bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Portfolio Investment, Institutional Quality, and Income Inequality: Evidence from Global Sample
Authors: Arogundade Sodiq , Yeboua Kouassi , Mdud Biyase 
Published: July 2023

Abstract
This study examines the effect of total portfolio investment and its sub-categories (debt and equity) on income inequality using a sample of 76 countries. The empirical results show that foreign portfolio flows worsen income inequality in recipient countries, regardless of the inequality indicators used. The study also digs deeper to examine the conditions under which international portfolio investment can have an inequality-reducing effect. The empirical evidence confirms our hunch that FPI, in the presence of good institutions, serves as a catalyst for bridging the gap between the rich and poor. In other words, domestic factors such as the quality of institutions modulate the link between portfolio investment flows and income inequality. The estimated results are reassuringly robust to alternative measures of inequality (Gini-index and Palma ratio), sub-categories of total portfolio investment (debt and equity), and various estimators such as IV-2SLS, Machado and Silva quantile regression, and JKS Granger non-causality results.
JEL classification: F3; P0; I30
Neutrophil-lymphocyte ratio, high-sensitivity C-reactive protein and monocyte chemoattractant protein-1 as novel markers for patients with type 2 diabetic kidney disease
Authors: Fang Yaxuan , Wang Bin , Pang Bo , Zhou Zijun , Xing Yunze , Pang Pai , Zheng Dingyuan , Zhang Gang , Yang Bo 
Published: July 2023

Abstract
Objective
To investigate the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of type 2 diabetic kidney disease (T2DKD).
Materials and methods
This study used a cross-sectional survey research method. A total of 90 patients with type 2 diabetes mellitus (T2DM) were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1.
Results
High levels of NLR (OR=6.562, 95%CI 2.060-20.902, P=0.001) and MCP-1 (OR=1.060, 95%CI 1.026-1.095, P<0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95%CI 0.6577-0.863, P < 0.001) and 0.862 (95%CI0.7787-0.937, P < 0.001).
Conclusion
The inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.
Creation of a Self-Powered, Real-Time Sensor for Therapeutics in Blood: from Protein Engineering to Electronic Integration
Authors: Ajo-Franklin Caroline , Cai Rong , Ngwadom Chiagoziem , Saxena Ravindra , Soman Jayashree , Bruggeman Chase , Hickey David , Verduzco Rafael 
Published: July 2023

Abstract
Precision medicine is expected to revolutionize healthcare by prioritizing accuracy and efficacy over the traditional "one-fits-all" approach. Point-of-care (POC) sensors, which are low-cost and user-friendly, play a crucial role in driving this trend by providing quick results for individuals. Modeled after the 5G network, we conceptualized an innovative approach for transmitting biomolecular signals - encoding biomolecular binding by modulating the electrical signal from glucose oxidation. We implement this concept by engineering a hybrid protein that incorporates a biomarker binding domain within a glucose oxidoreductase. By constructing an effective bioelectrochemical interface, we could detect 4-hydroxytamoxifen, an estrogen antagonist, in human blood samples, as real-time changes in the electrical signal. Moreover, our design uses blood glucose to power this real-time sensor and an additional transistor, which yields a self-powered prototype with high signal-to-noise. We foresee this novel approach transforming the conventional glucometer into a therapeutic biosensor with add-in functions.
Cardiovascular Disease Pathogenicity Predictor (CVD-PP): A tissue-specific tool for discriminating pathogenicity cardiovascular disease gene variants
Authors: Shah Svati , Ramaker Megan , Abdulrahim Jawan , Corey Kristin , Ramaker Ryne , Kwee Lydia , Kraus William 
Published: July 2023

Abstract
Introduction.
The interpretation of variants of uncertain significance (VUS) remains a challenge in the care of patients with established or familial cardiovascular diseases. 56% of potential variants within known cardiovascular risk genes are characterized as VUS and unbiased machine learning algorithms trained upon large data resources can stratify VUS into higher vs. lower probability of contributing to a cardiovascular disease phenotype.
Methods.
ClinVar pathogenic or likely pathogenic (P/LP) and benign or likely benign (B/LB) from 47 genes previously associated with monogenic cardiovascular diseases (MCVDs) were identified. A random forest model was trained using six-fold cross validation on these variants to build a predictive model of variant pathogenicity using measures of evolutionary constraint, deleteriousness, splicogenicity, local pathogenic variation, cardiac-specific exon expression, and population allele frequency. Predicted pathogenicity was computed as a linear outcome coupled with a naïve Bayes classifier to determine an optimal cut-off to distinguish VUS of pathogenic interest versus VUS with low likelihood of pathogenicity. Performance of our model was validated using variants for which ClinVar pathogenicity assignment changed between 2014 to 2022. As a proof-of-concept we demonstrated the utility of our model in the (CATHeterization GENetics [CATHGEN]) cohort.
Results.
Random forest identified a top-ranked model using ClinVar known P/LP and B/LB variants that weighted evolutionary constraint (CADD score) most heavily. The model accurately prioritized variants for which ClinVar clinical significance had changed from 2014 to 2022 (precision recall AUC = 0.97) and had equal or greater performance when compared to conventional in-silico methods for predicting variant pathogenicity. In the CATHGEN cohort, there was a higher burden of VUS of pathogenic interest in individuals with DCM as compared to controls without DCM (p = 8.2x10− 15). Individuals in CATHGEN who harbored model predicted and ACMG/AMP reviewed pathogenic VUSs demonstrated that 27.6% had clinical evidence of the relevant disease. Lastly, variant prioritization using this model provided genetic diagnosis in 11.9% of CATHGEN patients diagnosed with HCM clinically who did not harbor a HCM genetic P/LP variant by initial ACMG/AMP review.
Conclusion.
We have developed a cardiac-specific model for prioritizing variants underlying familial cardiovascular disease syndromes. CVD-PP proves to have high performance in discriminating pathogenicity of VUS in MCVD genes. ACMG/AMP review and phenotyping of individuals carrying VUS of pathogenic interest in a large cardiovascular cohort support the clinical utility of this model.
Genetic Diversity and Genome-Wide Association Study for some agronomic traits in durum wheat (Triticum turgidum L.) Using whole genome DArTseq Markers
Authors: Ebrahimi Peyman , Karami Ezzat , Etminan Alireza , Talebi Reza , Mohammadi Reza 
Published: July 2023

Abstract
This research was conducted to study genetic diversity, population structure, linkage disequilibrium, and marker-trait relationship in durum wheat using DArTseq technology. Therefore, 94 durum wheat genotypes were evaluated in the form of augmented design (augment) with six repeated controls during the two cropping years, 2016-2017 and 2017-2018. Some Agronomic traits including the number of days to spike emergence, number of days to physiological maturity, plant height, thousand kernel weight, and grain yield were measured and recorded. The DNA samples were processed for DArTseq genotyping, using the Genotyping by Sequencing (GBS) platform at Diversity Array Technology Pty, Ltd, Australia. The values of polymorphism information content (PIC) of SilicoDArT markers varied from 0.023 to 0.499 with an average of 0.38. The average repeatability and readability of the sequences in all linkage groups were above 0.98 and 0.92, respectively. The number of mapped SilicoDArT markers varied from 300 markers in the linkage group (Chr1A) to 853 markers in the linkage group (Chr7B). The chromosome size covered by SilicoDArT markers ranged from 829200.1 kbp in the linkage group (Chr3B) to 589293.79 kbp in the linkage group (Chr1A). The studied durum wheat genotypes were grouped into four separate groups based on the Bayesian model. The four subpopulations showed a relatively high genetic diversity, which was variable, ranging from 0.02 in the subpopulation (POP4) to 0.34 in the subpopulation (POP3). LD analysis between A and B genomes showed that there is a high number of significant marker pairs (82052) in the B genome compared to the A genome (68885). In general, during two cropping years, 29 markers related to the studied traits were found, and out of these 29 related markers, 19 markers were identified in the first year and 10 markers were identified in the second year. The results revealed that the DArTseq markers are a very powerful tool for evaluating the genetic diversity and population structure of durum wheat genotypes and can be used in genotype screening as breeding parents and marker-assisted selection in breeding programs.
SMYD3: a new regulator of the early steps of adipocyte differentiation
Authors: Gilardi Federica , Sajic Tatjana , Gasser Marie , Caputo Tiziana , Bararpour Nasim , Augsburger Marc , Walter Nadia , Hainard Alexander , Fracasso Tony , Thomas Aurelien 
Published: July 2023

Abstract
Background In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The individual ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to the development of inflammation and detrimental metabolic consequences. However, the molecular mechanisms underlying this fine-tuned regulation are far from being understood.
Methods We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low inflammation (Low-INFL), showed a low susceptibility to the onset of adipose tissue inflammation, as opposed to those developing the expected inflammatory response (Hi-INFL). We identified the discriminants between Low-INFL and Hi-INFL vWAT samples and explored their function in Adipose Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes.
Results We quantified 6051 proteins. Among the candidates that most differentiate Low-INFL from Hi-INFL vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in Low-INFL, as compared to Hi-INFL. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was so far unknown, was another top-scored hit. SMYD3 expression was significantly higher in Low-INFL vWAT, as confirmed by western blot analysis. In vitro, we found that SMYD3 mRNA and protein levels decrease rapidly along the differentiation process of AD-hMSCs. Moreover, SMYD3 knock-down at the beginning of adipocyte differentiation resulted in reduced cell proliferation and, at longer term, reduced lipid accumulation in adipocytes.
Conclusions Our study describes an important role for SMYD3 as a newly discovered regulator of adipocyte proliferation during the early steps of adipogenesis.
Neutrophil-lymphocyte ratio reflects tumor infiltrating lymphocytes, tumor associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy
Authors: Li Joshua , Ni Shelly Y. B. , Tsang Julia Y. S. , Chan Wai Yin , Hung Ray K. W. , Lui Joshua W. H. , Ng Sally W. Y. , Shum Leong Kwong , Tang Ying Fei , Tse Gary M. 
Published: July 2023

Abstract
Introduction
The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumor microenvironment, tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aims to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC).
Methods
A cohort of breast cancer patients receiving NAC with subsequent was retrieved. Clinical data were reviewed. Histologic slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (post-chemotherapy) specimens were assessed for TILs and TAMs.
Results
Totally 146 patients were included. There was significant positive correlation between pre-chemotherapy and post-surgery NLR at a cutoff of 2.6 (median pre-chemotherapy NLR) (p<.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (p=.027) and excision (p=.021) and TAMs on excision (p=.049). NLR one-year post-surgery was associated with high tumor stage (p=.050) and low histologic grade (p=.008). TIL count was lower in NLR-high cases at nearly all time points, by histologic assessment and CD8 immunostaining (p<.050). In multivariate analysis, post-surgery NLR is an independent predictor for overall survival (OS) (HR=9.524, p<.001), breast cancer specific survival (BCSS) (HR=10.059, p=.001) and disease-free survival (DFS) (HR=2.824, p=.016).
Conclusion
The association between NLR with tumor necrosis, TAM and TIL illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.
An atypical presentation of Retain Product of Conception in the Cervix
Authors: Livani Somayeh , Fatemi Alireza , Jahanshahi Moghadese 
Published: July 2023

Abstract
Background: Retained product of conception (RPOC) occurs when fragments of the placenta or decidual tissues are retained in the uterus, often leading to postpartum hemorrhage. Early and accurate diagnosis, aided by ultrasonography, is essential for appropriate management and prevention of complications.
Case presentation: We reported a case of a 22 years old woman admitted to our tertiary medical department with irregular vaginal bleeding and abdominal pain and no past medical history. Her abdominal ultrasonography revealed a normal-sized uterus and homogenous myometrial echogenicity. an heterogenous echogenic mass containing considerable vascularity and feeding vessels from the endometrial cavity was observed in the cervix. Additionally, the patient’s beta human chorionic gonadotrophin (Beta-HCG) concentration was positive despite her claiming to be a virgin. Subsequently, the patient underwent hysteroscopy, and the infected and malodorous lesion was removed from the uterus with the diagnosis of RPOC. In the follow up she had no complications.
Conclusion: Assuming the expected location of RPOC, which is in the endometrial cavity, no case of RPOC in the cervix has been reported heretofore. The purpose of this study is to report our experience in considering the differential diagnosis of RPOC as a cervical lesions and the importance of ultrasonography in early pregnancy.
Amyloid-beta peptides trigger premature functional and gene expression alterations in human-induced neurons
Authors: de Farias Ana Raquel Melo , Pelletier Alexandre , Iohan Lukas da Cruz Carvalho , Saha Orthis , Bonnefond Amelie , Amouyel Philippe , Delahaye Fabien , Lambert Jean-Charles , Costa Marcos R. 
Published: July 2023

Abstract

Background
Alzheimer’s disease (AD) is the most prevalent cause of dementia in the elderly, characterized by the presence of amyloid beta (Aβ) plaques, neurofibrillary tangles, neuroinflammation, synapse loss and neurodegeneration in the brain. The amyloid cascade hypothesis postulates that deposition of Aβ peptides is the causative agent of AD pathology, but we still lack comprehensive understanding about the molecular mechanisms connecting Aβ peptides to neuronal dysfunctions in AD. In this work, we investigated the early effects of Aβ peptides accumulation on the functional properties and gene expression profiles of human-induced neurons (hiNs).
Methods
We exposed 6-weeks-old hiNs to low concentrations of cell-secreted Aβ oligomers or synthetic Aβ and performed time-lapse time microscopy to detect fast calcium transients as an indirect readout of neuronal electrical function. Next, we used single-nucleus RNA sequencing (snRNA-seq) to probe early Aβ-mediated gene expression alterations in hiNs and human-induced astrocytes (hiAs). Lastly, we leveraged snRNA-seq data to identify patterns of intercellular communication modulated by Aβ oligomers.
Results
We show that hiNs acutely exposed to low concentrations of both cell-secreted Aβ peptides or synthetic Aβ1−42 exhibit alterations in the frequency of calcium transients suggestive of increased neuronal excitability. We also show that cell-secreted Aβ up-regulates the expression of several synaptic-related genes and down-regulates the expression of genes associated with metabolic stress mainly in glutamatergic neurons and to a lesser degree in GABAergic neurons and astrocytes. These neuronal alterations correlate with activation of SEMA5, EPHA and NECTIN signaling pathways, which are important regulators of synaptic plasticity.
Conclusions
Our findings indicate that slight elevations in Aβ concentrations are sufficient to elicit transcriptional changes in human neurons with long lasting consequences to neural network activity and suggest that at least part of the effects of Aβ on synapses might be mediated by semaphorin, ephrin and nectin signaling pathways.
ATR-Dependent Activation of S-Phase Checkpoint: The Influence of Replication Stress Severity and Duration on Cdc6 Mediation
Authors: Musiałek Marcelina W. , Rybaczek Dorota 
Published: July 2023

Abstract

The CDC6 protein is well-known to facilitate replication origin activation in eukaryotic cells. The Cdc6 protein is part of the pre-replication complex, which initiates DNA replication by binding to specific sites on the genome called origins of replication. In doing so, it helps recruit other proteins that are required for DNA synthesis. It is also an important factor in response to replication stress, where it has been shown to physically interact with ATR in order to activate the S-phase checkpoint response. The ATR, though, can also activate the S-phase checkpoint without interacting with Cdc6. Up to this day, the Cdc6-ATR binding was thought occur where there is a low level of replication stress. Here we show that it can also occur when high levels of replication stress persist for long time. Our research shows that in root meristem cells of V. faba, subjected to long-term replication stress (24–32 hours) induced by hydroxyurea, some DNA damage sites express ATR activity through binding with Cdc6. We conclude that the Cdc6-ATR cooperation may not only depend on the dose of the stressor but also on the longitude of the treatment.
Quality of Life of Colorectal Cancer patients and its association with Anxiety and Depression: Cross sectional study at a tertiary care hospital in low-middle income country
Authors: Siddiqui Muhammad Tayyab , Shaukat Fatima , Khan Muhammad Rizwan , Zahid Nida , Shahzad Shumaila 
Published: July 2023

Abstract

Background: Colorectal cancer (CRC) and its therapy have an enormous impact on the health related quality of life (QoL) of cancer patients. The emotional distress like anxiety & depression also negatively affect wellbeing of such patients. This study aims to evaluate the QoL, anxiety & depression in CRC patients and their association with clinic-pathological features at a tertiary care hospital in Karachi Pakistan, a low middle income country (LMIC).
Methods: An analytical cross sectional study was conducted on adult patients with CRC presenting to Aga Khan University Hospital, Karachi, Pakistan. The European Organization for Research and Treatment of Cancer, QoL questionnaire C30 and CR29 were used to assess the QoL; while Hospital Anxiety & Depression Score (HADS) was utilized to evaluate the anxiety and depression. Data were analyzed using STATA version 12. Multivariable linear and MANOVA were performed to analyze the correlation between independent factors and the global QoL as well as the item specific QoL scores, respectively. A p value of <0.05 was considered as significant.
Results: A total of 127 CRC patients were included in this study with a mean age of 53±15 years. Majority were male (70%), married (83.5%), and living in combined family system (52.7%). Mean Global QoL score in our patients was 69.08±1.78. Among symptoms scales, stoma care problem, dry mouth and urinary frequency were 3 worst symptoms respectively. Among functional scales, sexual interest (women > men) was the most significantly affected aspect. Anxiety and Depression were seen in 26 (20.9%) and 24 (18.9%) patients, respectively. On multivariable linear regression adjusted for covariates, lower global QoL was significantly associated with depression (Adjusted Beta Coefficient: -25.33 [95% Confidence Interval: −34.4, −16.23]), patients on adjuvant treatment (−15.14 [−21.84, −8.44]), and those who received neo adjuvant treatment (-11.75 [-19.84, -3.65]).
Conclusions: This is the first study to assess the QoL in CRC patients in Pakistan. Depression was found to be significantly associated with poor quality of life. Numerous factors were identified which correlated with QoL indicating the need to develop local guidelines to help our patients cope with the psychological distress.
High-performance Intrusion Detection Systemusing eBPF with Machine Learning algorithms
Authors: ANAND NEMALIKANTI , A SAIFULLA M , Aakula Pavan Kumar 
Published: July 2023

Abstract
Denial of Service (DoS) and Distributed DoS (DDoS) attacks are standard prob-lems organizations that rely on network services face. Detecting these attackspromptly and accurately is crucial to mitigating the damage caused. This paperproposes an Intrusion Detection System (IDS) that utilizes the extended Berke-ley Packet Filter (eBPF) with machine learning algorithms, namely Decision Tree(DT), Random Forest (RF), Support Vector Machine (SVM), and TwinSVM.eBPF is a bytecode-based virtual machine that runs programs without modifyingthe kernel source code. It can implement various services, such as observabil-ity, security, and networking. Socket filters are an eBPF program attached tothe socket in the Linux kernel that allows for efficient filtering and manip-ulation of network packets at the socket after packets are received from thenetwork stack. Packets that are filtered at the socket level before enteringthe user space. The steps involved in the proposed model are: a) collectingdata from famous repository, CIC-IDS-2017. b) Once the raw data is obtained,it undergoes preprocessing, which includes data transmission, cleaning, reduc-tion, and discretization. c) Following the preprocessing step, an ANOVA F-testextracts specific features from the preprocessed data. d) Lastly, the extractedfeatures are analyzed for intrusion detection using various ML algorithms:DT, RF, SVM, and TwinSVM. e) The eBPF program captures network traf-fic and utilizes trained model parameters to detect attacks within the kernel.Our experimental results show that the accuracy of our proposed ML algo-rithms, DT, RF, SVM, and TwinSVM, outperforms the existing related work:99.38, 99.44, 88.73, and 93.82, respectively. The experimental code available inhttps://github.com/NemalikantiAnand/Project.git