Power-law scaling in intratumoral microbiota of colorectal cancer.

It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies.

A Semiautonomous Deep Learning System to Reduce False Positives in Screening Mammography.

Purpose To evaluate the ability of a semiautonomous artificial intelligence (AI) model to identify screening mammograms not suspicious for breast cancer and reduce the number of false-positive examinations. Materials and Methods The deep learning algorithm was trained using 123 248 two-dimensional digital mammograms (6161 cancers) and a retrospective study was performed on three nonoverlapping datasets of 14 831 screening mammography examinations (1026 cancers) from two U.S. institutions and one U.K. institution (2008-2017). The stand-alone performance of humans and AI was compared. Human plus AI performance was simulated to examine reductions in the cancer detection rate, number of examinations, false-positive callbacks, and benign biopsies. Metrics were adjusted to mimic the natural distribution of a screening population, and bootstrapped CIs and P values were calculated. Results Retrospective evaluation on all datasets showed minimal changes to the cancer detection rate with use of the AI device (noninferiority margin of 0.25 cancers per 1000 examinations: U.S. dataset 1, P = .02; U.S. dataset 2, P < .001; U.K. dataset, P < .001). On U.S. dataset 1 (11 592 mammograms; 101 cancers; 3810 female patients; mean age, 57.3 years ± 10.0 [SD]), the device reduced screening examinations requiring radiologist interpretation by 41.6% (95% CI: 40.6%, 42.4%; P < .001), diagnostic examinations callbacks by 31.1% (95% CI: 28.7%, 33.4%; P < .001), and benign needle biopsies by 7.4% (95% CI: 4.1%, 12.4%; P < .001). U.S. dataset 2 (1362 mammograms; 330 cancers; 1293 female patients; mean age, 55.4 years ± 10.5) was reduced by 19.5% (95% CI: 16.9%, 22.1%; P < .001), 11.9% (95% CI: 8.6%, 15.7%; P < .001), and 6.5% (95% CI: 0.0%, 19.0%; P = .08), respectively. The U.K. dataset (1877 mammograms; 595 cancers; 1491 female patients; mean age, 63.5 years ± 7.1) was reduced by 36.8% (95% CI: 34.4%, 39.7%; P < .001), 17.1% (95% CI: 5.9%, 30.1%: P < .001), and 5.9% (95% CI: 2.9%, 11.5%; P < .001), respectively. Conclusion This work demonstrates the potential of a semiautonomous breast cancer screening system to reduce false positives, unnecessary procedures, patient anxiety, and medical expenses. Keywords: Artificial Intelligence, Semiautonomous Deep Learning, Breast Cancer, Screening Mammography Supplemental material is available for this article. Published under a CC BY 4.0 license.

Land-use change interacts with island biogeography to alter bird community assembly.

Anthropogenic activities have reshaped biodiversity on islands worldwide. However, it remains unclear how island attributes and land-use change interactively shape multiple facets of island biodiversity through community assembly processes. To answer this, we conducted bird surveys in various land-use types (mainly forest and farmland) using transects on 34 oceanic land-bridge islands in the largest archipelago of China. We found that bird species richness increased with island area and decreased with isolation, regardless of the intensity of land-use change. However, forest-dominated habitats exhibited lower richness than farmland-dominated habitats. Island bird assemblages generally comprised species that share more similar traits or evolutionary histories (i.e. functional and/or phylogenetic clustering) than expected if assemblages were randomly assembled. Contrary to our expectations, we observed that bird assemblages in forest-dominated habitats were more clustered on large and close islands, whereas assemblages in farmland-dominated habitats were more clustered on small islands. These contrasting results indicate that land-use change interacts with island biogeography to alter the community assembly of birds on inhabited islands. Our findings emphasize the importance of incorporating human-modified habitats when examining the community assembly of island biota, and further suggest that agricultural landscapes on large islands may play essential roles in protecting countryside island biodiversity.

Resource Deployment in Response to Trauma Patients.

Background Variance in the deployment of the trauma team to the emergency department (ED) can result in patient treatment delays and excess burden on ED personnel. Characteristics of trauma patients, including mechanism of injury, injury type, and age, have been associated with differences in trauma resource deployment. Therefore, this retrospective, single-site study aimed to examine the deployment patterns of trauma resources, the characteristics of the trauma patients associated with levels of trauma resource deployment, and the deployment impact on ED workforce utilization and non-trauma ED patients. Methodology This was an investigator-initiated, single-institution, retrospective cohort study of all patients designated as a trauma response and admitted to a community hospital's ED from July 01, 2019, through July 01, 2022. Results Resource deployment for trauma patients varied by mechanism of injury (p < 0.001), injury type (p < 0.001), and patient age groups (p < 0.001). Specifically, there was a lower average trauma activation for geriatric trauma patients with a fall as a mechanism of injury compared to all younger patient groups with any mechanism of injury (F(5) = 234.49, p < 0.001). In the subsample, there was an average of 3.35 ED registered nurses (RNs) allocated to each trauma patient. Additionally, the ED RNs were temporarily reallocated from an average of 4.09 non-trauma patients to respond to trauma patients, despite over a third of the trauma patients in the subsample being the trauma patients being discharged home from the ED. Conclusions Trauma activation responses need to be standardized with a specific plan for geriatric fall patients to ensure efficient use of trauma and ED personnel resources.

Extra terrestrials: drought creates niche space for rare invertebrates in a large-scale and long-term field experiment.

Freshwater habitats are drying more frequently and for longer under the combined pressures of climate change and overabstraction. Unsurprisingly, many aquatic species decline or become locally extinct as their benthic habitat is lost during stream droughts, but less is known about the potential 'winners': those terrestrial species that may exploit emerging niches in drying riverbeds. In particular, we do not know how these transient ecotones will respond as droughts become more extreme in the future. To find out we used a large-scale, long-term mesocosm experiment spanning a wide gradient of drought intensity, from permanent flows to full streambed dewatering, and analysed terrestrial invertebrate community assembly after 1 year. Droughts that caused stream fragmentation gave rise to the most diverse terrestrial invertebrate assemblages, including 10 species with UK conservation designations, and high species turnover between experimental channels. Droughts that caused streambed dewatering produced lower terrestrial invertebrate richness, suggesting that the persistence of instream pools may benefit these taxa as well as aquatic biota. Particularly intense droughts may therefore yield relatively few 'winners' among either aquatic or terrestrial species, indicating that the threat to riverine biodiversity from future drought intensification could be more pervasive than widely acknowledged.

L-band radar quantifies major disturbance of birds by fireworks in an urban area.

Fireworks and other pyrotechnics are acknowledged as sources of disturbance to wildlife, with evidence that many species react adversely to their sight and sound at discharge. However, how firework releases impact wildlife within a city landscape is poorly understood. Here, we explore the effect of fireworks on urban birds using an L-band staring radar (90-degree sector out to a 5 km range) to capture bird activity derived from flight tracks (i.e. 3D visualisation of individual flying birds built from radar detections) within the city of Birmingham, UK. Comparing the tracks between baseline periods with no fireworks and periods where fireworks are commonly discharged using a null model indicated that birds flew at higher elevations during firework periods (standardised effect sizes of 17.11, 26.54 and 5.83, for Diwali, Bonfire Night, and New Year's Eve, respectively). Birds also flew in more significant numbers (standardised effect sizes of 23.41, 7.98 and 7.19 for Diwali, Bonfire Night, and New Year's Eve, respectively). Therefore, bird activity was elevated during firework events at a time of night when many would otherwise be roosting. Such disturbance may have implications for avian biology since large public firework events occur at colder times of the year in the UK when birds have elevated thermoregulatory costs.

Evolution: The rise and fall of island dwarfs and giants.

Islands are arenas for a range of striking evolutionary phenomena, including the island rule - the tendency for larger animals to shrink and smaller animals to enlarge. A new study of insular mammals finds such body size shifts predispose these evolutionary marvels to greater extinction risk.

A Patient with a Brain Abscess Presenting as an Acute Stroke.

A brain abscess is an enclosed focal infection within the brain that is either initiated by haematogenous seeding or spreads contiguously from oto-sinusitis, local trauma or neurosurgery. We describe the case of a 71-year-old man presenting with acute confusion and unilateral neurology in the absence of systemic signs of sepsis or associated laboratory biomarkers. While his initial clinical presentation mimicked an acute cerebrovascular event or brain tumour, he was subsequently diagnosed with a particularly large spherical temporal lobe brain abscess of 5 cm diameter on neuroimaging. This abscess was treated successfully with craniotomy, evacuation and a prolonged course of anti-microbials, enabling him to return to his pre-morbid level of functioning. His prolonged course of anti-microbials was complicated by candidaemia and colonisation of an indwelling central venous catheter that was treated successfully with anti-fungals. LEARNING POINTS: A high index of suspicion for brain abscess should be maintained when a ring-enhancing lesion is found on neuroimaging, even in the absence of signs of sepsis or associated laboratory biomarkers.Commensal yeasts may colonise indwelling lines in patients treated with long-term broad-spectrum antibiotics.Distracting concomitant diagnoses may delay recognition of the primary pathological process.

Leveraging in vitro and pharmacokinetic models to support bench to bedside investigation of XTMAB-16 as a novel pulmonary sarcoidosis treatment.

Background: Sarcoidosis is a chronic, multisystem inflammatory disorder characterized by non-caseating epithelioid granulomas; infiltration of mononuclear cells; and destruction of microarchitecture in the skin, eye, heart, and central nervous system, and the lung in >90% of cases. XTMAB-16 is a chimeric anti-tumor necrosis factor alpha (TNFα) antibody, distinct from other anti-TNF antibodies based on its molecular structure. The efficacy of XTMAB-16 has not been clinically demonstrated, and it is still undergoing clinical development as a potential treatment for sarcoidosis. The current study demonstrates the activity of XTMAB-16 in a well-established in vitro sarcoidosis granuloma model, although XTMAB-16 is not yet approved by the United States Food and Drug Administration (FDA) for treatment of sarcoidosis, or any other disease. Objective: To provide data to guide safe and efficacious dose selection for the ongoing clinical development of XTMAB-16 as a potential treatment for sarcoidosis. Methods: First, XTMAB-16 activity was evaluated in an established in vitro model of granuloma formation using peripheral blood mononuclear cells from patients with active pulmonary sarcoidosis to determine a potentially efficacious dose range. Second, data obtained from the first-in-human study of XTMAB-16 (NCT04971395) were used to develop a population pharmacokinetic (PPK) model to characterize the pharmacokinetics (PK) of XTMAB-16. Model simulations were performed to evaluate the sources of PK variability and to predict interstitial lung exposure based on concentrations in the in vitro granuloma model. Results: XTMAB-16 dose levels of 2 and 4 mg/kg, once every 2 weeks (Q2W) or once every 4 weeks (Q4W) for up to 12 weeks, were supported by data from the non-clinical, in vitro secondary pharmacology; the Phase 1 clinical study; and the PPK model developed to guide dose level and frequency assumptions. XTMAB-16 inhibited granuloma formation and suppressed interleukin-1ß (IL-1ß) secretion in the in vitro granuloma model with a half maximal inhibitory concentration (IC50) of 5.2 and 3.5 µg/mL, respectively. Interstitial lung concentrations on average, following 2 or 4 mg/kg administered Q2W or Q4W, are anticipated to exceed the in vitro IC50 concentrations. Conclusion: The data presented in this report provide a rationale for dose selection and support the continued clinical development of XTMAB-16 for patients with pulmonary sarcoidosis.

A global analysis of avian island diversity-area relationships in the Anthropocene.

Research on island species-area relationships (ISAR) has expanded to incorporate functional (IFDAR) and phylogenetic (IPDAR) diversity. However, relative to the ISAR, we know little about IFDARs and IPDARs, and lack synthetic global analyses of variation in form of these three categories of island diversity-area relationship (IDAR). Here, we undertake the first comparative evaluation of IDARs at the global scale using 51 avian archipelagic data sets representing true and habitat islands. Using null models, we explore how richness-corrected functional and phylogenetic diversity scale with island area. We also provide the largest global assessment of the impacts of species introductions and extinctions on the IDAR. Results show that increasing richness with area is the primary driver of the (non-richness corrected) IPDAR and IFDAR for many data sets. However, for several archipelagos, richness-corrected functional and phylogenetic diversity changes linearly with island area, suggesting that the dominant community assembly processes shift along the island area gradient. We also find that archipelagos with the steepest ISARs exhibit the biggest differences in slope between IDARs, indicating increased functional and phylogenetic redundancy on larger islands in these archipelagos. In several cases introduced species seem to have 're-calibrated' the IDARs such that they resemble the historic period prior to recent extinctions.

Long-term changes in macroinvertebrate communities across high-latitude streams.

Long-term records of benthic macroinvertebrates in high-latitude streams are essential for understanding climatic changes, including extreme events (e.g. floods). Data extending over multiple decades are typically scarce. Here, we investigated macroinvertebrate community structural change (including alpha and beta diversity and gain and loss of species) over 22 years (1994-2016) in 10 stream systems across Denali National Park (Alaska, USA) in relation to climatological and meteorological drivers (e.g. air temperature, snowpack depth, precipitation). We hypothesised that increases in air temperature and reduced snowpack depth, due to climatic change, would reduce beta and gamma diversity but increase alpha diversity. Findings showed temporal trends in alpha diversity were variable across streams, with oscillating patterns in many snowmelt- and rainfall runoff-fed streams linked to climatic variation (temperature and precipitation), but increased over time in several streams supported by a mixture of water sources, including more stable groundwater-fed streams. Beta-diversity over the time series was highly variable, yet marked transitions were observed in response to extreme snowpack accumulation (1999-2000), where species loss drove turnover. Gamma diversity did not significantly increase or decrease over time. Investigating trends in individual taxa, several taxa were lost and gained during a relative constrained time period (2000-2006), likely in response to climatic variability and significant shifts in instream environmental conditions. Findings demonstrate the importance of long-term biological studies in stream ecosystems and highlight the vulnerability of high-latitude streams to climate change.

Discovery of 2-(3-Benzamidopropanamido)thiazole-5-carboxylate Inhibitors of the Kinesin HSET (KIFC1) and the Development of Cellular Target Engagement Probes.

The existence of multiple centrosomes in some cancer cells can lead to cell death through the formation of multipolar mitotic spindles and consequent aberrant cell division. Many cancer cells rely on HSET (KIFC1) to cluster the extra centrosomes into two groups to mimic the bipolar spindle formation of non-centrosome-amplified cells and ensure their survival. Here, we report the discovery of a novel 2-(3-benzamidopropanamido)thiazole-5-carboxylate with micromolar in vitro inhibition of HSET (KIFC1) through high-throughput screening and its progression to ATP-competitive compounds with nanomolar biochemical potency and high selectivity against the opposing mitotic kinesin Eg5. Induction of the multipolar phenotype was shown in centrosome-amplified human cancer cells treated with these inhibitors. In addition, a suitable linker position was identified to allow the synthesis of both fluorescent- and trans-cyclooctene (TCO)-tagged probes, which demonstrated direct compound binding to the HSET protein and confirmed target engagement in cells, through a click-chemistry approach.

Environmental drivers and spatial scaling of species abundance distributions in Palaearctic grassland vegetation.

Species abundance distributions (SADs) link species richness with species abundances and are an important tool in the quantitative analysis of ecological communities. Niche-based and sample-based SAD models predict different spatial scaling properties of SAD parameters. However, empirical research on SAD scaling properties is largely missing. Here we extracted percentage cover values of all occurring vascular plants as proxies of their abundance in 1725 10-m2 plots from the GrassPlot database, covering 47 regional data sets of 19 different grasslands and other open vegetation types of the Palaearctic biogeographic realm. For each plot, we fitted the Weibull distribution, a model that is able to effectively mimic other distributions like the log-series and lognormal, to the species-log abundance rank order distribution. We calculated the skewness and kurtosis of the empirical distributions and linked these moments, along with the shape and scale parameters of the Weibull distribution, to plot climatic and soil characteristics. The Weibull distribution provided excellent fits to grassland plant communities and identified four basic types of communities characterized by different degrees of dominance. Shape and scale parameter values of local communities on poorer soils were largely in accordance with log-series distributions. Proportions of subdominant species tended to be lower than predicted by the standard lognormal SAD. Successive accumulation of plots of the same vegetation type yielded nonlinear spatial scaling of SAD moments and Weibull parameters. This scaling was largely independent of environmental correlates and geographic plot position. Our findings caution against simple generalizations about the mechanisms that generate SADs. We argue that in grasslands, lognormal-type SADs tend to prevail within a wider range of environmental conditions, including more extreme habitats such as arid environments. In contrast, log-series distributions are mainly restricted to comparatively species-rich communities on humid and fertile soils.

Island biogeography.

Islands have fascinated biologists since the days of Charles Darwin and Alfred Russel Wallace and before, providing the inspiration for substantial theoretical development that has advanced our understanding of global biodiversity patterns and the mechanisms that underpin them. As such, they are often termed 'natural laboratories', providing the ideal setting to study the interface between ecology, evolution and conservation. Part of this fascination no-doubt arises from islands harboring a disproportionate amount of global biodiversity given the amount of land-mass they occupy (roughly 15-20% of global terrestrial species present in just 3.5% of global land), including large numbers of endemic forms not found anywhere else. Interestingly, more than 25% of human languages, many of which are also threatened with extinction, are also to be found on islands. In this primer, we provide an overview of the field of island biogeography, splitting it into three main sections. First, we explore some of the reasons that make islands, and the species that have evolved on them, unique and scientifically rewarding study systems for ecologists and biogeographers. Second, we delve into the key island biogeography works in order to provide an introductory summary of some of the main theoretical models developed to explain species diversity patterns on islands. Unfortunately, as well as representing captivating environments to study, islands are also highly threatened systems. As such, we end with an overview of the drivers and impacts of anthropogenic environmental change on islands, providing examples of some of the extraordinary island species that humans have driven extinct.

Marine debris knows no boundaries: Characteristics of debris accumulation in marine protected areas of the Florida Keys.

Marine debris is a persistent and pervasive threat worldwide including inside marine protected areas (MPAs). To assess marine debris accumulation rates and potential impacts, we counted and evaluated trap, non-trap fishing gear, and non-fishing debris in unprotected areas and MPAs with different management boundary regulations in the Florida Keys (USA). Analyses identified that neither MPA type nor size were strong drivers of debris density and that debris densities were not statistically different between unprotected areas and MPAs. Non-fishing and non-trap fishing gear debris densities were potentially related to unexplored local differences in human behavior, while trap debris density was likely associated with oceanographic forces that transported traps into the MPAs. Overall, our results suggested that the drivers of marine debris accumulation for each debris category were different and may vary with each individual MPA, and that marine debris is not constrained by MPA boundaries.

A Multisite Study of a Breast Density Deep Learning Model for Full-Field Digital Mammography and Synthetic Mammography.

PURPOSE: To develop a Breast Imaging Reporting and Data System (BI-RADS) breast density deep learning (DL) model in a multisite setting for synthetic two-dimensional mammographic (SM) images derived from digital breast tomosynthesis examinations by using full-field digital mammographic (FFDM) images and limited SM data. MATERIALS AND METHODS: A DL model was trained to predict BI-RADS breast density by using FFDM images acquired from 2008 to 2017 (site 1: 57 492 patients, 187 627 examinations, 750 752 images) for this retrospective study. The FFDM model was evaluated by using SM datasets from two institutions (site 1: 3842 patients, 3866 examinations, 14 472 images, acquired from 2016 to 2017; site 2: 7557 patients, 16 283 examinations, 63 973 images, 2015 to 2019). Each of the three datasets were then split into training, validation, and test. Adaptation methods were investigated to improve performance on the SM datasets, and the effect of dataset size on each adaptation method was considered. Statistical significance was assessed by using CIs, which were estimated by bootstrapping. RESULTS: Without adaptation, the model demonstrated substantial agreement with the original reporting radiologists for all three datasets (site 1 FFDM: linearly weighted Cohen κ [κw] = 0.75 [95% CI: 0.74, 0.76]; site 1 SM: κw = 0.71 [95% CI: 0.64, 0.78]; site 2 SM: κw = 0.72 [95% CI: 0.70, 0.75]). With adaptation, performance improved for site 2 (site 1: κw = 0.72 [95% CI: 0.66, 0.79], 0.71 vs 0.72, P = .80; site 2: κw = 0.79 [95% CI: 0.76, 0.81], 0.72 vs 0.79, P < .001) by using only 500 SM images from that site. CONCLUSION: A BI-RADS breast density DL model demonstrated strong performance on FFDM and SM images from two institutions without training on SM images and improved by using few SM images.Supplemental material is available for this article.Published under a CC BY 4.0 license.

Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization.

OBJECTIVE: Stimulant medications are the most prevalent first-line pharmacotherapy for attention-deficit/hyperactivity disorder, but children with aggressive behavior often receive multiagent treatment. There is sparse evidence for the benefits of adjunctive medications when stimulant monotherapy provides inadequate benefit for aggressive behavior, yet the adverse effects of common adjuncts are well established. This study compared the efficacy in reducing aggressive behavior of risperidone (RISP), divalproex sodium (DVPX), and placebo (PBO) added to stimulant medication among childrenwhose symptoms persisted after individually optimized stimulant treatment. METHOD: This trial enrolled 6- to 12-year-old with attention-deficit/hyperactivity disorder, a disruptive disorder, significant aggressive behavior, and prior stimulant treatment. Open, systematically titrated stimulant treatment identified patients with inadequate reductions in aggressive behavior, who were then randomly assigned to receive adjunctive RISP, DVPX, or PBO under double-blinded conditions for 8 weeks. Family-based behavioral treatment was offered throughout the trial. The primary outcome was the parent-completed Retrospective Modified Overt Aggression Scale. RESULTS: Participants included 175 children (mean [SD] age 9.48 [2.04] years, 19% female). Of participants, 151 completed the stimulant optimization phase, with aggression remitting among 96 (63%), and 45 were randomly assigned to adjunctive treatment groups. The adjunctive RISP group showed greater reductions in aggression ratings than the PBO group (least squares means difference [ΔLSM], -2.33; 95% CI, -3.83 to -0.82; effect size [ES], -1.32), as did the DVPX group (ΔLSM, -1.60; 95% CI, -3.18 to -0.03; ES, -0.91). Mean standardized body mass index scores increased more among RISP-treated participants than participants receiving PBO (ΔLSM, 1.54; 95% CI, 0.68 to 2.40; ES, 0.58). CONCLUSION: High response rate during the trial's open stimulant optimization phase suggests that rigorous titration of stimulant medication and concurrent behavioral therapy may avert the need for additional medications. Among nonremitters, RISP and DVPX were efficacious adjunctive treatments, although RISP was associated with weight gain. CLINICAL TRIAL REGISTRATION INFORMATION: Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study); https://www.clinicaltrials.gov; NCT00794625.

Elemental metal variance in cell culture raw materials for process risk profiling.

Elemental metals are critical raw material attributes which can impact cell culture performance and associated therapeutic protein product quality profiles. Metals such as copper and manganese act as cofactors and reagents for numerous metabolic pathways which govern cell growth, protein expression, and glycosylation, thus mandating elemental monitoring. The growing complexity of modern cell culture media formulations adds additional opportunities for elemental variance and its associated impact risks. This article describes an analytical technique applying inductively coupled plasma mass spectrometry to characterize a list of common raw materials and media powders used in mammalian cell culture and therapeutic protein production. We aim to describe a method qualification approach suitable for biopharmaceutical raw materials. Furthermore, we present detailed profiles of many common raw materials and discuss trends in raw material subtypes. Finally, a case study demonstrating the impact of an unexpected source of raw material variation is presented along with recommendations for raw material elemental risk profiling and control.

Cytogenetic analysis of 130 renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations.

The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (49%) cases, which could be categorized into three classes of mutually exclusive cytogenetic categories. Class 1 (N = 20) RO had diploid karyotypes with characteristic 11q13 rearrangement in balanced translocations with 10 or more different chromosome partners in all cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14, and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO (N = 25) exhibited hypodiploid karyotypes with loss of chromosome 1 and/or losses of Y in males and X in females in all cases. The class 3 tumors comprising of 18 cases showed diverse types of abnormalities with the involvement of two or more chromosomes exclusive of abnormalities seen in classes 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify classes 1 and 2 abnormalities. In this group, we found similar frequencies of CCND1 rearrangement, loss of chromosome 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mitelman database. Correlation of clinical data with all the three classes of ROs showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit three principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO.