Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor mutation burden in gastro-entero-pancreatic-neuroendocrine neoplasms

Background As rare tumors, there are limited treatment options for neuroendocrine neoplasms (NENs). Recently, microsatellite instability (MSI) and tumor mutation burden (TMB) have been emerging as potential biomarkers in various tumors. However, there is a lack of research on the use of these biomarkers in gastro-entero-pancreatic (GEP)-NENs. Methods We analyzed 31 patients diagnosed with GEP-NEN between 2013 to 2022. The TMB and MSI analyses using next-generation sequencing (NGS) were performed for all patients. The TruSightTM Oncology 500 assay from Illumina was used as the NGS panel. Results Out of the 31 patients analyzed, the most frequent primary origin was the pancreas (12 patients, 38.7%), followed by the stomach (4 patients, 12.9%), gallbladder (4 patients, 12.9%), rectum (7 patients, 22.6%), small bowel (2 patients, 6.5%), and bile duct (1 patient, 3.2%). Among these patients, 19 (61.3%) were diagnosed with well-differentiated neuroendocrine tumors, with grade 2 being the most common (15 patients, 48.4%), followed by grade 3 (3 patients, 9.7%) and grade 1 (1 patient, 3.2%). Neuroendocrine carcinoma was confirmed in 12 patients (38.7%). The median number of metastases was 2.0 [interquartile range (IQR), 1.0–3.0], and the liver was the most common site of metastasis (23 patients, 74.2%). The median TMB was 4.7 (IQR, 3.1–6.3) mutations/Mb, and all tumors were classified as microsatellite stability (MSS). Only one patient had a high TMB (266.4 mutations/Mb), which was a grade 3 neuroendocrine tumor originating from the pancreas. The TMB value did not vary depending on the primary tumor site or World Health Organization (WHO) grade. Conclusions This analysis showed that, despite very low incidence, there are GEP-NENs with high TMB. For precision medicine, testing for MSI and TMB is needed for this tumor type.
Matrices: Theory and Applications

Preface to the Second Edition. - Preface to the First Edition. - List of Symbols. - 1 Elementary Linear and Multilinear Algebra. - 2 What Are Matrices. - 3 Square Matrices. - 4 Tensor and Exterior Products. - 5 Matrices with Real or Complex Entries. - 6 Hermitian Matrices. - 7 Norms. - 8 Nonnegative Matrices. - 9 Matrices with Entries in a Principal Ideal Domain Jordan Reduction. - 10 Exponential of a Matrix, Polar Decomposition, and Classical Groups. - 11 Matrix Factorizations and Their Applications. - 12 Iterative Methods for Linear Systems. - 13 Approximation of Eigenvalues. - References. - Index of Notation. - General Index. - Cited Names. -
Comparison of Different Convolutional Neural Network Activation Functions and Methods for Building Ensembles for Small to Midsize Medical Data Sets

CNNs and other deep learners are now state-of-the-art in medical imaging research. However, the small sample size of many medical data sets dampens performance and results in overfitting. In some medical areas, it is simply too labor-intensive and expensive to amass images numbering in the hundreds of thousands. Building Deep CNN ensembles of pre-trained CNNs is one powerful method for overcoming this problem. Ensembles combine the outputs of multiple classifiers to improve performance. This method relies on the introduction of diversity, which can be introduced on many levels in the classification workflow. A recent ensembling method that has shown promise is to vary the activation functions in a set of CNNs or within different layers of a single CNN. This study aims to examine the performance of both methods using a large set of twenty activations functions, six of which are presented here for the first time: 2D Mexican ReLU, TanELU, MeLU + GaLU, Symmetric MeLU, Symmetric GaLU, and Flexible MeLU. The proposed method was tested on fifteen medical data sets representing various classification tasks. The best performing ensemble combined two well-known CNNs (VGG16 and ResNet50) whose standard ReLU activation layers were randomly replaced with another. Results demonstrate the superiority in performance of this approach.
LATE SPRING SURVEY AND RICHNESS ESTIMATION OF THE AQUATIC BENTHIC INSECT COMMUNITY IN THE UPPER PORTION OF THE LUSK CREEK WATERSHED

The Lusk Creek Watershed, located in Pope County, IL, long has been recognized as a high quality area and as biologically significant. Yet, surveys of the macroinvertebrate fauna have been limited. Thus, a survey of the benthic insect community in the upper portion of Lusk Creek was conducted from May 2003 to April 2005. Eleven sites were selected and characterized by physical properties and water chemistry. Insect distribution patterns, abundance, and diversity (richness, evenness) were examined. A total of 20,888 specimens, mostly immatures, were examined during the study and represented eight orders. The Diptera, by far, was the most common order, with 18,590 specimens, almost all of which were members of the Chironomidae and Simuliidae. The EPT (Ephemeroptera, Plecoptera, Trichoptera) combined were common with 1,550 specimens but paled in comparison to the Diptera. The Coleoptera was represented by 647 specimens, almost all of which were members of Stenelmis (n = 612). The Shannon diversity index (H') showed that the H' values for individual sites were similar to those reported for other relatively undisturbed streams. Analyses of richness suggested that as many as 37 taxa were unobserved, indicating the survey was incomplete.
The impact of a self-management program on exercise adherence among patients discharged after coronary artery bypass grafts: A quasi-experimental study in Thailand

Background Exercise adherence is essential for maintaining the physical and mental health of patients after coronary artery bypass grafts (CABG). However, adherence is often poor, particularly in the early weeks after hospital discharge, leading to adverse health outcomes. Therefore, implementing self-management programs is crucial to promote and sustain long-term exercise adherence among these patients. Objective This study aimed to examine the impact of self-management programs on exercise adherence in post-CABG patients. Methods A quasi-experimental posttest-only control group study was conducted from April to November 2022 at Surat Thani Hospital in Thailand. Forty post-CABG patients were gender and age-matched and randomly assigned to either the control group (n = 20) or the experimental group (n = 20). The experimental group participated in a six-week self-management program for exercise adherence, utilizing telephone and LINE applications, while the control group received standard care. Data were collected using validated exercise adherence rating scales and a self-management questionnaire. Descriptive statistics and independent t-tests were employed for data analysis. Results The mean exercise adherence score in the control group was 9.30 (SD = 4.91), whereas it was 21.30 (SD = 3.20) in the experimental group. The experimental group, which received the self-management program, exhibited significantly higher exercise adherence scores compared to the control group (t = 9.16, df = 32.65, p <0.001). Conclusions This study demonstrates the effectiveness of a post-CABG self-management program in improving exercise adherence. Nurses play a crucial role in promoting and enhancing self-management during the pre-and post-discharge phases, and regular phone or LINE application contacts can have a positive impact on post-CABG patients. Policymakers should consider implementing self-management programs to encourage patients to maintain their exercise routines, leading to improved physical and mental well-being.
Contributions of the Sodium Leak Channel NALCN to Pacemaking of Medial Ventral Tegmental Area and Substantia Nigra Dopaminergic Neurons

We tested the role of the sodium leak channel, NALCN, in pacemaking of dopaminergic neuron (DAN) subpopulations from adult male and female mice. In situ hybridization revealed NALCN RNA in all DANs, with lower abundance in medial ventral tegmental area (VTA) relative to substantia nigra pars compacta (SNc). Despite lower relative abundance of NALCN, we found that acute pharmacological blockade of NALCN in medial VTA DANs slowed pacemaking by 49.08%. We also examined the electrophysiological properties of projection-defined VTA DAN subpopulations identified by retrograde labeling. Inhibition of NALCN reduced pacemaking in DANs projecting to medial nucleus accumbens (NAc) and others projecting to lateral NAc by 70.74% and 31.98%, respectively, suggesting that NALCN is a primary driver of pacemaking in VTA DANs. In SNc DANs, potentiating NALCN by lowering extracellular calcium concentration speeded pacemaking in wildtype but not NALCN conditional knockout mice, demonstrating functional presence of NALCN. In contrast to VTA DANs, however, pacemaking in SNc DANs was unaffected by inhibition of NALCN. Instead, we found that inhibition of NALCN increased the gain of frequency-current plots at firing frequencies slower than spontaneous firing. Similarly, inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) conductance increased gain but had little effect on pacemaking. Interestingly, simultaneous inhibition of NALCN and HCN resulted in significant reduction in pacemaker rate. Thus, we found NALCN makes substantial contributions to driving pacemaking in VTA DAN subpopulations. In SNc DANs, NALCN is not critical for pacemaking but inhibition of NALCN makes cells more sensitive to hyperpolarizing stimuli. SIGNIFICANCE STATEMENT Pacemaking in midbrain dopaminergic neurons (DAN) relies on multiple subthreshold conductances, including a sodium leak. Whether the sodium leak channel, NALCN, contributes to pacemaking in DANs located in the VTA and the SNc has not yet been determined. Using electrophysiology and pharmacology, we show that NALCN plays a prominent role in driving pacemaking in projection-defined VTA DAN subpopulations. By contrast, pacemaking in SNc neurons does not rely on NALCN. Instead, the presence of NALCN regulates the excitability of SNc DANs by reducing the gain of the neuron’s response to inhibitory stimuli. Together, these findings will inform future efforts to obtain DAN subpopulation-specific treatments for use in neuropsychiatric disorders.
Cost Effectiveness and Resource Allocation Open Access Estimating Average Inpatient and Outpatient Costs and Childhood Pneumonia and Diarrhoea Treatment Costs in an Urban Health Centre in Zambia

Background: Millions of children die every year in developing countries, from preventable diseases such as pneumonia and diarrhoea, owing to low levels of investment in child health. Investment efforts are hampered by a general lack of adequate information that is necessary for priority setting in this sector. This paper measures the health system costs of providing inpatient and outpatient services, and also the costs associated with treating pneumonia and diarrhoea in under-five children at a health centre in Zambia.
Scaling of Complex Craters

The empirical relation between the transient crater diameter (Dg) and final crater diameter (Dr) of complex craters and basins is estimated using cumulative terrace widths, central uplift diameters, continuous ejecta radii, and transient crater reconstructions determined from lunar and terrestrial impact structures. The ratio Dg/Dr is a power law function of Dr, decreasing uniformly from unity at the diameter of the simple-complex crater morphology transition to about 0.5 for large multiring basins like Imbrium on the moon. The empirical constants in the Dg/Dr relation are interpreted physically to mean that the position of the final rim relative to the transient crater, and hence the extent of collapse, is controlled or greatly influenced by the properties of the zone of dissociated material produced by the impact shock. The continuity of the Dg/Dr relation over the entire spectrum of morphologic types from complex craters to multiring basins implies that the rims of all these structures form in the same tectonic environment despite morphologic differences.
Structural identifiability of biomolecular controller motifs with and without flow measurements as model output

Controller motifs are simple biomolecular reaction networks with negative feedback. They can explain how regulatory function is achieved and are often used as building blocks in mathematical models of biological systems. In this paper we perform an extensive investigation into structural identifiability of controller motifs, specifically the so–called basic and antithetic controller motifs. Structural identifiability analysis is a useful tool in the creation and evaluation of mathematical models: it can be used to ensure that model parameters can be determined uniquely and to examine which measurements are necessary for this purpose. This is especially useful for biological models where parameter estimation can be difficult due to limited availability of measureable outputs. Our aim with this work is to investigate how structural identifiability is affected by controller motif complexity and choice of measurements. To increase the number of potential outputs we propose two methods for including flow measurements and show how this affects structural identifiability in combination with, or in the absence of, concentration measurements. In our investigation, we analyze 128 different controller motif structures using a combination of flow and/or concentration measurements, giving a total of 3648 instances. Among all instances, 34% of the measurement combinations provided structural identifiability. Our main findings for the controller motifs include: i) a single measurement is insufficient for structural identifiability, ii) measurements related to different chemical species are necessary for structural identifiability. Applying these findings result in a reduced subset of 1568 instances, where 80% are structurally identifiable, and more complex/interconnected motifs appear easier to structurally identify. The model structures we have investigated are commonly used in models of biological systems, and our results demonstrate how different model structures and measurement combinations affect structural identifiability of controller motifs.
NK and T Cell Subtypes in the Endometrium of Patients with Recurrent Pregnancy Loss and Recurrent Implantation Failure: Implications for Pregnancy Success

Background: RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy complications. Immunological changes have been associated with RPL and RIF. Understanding immune dysregulation especially in NK and T cell subtypes may lead to better diagnostic concepts and treatments. From July 2019 to August 2020 patients with RPL and RIF underwent a standardized diagnostic procedure including endometrial biopsies. Immune cell analysis was performed using flow cytometry. Patients were contacted in March 2023 and interviewed concerning their pregnancy outcomes following diagnostics. Results: Out of 68 patients undergoing endometrial biopsies, 49 patients were finally included. Live birth rates were high with 72% in RPL and 86% in RIF. Immune cell analysis revealed that patients with RPL had more cytotoxic CD56dimCD16high cells, while RIF patients had more CD56+ uNK cells. RPL patients with pregnancy complications showed increased NKT cell percentages. Conclusion: Our findings suggest specific immune changes in RPL and RIF patients, offering potential therapeutic targets. Tailored immunotherapy based on endometrial immunophenotyping might be an option, but further research is needed.
STRUCTURAL EQUATION MODEL ON DETERMINANTS OF INTENTION TO USE E-COMMERCE

Although e-commerce is being utilised, its application expanded exponentially during the pandemic due to government restrictions on mobility. Most of the existing literature points to the effect of perceived usefulness and ease of use toward attitudes that affect the intention to use technology. Issues surface relative to the effect of customers' trust in the system and the risks involved. Using Structural Equation Modelling (SEM), the study aimed to investigate the effect of these factors on users' intention to use online shopping. Specifically, it looks into the effect of trust and risk on attitude and intention. Results established that trust affects attitude but not intention, while risk did not significantly affect both. With the online experience over time, consumers generally view e-commerce as easy and useful, especially in acquiring significant information about the product and services and navigating through e-commerce tools. The respondents are aware that there is risk in online transactions such that they prefer to pay cash or GCash upon delivery. However, the effect of risk was not supported partly due to the mobility restrictions during the pandemic. This highlights the need to improve e-commerce designs for consumer protection and more pronounced government policies on online transactions.
A retrospective study of consistency between immunohistochemistry and polymerase chain reaction of microsatellite instability in endometrial cancer

Objectives Identification of endometrial cancers (EC) with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) is essential for Lynch syndrome screening and treatment stratification. We aimed to assess the utility of immunohistochemistry (IHC) staining for MMR protein expression and polymerase chain reaction (PCR)-based MSI assays in EC and the correlation between MMR/MSI status and various clinicopathological parameters. Methods We reviewed the clinical and pathological information of 333 patients with EC. MMR protein expression was assessed as retained or lost to determine MMR status by IHC staining, and MSI status was identified by PCR capillary electrophoresis (PCR-CE) testing with a National Cancer Institute (NCI) panel. The correlation of MMR/MSI status with clinicopathological features was determined by statistical analysis. Discrepant results were further analyzed using an alternative PCR-CE MSI (Promega panel) method, MLH1 promoter methylation assays, and next-generation sequencing (NGS). Results Among the EC patients, the overall percentage of dMMR was 25.2%, and the overall percentage of MSI-H was 24%. Among the dMMR patients, 50 (59.5%) showed loss of MLH1 and PMS2 expression, 19 (22.6%) loss of MSH2 and MSH6 expression, and seven (8.3%) and eight (9.5%) loss of PMS2 and MSH6 expression, respectively. The dMMR subgroup was significantly younger than the pMMR subgroup, especially for <60-years-old patients (p = 0.038). In addition, we identified a strong correlation between MMR/MSI status and high-grade endometrioid or nonendometrioid components (p = 0.004 or p = 0.003). IHC staining and PCR-CE assay results showed a high level of overall concordance (98.8%, Cohen’s κ = 0.98). Four patients were found to have dMRR/MSS in both examinations. We reanalyzed them with additional methods. One case showed MLH1 promotor methylation, and the other three cases harbored MSH6 germline pathogenic variations. One of the cases with MSH6 deficiency was reanalyzed as MSI-H by alternative PCR-CE assay or NGS testing. Conclusions This study indicates that the combined use of MMR-IHC and PCR-CE MSI analyses may effectively avoid misdiagnoses of EC patients with dMMR/MSI-H. However, use of PCR-CE alone to evaluate MMR/MSI status may lead to missed diagnosis, especially for EC patients with MSH6 deficiency and presenting MSS.
Analysis of ethics dumping and proposed solutions in the field of biomedical research in China

As international academic exchanges and cooperation deepen, China has actively engaged in international biomedical research collaboration and achieved significant success. However, these accomplishments have been accompanied by ethical controversies and issues, with ethics dumping being a recurrently discussed focus among scholars. This paper reviews ethics dumping incidents in China’s biomedical research field and analyzes the underlying causes to answer why China is often susceptible to ethics dumping. We argue that the primary reasons include weak ethical awareness among some researchers, an oversimplified research evaluation system, gaps in relevant ethics governance and oversight mechanisms, and limited capabilities of certain ethics committees. To address these issues, we propose five ethics governance recommendations: establishing refined ethics committees at various levels and types; advancing theoretical and practical research on science and technology ethics governance; strengthening legislation and regulation related to emerging science and technology; emphasizing self-regulation and capacity building of research institutions; and providing special protection and healthcare for victims of ethics dumping. The aim is to enhance China’s research supervision system and prevent similar ethics dumping incidents from recurring.
Incidence of Post-laparotomy Acute Kidney Injury Among Abdominal Trauma Patients and Its Associated Risk Factors at King Abdulaziz Medical City, Riyadh

Background This research study investigates the prevalence of acute kidney injury (AKI) in trauma patients undergoing emergency laparotomies. AKI is a common complication in major surgeries and is associated with various adverse effects. The study aims to explore the relationship between AKI and other comorbidities in this specific context. Methodology This is a retrospective cohort study. All patients who had laparotomy after abdominal trauma at King Abdulaziz Medical City (KAMC) and met the inclusion criteria were included in the study. Nonprobability consecutive sampling was used. Data were collected by chart review using the Best-Care system at KAMC. Descriptive statistics were used to summarize and describe the characteristics of the study participants. Frequencies and percentages were calculated for categorical variables, such as comorbidities. For continuous variables, mean and standard deviations were calculated and tabulated. All statistical calculations were performed using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp., Armonk, NY, USA). Results This research study included 152 patients who underwent laparotomy, and the majority of patients (146, 96%) did not experience AKI. Several comorbidities were observed, with hypertension and diabetes being the most prevalent at 37 (24.3%) and 35 (23%), respectively. Intraoperative hypotension was experienced by 23 (15.1%) patients, while 129 (84.9%) did not have this issue. Norepinephrine was the most common vasopressor used (25.7%), followed by ephedrine and a combination of norepinephrine and epinephrine. Gender and age groups did not show significant associations with AKI, comorbidities like diabetes, heart failure, and chronic kidney disease (CKD) demonstrated significant relationships with AKI. There was no significant difference in eGFR and serum creatinine baseline levels between patients meeting AKI criteria and those who did not. Conclusions The low overall incidence of AKI in this patient population is encouraging. However, healthcare professionals must be aware of the significant impact of comorbidities such as diabetes, heart failure, and CKD on AKI development. Vigilant monitoring of postoperative kidney function, particularly serum creatinine levels within the first 48 hours, is essential for early detection and timely intervention. By understanding and addressing these risk factors, healthcare providers can take proactive steps to prevent and manage AKI in patients undergoing laparotomy, ultimately leading to improved patient outcomes and reduced healthcare costs.