Miracle-dz/UniFAR-FTUs huggingface dataset:
Metastatic breast cancer in Kenya: survival, prognosis and management at a tertiary referral centre

There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at Aga Khan University Hospital, Nairobi of patients diagnosed with MBC between 2009 and 2017. Survival data was collected on metastatic free survival, survival time between diagnosis of first metastasis and death and overall survival. Data on patient’s age, menopausal status and stage at diagnosis, tumour grade, receptor status, site of metastasis and treatment given was also collected. The Kaplan-Meier Estimator was used to estimate survival. Prognostic factors for survival outcomes were analysed using univariate analysis. Standard descriptive statistics were used to describe patient characteristics. A total of 131 patients were included in the study. The median survival was 22 months. The 3 and 5-year survivals were 31.3% and 10.7%, respectively. On univariate analysis, the Luminal A molecular subtype was a significant positive prognostic factor hazard ratios (HR 0.652 95% confidence interval (CI) 0.473–0.899) while metastasis to the liver or brain were significant negative prognostic factors (HR 0.615 95% CI 0.413–0.915 and HR 0.566 95% CI 0.330–0.973, respectively). A large proportion (87.0%) received some treatment for metastatic disease. Our study concluded that survival rates for patients diagnosed with MBC were lower compared to studies from Western countries but higher than in studies from Sub-Saharan Africa. Luminal A molecular subtype was found to be a positive prognostic factor and metastasis to the liver or brain were found to be negative prognostic factors. Improved access to adequate treatment for MBC is required in the region.
A predictive risk map for human leptospirosis guiding further investigations in brown rats and surface water

ABSTRACT Leptospirosis is a zoonosis caused by the spirochete Leptospira spp. It is often not clear why certain areas appear to be hotspots for human leptospirosis. Therefore, a predictive risk map for the Netherlands was developed and assessed, based on a random forest model for human leptospirosis incidence levels with various environmental factors and rat density as variables. Next, it was tested whether misclassifications of the risk map could be explained by the prevalence of Leptospira spp. in brown rats. Three recreational areas were chosen, and rats (≥25/location) were tested for Leptospira spp. Concurrently, it was investigated whether Leptospira spp. prevalence in brown rats was associated with Leptospira DNA concentration in surface water, to explore the usability of this parameter in future studies. Approximately 1 L of surface water sample was collected from 10 sites and was tested for Leptospira spp. Although the model predicted the locations of patients relatively well, this study showed that the prevalence of Leptospira spp. infection in rats may be an explaining variable that could improve the predictive model performance. Surface water samples were all negative, even if they had been taken at sites with a high Leptospira spp. prevalence in rats.
The Retrieval and Effect of Core Parameters for Near-Field Inter-Body Coupling Communication

The potential of the Internet of Body (IoB) to support healthcare systems in the future lies in its ability to enable proactive wellness screening through the early detection and prevention of diseases. One promising technology for facilitating IoB applications is near-field inter-body coupling communication (NF-IBCC), which features lower power consumption and higher data security when compared to conventional radio frequency (RF) communication. However, designing efficient transceivers requires a profound understanding of the channel characteristics of NF-IBCC, which remain unclear due to significant differences in the magnitude and passband characteristics of existing research. In response to this problem, this paper clarifies the physical mechanisms of the differences in the magnitude and passband characteristics of NF-IBCC channel characteristics in existing research work through the core parameters that determine the gain of the NF-IBCC system. The core parameters of NF-IBCC are extracted through the combination of transfer functions, finite element simulations, and physical experiments. The core parameters include the inter-body coupling capacitance (CH), the load impedance (ZL), and the capacitance (Cair), coupled by two floating transceiver grounds. The results illustrate that CH, and particularly Cair, primarily determine the gain magnitude. Moreover, ZL mainly determines the passband characteristics of the NF-IBCC system gain. Based on these findings, we propose a simplified equivalent circuit model containing only core parameters, which can accurately capture the gain characteristics of the NF-IBCC system and help to concisely describe the channel characteristics of the system. This work lays a theoretical foundation for developing efficient and reliable NF-IBCC systems that can support IoB for early disease detection and prevention in healthcare applications. The potential benefits of IoB and NF-IBCC technology can, thus, be fully realized by developing optimized transceiver designs based on a comprehensive understanding of the channel characteristics.
Identifying important factors for successful surgery in patients with lateral temporal lobe epilepsy

Objective Lateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE. Methods This retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups. Results Sixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588–0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected). Conclusions The identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group.
Prediction of Continuous Emotional Measures through Physiological and Visual Data

The affective state of a person can be measured using arousal and valence values. In this article, we contribute to the prediction of arousal and valence values from various data sources. Our goal is to later use such predictive models to adaptively adjust virtual reality (VR) environments and help facilitate cognitive remediation exercises for users with mental health disorders, such as schizophrenia, while avoiding discouragement. Building on our previous work on physiological, electrodermal activity (EDA) and electrocardiogram (ECG) recordings, we propose improving preprocessing and adding novel feature selection and decision fusion processes. We use video recordings as an additional data source for predicting affective states. We implement an innovative solution based on a combination of machine learning models alongside a series of preprocessing steps. We test our approach on RECOLA, a publicly available dataset. The best results are obtained with a concordance correlation coefficient (CCC) of 0.996 for arousal and 0.998 for valence using physiological data. Related work in the literature reported lower CCCs on the same data modality; thus, our approach outperforms the state-of-the-art approaches for RECOLA. Our study underscores the potential of using advanced machine learning techniques with diverse data sources to enhance the personalization of VR environments.
Molecular and Clinical Features of Fluconazole Non-susceptible Candida albicans Bloodstream Isolates Recovered in Korean Multicenter Surveillance Studies

Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006–2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1, MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.
Prmt5 deficient mouse B cells display RNA processing complexity and slower colorectal tumor progression

Protein arginine methyltransferase 5 (Prmt5) is essential for normal B‐cell development; however, the roles of Prmt5 in tumor‐infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19‐cre‐Prmt5fl/fl (Prmt5cko) mice showed smaller tumor weights and volumes in the colorectal cancer mouse model; B cells expressed higher levels of Ccl22 and Il12a, which attracted T cells to the tumor site. Furthermore, we used direct RNA sequencing to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms. We found significantly differentially expressed isoforms, mRNA splicing, poly(A) tail lengths, and m6A modification changes between the Prmt5cko and control groups. Cd74 isoform expressions might be regulated by mRNA splicing; the expression of two novel Cd74 isoforms was decreased, while one isoform was elevated in the Prmt5cko group, but the Cd74 gene expression showed no changes. We observed Ccl22, Ighg1, and Il12a expression was significantly increased in the Prmt5cko group, whereas Jak3 and Stat5b expression was decreased. Ccl22 and Ighg1 expression might be associated with poly(A) tail length, Jak3, Stat5b, and Il12a expression might be modulated by m6A modification. Our study demonstrated that Prmt5 regulates B‐cell function through different mechanisms and supported the development of Prmt5‐targeted antitumor treatments.
Gbb glutathionylation promotes its proteasome-mediated degradation to inhibit synapse growth

GstO1 postsynaptically suppresses the growth of the Drosophila neuromuscular junctions by inhibiting the BMP signaling pathway. GstO1 interacts with Gbb and prompts its glutathionylation. E3 ligase Ctrip binds glutathionylated Gbb and facilitates its proteasome-mediated degradation, indicating a crosstalk between glutathionylation and ubiquitination in regulating Gbb homeostasis.
Latency-information theory: the mathematical-physical theory of communication-observation

In this paper the mathematical-physical theory of communication-observation that is part of latency-information theory (LIT) is reviewed. LIT surfaced from the confluence of classical information theory, relativity theory, quantum mechanics, statistical physics and a 1978 conjecture by the author of a structural-physical certainty-uncertainty duality for quantized control. Control, radar, physics and biochemistry applications illustrate the theory. As part of the review, LIT is revealed to communicate through latency-certainty channels and/or informationun-certainty channels for observation across latency-certainty sensors and/or information-uncertainty sensors, a mathematical-physical efficiency perspective of the Universe in a four quadrants revolution. While the first and third quadrants are concerned with the life time of physical signal movers and the life space of physical signal retainers, respectively, the second and fourth quadrants are about the intelligence space of mathematical signal sources and the processing time of mathematical signal processors, respectively. The four quadrants of LIT are conjectured to be physically independent with their system design methodologies guided by dualities and performance bounds. Moreover, the tools of statistical physics bridge them, and inherently lead to the discovery of a novel certainty dual for thermodynamics named lingerdynamics.
Workout Logging Through an mHealth App for Weight Reduction Among Different Generations: Secondary Analysis of the MED PSU×ThaiSook Healthier Challenge

Background Being overweight or obese presents a major risk factor for noncommunicable diseases (NCDs) such as cardiovascular disease, diabetes, and musculoskeletal disorders. These problems are preventable and solvable via weight reduction and increased physical activity and exercise. The number of adults who are overweight or affected by obesity has tripled in the last 4 decades. Using mobile health (mHealth) apps can help users with health issues, including reducing their weight by restricting their daily calorie intake, which can be recorded along with other parameters, such as physical activity and exercise. These features could further enhance health and prevent NCDs. ThaiSook, a Thai mHealth app developed by the National Science and Technology Development Agency, aims to promote healthy lifestyles and reduce the risk behaviors of NCDs. Objective This study aimed to determine whether ThaiSook users were successful in 1-month weight reduction and identify which demographic factors or logging functions were associated with significant weight reduction. Methods A secondary data analysis was performed using data collected from the “MED PSU×ThaiSook Healthier Challenge,” a month-long challenge to encourage a healthy lifestyle. We enrolled 376 participants to evaluate the study outcomes. The variables, comprising demographic characteristics (ie, sex, generation, group size, and BMI), were classified into 4 groups: normal (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), obese I (25-29.9 kg/m2), and obese II (BMI ≥30 kg/m2). Logging functions (ie, water, fruit and vegetables, sleep, workout, step, and run) were classified into 2 groups: consistent (≥80%) and inconsistent (<80%) users. Weight reduction was categorized into 3 groups: no weight reduction, slight weight reduction (0%-3%), and significant weight reduction (>3%). Results Of 376 participants, most were female (n=346, 92%), had normal BMI (n=178, 47.3%), belonged to Generation Y (n=147, 46.7%), and had a medium group size (6-10 members; n=250, 66.5%). The results showed that 56 (14.9%) participants had 1-month significant weight loss, and the median weight reduction of the group was −3.85% (IQR −3.40% to −4.50%). Most participants (264/376, 70.2%) experienced weight loss, with an overall median weight loss of −1.08% (IQR −2.40% to 0.00%). The factors associated with significant weight reduction were consistently logging workouts (adjusted odds ratio [AOR] 1.69, 95% CI 1.07-2.68), being Generation Z (AOR 3.06, 95% CI 1.01-9.33), and being overweight or being obese compared to those with normal BMI (AOR 2.66, 95% CI 1.41-5.07; AOR 1.76, 95% CI 1.08-2.87, respectively). Conclusions More than half of the “MED PSU×ThaiSook Healthier Challenge” participants achieved a slight weight reduction, and 14.9% (56/376) of users lost significant weight. Factors including workout logging, being Generation Z, being overweight, and being obese were associated with significant weight reduction.
DYRK1A-mediated PLK2 phosphorylation regulates the proliferation and invasion of glioblastoma cells

Polo-like kinases (PLKs) are a family of serine-threonine kinases that exert regulatory effects on diverse cellular processes. Dysregulation of PLKs has been implicated in multiple cancers, including glioblastoma (GBM). Notably, PLK2 expression in GBM tumor tissue is lower than that in normal brains. Notably, high PLK2 expression is significantly correlated with poor prognosis. Thus, it can be inferred that PLK2 expression alone may not be sufficient for accurate prognosis evaluation, and there are unknown mechanisms underlying PLK2 regulation. In the present study, it was demonstrated that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) interacts with and phosphorylates PLK2 at Ser358. DYRK1A-mediated phosphorylation of PLK2 increases its protein stability. Moreover, PLK2 kinase activity was markedly induced by DYRK1A, which was exemplified by the upregulation of alpha-synuclein S129 phosphorylation. Furthermore, it was found that phosphorylation of PLK2 by DYRK1A contributes to the proliferation, migration and invasion of GBM cells. DYRK1A further enhances the inhibition of the malignancy of GBM cells already induced by PLK2. The findings of the present study indicate that PLK2 may play a crucial role in GBM pathogenesis partially in a DYRK1A-dependent manner, suggesting that PLK2 Ser358 may serve as a therapeutic target for GBM.
Cost-Effectiveness Analysis of Three Diagnostic Strategies for the Detection of EGFR Mutation in Advanced Non-Small Cell Lung Cancer

Background In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed. Results The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors. Conclusions The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.
Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in Japanese healthy adults: A Phase I study

ABSTRACT V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) to address the burden of residual adult pneumococcal disease after the introduction of pediatric PCVs into national immunization programs (NIPs) and includes serotypes highly prevalent in adult invasive pneumococcal disease (IPD). This Phase I study assessed the safety, tolerability, and immunogenicity of V116 in Japanese adults. Participants ≥20 years of age were randomized to receive a single dose of V116 or 23-valent pneumococcal polysaccharide vaccine (PPSV23) at day 1. Outcomes were solicited injection-site and systemic adverse events (AEs) from day 1 to day 5, vaccine-related serious AEs from day 1 through day 30, and serotype-specific opsonophagocytic antibody (OPA) titers and immunoglobulin G (IgG) concentrations at day 30. Overall, 102 participants were randomized 1:1 to each group. Comparable proportions vaccinated with V116 and PPSV23 experienced ≥1 solicited injection-site AE and ≥1 solicited systemic AE. The most common injection-site AEs were injection-site pain (V116: 54.9%; PPSV23: 66.7%) and swelling (V116 and PPSV23: 13.7%), and the most common systemic AEs were myalgia (V116: 17.6%; PPSV23: 19.6%) and fatigue (V116: 13.7%; PPSV23: 9.8%). Solicited AEs were mostly mild and of ≤3 days duration. No vaccine-related serious AEs or deaths were reported. The OPA and IgG findings showed that the immunogenicity of V116 and PPSV23 were comparable for the 12 common serotypes and V116 was more immunogenic for the nine unique serotypes compared with PPSV23. V116 was well tolerated, with a safety profile similar to PPSV23, and induced functional antibodies against all 21 serotypes.