HP1B demonstrates that genes with functions in various metabolic processes are affected primarily by HP1B loss. Our findings suggest that there is a link between the chromatin protein HP1B and the regulation of metabolism., Competing Interests: The authors have declared that no competing interests exist.

Drosophila melanogaster is a new model organism for studies in exercise biology. To date, two main exercise systems, the Power Tower and the Treadwheel have been described. However, a method to measure the amount of additional animal activity induced through the exercise treatment has been lacking. The Rotating Exercise Quantification System (REQS) fills this need, providing a measure of animal activity for animals experiencing rotational exercise. This protocol details how to use the REQS to assess animal activity during rotational exercise and illustrates the type of data that can be generated. Here, we demonstrate how the REQS is used to measure sex- and strain-specific differences in exercise induced activity. The REQS can also be used to evaluate the impact of various other experimental parameters such as age, diet, or population size on exercise induced activity. In addition, it can be used to compare the efficacy of different exercise training protocols. Importantly, it provides an opportunity to standardize exercise treatments between strains, allowing the researcher to achieve equal amounts of activity between groups if needed. Thus, the REQS is a notable new resource for exercise biologists working with the Drosophila model system and complements existing exercise systems.

Aging is characterized by decreasing physiological integration, reduced function, loss of resilience, and increased risk of death. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist. While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal. Among fruit flies, nematodes, and mice, sex differences in lifespan vary depending on strain and treatment. In this review, we focus on sex differences in age-related alterations in DNA damage and mutation rates, telomere attrition, epigenetics, and nuclear architecture. We find that robust sex differences exist, eg, the higher incidence of DNA damage in men compared to women, but sex differences are not often conserved between species. For most mechanisms reviewed here, there are insufficient data to make a clear determination regarding the impact of sex, largely because sex differences have not been analyzed. Overall, our findings reveal an urgent need for well-designed studies that explicitly examine sex differences in molecular drivers of aging., (© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Obesity is a disease that has reached epidemic proportions in the United States and has prompted international legislation in an attempt to curtail its prevalence. Despite the fact that one of the most prescribed treatment options for obesity is exercise, the genetic mechanisms underlying exercise response in individuals are still largely unknown. The fruit fly Drosophila melanogaster is a promising new model for studying exercise genetics. Currently, the lack of an accurate method to quantify the amount of exercise performed by the animals is limiting the utility of the Drosophila model for exercise genetics research. To address this limitation, we developed the Rotational Exercise Quantification System (REQS), a novel apparatus that is able to simultaneously induce exercise in flies while recording their activity levels. Thus, the REQS provides a method to standardize Drosophila exercise and ensure that all animals irrespective of genotype and sex experience the same level of exercise. Here, we provide a basic characterization of the REQS, validate its measurements using video-tracking technology, illustrate its potential use by presenting a comparison of two different exercise regimes, and demonstrate that it can be used to detect genotype-dependent variation in activity levels.

Obesity is one of the dramatic health issues affecting developed and developing nations, and exercise is a well-established intervention strategy. While exercise-by-genotype interactions have been shown in humans, overall little is known. Using the natural negative geotaxis of Drosophila melanogaster, an important model organism for the study of genetic interactions, a novel exercise machine, the TreadWheel, can be used to shed light on this interaction. The mechanism for inducing exercise with the TreadWheel is inherently gentle, thus minimizing possible confounding effects of other stressors. Using this machine, we were able to assess large cohorts of adult flies from eight genetic lines for their response to exercise after one week of training. We measured their triglyceride, glycerol, protein, glycogen, glucose content, and body weight, as well as their climbing ability and feeding behavior in response to exercise. Exercised flies showed decreased stored triglycerides, glycogen, and body weight, and increased stored protein and climbing ability. In addition to demonstrating an overall effect of TreadWheel exercise on flies, we found significant interactions of exercise with genotype, sex, or genotype-by-sex effects for most of the measured phenotypes. We also observed interaction effects between exercise, genotype, and tissue (abdomen or thorax) for metabolite profiles, and those differences can be partially linked to innate differences in the flies' persistence in maintaining activity during exercise bouts. In addition, we assessed gene expression levels for a panel of 13 genes known to be associated with respiratory fitness and found that many responded to exercise. With this study, we have established the TreadWheel as a useful tool to study the effect of exercise in flies, shown significant genotype-specific and sex-specific impacts of exercise, and have laid the ground work for more extensive studies of how genetics, sex, environment, and aging interact with exercise to influence metabolic fitness in Drosophila., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Approximately 3% to 5% of endometrial cancers (EC) are associated with Lynch syndrome (LS). The clinical characteristics and prevalence of LS have not been well studied in the US Hispanic population. Hispanics are the largest and fastest growing ethnic minority group in the United States. We sought to characterize the demographics, tumor characteristics, and prevalence of loss of mismatch repair (MMR) protein expression in a large Hispanic population with EC., Methods: From January 1, 2005, to August 1, 2012, 83 women of Hispanic ethnicity diagnosed with EC 50 years and younger were identified. Clinical and pathologic data were abstracted from the electronic medical record. Tumor studies included immunohistochemistry of MLH1, MSH2, MSH6, and PMS2 and methylation of the MLH1 promoter., Results: Ninety-five percent of patients were overweight or obese. The mean body mass index was 40.1 kg/m, 75% had irregular menses, 36% had diabetes, 46% were nulliparous, and 95% had endometrioid histology. Thirteen patients (15.7%) had tumor MMR deficiency due to a presumed germline mutation (9 MSH6, 3 MSH2, and 1 MLH1). The pattern of MMR protein loss was consistent with the expected binding properties of the MMR heterodimer complexes. No significant difference was found in clinical or pathological variables between patients with and without MMR deficient tumors., Conclusions: The prevalence of molecular findings consistent with LS was at least as high as other populations of varied geography, race, and ethnicity. We found no reliable factors to include body mass index, family history, synchronous tumors, or pathologic tumor features to serve as triage markers for which ECs should be screened for MMR protein loss. Our findings support a recommendation for universal screening of ECs utilizing 2-antibody testing with MLH1 promoter methylation testing as indicated up to 60 years or older. Our recommendations should be generalizable to other Hispanic populations in the Southern United States.

Certain tumors suggest the possibility of a patient harboring a genetic syndrome, particularly in children. Syndrome-associated tumors of the gastrointestinal tract, genitourinary tract, gynecologic tract, heart, lungs, brain, eye, endocrine organs, and hematopoietic system will be briefly discussed.

On the basis of the similarities in the histopathologic findings and the clinical-biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance., ((©)RSNA, 2016.)

Heterochromatin is a common DNA packaging form employed by eukaryotes to constitutively silence transposable elements. Determining which sequences to package as heterochromatin is vital for an organism. Here, we use Drosophila melanogaster to study heterochromatin formation, exploiting position-effect variegation, a process whereby a transgene is silenced stochastically if inserted in proximity to heterochromatin, leading to a variegating phenotype. Previous studies identified the transposable element 1360 as a target for heterochromatin formation. We use transgene reporters with either one or four copies of 1360 to determine if increasing local repeat density can alter the fraction of the genome supporting heterochromatin formation. We find that including 1360 in the reporter increases the frequency with which variegating phenotypes are observed. This increase is due to a greater recovery of insertions at the telomere-associated sequences (∼50% of variegating inserts). In contrast to variegating insertions elsewhere, the phenotype of telomere-associated sequence insertions is largely independent of the presence of 1360 in the reporter. We find that variegating and fully expressed transgenes are located in different types of chromatin and that variegating reporters in the telomere-associated sequences differ from those in pericentric heterochromatin. Indeed, chromatin marks at the transgene insertion site can be used to predict the eye phenotype. Our analysis reveals that increasing the local repeat density (via the transgene reporter) does not enlarge the fraction of the genome supporting heterochromatin formation. Rather, additional copies of 1360 appear to target the reporter to the telomere-associated sequences with greater efficiency, thus leading to an increased recovery of variegating insertions., (Copyright © 2016 by the Genetics Society of America.)

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative four-repeat tauopathies with no cure. Mitigating pathogenic tau levels is a rational strategy for tauopathy treatment, but therapeutic targets with clinically available drugs are lacking. Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains. RNAi depletion of ROCK1 or ROCK2 reduced tau mRNA and protein level in human neuroblastoma cells. However, additional phenotypes were observed under ROCK2 knockdown, including decreased S6K and phosphorylated mTOR levels. Pharmacologic inhibition of Rho kinases in neurons diminished detergent-soluble and -insoluble tau through a combination of autophagy enhancement and tau mRNA reduction. Fasudil, a clinically approved ROCK inhibitor, suppressed rough eye phenotype and mitigated pathogenic tau levels by inducing autophagic pathways in a Drosophila model of tauopathy. Collectively, these findings highlight the Rho kinases as rational therapeutic targets to combat tau accumulation in PSP and CBD., Significance Statement: Studies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) suggest that mitigating pathogenic tau levels is a rational strategy for tauopathy treatment. In this report, the Rho-associated protein kinases (ROCK1 and ROCK2) are identified as novel drug targets for PSP and CBD. We show that elevated insoluble tau levels are associated with increased ROCK1 and ROCK2 in PSP and CBD brains, whereas experiments in cellular and animal models identify pharmacologic inhibition of ROCKs as a mechanism-based approach to reduce tau levels. Our study correlates bona fide changes in PSP and CBD brains with cellular models, identifies drug targets, and tests the therapeutic in vivo., (Copyright © 2016 the authors 0270-6474/16/361316-08$15.00/0.)

Little is known about the etiology or pathogenesis of angiosarcoma (AS). We describe a series of 5 cases of AS arising in chronic expanding hematomas. Inclusion criteria were the presence of a hematoma of at least 1-year duration and a thick fibrous wall surrounding the hematoma. Patients were 4 men and 1 woman; ages ranged from 43 to 71 years. Locations were the thigh (3), chest wall (1), and pelvic soft tissue involving the ischial bone (1). Hematoma duration ranged from 2 to 25 years. All cases had large cystic hematomas >10 cm; 2 had prior radiation. Thick fibrous walls surrounded the hematomas, with foci of hemosiderin and foamy histiocytes. Wall thickness ranged from 0.2 to 1.0 cm and varied within lesions. All AS were epithelioid, and in 3 cases the tumor invaded through the cyst wall. Immunoreactive nuclear c-myc was noted in 3/3 cases available for testing. Follow-up disclosed 4 patients developed metastatic disease, 3 of whom died of disease, 4, 8, and 15 months after diagnosis; the fourth patient is alive without disease after chemotherapy at 59 months. One patient without metastases is alive without disease 18 months after diagnosis; this tumor was confined to the cyst without penetration through the wall. We identified 4 similar cases in the literature, 3 as individual case reports (all epithelioid AS), and 1 as part of a series of AS. To our knowledge, this is the first series of AS arising in chronic expanding hematomas. Recognition of this unusual complication should alert clinicians to provide periodic clinical follow-up to these patients and to biopsy any case with sudden or uncontrolled enlargement. We recommend that excised chronic hematomas be well sampled histologically to search for AS and, if identified, to determine its extent and invasiveness.

Soft tissue pathology is a rapidly changing subspecialty. New entities are described relatively often, and new molecular findings for soft tissue tumors are reported in the literature almost every month. This article summarizes the major features and diagnostic approach to several recently characterized entities: superficial CD34-positive fibroblastic tumor, fibrosarcoma-like lipomatous neoplasm, angiofibroma of soft tissue, low-grade sinonasal sarcoma with neural and myogenic features, malignant gastrointestinal neuroectodermal tumor, hemosiderotic fibrolipomatous tumor, and epithelioid inflammatory myofibroblastic sarcoma. Additionally, the article also provides a summary table of recent molecular findings in soft tissue tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1. The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities. SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor. In addition, numerous benign tissues were tested for SIRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, smooth muscle, and striated muscle. A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76.5%), and rhabdomyosarcoma (87%). The other lesions examined were negative. Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry. Furthermore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy. Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms., (Copyright © 2013 Elsevier Inc. All rights reserved.)