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Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens. The application of pulsed electric field (PEF) technology is commonly used in French fry processing operations to prolong cutting blade sharpness and reduce waste, energy consumption, and water usage. Despite these attributes, PEF systems have not yet gained widespread adoption by potato chip producers. In the current study, Lamoka potatoes were PEF-treated prior to continuous frying into potato chips. The effect of specific energy at 0.75 kJ/kg (Low-PEF) and 1.5 kJ/kg (High-PEF) and electric field strength of 1 kV/cm, frequency of 24 kV, and pulse width of 6 μs versus untreated (control) samples was studied, then batches of 250 g of slices were fried at 170 °C or 185 °C for two frying times to obtain potato chips with acrylamide levels below the California Proposition 65 limit (275 ng/g). The Lamoka potato chip product quality metrics that were assessed include moisture, fat, reducing sugars, asparagine, acrylamide, chip color, and texture. PEF treatment of Lamoka potatoes resulted in chips fried in 10 % less time, lower oil content by 8 %, and a decrease of reducing sugars by 19.2 %, asparagine by 42.0 %, and acrylamide by 28.9 %. The PEF fried chips were lighter in color but maintained textural attributes compared to continuous frying cooking. The process of frying potato slices at 170 °C for 150 s with High-PEF yielded potato chips with acrylamide content below the California Proposition 65 limit; which speaks to the health implications for consumers and the quality and safety of these chips., Competing Interests: The authors declare that the work described in this article has not been published previously, nor is it under consideration for publication in any other venue. All authors have approved the content of this manuscript for publication. The authors have no declarations of interest to report, i.e., Declarations of interest: none., (© 2024 The Authors.)

Archaeological systematics, together with spatial and chronological information, are commonly used to infer cultural evolutionary dynamics in the past. For the study of the Palaeolithic, and particularly the European Final Palaeolithic and earliest Mesolithic, proposed changes in material culture are often interpreted as reflecting historical processes, migration, or cultural adaptation to climate change and resource availability. Yet, cultural taxonomic practice is known to be variable across research history and academic traditions, and few large-scale replicable analyses across such traditions have been undertaken. Drawing on recent developments in computational archaeology, we here present a data-driven assessment of the existing Final Palaeolithic/earliest Mesolithic cultural taxonomy in Europe. Our dataset consists of a large expert-sourced compendium of key sites, lithic toolkit composition, blade and bladelet production technology, as well as lithic armatures. The dataset comprises 16 regions and 86 individually named archaeological taxa ('cultures'), covering the period between ca. 15,000 and 11,000 years ago (cal BP). Using these data, we use geometric morphometric and multivariate statistical techniques to explore to what extent the dynamics observed in different lithic data domains (toolkits, technologies, armature shapes) correspond to each other and to the culture-historical relations of taxonomic units implied by traditional naming practice. Our analyses support the widespread conception that some dimensions of material culture became more diverse towards the end of the Pleistocene and the very beginning of the Holocene. At the same time, cultural taxonomic unit coherence and efficacy appear variable, leading us to explore potential biases introduced by regional research traditions, inter-analyst variation, and the role of disjunct macroevolutionary processes. In discussing the implications of these findings for narratives of cultural change and diversification across the Pleistocene-Holocene transition, we emphasize the increasing need for cooperative research and systematic archaeological analyses that reach across research traditions., Competing Interests: We declare no competing interests., (Copyright: © 2024 Riede et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Comparative macro-archaeological investigations of the human deep past rely on the availability of unified, quality-checked datasets integrating different layers of observation. Information on the durable and ubiquitous record of Paleolithic stone artefacts and technological choices are especially pertinent to this endeavour. We here present a large expert-sourced collaborative dataset for the study of stone tool technology and artefact shape evolution across Europe between ~15.000 and 11.000 years before present. The dataset contains a compendium of key sites from the study period, and data on lithic technology and toolkit composition at the level of the cultural taxa represented by those sites. The dataset further encompasses 2D shapes of selected lithic artefact groups (armatures, endscrapers, and borers/perforators) shared between cultural taxa. These data offer novel possibilities to explore between-regional patterns of material culture change to reveal scale-dependent processes of long-term technological evolution in mobile hunter-gatherer societies at the end of the Pleistocene. Our dataset facilitates state-of-the-art quantitative analyses and showcases the benefits of collaborative data collation and synthesis., (© 2023. Springer Nature Limited.)

Mechanisms for breast cancer metastasis remain unclear. Whether truncated glioma-associated oncogene homolog 1 (TGLI1), a transcription factor known to promote angiogenesis, migration and invasion, plays any role in metastasis of any tumor type has never been investigated. In this study, results of two mouse models of breast cancer metastasis showed that ectopic expression of TGLI1, but not GLI1, promoted preferential metastasis to the brain. Conversely, selective TGLI1 knockdown using antisense oligonucleotides led to decreased breast cancer brain metastasis (BCBM) in vivo. Immunohistochemical staining showed that TGLI1, but not GLI1, was increased in lymph node metastases compared to matched primary tumors, and that TGLI1 was expressed at higher levels in BCBM specimens compared to primary tumors. TGLI1 activation is associated with a shortened time to develop BCBM and enriched in HER2-enriched and triple-negative breast cancers. Radioresistant BCBM cell lines and specimens expressed higher levels of TGLI1, but not GLI1, than radiosensitive counterparts. Since cancer stem cells (CSCs) are radioresistant and metastasis-initiating cells, we examined TGLI1 for its involvement in breast CSCs and found TGLI1 to transcriptionally activate stemness genes CD44, Nanog, Sox2, and OCT4 leading to CSC renewal, and TGLI1 outcompetes with GLI1 for binding to target promoters. We next examined whether astrocyte-priming underlies TGLI1-mediated brain tropism and found that TGLI1-positive CSCs strongly activated and interacted with astrocytes in vitro and in vivo. These findings demonstrate, for the first time, that TGLI1 mediates breast cancer metastasis to the brain, in part, through promoting metastasis-initiating CSCs and activating astrocytes in BCBM microenvironment.

Signal transducer and activator of transcription 3 (STAT3), glioma oncogene homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1 isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1 has not been explored. To address this knowledge gap, we analyzed 47 node-positive breast cancer specimens using immunohistochemical staining and found that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%) breast carcinomas, and in lymph node metastases (65%). Using gene set enrichment analysis, we analyzed 710 breast tumors and found that STAT3 activation and GLI1/tGLI1 activation signatures are co-enriched in triple-negative subtypes of breast cancers and HER2-enriched subtypes of breast cancers, but not in luminal subtypes of breast cancers. Patients with high levels of STAT3 and GLI1/tGLI1 co-activation in their breast tumors had worse metastasis-free survival compared to those with low levels. Since these proteins co-overexpress in breast tumors, we examined whether they form complexes and observed that STAT3 interacted with both GLI1 and tGLI1. We further found that the STAT3-GLI1 and STAT3-tGLI1 complexes bind to both consensus GLI1-binding and STAT3-binding sites using chromatin immunoprecipitation (ChIP) assay, and that the co-overexpression markedly activated a promoter controlled by GLI1-binding sites. To identify genes that can be directly co-activated by STAT3 and GLI1/tGLI1, we analyzed three ChIP-seq datasets and identified 34 potential target genes. Following validations using reverse transcription polymerase chain reaction and survival analysis, we identified three genes as novel transcriptional targets of STAT3 and GLI1/tGLI1, R-Ras2, Cep70, and UPF3A. Finally, we observed that co-overexpression of STAT3 with GLI1/tGLI1 promoted the ability of breast cancer cells to form mammospheres and that STAT3 only cooperates with tGLI1 in immortalized mammary epithelial cells. In summary, our study identified novel physical and functional cooperation between two families of oncogenic transcription factors, and the interaction contributes to aggressiveness of breast cancer cells and poor prognosis of triple-negative breast cancers and HER2-enriched breast cancers.

Breast cancer is the most common cancer in women and the second leading cause of cancer deaths in women. Over 90% of breast cancer deaths are attributable to metastasis. Our lab has recently reported that AKT activates heat shock factor 1 (HSF1), leading to epithelial-to-mesenchymal transition in HER2-positive breast cancer. However, it is unknown whether the AKT-HSF1 pathway plays an important role in other breast cancer subtypes, breast cancer stem cells, or breast cancer growth and metastasis. Herein, we showed AKT and HSF1 to be frequently co-activated in breast cancer cell lines and specimens across different subtypes. Activated AKT (S473) and HSF1 (S326) are strongly associated with shortened time to metastasis. Inhibition of the AKT-HSF1 signaling axis using small molecule inhibitors, HSF1 knockdown or the dominant-negative HSF1 mutant (S326A) reduced the growth of metastatic breast cancer cells and breast cancer stem cells. The combination of small molecule inhibitors targeting AKT (MK-2206) and HSF1 (KRIBB11) resulted in synergistic killing of breast cancer cells and breast cancer stem cells across different molecular subtypes. Using an orthotopic xenograft mouse model, we found that combined targeting of AKT and HSF1 to significantly reduce tumor growth, induce tumor apoptosis, delay time to metastasis, and prolong host survival. Taken together, our results indicate AKT-HSF1 signaling mediates breast cancer stem cells self-renewal, tumor growth and metastasis, and that dual targeting of AKT and HSF1 resulted in synergistic suppression of breast cancer progression thereby supporting future testing of AKT-HSF1 combination therapy for breast cancer patients., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Tumor suppressor candidate 2 (TUSC2, also known as FUS1) was identified in 2000 as a candidate tumor suppressor gene located in a region on chromosome 3p21.3 that is homozygously deleted in some lung and breast cancers. The deletion is rare in lung and breast cancers, but is frequent in malignant pleural mesothelioma. Evidence to date indicates that TUSC2 behaves as a tumor suppressor in lung cancer; however, its role as a tumor suppressor for other tumor types has not been fully established. Loss of TUSC2 expression at the mRNA and protein levels has been reported in various cancers. While the mechanisms underlying the loss are still not well understood, several microRNAs have been reported to downregulate TUSC2 expression. TUSC2 elicits its anti-tumor effects through regulating G1 cell cycle progression, apoptosis, calcium homeostasis, gene expression, and the activity of various protein tyrosine kinases and Ser/Thr kinases, albeit the precise mechanisms that TUSC2 utilizes to regulate these cellular processes and signaling molecules are still elusive. TUSC2 restoration has been exploited as an anti-cancer therapy in various cancers in preclinical models, and clinically in patients with lung cancer. The first-in-human phase I trial demonstrated desirable safety outcomes. Phase I/II trials are being conducted to evaluate the efficacy of combining TUSC2-nanoparticles with erlotinib, an FDA-approved EGFR inhibitor. This review summarizes recent findings that advanced our understanding of TUSC2 as a novel tumor suppressor and a therapeutic opportunity for treating TUSC2-deficient cancers.

Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis.

Objective: Intraoperative awareness, and especially the perception of auditory stimuli occur occasionally under general anaesthesia with high-dose opioids. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. Hence, we studied the effects of fentanyl on MLAEP., Methods: Institutional approval and informed consent was obtained in 20 patients scheduled for cardiac surgery. Anaesthesia was induced with fentanyl (10 micrograms/kg every 7[ up to a total dosage of 50 micrograms/kg). Auditory evoked potentials were recorded before and 5[ after every fentanyl dose on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms post-stimulus interval and analysed off-line. Latencies of the peak V, Na, Pa, Nb P1 and amplitudes Na/Pa, Pa/Nb, Nb/P1 were measured. V belongs to the brainstem generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa, Nb, P1 are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. By means of a Fast-Fourier transformation power spectra of the AEP were calculated., Results: In the awake state AEP peak latencies were in the normal range. Power spectra indicated high energy in the 30-40 Hz frequency range. During increasing dosages of fentanyl the brainstem response V was stable. P1 increased in latency and Nb/P1 decreased in amplitude after 10 micrograms/kg of fentanyl significantly. The primary cortical potentials Na, Pa, Nb changed only very slightly in latencies or amplitudes even under highest doses of fentanyl (50 micrograms/kg) and could be identified like in the awake patients. In the power spectra high energy persisted in the 30 Hz frequency range., Conclusion: MLAEP and especially the primary cortical potentials Na, Pa, Nb did not change markedly in amplitude or latency during high-dose fentanyl analgesia. There is no dose-dependent effect of fentanyl on MLAEP as it can be observed under volatile anaesthetics (isoflurane, enflurane). The primary cortical processing of auditory stimuli can be completely blocked by volatile anaesthetics, but is still preserved under highest doses of fentanyl. This may be seen in connection with cases of awareness and perception of auditory stimuli during high-dose fentanyl analgesia.