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Abstract In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection. Results showed that at surgery, Ki67 and the PAM50 proliferation scores were lower after ribociclib compared to chemotherapy. However, consistent reactivation of tumor cell proliferation from day 14 to surgery was only observed in the ribociclib arm. In tumors with complete cell cycle arrest (CCCA) at surgery, PAM50 proliferation scores were lower in the ribociclib arm compared to chemotherapy (p

The proliferation of online social networking websites has resulted in the growth of online communities and increased communication among users. However, sharing personal information can pose a privacy threat to users, leaving them vulnerable to attacks like blackmail and fraud. Also, with the rise in scandals such as Geofeedia and Cambridge Analytica, as well as Facebook’s admission of sharing user data with top mobile phone manufacturers, worries about privacy on social networking platforms have become increasingly palpable. This paper discusses the privacy risks of sharing personal information on social networking websites. The proposed approaches offer a comprehensive protection of user privacy and prevents unauthorized access to user’s data and information by social network providers and unauthorized users. The study employs a preferential selective encryption approach that encompasses not only tweets but also other personally identifiable components, including images, memes, and metadata. This approach serves as a comprehensive solution to encrypt all elements within a social network, making it a one-stop destination for privacy protection in online social networks (OSN). When compared to other investigated schemes, the proposed approach significantly reduces privacy leakage to 0.48 units while achieving a high utility score of 0.8116 units for non-sensitive attributes in tweets. Moreover, it demonstrates remarkable performance in maintaining sensitive information coverage with notably minimal information loss: 0.4 units for images, 0.3 units for memes, and 12.7 units for metadata. Thus, in essence these findings, backed by quantifiable measures of privacy and utility, strongly validate the effectiveness of the proposed methods in achieving a superior balance between privacy preservation and utility when compared to its contemporaries, particularly in applications like online social networks (OSNs). Furthermore, the suggested method’s architecture makes it platform-neutral; it can be customized for any social networking website, such as Facebook, Instagram, and LinkedIn, and it may include any attribute that the user chooses to keep private.

Cosmic dawn represents a critical juncture in cosmic history when the first population of stars emerged. The astrophysical processes that govern this transformation need to be better understood. The detection of redshifted 21 cm radiation emitted from neutral hydrogen during this era offers a direct window into the thermal and ionization state of the Universe. This emission manifests as differential brightness between spin temperature and the cosmic microwave background. The SARAS experiment aims to detect the sky-averaged signal in the frequency range 40–200 MHz. SARAS’s unique design and operational strategy to float the antenna over a water body minimizes spectral features that may arise due to stratified ground beneath the antenna. However, the antenna environment can be prone to configuration changes due to variations in critical design parameters such as conductivity and antenna tilt. In this paper, we connect the variations in antenna properties to signal detection prospects. By using realistic simulations of a direction- and frequency-dependent radiation pattern of the SARAS antenna and its transfer function, we establish critical parameters and estimate bias in the detectability of different models of the global 21 cm signal. We find a correlation between the nature of chromaticity in antenna properties and the bias in the recovered spectral profiles of 21 cm signals. We also find stringent requirements for transfer function corrections, which can otherwise make detection prospects prohibitive. We finally explore a range of critical parameters that allow robust signal detection.

Background: Oral submucous fibrosis (OSMF) causes changes over the pharynx that may cause changes in airway dimensions. Cephalometry could be a reliable diagnostic tool for evaluation of the changes happening in the pharyngeal structures, so that preventive measures such as areca nut habit cessation could be initiated at an earlier stage. Aim: To test pharyngeal changes and airway dimensions in OSMF patients using digital lateral cephalograms. Setting and Design: This was a crossectional observational study done in the Department of Oral Medicine and Radiology. Material and Method: Twenty-two subjects with clinically diagnosed OSMF formed the study group A, and 30 healthy subjects formed the control group B. OSMF subjects were further divided into stage I, II, III according to Nagesh And Bailoor (1993) criteria. We tested all study subjects for velopharyngeal and upper airway dimensions as measured on Digital Lateral Cephalographs using Sirona Sidexis software. The findings were compiled to arrive at data in the study population. Result: Statistically significant difference was observed for mouth opening tongue between different stages of OSMF (p = 0.000) and significant difference was also observed for hyoid position to vertical, AH-FH (p = 0.023), tongue length (VT) (p = 0.002), mid airway width (p = 0.031), soft palate width (p = 0.012) between the groups. Conclusion: There was a significant change in the pharyngeal airway with the advancing stage of OSMF. Lateral cephalometric radiographs are a useful, non-invasive diagnostic tool to analyze pharyngeal airway changes in OSMF patient's to prevent the development of complications associated with advanced stages.

Introduction: Low- and middle-income countries (LMICs) are continuing to experience a “triple burden” of disease - traumatic injury, non-communicable diseases (NCDs), and communicable disease with maternal and neonatal conditions (CD&Ms). The epidemiology of this triad is not well characterised and poses significant challenges to resource allocations, administration, and education of emergency care providers. The data collected in this study provide a comprehensive description of the emergency centre at Kenya's largest public tertiary care hospital. Methods: This study is a retrospective chart review conducted at Kenyatta National Hospital of all patient encounters over a four-month period. Data were collected from financial and emergency centre triage records along with admission and mortality logbooks. Chief complaints and discharge diagnoses collected by specially trained research assistants were manually converted to standardised diagnoses using International Classification of Disease 10 (ICD-10) codes. ICD-10 codes were categorised into groups based on the ICD-10 classification system for presentation. Results: A total of 23,941 patients presented to the emergency centre during the study period for an estimated annual census of 71,823. The majority of patients were aged 18-64 years (58%) with 50% of patients being male and only 3% of unknown sex. The majority of patients (61%) were treated in the emergency centre, observed, and discharged home. Admission was the next most common disposition (33%) followed by death (6%). Head injury was the overall most common diagnosis (11%) associated with admission. Conclusions: Trends toward NCDs and traumatic diseases have been described by this study and merit further investigation in both the urban and rural setting. Specifically, the significance of head injury on healthcare cost, utilisation, and patient death and disability points to the growing need of additional resources at Kenyatta National Hospital for acute care. It further demonstrates the mounting impact of trauma in Kenya and throughout the developing world. Keywords: Kenya, Head injury, Trauma, Triple burden of disease, Emergency medicine, Kenyatta National Hospital

Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices.We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA-with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA.Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active enzymes on NPs as the basis for a highly rapid and sensitive biomarker detection platform. This addresses a key challenge in developing a PoCT platform for time sensitive and difficult to diagnose pathologies.

Introduction: Chronic suppurative otitis media (CSOM) is defined as chronic inflammation of the middle ear and mastoid mucosa with recurrent discharge (at least 2 weeks) through a perforated tympanic membrane. The study was undertaken to see microbiological profile and antibiotic susceptibility pattern in chronic suppurative otitis media patients in a tertiary care hospital. Methodology: This descriptive cross-sectional study was carried out in the ENT and Microbiology department at a tertiary care government teaching hospital, from June 2021 to May 2022. Ear discharge samples from 100 clinically diagnosed chronic suppurative otitis media (CSOM) patients were collected and processed. Microbial isolates were identified and drug susceptibility testing was conducted using Kirby-Bauer disc diffusion method. Results: Among 100 patients included in the study, Staphylococcus aureus (S aureus) (44/100, 44%) was the predominant isolate followed by Pseudomonas aeruginosa (P aeruginosa) (36/100, 36%). All isolates of S aureus were susceptible to Vancomycin, Tigecycline, and Linezolid (100%). Susceptibility of 100% was observed with Colistin and Piperacillin-Tazobactum among P aeruginosa isolates. All isolates of Klebsiella spp and Enterobacter aerogenes showed multi-drug resistance while 88.90% Escherichia coli, 77.27% S aureus, and 19.44% P aeruginosa were multi-drug resistant (MDR). Multi-drug resistance was not observed among Proteus mirabilis isolates. Conclusion: A continuous and periodic evaluation of microbiological pattern of CSOM and antimicrobial susceptibility of isolates is necessary for forming the basis of empirical treatment which shall aid in decreasing the potential risk of complications.