National Comparison of Burnout for a Cohort of Surgical and Nonsurgical Female Trainees.

INTRODUCTION: Studies have shown that female physician trainees have an increased risk of burnout. We describe the current state of surgical and nonsurgical female trainee well-being and examine differences between surgical and nonsurgical specialties. METHODS: Survey responses were received from 1017 female identifying trainees from 26 graduate medical education institutions across the United States. These survey responses included demographic data and well-being measures. Specifically, burnout was assessed using the Maslach Burnout Inventory. Data were analyzed using Wilcoxon rank sum test, Fisher's exact test, and Pearson's Chi-squared test data with significance defined as a P < 0.05. This survey was reported in line with strengthening the reporting of cohort studies in surgery criteria. RESULTS: Nine-hundred ninety-nine participants completed the demographic and well-being section of the surveys and were included in analysis. Demographic data between the surgical versus nonsurgical group were similar, aside from surgeons being slightly older. Burnout was prevalent among all surveyed trainees with 63% scoring positive. Trainees also scored high in imposter syndrome and moral injury with low levels of self-compassion, although respondents also reported themselves flourishing. Surgical trainees scored higher than nonsurgical trainees in the personal accomplishment domain of burnout (P < 0.048). There was no difference between surgical and nonsurgical trainees in measures of the emotional exhaustion or depersonalization domains of burnout, or in impostor syndrome, self-compassion, moral injury, or flourishing. CONCLUSIONS: While personal accomplishment was noted to be higher in surgical trainees as compared to nonsurgical trainees, overall rates of burnout are high among both groups. Targeted interventions for well-being, such as coaching, can help decrease the levels of burnout experienced by female physician trainees and do not need to be specialty specific.

Ancient and Nonuniform Loss of Olfactory Receptor Expression Renders the Shark Nose a De Facto Vomeronasal Organ.

Cartilaginous fishes are renowned for a keen sense of smell, a reputation based on behavioral observations and supported by the presence of large and morphologically complex olfactory organs. At the molecular level, genes belonging to the four families coding for most olfactory chemosensory receptors in other vertebrates have been identified in a chimera and a shark, but it was unknown whether they actually code for olfactory receptors in these species. Here, we describe the evolutionary dynamics of these gene families in cartilaginous fishes using genomes of a chimera, a skate, a sawfish, and eight sharks. The number of putative OR, TAAR, and V1R/ORA receptors is very low and stable, whereas the number of putative V2R/OlfC receptors is higher and much more dynamic. In the catshark Scyliorhinus canicula, we show that many V2R/OlfC receptors are expressed in the olfactory epithelium in the sparsely distributed pattern characteristic for olfactory receptors. In contrast, the other three vertebrate olfactory receptor families are either not expressed (OR) or only represented with a single receptor (V1R/ORA and TAAR). The complete overlap of markers of microvillous olfactory sensory neurons with pan-neuronal marker HuC in the olfactory organ suggests the same cell-type specificity of V2R/OlfC expression as for bony fishes, that is, in microvillous neurons. The relatively low number of olfactory receptors in cartilaginous fishes compared with bony fishes could be the result of an ancient and constant selection in favor of a high olfactory sensitivity at the expense of a high discrimination capability.

Staff Experiences with a Team-based Approach to Sleep Medicine Referrals: A Qualitative Evaluation.

Rationale: Sleep disorders are highly prevalent, and the volume of referrals sent to sleep specialists frequently exceeds their capacity. To manage this demand, we will need to consider sustainable strategies to expand the reach of our sleep medicine workforce. The Referral Coordination Initiative (RCI) takes a team-based approach to streamlining care for new specialty care referrals by 1) incorporating registered nurses into initial decision-making, 2) integrating administrative staff for coordination, and 3) sharing resources across facilities. Although prior work shows that the RCI can improve access to sleep care, we have a limited understanding around staff experiences and perspectives with this approach. Objectives: To assess staff experiences with a team-based approach to sleep medicine referrals. Methods: From June 2019 to September 2020, we conducted semistructured interviews with staff members who interacted with the RCI in sleep medicine. We recruited a variety of staff, including RCI team members (nurses and medical support assistants), sleep specialists, and referring providers. Two analysts used content analysis to identify themes. Results: We conducted 48 interviews among 35 unique staff members and identified six themes: 1) efficiency, in which staff described the impacts of the RCI program regarding efficient use of staff time and resources; 2) patient access and experience, in which staff noted improvements to patients' ability to receive care; 3) staff well-being and satisfaction, in which specialists and RCI staff described how the RCI mitigated the adverse impact of triage volume on staff well-being; 4) sharing specialty knowledge, in which nurses and specialists discussed the challenges of sharing specialty knowledge and training nurses to triage; 5) nurse autonomy, in which staff discussed nurses' ability to make triage decisions in the RCI system and highlighted the crucial role that decision support tools play in supporting that autonomy; and 6) coordination and communication, in which staff noted the importance, challenges, and facilitators of coordination and communication across facilities and at the interface of primary and specialty care. Conclusions: Staff endorsed positive and negative experiences around the RCI system, identifying opportunities to further streamline the referral process in support of access, patient experience, and staff well-being.

Safe and effective pool testing for SARS-CoV-2 detection.

OBJECTIVES: The global spread of SARS-CoV-2 is a serious public health issue. Large-scale surveillance screenings are crucial but can exceed test capacities. We (A) optimized test conditions and (B) implemented pool testing of respiratory swabs into SARS-CoV-2 diagnostics. STUDY DESIGN: (A) We determined the optimal pooling strategy and pool size. In addition, we measured the impact of vortexing prior to sample processing, compared a pipette-pooling method (by combining transport medium of several specimens) and a swab-pooling method (by combining several swabs into a test tube filled with PBS) as well as determined the sensitivities of three PCR assays. (B) Finally, we applied high-throughput pool testing for diagnostics. RESULTS: (A) In a low prevalence setting, we defined a preferable pool size of ten in a two-stage hierarchical pool testing strategy. Vortexing of swabs (n = 33) increased cellular yield by a factor of 2.34. By comparing Ct-values of 16 pools generated with two different pooling strategies, pipette-pooling was more efficient compared to swab-pooling. Measuring dilution series of 20 SARS-CoV-2 positive samples in three PCR assays simultaneously revealed detection rates of 85% (assay I), 50% (assay II), and 95% (assay III) at a 1:100 dilution. (B) We systematically pooled 55,690 samples in a period of 44 weeks resulting in a reduction of 47,369 PCR reactions. CONCLUSIONS: For implementing pooling strategies into high-throughput diagnostics, we recommend utilizing a pipette-pooling method, performing sensitivity validation of the PCR assays used, and vortexing swabs prior to analyses. Pool testing for SARS-CoV-2 detection is feasible and effective in a low prevalence setting.

Patient experiences with telehealth in sleep medicine: a qualitative evaluation.

STUDY OBJECTIVES: The field of sleep medicine has been an avid adopter of telehealth, particularly during the COVID-19 pandemic. The goal of this study was to assess patients' experiences receiving sleep care by telehealth. METHODS: From June 2019 to May 2020, the authors recruited a sample of patients for semi-structured interviews, including patients who had 1 of 3 types of telehealth encounters in sleep medicine: in-clinic video, home-based video, and telephone. Two analysts coded transcripts using content analysis and identified themes that cut across patients and categories. RESULTS: The authors conducted interviews with 35 patients and identified 5 themes. (1) Improved access to care: Patients appreciated telehealth as providing access to sleep care in a timely and convenient manner. (2) Security and privacy: Patients described how home-based telehealth afforded them greater feelings of safety and security due to avoidance of anxiety-provoking triggers (eg, crowds). Patients also noted a potential loss of privacy with telehealth. (3) Personalization of care: Patients described experiences with telehealth care that either improved or hindered their ability to communicate their needs. (4) Patient empowerment: Patients described how telehealth empowered them to manage their sleep disorders. (5) Unmet needs: Patients recognized specific areas where telehealth did not meet their needs, including the need for tangible services (eg, mask fitting). CONCLUSIONS: Patients expressed both positive and negative experiences, highlighting areas where telehealth can be further adapted. As telehealth in sleep medicine continues to evolve, the authors encourage providers to consider these aspects of the patient experience. CITATION: Donovan LM, Mog AC, Blanchard KN, et al. Patient experiences with telehealth in sleep medicine: a qualitative evaluation. J Clin Sleep Med. 2021;17(8):1645-1651.

Agreement of sleep specialists with registered nurses' sleep study orders in supervised clinical practice.

STUDY OBJECTIVES: Incorporating registered nurses (RN-level) into obstructive sleep apnea (OSA) management decisions has the potential to augment the workforce and improve patient access, but the appropriateness of such task-shifting in typical practice is unclear. METHODS: Our medical center piloted a nurse triage program for sleep medicine referrals. Using a sleep specialist-designed decision-making tool, nurses triaged patients referred for initial sleep studies to either home sleep apnea test (HSAT) or in-laboratory polysomnography (PSG). During the first 5 months of the program, specialists reviewed all nurse triages. We compared agreement between specialists and nurses. RESULTS: Of 280 consultations triaged by nurses, nurses deferred management decisions to sleep specialists in 6.1% (n = 17) of cases. Of the remaining 263 cases, there was 88% agreement between nurses and specialists (kappa 0.80, 95% confidence interval 0.74-0.87). In the 8.8% (n = 23) of cases where supervising specialists changed sleep study type, specialists changed from HSAT to PSG in 16 cases and from PSG to HSAT in 7. The most common indication for change in sleep study type was disagreement regarding OSA pretest probability (n = 14 of 23). Specialists changed test instructions in 3.0% (n = 8) of cases, with changes either related to the use of transcutaneous carbon dioxide monitoring (n = 4) or adaptive servo-ventilation (n = 4). CONCLUSIONS: More than 80% of sleep study triages by registered nurses in a supervised setting required no sleep specialist intervention. Future research should focus on how to integrate nurses into the sleep medicine workforce in a manner that maximizes efficiency while preserving or improving patient outcomes.

HPV8 activates cellular gene expression mainly through Sp1/3 binding sites.

The human papillomavirus type 8 (HPV8) is associated with skin cancer development. The goal of this study was to investigate the effects of HPV8 oncoproteins on cellular gene expression and the identification of key regulators. We performed affymetrix microarray analyses to identify differentially expressed genes and common sequence motifs and identified Sp1/3 binding sites as being crucial. In transient transfection assays, we confirmed that HPV8-E7 stimulates the activity of Sp1/3 promoters. Interestingly, the HPV8-E7L23A mutant, which cannot trigger keratinocyte invasion was unable to activate fibronectin gene expression. In skin models or HPV8 positive skin cancers we found a peculiar deposition of fibronectin in the dermal compartment, and a correlation of Sp3 and fibronectin in the nucleus of HPV8-positive keratinocytes. Taken together, we identified that HPV8-E7 exerts control over cellular gene expression through Sp1/3 binding motifs, which may contribute to HPV8-mediated keratinocyte transformation and subsequent fibronectin-dependent invasion.

The Chemosensory Receptor Repertoire of a True Shark Is Dominated by a Single Olfactory Receptor Family.

Throughout the animal kingdom chemical senses are one of the primary means by which organisms make sense of their environment. To achieve perception of complex chemosensory stimuli large repertoires of olfactory and gustatory receptors are employed in bony vertebrates, which are characterized by high evolutionary dynamics in receptor repertoire size and composition. However, little is known about their evolution in earlier diverging vertebrates such as cartilaginous fish, which include sharks, skates, rays, and chimeras. Recently, the olfactory repertoire of a chimera, elephant shark, was found to be curiously reduced in odorant receptor number. Elephant sharks rely heavily on electroreception to localize prey; thus, it is unclear how representative their chemosensory receptor repertoire sizes would be for cartilaginous fishes in general. Here, we have mined the genome of a true shark, Scyliorhinus canicula (catshark) for olfactory and gustatory receptors, and have performed a thorough phylogenetic study to shed light on the evolution of chemosensory receptors in cartilaginous fish. We report the presence of several gustatory receptors of the TAS1R family in catshark and elephant shark, whereas TAS2R receptors are absent. The catshark olfactory repertoire is dominated by V2R receptors, with 5-8 receptors in the other three families (OR, ORA, TAAR). Species-specific expansions are mostly limited to the V2R family. Overall, the catshark chemosensory receptor repertoires are generally similar in size to those of elephant shark, if somewhat larger, showing similar evolutionary tendencies across over 400 Myr of separate evolution between catshark and elephant shark.

Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones.

BACKGROUND: The sense of smell is unrivaled in terms of molecular complexity of its input channels. Even zebrafish, a model vertebrate system in many research fields including olfaction, possesses several hundred different olfactory receptor genes, organized in four different gene families. For one of these families, the initially discovered odorant receptors proper, segregation of expression into distinct spatial subdomains within a common sensory surface has been observed both in teleost fish and in mammals. However, for the remaining three families, little to nothing was known about their spatial coding logic. Here we wished to investigate, whether the principle of spatial segregation observed for odorant receptors extends to another olfactory receptor family, the V2R-related OlfC genes. Furthermore we thought to examine, how expression of OlfC genes is integrated into expression zones of odorant receptor genes, which in fish share a single sensory surface with OlfC genes. RESULTS: To select representative genes, we performed a comprehensive phylogenetic study of the zebrafish OlfC family, which identified a novel OlfC gene, reduced the number of pseudogenes to 1, and brought the total family size to 60 intact OlfC receptors. We analyzed the spatial pattern of OlfC-expressing cells for seven representative receptors in three dimensions (height within the epithelial layer, horizontal distance from the center of the olfactory organ, and height within the olfactory organ). We report non-random distributions of labeled neurons for all OlfC genes analysed. Distributions for sparsely expressed OlfC genes are significantly different from each other in nearly all cases, broad overlap notwithstanding. For two of the three coordinates analyzed, OlfC expression zones are intercalated with those of odorant receptor zones, whereas in the third dimension some segregation is observed. CONCLUSION: Our results show that V2R-related OlfC genes follow the same spatial logic of expression as odorant receptors and their expression zones intermingle with those of odorant receptor genes. Thus, distinctly different expression zones for individual receptor genes constitute a general feature shared by teleost and tetrapod V2R/OlfC and odorant receptor families alike.

Coordinated shift of olfactory amino acid responses and V2R expression to an amphibian water nose during metamorphosis.

All olfactory receptors identified in teleost fish are expressed in a single sensory surface, whereas mammalian olfactory receptor gene families segregate into different olfactory organs, chief among them the main olfactory epithelium expressing ORs and TAARs, and the vomeronasal organ expressing V1Rs and V2Rs. A transitional stage is embodied by amphibians, with their vomeronasal organ expressing more 'modern', later diverging V2Rs, whereas more 'ancient', earlier diverging V2Rs are expressed in the main olfactory epithelium. During metamorphosis, the main olfactory epithelium of Xenopus tadpoles transforms into an air-filled cavity (principal cavity, air nose), whereas a newly formed cavity (middle cavity) takes over the function of a water nose. We report here that larval expression of ancient V2Rs is gradually lost from the main olfactory epithelium as it transforms into the air nose. Concomitantly, ancient v2r gene expression begins to appear in the basal layers of the newly forming water nose. We observe the same transition for responses to amino acid odorants, consistent with the hypothesis that amino acid responses may be mediated by V2R receptors.

Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors.

Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors.

Molecular and neuronal homology between the olfactory systems of zebrafish and mouse.

Studies of the two major olfactory organs of rodents, the olfactory mucosa (OM) and the vomeronasal organ (VNO), unraveled the molecular basis of smell in vertebrates. However, some vertebrates lack a VNO. Here we generated and analyzed the olfactory transcriptome of the zebrafish and compared it to the olfactory transcriptomes of mouse to investigate the evolutionary and molecular relationship between single and dual olfactory systems. Our analyses revealed a high degree of molecular conservation, with orthologs of mouse olfactory cell-specific markers and all but one of their chemosensory receptor classes expressed in the single zebrafish olfactory organ. Zebrafish chemosensory receptor genes are expressed across a large dynamic range and their RNA abundance correlates positively with the number of neurons expressing that RNA. Thus we estimate the relative proportions of neuronal sub-types expressing different chemosensory receptors. Receptor repertoire size drives the absolute abundance of different classes of neurons, but we find similar underlying patterns in both species. Finally, we identified novel marker genes that characterize rare neuronal populations in both mouse and zebrafish. In sum, we find that the molecular and cellular mechanisms underpinning olfaction in teleosts and mammals are similar despite 430 million years of evolutionary divergence.

Positive Darwinian selection in the singularly large taste receptor gene family of an 'ancient' fish, Latimeria chalumnae.

BACKGROUND: Chemical senses are one of the foremost means by which organisms make sense of their environment, among them the olfactory and gustatory sense of vertebrates and arthropods. Both senses use large repertoires of receptors to achieve perception of complex chemosensory stimuli. High evolutionary dynamics of some olfactory and gustatory receptor gene families result in considerable variance of chemosensory perception between species. Interestingly, both ora/v1r genes and the closely related t2r genes constitute small and rather conserved families in teleost fish, but show rapid evolution and large species differences in tetrapods. To understand this transition, chemosensory gene repertoires of earlier diverging members of the tetrapod lineage, i.e. lobe-finned fish such as Latimeria would be of high interest. RESULTS: We report here the complete T2R repertoire of Latimeria chalumnae, using thorough data mining and extensive phylogenetic analysis. Eighty t2r genes were identified, by far the largest family reported for any species so far. The genomic neighborhood of t2r genes is enriched in repeat elements, which may have facilitated the extensive gene duplication events resulting in such a large family. Examination of non-synonymous vs. synonymous substitution rates (dN/dS) suggests pronounced positive Darwinian selection in Latimeria T2Rs, conceivably ensuring efficient neo-functionalization of newly born t2r genes. Notably, both traits, positive selection and enrichment of repeat elements in the genomic neighborhood, are absent in the twenty v1r genes of Latimeria. Sequence divergence in Latimeria T2Rs and V1Rs is high, reminescent of the corresponding teleost families. Some conserved sequence motifs of Latimeria T2Rs and V1Rs are shared with the respective teleost but not tetrapod genes, consistent with a potential role of such motifs in detection of aquatic chemosensory stimuli. CONCLUSIONS: The singularly large T2R repertoire of Latimeria may have been generated by facilitating local gene duplication via increased density of repeat elements, and efficient neofunctionalization via positive Darwinian selection.The high evolutionary dynamics of tetrapod t2r gene families precedes the emergence of tetrapods, i.e. the water-to-land transition, and thus constitutes a basal feature of the lobe-finned lineage of vertebrates.

Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval Xenopus laevis.

Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal epithelium is first observed in amphibians. In contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. The transient receptor potential channel TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red-legged salamander (Plethodon shermani). Here we examined the localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2 gene. We show that it is expressed in both the MOE and the vomeronasal epithelium. This is the first description of a broad trpc2 expression in the MOE of a tetrapod. The expression pattern of trpc2 in the MOE is virtually undistinguishable from that of MOE-specific v2rs, indicating that they are co-expressed in the same neuronal subpopulation.

Phospholipase C and diacylglycerol mediate olfactory responses to amino acids in the main olfactory epithelium of an amphibian.

The semi-aquatic lifestyle of amphibians represents a unique opportunity to study the molecular driving forces involved in the transition of aquatic to terrestrial olfaction in vertebrates. Most amphibians have anatomically segregated main and vomeronasal olfactory systems, but at the cellular and molecular level the segregation differs from that found in mammals. We have recently shown that amino acid responses in the main olfactory epithelium (MOE) of larval Xenopus laevis segregate into a lateral and a medial processing stream, and that the former is part of a vomeronasal type 2 receptor expression zone in the MOE. We hypothesized that the lateral amino acid responses might be mediated via a vomeronasal-like transduction machinery. Here we report that amino acid-responsive receptor neurons in the lateral MOE employ a phospholipase C (PLC) and diacylglycerol-mediated transduction cascade that is independent of Ca(2+) store depletion. Furthermore, we found that putative transient receptor potential (TRP) channel blockers inhibit most amino acid-evoked responses in the lateral MOE, suggesting that ion channels belonging to the TRP family may be involved in the signaling pathway. Our data show, for the first time, a widespread PLC- and diacylglycerol-dependent transduction cascade in the MOE of a vertebrate already possessing a vomeronasal organ.

Ancestral amphibian v2rs are expressed in the main olfactory epithelium.

Mammalian olfactory receptor families are segregated into different olfactory organs, with type 2 vomeronasal receptor (v2r) genes expressed in a basal layer of the vomeronasal epithelium. In contrast, teleost fish v2r genes are intermingled with all other olfactory receptor genes in a single sensory surface. We report here that, strikingly different from both lineages, the v2r gene family of the amphibian Xenopus laevis is expressed in the main olfactory as well as the vomeronasal epithelium. Interestingly, late diverging v2r genes are expressed exclusively in the vomeronasal epithelium, whereas "ancestral" v2r genes, including the single member of v2r family C, are restricted to the main olfactory epithelium. Moreover, within the main olfactory epithelium, v2r genes are expressed in a basal zone, partially overlapping, but clearly distinct from an apical zone of olfactory marker protein and odorant receptor-expressing cells. These zones are also apparent in the spatial distribution of odor responses, enabling a tentative assignment of odor responses to olfactory receptor gene families. Responses to alcohols, aldehydes, and ketones show an apical localization, consistent with being mediated by odorant receptors, whereas amino acid responses overlap extensively with the basal v2r-expressing zone. The unique bimodal v2r expression pattern in main and accessory olfactory system of amphibians presents an excellent opportunity to study the transition of v2r gene expression during evolution of higher vertebrates.

Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream.

In contrast to the single sensory surface present in teleost fishes, several spatially segregated subsystems with distinct molecular and functional characteristics define the mammalian olfactory system. However, the evolutionary steps of that transition remain unknown. Here we analyzed the olfactory system of an early diverging tetrapod, the amphibian Xenopus laevis, and report for the first time the existence of two odor-processing streams, sharply segregated in the main olfactory bulb and partially segregated in the olfactory epithelium of pre-metamorphic larvae. A lateral odor-processing stream is formed by microvillous receptor neurons and is characterized by amino acid responses and Gαo/Gαi as probable signal transducers, whereas a medial stream formed by ciliated receptor neurons is characterized by responses to alcohols, aldehydes, and ketones, and Gαolf/cAMP as probable signal transducers. To reveal candidates for the olfactory receptors underlying these two streams, the spatial distribution of 12 genes from four olfactory receptor gene families was determined. Several class II and some class I odorant receptors (ORs) mimic the spatial distribution observed for the medial stream, whereas a trace amine-associated receptor closely parallels the spatial pattern of the lateral odor-processing stream. Other olfactory receptors (some class I odorant receptors and vomeronasal type 1 receptors) and odor responses (to bile acids, amines) were not lateralized, the latter not even in the olfactory bulb, suggesting an incomplete segregation. Thus, the olfactory system of X. laevis exhibits an intermediate stage of segregation and as such appears well suited to investigate the molecular driving forces behind olfactory regionalization.

Network of Cancer Genes: a web resource to analyze duplicability, orthology and network properties of cancer genes.

The Network of Cancer Genes (NCG) collects and integrates data on 736 human genes that are mutated in various types of cancer. For each gene, NCG provides information on duplicability, orthology, evolutionary appearance and topological properties of the encoded protein in a comprehensive version of the human protein-protein interaction network. NCG also stores information on all primary interactors of cancer proteins, thus providing a complete overview of 5357 proteins that constitute direct and indirect determinants of human cancer. With the constant delivery of results from the mutational screenings of cancer genomes, NCG represents a versatile resource for retrieving detailed information on particular cancer genes, as well as for identifying common properties of precompiled lists of cancer genes. NCG is freely available at: http://bio.ifom-ieo-campus.it/ncg.