Comparison of Pathologist and Artificial Intelligence-based Grading for Prediction of Metastatic Outcomes After Radical Prostatectomy.

Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning-based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin-stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence-based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell's C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence-assigned GG was 0.77 (95% confidence interval [CI]: 0.73-0.81), compared with 0.77 (95% CI: 0.73-0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73-0.82). PATIENT SUMMARY: Artificial intelligence-enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.

Medical Imagery: Cytomegalovirus sialadenitis in a patient with B-cell acute lymphoblastic leukemia.

Cytomegalovirus (CMV) can cause a broad range of diseases, with severity depending on immune status, comorbidities, and age. Initial CMV infection usually occurs in childhood and is typically asymptomatic, leading to lifelong latency. In immunocompromised patients, CMV can affect multiple organs, but salivary gland infections are rare. This study presents a case of a 66-year-old woman with B-cell acute lymphoblastic leukemia who developed swelling and pain in the right preauricular region during pre-transplant consolidation therapy. Despite a recent bone marrow biopsy indicating morphological remission and a flow cytometry analysis detecting only 0.04 % B lymphoblasts, she exhibited these symptoms. A CT scan revealed enlargement, hyperdensity, and enhancement of the right parotid glands, with accompanying subcutaneous edema. A biopsy of the right parotid gland showed a dense interstitial lymphoplasmacytic infiltrate with numerous Cowdry bodies and smaller granular cytoplasmic inclusions, all testing positive for CMV immunohistochemistry. The findings confirm the diagnosis of CMV sialadenitis in an immunocompromised patient. This case underscores the importance of considering CMV infections in similar clinical scenarios, particularly in patients with compromised immune systems.

Clinical, paraclinical, and genetic profile of patients with cystic fibrosis from Colombian Caribbean.

Background: Cystic fibrosis (CF) is a serious autosomal recessive disorder. Early diagnosis, comorbidity prevention, and control are cornerstones for a quality life and for improving life expectancy. In Colombian Caribbean, where there is a genetically admixed population, CF is an orphan disease affecting children and adults, and it remains a challenging issue to be addressed carefully. This work describes the genetic, clinical, and paraclinical profiles of CF patients from Cartagena de Indias, Colombia. Methods: Thirty-six patients were included in the study. The subjects were identified and evaluated through the Regional Program for CF patients. CFTR gene mutations, anthropometric parameters, microbiological infections, and pulmonary function were analyzed. Data on demographic parameters, pharmacological treatments, and comorbidities were reported. Frequency and percentages were established for the categorical variables and mean or median for the quantitative variables. In addition, comparisons were made by sex. Results: The average age of the patients was 11.9 ± 5.3 years and the median age at diagnosis was 14 months. 55.5% were women and 44.5% were men. The mean values for weight, height, and body mass index were 35 ± 17.6 kg, 139.9 ± 28 cm, and 16.5 ± 2.9 kg/m2, respectively. The clinical manifestations that occurred more frequently were steatorrhea (65.4%) and recurrent pneumonia (46.2%). Chronic airway infection with Pseudomonas aeruginosa was identified in 71.4% of the cases and the p.F508del mutation was found in 47.2% of the subjects. Conclusion: The current profile of CF patients from the Colombian Caribbean showed some concerning features, such as nutritional status; however, progress in early diagnosis and clinical follow-up could contribute to improve the general conditions of patients. It is necessary to continue efforts to increase the life expectancy and quality of life of the patients.

Predicting Prostate Cancer Molecular Subtype With Deep Learning on Histopathologic Images.

Microscopic examination of prostate cancer has failed to reveal a reproducible association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H&E)-stained whole slide images (WSI) may outperform the human eye and help to screen for clinically-relevant genomic alterations. We created deep-learning algorithms to identify prostate tumors with underlying ETS-related gene (ERG) fusions or PTEN deletions using the following 4 stages: (1) automated tumor identification, (2) feature representation learning, (3) classification, and (4) explainability map generation. A novel transformer-based hierarchical architecture was trained on a single representative WSI of the dominant tumor nodule from a radical prostatectomy (RP) cohort with known ERG/PTEN status (n = 224 and n = 205, respectively). Two distinct vision transformer-based networks were used for feature extraction, and a distinct transformer-based model was used for classification. The ERG algorithm performance was validated across 3 RP cohorts, including 64 WSI from the pretraining cohort (AUC, 0.91) and 248 and 375 WSI from 2 independent RP cohorts (AUC, 0.86 and 0.89, respectively). In addition, we tested the ERG algorithm performance in 2 needle biopsy cohorts comprised of 179 and 148 WSI (AUC, 0.78 and 0.80, respectively). Focusing on cases with homogeneous (clonal) PTEN status, PTEN algorithm performance was assessed using 50 WSI reserved from the pretraining cohort (AUC, 0.81), 201 and 337 WSI from 2 independent RP cohorts (AUC, 0.72 and 0.80, respectively), and 151 WSI from a needle biopsy cohort (AUC, 0.75). For explainability, the PTEN algorithm was also applied to 19 WSI with heterogeneous (subclonal) PTEN loss, where the percentage tumor area with predicted PTEN loss correlated with that based on immunohistochemistry (r = 0.58, P = .0097). These deep-learning algorithms to predict ERG/PTEN status prove that H&E images can be used to screen for underlying genomic alterations in prostate cancer.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

Evidence of human impact in Antarctic region by studying atmospheric aerosols.

Air quality is a global concerning topic because of its great impact on the environment and health. Because of that, the study of atmospheric aerosols looking for harmful pollutants is rising, as well as the interest in the origin of the contaminants. Depending on the nature and size of the aerosols, some elements can be detected at a great distance from the emission source, even in Antarctica, where this study is conducted. Several samples of PM filters from 2018 to 2019 (Deception Island) and 2019-2020 (Livingston Island) campaigns have been analyzed by three powerful spectroscopic techniques: FESEM (Field Emission Scanning Electron Microscopy), LIBS (Laser Induced Breakdown Spectroscopy), and ICP-MS (Inductively Coupled Plasma Mass Spectrometry). These techniques have allowed us to find some heavy metals in the air of the Antarctic region (Al, Fe, Ti, Ni, Cr, and Mn). Deeper studies on ICP-MS results have confirmed those results and have also provided information on their potential sources. Thus, while Al, Fe, Ti and Mn concentrations can be explained by crustal origin, Ni and Cr presented high values only coherent with important human contribution. The results point out that the Antarctic region is no longer a clean and isolated environment from human pollution.

COVID-19 Flow-Maps an open geographic information system on COVID-19 and human mobility for Spain.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has spread all over the world leading to a global pandemic. The fast progression of COVID-19 has been mainly related to the high contagion rate of the virus and the worldwide mobility of humans. In the absence of pharmacological therapies, governments from different countries have introduced several non-pharmaceutical interventions to reduce human mobility and social contact. Several studies based on Anonymized Mobile Phone Data have been published analysing the relationship between human mobility and the spread of coronavirus. However, to our knowledge, none of these data-sets integrates cross-referenced geo-localised data on human mobility and COVID-19 cases into one all-inclusive open resource. Herein we present COVID-19 Flow-Maps, a cross-referenced Geographic Information System that integrates regularly updated time-series accounting for population mobility and daily reports of COVID-19 cases in Spain at different scales of time spatial resolution. This integrated and up-to-date data-set can be used to analyse the human dynamics to guide and support the design of more effective non-pharmaceutical interventions.

Transverse barrier formation by electrical triggering of a metal-to-insulator transition.

Application of an electric stimulus to a material with a metal-insulator transition can trigger a large resistance change. Resistive switching from an insulating into a metallic phase, which typically occurs by the formation of a conducting filament parallel to the current flow, is a highly active research topic. Using the magneto-optical Kerr imaging, we found that the opposite type of resistive switching, from a metal into an insulator, occurs in a reciprocal characteristic spatial pattern: the formation of an insulating barrier perpendicular to the driving current. This barrier formation leads to an unusual N-type negative differential resistance in the current-voltage characteristics. We further demonstrate that electrically inducing a transverse barrier enables a unique approach to voltage-controlled magnetism. By triggering the metal-to-insulator resistive switching in a magnetic material, local on/off control of ferromagnetism is achieved using a global voltage bias applied to the whole device.

Spatiotemporal characterization of the field-induced insulator-to-metal transition.

Many correlated systems feature an insulator-to-metal transition that can be triggered by an electric field. Although it is known that metallization takes place through filament formation, the details of how this process initiates and evolves remain elusive. We use in-operando optical reflectivity to capture the growth dynamics of the metallic phase with space and time resolution. We demonstrate that filament formation is triggered by nucleation at hotspots, with a subsequent expansion over several decades in time. By comparing three case studies (VO2, V3O5, and V2O3), we identify the resistivity change across the transition as the crucial parameter governing this process. Our results provide a spatiotemporal characterization of volatile resistive switching in Mott insulators, which is important for emerging technologies, such as optoelectronics and neuromorphic computing.

GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States.

GSTP1 is a member of the Glutathione-S-transferase (GST) family silenced by CpG island DNA hypermethylation in 90-95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on tissue microarrays (TMAs) with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). In terms of association with other molecular alterations, GSTP1 positivity was enriched in ERG positive cancers among Black men. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that GSTP1-positive prostate cancers are substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men.

Energy-efficient Mott activation neuron for full-hardware implementation of neural networks.

To circumvent the von Neumann bottleneck, substantial progress has been made towards in-memory computing with synaptic devices. However, compact nanodevices implementing non-linear activation functions are required for efficient full-hardware implementation of deep neural networks. Here, we present an energy-efficient and compact Mott activation neuron based on vanadium dioxide and its successful integration with a conductive bridge random access memory (CBRAM) crossbar array in hardware. The Mott activation neuron implements the rectified linear unit function in the analogue domain. The neuron devices consume substantially less energy and occupy two orders of magnitude smaller area than those of analogue complementary metal-oxide semiconductor implementations. The LeNet-5 network with Mott activation neurons achieves 98.38% accuracy on the MNIST dataset, close to the ideal software accuracy. We perform large-scale image edge detection using the Mott activation neurons integrated with a CBRAM crossbar array. Our findings provide a solution towards large-scale, highly parallel and energy-efficient in-memory computing systems for neural networks.

Operando characterization of conductive filaments during resistive switching in Mott VO2.

Vanadium dioxide (VO2) has attracted much attention owing to its metal-insulator transition near room temperature and the ability to induce volatile resistive switching, a key feature for developing novel hardware for neuromorphic computing. Despite this interest, the mechanisms for nonvolatile switching functioning as synapse in this oxide remain not understood. In this work, we use in situ transmission electron microscopy, electrical transport measurements, and numerical simulations on Au/VO2/Ge vertical devices to study the electroforming process. We have observed the formation of V5O9 conductive filaments with a pronounced metal-insulator transition and that vacancy diffusion can erase the filament, allowing for the system to "forget." Thus, both volatile and nonvolatile switching can be achieved in VO2, useful to emulate neuronal and synaptic behaviors, respectively. Our systematic operando study of the filament provides a more comprehensive understanding of resistive switching, key in the development of resistive switching-based neuromorphic computing.

Nanoscale Imaging and Control of Volatile and Non-Volatile Resistive Switching in VO2.

Control of the metal-insulator phase transition is vital for emerging neuromorphic and memristive technologies. The ability to alter the electrically driven transition between volatile and non-volatile states is particularly important for quantum-materials-based emulation of neurons and synapses. The major challenge of this implementation is to understand and control the nanoscale mechanisms behind these two fundamental switching modalities. Here, in situ X-ray nanoimaging is used to follow the evolution of the nanostructure and disorder in the archetypal Mott insulator VO2 during an electrically driven transition. Our findings demonstrate selective and reversible stabilization of either the insulating or metallic phases achieved by manipulating the defect concentration. This mechanism enables us to alter the local switching response between volatile and persistent regimes and demonstrates a new possibility for nanoscale control of the resistive switching in Mott materials.

Non-thermal resistive switching in Mott insulator nanowires.

Resistive switching can be achieved in a Mott insulator by applying current/voltage, which triggers an insulator-metal transition (IMT). This phenomenon is key for understanding IMT physics and developing novel memory elements and brain-inspired technology. Despite this, the roles of electric field and Joule heating in the switching process remain controversial. Using nanowires of two archetypal Mott insulators-VO2 and V2O3 we unequivocally show that a purely non-thermal electrical IMT can occur in both materials. The mechanism behind this effect is identified as field-assisted carrier generation leading to a doping driven IMT. This effect can be controlled by similar means in both VO2 and V2O3, suggesting that the proposed mechanism is generally applicable to Mott insulators. The energy consumption associated with the non-thermal IMT is extremely low, rivaling that of state-of-the-art electronics and biological neurons. These findings pave the way towards highly energy-efficient applications of Mott insulators.

An in Situ Atlas of Mitochondrial DNA in Mammalian Tissues Reveals High Content in Stem and Proliferative Compartments.

Mitochondria regulate ATP production, metabolism, and cell death. Alterations in mitochondrial DNA (mtDNA) sequence and copy number are implicated in aging and organ dysfunction in diverse inherited and sporadic diseases. Because most measurements of mtDNA use homogenates of complex tissues, little is known about cell-type-specific mtDNA copy number heterogeneity in normal physiology, aging, and disease. Thus, the precise cell types whose loss of mitochondrial activity and altered mtDNA copy number that result in organ dysfunction in aging and disease have often not been clarified. Here, an in situ hybridization approach to generate a single-cell-resolution atlas of mtDNA content in mammalian tissues was validated. In hierarchically organized self-renewing tissues, higher levels of mtDNA were observed in stem/proliferative compartments compared with differentiated compartments. Striking zonal patterns of mtDNA levels in the liver reflected the known oxygen tension gradient. In the kidney, proximal and distal tubules had markedly higher mtDNA levels compared with cells within glomeruli and collecting duct epithelial cells. In mice, decreased mtDNA levels were visualized in renal tubules as a function of aging, which was prevented by calorie restriction. This study provides a novel approach for quantifying species- and cell-type-specific mtDNA copy number and dynamics in any normal or diseased tissue that can be used for monitoring the effects of interventions in animal and human studies.

A caloritronics-based Mott neuristor.

Machine learning imitates the basic features of biological neural networks at a software level. A strong effort is currently being made to mimic neurons and synapses with hardware components, an approach known as neuromorphic computing. While recent advances in resistive switching have provided a path to emulate synapses at the 10 nm scale, a scalable neuron analogue is yet to be found. Here, we show how heat transfer can be utilized to mimic neuron functionalities in Mott nanodevices. We use the Joule heating created by current spikes to trigger the insulator-to-metal transition in a biased VO2 nanogap. We show that thermal dynamics allow the implementation of the basic neuron functionalities: activity, leaky integrate-and-fire, volatility and rate coding. This approach could enable neuromorphic hardware to take full advantage of the rapid advances in memristive synapses, allowing for much denser and complex neural networks.

T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer.

PURPOSE: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown. PATIENTS AND METHODS: We conducted a neoadjuvant, randomized study to quantify the immunologic effects of a GM-CSF-secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy. RESULTS: Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T-cell infiltration and PD-L1 expression as compared with a cohort of untreated, matched controls. However, the CD8+ T-cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment, as well as an increase in PD-L1, there was no difference in the CD8+ T-cell infiltrate as compared with degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared with degarelix alone. CONCLUSIONS: Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer.

IL8 Expression Is Associated with Prostate Cancer Aggressiveness and Androgen Receptor Loss in Primary and Metastatic Prostate Cancer.

Chronic inflammation and African ancestry are implicated in prostate cancer aggressiveness, and inflammation-related genes are more highly expressed in prostate cancer in African American men. IL8 secretion is also implicated in prostate cancer progression and castration resistance. We used RNA in situ hybridization to localize IL1ß, IL6, IL8, and IL10 mRNA in low- and high-grade prostate cancer from African American and European American men. IL8 was the most abundantly expressed and the only interleukin detected in tumor cells. We further interrogated IL8 expression in primary and metastatic prostate cancer tissue microarrays and both androgen-dependent and castration-resistant patient-derived xenografts (PDX). IL8 was significantly increased in both tumor and benign regions of higher grade cases (ISUP Grade Group 4-5), but there was no difference between races. We determined that IL8 expression in prostate cancer cell lines, distant metastases, and PDX lines was associated with androgen receptor (AR) loss, but not castration resistance. Reciprocal IL8 and AR expression was also observed in high IL8-expressing atrophy lesions with simultaneous AR downregulation. Finally, we show that IL8 is likely repressed by AR binding to the IL8 promoter and is inducible in prostate cancer cells stimulated with lipopolysaccharide only in cells with AR loss. Likewise, AR knockdown in androgen-dependent cells induced IL8 expression, further demonstrating that AR represses IL8 expression. In conclusion, IL8 expression in the tumor microenvironment is associated with aggressive prostate cancer and with AR loss in metastatic disease. IMPLICATIONS: IL8 expression is repressed by AR and is associated with prostate cancer aggressiveness and AR loss in metastatic disease.

Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells.

A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the ATRX-DAXX chromatin-remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of ATRX and telomerase in a telomerase-positive adenocarcinoma cell line. Inactivating mutations in ATRX were introduced using CRISPR-cas9 nickase into two prostate cancer cell lines, LAPC-4 (derived from a lymph node metastasis) and CWR22Rv1 (sourced from a xenograft established from a primary prostate cancer). In LAPC-4, but not CWR22Rv1, abolishing ATRX was sufficient to induce multiple ALT-associated hallmarks, including the presence of ALT-associated promyelocytic leukemia bodies (APB), extrachromosomal telomere C-circles, and dramatic telomere length heterogeneity. However, telomerase activity was still present in these ATRXKO cells. Telomerase activity was subsequently crippled in these LAPC-4 ATRXKO cells by introducing mutations in the TERC locus, the essential RNA component of telomerase. These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance. IMPLICATIONS: These prostate cancer cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.