Key Signature Research Articles

LSTM based artificial intelligence predictive maintenance technique for availability rate and OEE improvement in a TPM implementing plant through Industry 4.0 transformation

PurposeThe artificial intelligence (AI) based total productive maintenance (TPM) condition based maintenance (CBM) approach through Industry 4.0 transformation can well predict the breakdown in advance to eliminate breakdown.Design/methodology/approachMeeting the customer requirement as per the delivery schedule with the existing resources are always a big challenge in industries. Any catastrophic breakdown in the equipment leads to increase in production loss, damage to machines, repair cost, time and affects delivery. If these breakdowns are predicted in advance, the breakdown can be addressed before its occurrence and the demand supply chain can be met. TPM is one of the essential operational excellence tool used in industries to utilize the existing resources of a plant in a optimal way. The conventional time based maintenance (TBM) and CBM approach of TPM in Industry 3.0 is time consuming and not accurate enough to achieve zero down time.FindingsThe proposed AI and IIoT based TPM is achieved in a digitalized data oriented platform to monitor and control the health status of the machine which may reduce the catastrophic breakdown by 95% and also improves the quality rate and machine performance rate. Based on the identified key signature parameters related to major breakdown are measured using the sensors, digitalised by programmable logic controller (PLC) and monitored by supervisory control and data acquisition (SCADA) and predicted in server or cloud.Originality/valueLong short term memory based deep learning network was developed as a regression forecasting model to predict the remaining useful life RUL of the part or assembly and based on the predictions, corrective action has been implemented before the occurrence of breakdown. The reliability and consistency of the proposed approach are validated and horizontally deployed in similar machines to achieve zero downtime.

Understanding the molecular response of non-mammalian toll-like receptor 22 (TLR22) in amphibious air-breathing catfish, Clarias magur (Hamilton, 1822) to bacterial infection or ligand stimulation through molecular cloning and expression profiling

Toll-like receptor (TLR) 22 is a non-mammalian TLR, which is identified initially as a functional substitute of mammalian TLR3 in recognizing cell surface long dsRNA in teleosts. To understand the pathogen surveillance role played by TLR22 in an air-breathing catfish model the full-length cDNA of TLR22 was identified in Clarias magur and found to be consisted of 3597 nucleotides encoding for 966 amino acids. In the deduced amino acid sequence of C. magur TLR22 (CmTLR22) key signature domains such as one signal peptide, 13 LRRs, one transmembrane domain, one LRR_CT domain and an intracellular TIR domain could be identified. The CmTLR22 formed a separate cluster with other catfish TLR22 genes and situated within the TLR22 cluster in the phylogenetic analysis of teleost TLR groups. The CmTLR22 was constitutively expressed in all the 12 tested tissues of healthy C. magur juveniles with the highest transcript abundance in spleen followed by brain, intestine and head kidney. Following induction with the dsRNA viral analogue, poly (I:C), the level of expression of CmTLR22 was up-regulated in tissues such as kidney, spleen and gills. Whereas, in Aeromonas hydrophila-challenged C. magur, the expression levels of CmTLR22 was found to be up-regulated in gills, kidney and spleen, and down-regulated in liver. The findings of the current study suggest that the specific function of TLR22 is evolutionarily conserved in C. magur and might play a key role in mounting immune response by recognizing Gram-negative fish pathogen such as A. hydrophila and aquatic viruses in air-breathing amphibious catfishes.

PCAS: Cryptanalysis and improvement of pairing-free certificateless aggregate signature scheme with conditional privacy-preserving for VANETs

Certificateless aggregate signature (CLAS) is an effective approach for the multiple authentications in multi-users and multi-information environments like the vehicular ad hoc networks (VANETs), which can address the certificate management issue in the traditional public key cryptography (PKC) and solve the key escrow problem in identity-based cryptography (IBC). In recent years, a new CLAS mechanism (LICLAS) is presented for the authentication of sensors in healthcare wireless medical sensor networks (HWMSNs). In this paper, we make an analysis and prove that LICLAS is not able to against forgery attacks. Thus, we present an improved CLAS scheme (PCAS) for vehicle authentication in VANETs, which satisfies the privacy and security requirements. PCAS constructs the signature algorithm based on Elliptic Curve Cryptography (ECC) to avoid bilinear pairing and Map-to-Hash function operations. In order to further improve security and efficiency of PCAS, the vehicle key generation and signature algorithm is revised. The pseudonym mechanism is also adopted to achieve conditional privacy preservation. Besides, PCAS allows to execute a batch verification of messages, where RSUs may verify the aggregated signatures from vehicles to reduce time overhead. Under the assumption that the elliptic curve discrete logarithm problem (ECDLP) is hard, PCAS is proved to be existentially unforgeable against adaptive chosen message attacks in the random oracle model. Through the performance analysis, under the same time complexity, PCAS is shown to more effective. Compared with LICLAS, for a single message and 2000 messages, the transmission overhead of PCAS is reduced by 25% and 25% respectively, and the computation overhead is reduced by 16.56% and 25.34% respectively.

Progress in Multivariate Cryptography: Systematic Review, Challenges, and Research Directions

Multivariate Public Key Cryptosystem (MPKC) seem to be promising toward future digital security even in the presence of quantum adversaries. MPKCs derive their security from the difficulty of solving a random system of multivariate polynomial equations over a finite field, which is known to be an NP-hard problem. This article aims at presenting a comprehensive survey that covers multivariate public key encryption and signature schemes specifically targeting toward security, efficiency, and parameter choice. The survey starts by giving an overview of the existing security challenges which include structural attacks such as MinRank attack, differential attack , and finding Gröbner basis for direct attack , and so on. Additionally, it discusses the necessary algorithms for the implementation of the multivariate schemes. This study also compares the promising multivariate encryption and signature schemes. The critical open challenges that are reviewed in this survey will serve as a single comprehensive source of information on multivariate encryption and signature schemes and a ready reference for researchers working in this rising area of public key cryptography.

Homeostatic normalization of alpha brain rhythms within the default-mode network and reduced symptoms in post-traumatic stress disorder following a randomized controlled trial of electroencephalogram neurofeedback.

Collective research has identified a key electroencephalogram signature in patients with post-traumatic stress disorder, consisting of abnormally reduced alpha (8-12 Hz) rhythms. We conducted a 20-session, double-blind, randomized controlled trial of alpha desynchronizing neurofeedback in patients with post-traumatic stress disorder over 20 weeks. Our objective was to provide mechanistic evidence underlying potential clinical improvements by examining changes in aberrant post-traumatic stress disorder brain rhythms (namely, alpha oscillations) as a function of neurofeedback treatment. We randomly assigned participants with a primary diagnosis of post-traumatic stress disorder (n = 38) to either an experimental group (n = 20) or a sham-control group (n = 18). A multichannel electroencephalogram cap was used to record whole-scalp resting-state activity pre- and post-neurofeedback treatment, for both the experimental and sham-control post-traumatic stress disorder groups. We first observed significantly reduced relative alpha source power at baseline in patients with post-traumatic stress disorder as compared to an age/sex-matched group of neurotypical healthy controls (n = 32), primarily within regions of the anterior default mode network. Post-treatment, we found that only post-traumatic stress disorder patients in the experimental neurofeedback group demonstrated significant alpha resynchronization within areas that displayed abnormally low alpha power at baseline. In parallel, we observed significantly decreased post-traumatic stress disorder severity scores in the experimental neurofeedback group only, when comparing baseline to post-treatment (Cohen's d = 0.77) and three-month follow-up scores (Cohen's d = 0.75), with a remission rate of 60.0% at the three-month follow-up. Overall, our results indicate that neurofeedback training can rescue pathologically reduced alpha rhythmicity, a functional biomarker that has repeatedly been linked to symptoms of hyperarousal and cortical disinhibition in post-traumatic stress disorder. This randomized controlled trial provides long-term evidence suggesting that the 'alpha rebound effect' (i.e. homeostatic alpha resynchronization) occurs within key regions of the default mode network previously implicated in post-traumatic stress disorder.

Analysis of the Form and Structure of the Song Dealova by Opick

This study aims to describe the form and structure of Opick's Dealova song which consists of rhythm/rhythm, melody, motif, phrase, and period. This type of qualitative research with content analysis approach that is systematic, objectivity, and generalization. The research instrument is the researcher himself. Data were collected through literature study, observation, labor and documentation. Data analysis goes through the procedure of recording observations and labor work, collecting, sorting, finding patterns and relationships which ultimately make findings.Based on the results of the analysis, it was found that the song Dealova by Opick is a popular religious song, created in 1999, although it is religious but the song was used as a sound track for a film with the title Dealova in 2005. This song received an award in 2006 sung by Once. The rhythm of the song uses a time signature of 6/8 with a total of 98 bars. The melody of Dealova's song is more dominantly syllabic and slightly melismatic. In terms of form, Dealova's song includes a three-part song with sentences A, B and C, and undergoes modulation/change of basic tone from E Minor to D minor or from the use of key signature key signature of 1 sharp to 1 mol.

Design choices in Max and Pure Data

Max and Pure Data are widely used patch languages for real-time media computation, especially live electronic music. Each program was developed with a particular musical production in mind: Philippe Manoury's Pluton (1998) for Max, and Sorensen/Steiger/Puckette's Lemma 1 in 1997 for Pure Data. At the same time, care was taken to make the features of both programs as aesthetically neutral as possible, in order to be useful in as wide a variety of applications as possible. One design principle has been to avoid encoding musical structures such as time or key signatures in either program. Noticeably absent is any built-in facility for machine learning or artificial intelligence. On the other hand, heuristics from programming language design such as modularity, encapsulation, and abstraction have been fundamentally influential in the designs of both Max and Pure Data.

Abstract PD4-07: PD4-07 Uncovering molecular heterogeneity of mixed ductal and lobular carcinoma using digital spatial profiling

Abstract Background Mixed invasive ductal and lobular carcinoma (mDLC) is a rare special subtype (3-6%, ~10,000 cases/annually in US) of invasive breast cancer with elusive pathophysiology. This entity exhibits a mix of ductal-like and lobular-like tumor sub-components within the same tumor. With few seminal studies, mDLC remains poorly understood with little molecular understanding of its sub-components including their origin and implications on disease evolution, prognosis, and treatment response. With increasing recognition of no special type (NST) and invasive lobular carcinoma (ILC) as distinct diseases with unique biology, it is important to understand whether this mixed entity, and its sub-components are like NST and ILC subtypes or a distinct disease. Methods We identified mDLC cases from the UPMC cancer registry. These underwent comprehensive evaluation by a panel of expert pathologists. Three cases (each with a ductal and lobular sub-component on the same FFPE block) were shortlisted. These cases underwent digital spatial profiling (DSP) using Nanostring GeoMX Human Whole Transcriptome Atlas. Briefly, 5um slides were stained using RNAscope morphology marker probes (E-cadherin and PanCK) and GeoMX DSP oligo-conjugated RNA detection probes. Between 3-6 ductal and lobular regions of interest (ROI) per tumor were selected by pathologists. DSP barcodes were cleaved off using UV light and collected into 96-well plate. These underwent library preparation and sequencing. Raw reads were aligned to reference probes to quantify RNA counts. Q3 normalized counts were used in downstream analyses using R version 4.1. Linear modeling was used to assess differentially expressed genes (DEGs). Hypergeometric enrichment tests were used for geneset enrichment. T-tests was used to compare gene expression between two groups. Results In total 26 ROIs (14 ductal and 15 lobular) were profiled across the three mDLC FFPE slides. Overall data quality was excellent with > 90% sequencing saturation across profiled ROIs. Principle component analysis and consensus clustering showed that lobular and ductal ROIs clustered separately indicating distinct molecular profiles. Similarly, PAM50 analysis showed that ductal and lobular ROIs within each patient tumor had distinct PAM50 subtypes. To further investigate the molecular differences between ductal vs lobular ROIs, we performed differential gene expression analysis. We identified 38 up-regulated and 78 down-regulated genes in lobular compared to ductal ROIs. To assess whether mDLC sub-components share any molecular similarities to pure counterparts i.e., ILC and NST, we compared mDLC lobular vs ductal DEGs with those from TCGA ILC vs NST comparison. SHROOM1, KLK10 and KLK11 were up-regulated while CDH1, DCD, and CPB1 were down-regulated in both mDLC lobular ROIs and ILC vs mDLC ductal ROIs and NST, respectively. Pathway analysis revealed estrogen response, adhesion, and metabolism related differences between mDLC lobular vs ductal ROIs. Furthermore, key transcription factor signatures enriched in the up-regulated genes in lobular vs ductal ROIs included ESR1, FOXA2, GATA1/2 and AR signatures while those enriched in the down-regulated genes in lobular vs ductal ROIs included RCOR1, MYC, ZBTB7A, NELFE, and SPI1 signatures. Conclusion and Future Work Using DSP, we uncovered the molecular heterogeneity of mDLC. We revealed that lobular and ductal sub-components have distinct biology with differences in transcriptional signatures and hormone signaling, adhesion and metabolism related pathways. Our pilot study is the first to shed light on this elusive mixed entity using spatial profiling. Our future work will focus on DNA sequencing of mDLC sub-components to identify sub-component specific driver mutations. Our findings will need further investigation in larger mDLC cohorts to better understand their clinical implications in terms of evolution of this disease and its prognosis. Citation Format: Osama Shiraz Shah, Azadeh Nasrazadani, Jennifer M. Atkinson, Celina Kleer, Priscilla F. McAuliffe, Rohit Bhargava, Jorge Reis-Filho, Peter C. Lucas, ADRIAN V. LEE, Steffi Oesterreich. PD4-07 Uncovering molecular heterogeneity of mixed ductal and lobular carcinoma using digital spatial profiling [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD4-07.

Efficient Blockchain-Based Group Key Distribution for Secure Authentication in VANETs

This letter proposes a group key distribution scheme using smart contract-based blockchain technology. The smart contract’s functions allow for securely distributing the group session key, following the initial legitimacy detection using public key infrastructure-based authentication. For message authentication, we propose a lightweight symmetric key cryptography-based group signature method, supporting the security and privacy requirements of vehicular ad hoc networks (VANETs). Our discussion examined the scheme’s robustness against typical adversarial attacks. To evaluate the gas costs associated with smart contracts functions, we implemented it on the Ethereum main network. Finally, comprehensive analyses of computation and communication costs demonstrate the scheme’s effectiveness.

Abstract P4-08-25: Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression

Abstract Human endogenous retrovirus K (HERV-K) belongs to a family of endogenous retroviruses that are present in our genome with similarities to present day exogenous retroviruses. This virus can express several proteins but our knowledge of HERV-K expression in human cancers is mainly limited to the envelope (Env) protein. Elevated HERV-K env protein expression has been shown in breast cancer both in in vitro and in vivo studies. This project aimed to decipher mechanisms of HERV-K induction in triple negative breast cancer (TNBC), and the impact of HERV-K targeting shRNA mediated knockdown on TNBC characteristics including cell migration, invasion and proliferative capacity in 2D and 3D cell culture models. Our results show that a role for inducible nitric oxide synthase (iNOS) in the induction of HERV-K in TNBC cell lines. RNA seq and bioinformatics analysis was performed to identify key molecular processes regulated by HERV-K and nitric oxide (NO) in MDA-MB-231 TNBC cells. Reduced rates of migration, invasion and proliferation in HERV-K knockdowns points towards the essential role of HERV-K in tumorigenesis and metastasis. HERV-K knockdown also modulated key gene expression signatures traditionally associated with the basal and mesenchymal phenotypes in breast cancer, cellular senescence and MHC class gene regulation. The co-expression of iNOS and HERV-K was assessed in over 150 TNBC cases and the association with patient outcomes assessed. Taken together, our findings indicate that NO and HERV-K may be a useful molecular target for the treatment of TNBC. Citation Format: Dibyangana Bhattacharyya, Eoin Dervan, Sharon Glynn, Grace Callagy. Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-25.

Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. A total of 164715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Neural substrates of verbal memory impairment in schizophrenia: A multimodal connectomics study.

While verbal memory is among the most compromised cognitive domains in schizophrenia (SZ), its neural substrates remain elusive. Here, we explored the structural and functional brain network correlates of verbal memory impairment in SZ. We acquired diffusion and resting-state functional MRI data of 49 SZ patients, classified as having preserved (VMP, n=22) or impaired (VMI, n=26) verbal memory based on the List Learning task, and 55 healthy controls (HC). Structural and functional connectivity matrices were obtained and analyzed to assess associations with disease status (SZ vs. HC) and verbal memory impairment (VMI vs. VMP) using two complementary data-driven approaches: threshold-free network-based statistics (TFNBS) and hybrid connectivity independent component analysis (connICA). TFNBS showed altered connectivity in SZ patients compared with HC (p < .05, FWER-corrected), with distributed structural changes and functional reorganization centered around sensorimotor areas. Specifically, functional connectivity was reduced within the visual and somatomotor networks and increased between visual areas and associative and subcortical regions. Only a tiny cluster of increased functional connectivity between visual and bilateral parietal attention-related areas correlated with verbal memory dysfunction. Hybrid connICA identified four robust traits, representing fundamental patterns of joint structural-functional connectivity. One of these, mainly capturing the functional connectivity profile of the visual network, was significantly associated with SZ (HC vs. SZ: Cohen's d=.828, p < .0001) and verbal memory impairment (VMP vs. VMI: Cohen's d=-.805, p=.01). We suggest that aberrant connectivity of sensorimotor networks may be a key connectomic signature of SZ and a putative biomarker of SZ-related verbal memory impairment, in consistency with bottom-up models of cognitive disruption.

NEOICHNOLOGY OF ARMADILLOS: KEYS FOR THE PALEOECOLOGICAL AND BEHAVIORAL INTERPRETATION OF FOSSIL TETRAPOD BURROWS

ABSTRACTThis study is based on the analysis of burrow casts of three species of armadillos from central Argentina: Chaetophractus villosus, Chaetophractus vellerosus, and Zaedyus pichiy (Chlamyphoridae: Euphractinae). The aim of this work was to identify key ichnologic signatures of Euphractinae armadillo burrows for application to the paleoecological and behavioral interpretation of fossil examples. A total of 15 active burrows from different biogeographic provinces were casted with polyurethane foam and then excavated. About two hundred uncasted burrows and foraging pits were also measured at the same localities. Euphractinae burrows are clearly distinguished from Chlamyphorinae burrows by its filling, surface ornamentation, and size. It is suggested that fossil armadillo (Euphractinae) burrows would be characterized by a single ramp with one entrance and massive or laminated fill, horizontal diameter larger than 100 mm, strongly marked sets of three claw traces that are arranged oblique to the ramp axis, and absence of feces or plant remains. The distinctive surface ornamentation present in the casted burrows is tentatively linked to a particular excavation mechanism involving rotation of the body along the antero-posterior axis. Burrow systems with a chamber are interpreted as permanent burrows, whereas those lacking chamber are considered as temporary/shelter burrows. Armadillo burrow systems (either temporary or permanent) are longer, less inclined, and have lower relative diameter indices (RDI) than armadillo foraging pits. Euphractinae burrows are linked to producers with solitary, fossorial, opportunistic omnivorous habits that excavate several burrows during their lives. They are left open after abandonment, and preferably located in xeric shrub lands and grasslands. The described morphological features of the burrows systems can be useful for the interpretation of fossil (post-Eocene) burrows.

Erosion Modelling Indicates a Decrease in Erosion Susceptibility of Historic Ridge and Furrow Fields Near Albershausen, Southern Germany

Ridge and furrow fields are land-use-related surface structures that are widespread in Europe and represent a geomorphological key signature of the Anthropocene. Previous research has identified various reasons for the intentional and unintentional formation of these structures, such as the use of a mouldboard plough, soil improvement and drainage. We used GIS-based quantitative erosion modelling according to the Universal Soil Loss Equation (USLE) to calculate the erosion susceptibility of a selected study area in Southern Germany. We compared the calculated erosion susceptibility for two scenarios: (1) the present topography with ridges and furrows and (2) the smoothed topography without ridges and furrows. The ridges and furrows for the studied site reduce the erosion susceptibility by more than 50% compared to the smoothed surface. Thus, for the first time, we were able to identify lower soil erosion susceptibility as one of the possible causes for the formation of ridge and furrow fields. Finally, our communication paper points to future perspectives of quantitative analyses of historical soil erosion.

Using microfluidic models to evaluate whether monocyte preconditioning plays a role in tumor-associated macrophage mediated resistance to hormone therapy in men with prostate cancer.

228 Background: While men with metastatic castrate-resistant prostate cancer benefit greatly from 2nd generation androgen targeted therapies (ATTs), the utility of these therapies is inevitably limited by the development of resistance. Tumor associated macrophages (TAMs) are a myeloid immune cell population within the prostate tumor microenvironment (TME) that have been shown to play an integral role in development of ATT-resistance. However, the pathways that underlie TAM-mediated ATT resistance remain under investigation. In particular, many TAMs within the TME are derived from circulating monocytes and it is not yet clear whether the pathways driving TAM-mediated resistance are activated exclusively within the TME or if the activation of critical resistance pathways begins while the cells are circulating as monocytes. In this study, we utilized novel microscale technologies to investigate the transcriptome of monocytes and macrophages derived from patients progressing and responding to ATTs as well as the degree to which the macrophages promote ATT resistance in prostate tumor models. Methods: Primary monocytes were isolated from 22 men with prostate cancer who were either progressing or responding to 2ndgeneration ATTs. A portion of the monocytes from each patient were isolated for transcriptome analysis and the rest were differentiated into monocyte-derived macrophages (MDMs). MDMs were then cultured in monoculture or in co-culture with androgen-independent prostate tumor cells (22Rv1 and C42B). Each culture was then left untreated or treated with enzalutamide therapy. Following culture/treatment, each macrophage condition was isolated for transcriptome analysis and tumor cell populations from each condition were evaluated for treatment cytotoxicity. Results: Viability data from MDM-C42B co-culture demonstrated a 20% increase in tumor cell viability following enzalutamide treatment when C42B cells were cultured with primary MDMs from castrate-sensitive patients as compared to MDMs from castrate-resistant patients. Subsequent transcriptome analysis demonstrated key signatures in monocyte/macrophage populations that were associated ATT response. Conclusions: Leveraging a novel microfluidic culture platform known as Stacks, we were able to utilize primary, patient-derived cells to demonstrate that the role of TAMs in ATT resistance within the prostate TME is dependent, at least in part, on factors that are present prior to extravasation into the TME. Transcriptome analysis identified candidate pathways, which may be driving TAM-mediated differences in ATT response. These findings have the potential to lead to future use of circulating monocytes as a predictive biomarker as well as lead to the identification and targeting of ATT resistance pathways in patients.

Complimentary genomic, pathologic, and artificial intelligence analysis on low-grade noninvasive bladder cancer to predict downstream recurrence.

553 Background: Low-grade noninvasive (LGTa) bladder cancer is a relatively quiescent but heterogenous malignancy, characterized by downstream recurrences requiring repeated transurethral resections and frequent surveillance. Investigations to elucidate drivers of recurrence have been sparse, but will help risk-stratify patients with LGTa and allow augmentation of follow up protocols. Methods: Patients with LGTa index tumors were stratified by those with no downstream recurrences (nonrecurrent) vs. those with later recurrences (recurrent). RNA sequencing identified differentially expressed genes (DEGs), deconvoluted for cell-type using xCell. Pathologic analysis was performed by a genitourinary pathologist, then a deep-learning artificial intelligence (AI) platform was leveraged to correlate recurrence risk and recurrence-free survival (RFS) based on deep-learning algorithm of segmented nuclei. Results: Thirty index bladder tumors/patients were identified, 18 (60%) of which had later recurrence (Table). There were 238 DEGs recognized, with recurrent tumors expressing signatures for epithelial mesenchymal transition, myogenesis, TNFα signaling via NFκB, and angiogenesis. Recurrent tumors also demonstrated a higher tissue micoenvironment, stroma, and cancer-associated fibroblast score. Pathologic TME analysis validated these findings, with recurrent tumors demonstrating a higher frequency of inverted growth pattern and a higher median stroma percentage. Finally, the AI-derived signature was predictive of recurrence and risk-stratified the cohort (HR= 5.43 [95% CI 1.1-26.76]) for predicting high vs. low risk of recurrence. Patients in the high risk group had a 87.5% recurrence rate while those in the low risk group had a 28.5% recurrence rate (p&lt;0.01). Conclusions: Using a multi-disciplinary approach, we identified key signatures in recurrent LGTa bladder cancer. Characterization of these factors is a critical first step in the risk-stratification of LGTa tumors, and may allow risk-stratification of surveillance protocols and identification of possible targets for chemoprevention trials. [Table: see text]

Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma

BackgroundLung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking MethodThe GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study. ResultsThe 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein–protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort ConclusionsThe identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.

The sound of stress recovery: an exploratory study of self-selected music listening after stress

BackgroundEmpirical support for the notion that music listening is beneficial for stress recovery is inconclusive, potentially due to the methodological diversity with which the effects of music on stress recovery have been investigated. Little is presently known about which recovery activities are chosen by individuals for the purpose of stress recovery, and whether audio feature commonalities exist between different songs that are selected by individuals for the purpose of stress recovery. The current pre-registered study investigated whether audio feature commonalities can be extracted from self-selected songs for the purpose of stress recovery. Furthermore, the present study exploratorily examined the relationship between audio features and participants’ desired recovery-related emotions while listening and after listening to self-selected music.MethodsParticipants (N = 470) completed an online survey in which they described what music they would listen to unwind from a hypothetical stressful event. Data analysis was conducted using a split-sample procedure. A k-medoid cluster analysis was conducted to identify audio feature commonalities between self-selected songs. Multiple regression analyses were conducted to examine the relationship between audio features and desired recovery emotions.ResultsParticipants valued music listening as a recovery activity to a similar extent as watching TV, sleeping, or talking to a significant other. Cluster analyses revealed that self-selected songs for the purpose of stress recovery can be grouped into two distinct categories. The two categories of songs shared similarities in key, loudness, speechiness, acousticness, instrumentalness, liveness, musical valence, tempo, duration, and time signature, and were distinguished by danceability, energy, and mode. No audio features were significantly associated with participants’ desired recovery emotions.ConclusionsAlthough a comprehensive portrait of the relationship between audio features and stress recovery still warrants further research, the present study provides a starting point for future enquiries into the nuanced effects of musical audio features on stress recovery.

Establishment of Ferroptosis-Related Key Gene Signature and Its Validation in Compression-Induced Intervertebral Disc Degeneration Rats.

Cell death and functional loss of nucleus pulposus cell play essential roles in intervertebral disc degeneration (IDD). Ferroptosis is a newly identified cell death type, and its role in IDD is still under investigation. Identifying the key genes of ferroptosis in IDD helps to identify the therapeutic targets of IDD. In this study, we downloaded the human IDD mRNA microarray data from the Gene Expression Omnibus and ferroptosis genes from FerrDb, then performed a series of analyses using strict bioinformatics algorithms. In general, we obtained 40 ferroptosis-related differential expression genes (FerrDEGs) and identified six ferroptosis key gene signatures, namely, ATF3, EIF2S1, AR, NQO1, TXNIP, and AKR1C3. In addition, enrichment analysis of the FerrDEGs was conducted, the protein-protein interaction network was constructed, the correlations between ferroptosis key genes and immune infiltrating cells were analyzed, and the lncRNA-miRNA-mRNA ceRNA network was constructed. In particular, ATF3 and EIF2S1 showed the strongest correlation with immune cell function, which might lead to the development of IDD. Finally, the expressions of ferroptosis key genes were verified in the rat compression-induced IDD. In conclusion, this preliminary study analyzed and verified the mechanism of ferroptosis in IDD, laid a foundation for the follow-up study of the mechanism of ferroptosis in IDD, and provided new targets for preventing and delaying IDD.

Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis.

Iron metabolism is considered to play the principal role in sepsis, but the key iron metabolism-related genetic signatures are unclear. In this study, we analyzed and identified the genetic signatures related to the iron-metabolism in sepsis by using a bioinformatics analysis of four transcriptomic datasets from the GEO database. A total of 21 differentially expressed iron metabolism-related signatures were identified including 9 transporters, 8 enzymes, and 4 regulatory factors. Among them, lipocalin 2 was found to have the highest diagnostic value as its expression showed significant differences in all the comparisons including sepsis vs healthy controls, sepsis vs non-sepsis diseases, and mild forms vs severe forms of sepsis. Besides, the cytochrome P450 gene CYP1B1 also showed diagnostic values for sepsis from the non-sepsis diseases. The CYP4V2, LTF, and GCLM showed diagnostic values for distinguishing the severe forms from mild forms of sepsis. Our analysis identified 21 sepsis-associated iron metabolism-related genetic signatures, which may represent diagnostic and therapeutic biomarkers of sepsis, and will improve our understanding of the molecular mechanism underlying the occurrence of sepsis.