Coexistence of Amyotrophic Lateral Sclerosis and Lymphoproliferative Disorders – Analysis from a Tertiary Center

Background: The coexistence of motor neuron diseases (MNDs) and lymphoproliferative disorders (LPDs) has been documented historically in a few small retrospective studies but an update is lacking.   Objective: The goal of this study is to expand the database of patients with these coexisting diseases, and to describe the natural history and overall outcomes including presumed or identified cause of mortality (neurologic versus oncologic). Materials and methods: A retrospective analysis of all patients within the Cleveland Clinic diagnosed with one or more LPDs between January 1, 2012 and June 30, 2021, was performed to identify patients with a diagnosis of MND. Results: A total of 20 patients with one MND diagnosis and one coexisting LPD were included in the final analysis. Their clinical features are characterized. In 17 patients, the diagnosis of LPD was made prior to the MND diagnosis. Eighteen patients passed away with a mean survival of 49.1 (range: 6 to 128) months from the MND onset. In 16 patients, the cause of death was MND related. The incidence rates of MNDs and myasthenia gravis were examined in a group of 6,169 patients with LPDs. The incidence rate of MNDs in LPDs seems to be higher than those of the general population, appeared over-represented when comparing to the occurrence of myasthenia gravis in LPDs. Conclusion: Coexisting MND and LPD continue to occur. There seems to be an over representation of MND in patients with LPDs

Therapeutic targeting of Aurora Kinase A in advanced prostate cancer

Prostate cancer (PCa) progresses from an androgen-dependent state to a castration-resistant form (CRPC) following androgen deprivation therapy (ADT), driven by adaptations that restore androgen receptor (AR) signaling. A subset of CRPC tumors evolves into neuroendocrine prostate cancer (NEPC), marked by AR independence, neuroendocrine marker expression, and poor prognosis. NEPC development is associated with genetic and epigenetic alterations, including loss of tumor suppressors (TP53, RB1) and activation of lineage plasticity pathways. Aurora kinase A (AURKA), a serine/threonine kinase regulating mitosis, is frequently overexpressed in NEPC and CRPC, promoting tumor aggressiveness. Recent studies highlight CXCR7\u27s role in driving enzalutamide-resistant CRPC by activating AURKA through β-arrestin recruitment. Targeting AURKA with inhibitors like alisertib shows potential but is hindered by toxicity and patient variability, emphasizing the need for biomarkers to stratify responders. AURKA inhibition is synthetically lethal with RB1 or TP53 loss and may exploit vulnerabilities in tumors with homologous recombination defects, linking AURKA activity to resistance against DNA-damaging therapies, including PARP inhibitors, AR pathway inhibitors, and chemotherapy. Further investigation into AURKA alterations in CRPC/NEPC and their correlation with therapeutic outcomes may refine treatment strategies. Targeting AURKA holds promise for overcoming resistance and improving outcomes in aggressive, treatment-refractory PCa subtypes

Light-by-light scattering in ultraperipheral collisions of heavy ions with future FoCal and ALICE 3 detectors

I present possible future studies of light-by-light scattering using FoCal@ALICE and ALICE 3 detectors. Different mechanisms are discussed. The PbPb → PbPb γγ cross section is calculated within the equivalent photon approximation in the impact parameter space. Several differential distributions are presented and discussed. We predict the cross section in the (mb-b) range for typical ALICE 3 cuts, a few orders of magnitude larger than for the current ATLAS or CMS experiments. We also consider the two-π⁰ background, which can, in principle, be eliminated in the new kinematical range for the ALICE 3 measurements by imposing dedicated cuts on diphoton transverse momentum and/or so-called vector asymmetry

Aberrant Immunohistochemical stains among 573 cases of Diffuse Mesothelioma

Background: Diagnosis of malignant mesothelioma often requires differentiating it from other metastatic malignancies including breast cancer, lung cancer, ovarian cancer, colorectal cancer, etc. Immunohistochemical stains (IHC) are important means to assist in confirming mesothelioma and ruling out metastatic cancers. Although mesothelial specific markers have been used for diagnosis, aberrant immunostains were also observed in clinical practice which often confounded the diagnosis. In this study, we analyzed the positive rate of commonly used IHC markers in the diagnosis of mesothelioma among 573 patients. Design: 427 cases of epithelioid mesothelioma, 87 cases of biphasic mesothelioma and 59 cases with sarcomatoid mesothelioma were retrieved from the pathology consultation files between 2020-2023. The positive rates of over 50 IHC markers including over 30 aberrant IHC markers were analyzed. Results: The positive rates of mesothelial markers, such as calretinin, WT-1 and D2-40, and epithelial markers, such as cytokeratins, were highest in epithelioid type, intermediate in biphasic type and lowest in sarcomatoid type mesothelioma. The mesenchymal marker vimentin and additional marker GATA-3 were highly expressed in sarcomatoid mesothelioma. The highest loss rate of BAP-1 was in epithelioid type, while the highest loss rate of MTAP was in sarcomatoid type. The CDKN2A (p16) deletion was observed equally in both epithelioid and sarcomatoid/biphasic types. Over 30 aberrant markers were observed. For epithelioid type, commonly observed aberrant IHC markers included MOC-31, BerEP4, PAX-8, p63, CK20, NKX3.1 and ER. For biphasic type, significant aberrant IHC markers included MOC-31, Ber-EP4, PAX8, CK20 and p40. For sarcomatoid type, notable aberrant IHC markers included p63, SMA, ERG and CD31. Among these aberrant IHC markers, MOC-31, Ber-EP4 and p63 were more commonly observed in pleural epithelioid mesothelioma, whereas PAX-8 in peritoneal epithelioid mesothelioma. Conclusions: Our data demonstrated that aberrant immunostains were common in all of the histological types of mesothelioma. Therefore, the diagnosis of mesothelioma should be based on correlation of clinical presentation, radiological findings, and selective panel of immunostains, and should not be distracted by aberrant immunostains

On Chilean Acting Training; Interview with Cristian Lagreze

Since the 1980s, European techniques have had a significant impact on actor training in Chile; however, with the restoration of democracy in the 1990s, actor training started to change. Prominent professionals such as Cristian Lagreze, who received his training outside, have brought fresh perspectives to the Chilean setting. Lagreze talks about his experience as an actor in this interview, beginning at the University of Chile. He notes that the training process, which is moulded by emotional and physical conditioning particular to the sociological and cultural dynamics of today, aids trainers in developing a sense of identity and community. Students\u27 relationships with their bodies in training are being impacted by modern challenges like the effects of technology, capitalist pressures, and the increased awareness of gender and body politics. Lagreze also draws attention to the difficulties caused by the commercialisation of education, which makes students feel like customers. His observations highlight the difficulties involved in actor training in Chile and show how instructors must strike a balance between teaching conventional methods and the changing demands of contemporary actors

Extracellular matrix in prostate cancer anti-androgen resistance

Extracellular matrix (ECM) within the tumour microenvironment (TME) of prostate cancer has been extensively reported to be associated with the development of androgen-deprivation therapy (ADT) resistance in prostate cancer. Recent-year investigations have illustrated that the deposition of ECM proteins contribute to this resistance by regulating cell behaviours of cancer cells directly or indirectly through modulating immune cells within the TME, thereby protecting cancer cells from the tumour-suppressing effects of ADT. Here we review these findings, offering new perspectives on prostate cancer research and highlighting the potential of ECM proteins as novel clinical targets for predicting and treating ADT-resistance