Miracle-dz/UniFAR-FTUs huggingface dataset:
A KRAS-Associated Signature for Prognostic, Immune and Chemical Anti-Cancer Drug-Response Prediction in Colon Cancer

Background: KRAS mutation, one of the most important biological processes in colorectal cancer, leads to poor prognosis in patients. Although studies on KRAS have concentrated for a long time, there are currently no ideal drugs against KRAS mutations. Methods: Different expression analysis and weighted gene coexpression network analysis was conducted to select candidate genes. Log-rank tests and Cox regression picked out the prognostic genes to build a KRAS-related gene prognostic score (KRGPS). A nomogram based on KRGPS was built to predict survival of clinical patients. Comprehensive analysis showed the prognosis, immune microenvironment and response to immune therapy and chemotherapy in KRGPS subgroups. Results: We collected a KRGPS from the set of two genes GJB6 and NTNG1, with low-KRGSP patients having better progression-free survival (PFS). Low KRGPS is correlated with high infiltration of activated NK cells, plasma cells and activated memory CD4 T cells and that these cells benefit more from immune checkpoint inhibitor therapy. However, high KRGPS is associated with high infiltration of activated mast cells, pathways of immune dysregulation and a high ratio of TP53 and KRAS mutations. KRGPS subgroups are also sensitive to chemotherapy differently. A nomogram, established based on the KRGPS and pathological stage, predict 3- and 5-years PFS well. Conclusions: The KRAS-associated score acts as a promising signature to distinguish prognosis, molecular and immune characteristics, and benefits from immune and chemical therapy. These KRAS-associated genes could be promising targets for drug design.
Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates With the Microbial Vaginal Environment

The cervicovaginal environment in pregnancy is proposed to influence risk of spontaneous preterm birth. The environment is shaped both by the resident microbiota and local inflammation driven by the host response (epithelia, immune cells and mucous). The contributions of the microbiota, metabolome and host defence peptides have been investigated, but less is known about the immune cell populations and how they may respond to the vaginal environment. Here we investigated the maternal immune cell populations at the cervicovaginal interface in early to mid-pregnancy (10–24 weeks of gestation, samples from N = 46 women), we confirmed neutrophils as the predominant cell type and characterised associations between the cervical neutrophil transcriptome and the cervicovaginal metagenome (N = 9 women). In this exploratory study, the neutrophil cell proportion was affected by gestation at sampling but not by birth outcome or ethnicity. Following RNA sequencing (RNA-seq) of a subset of neutrophil enriched cells, principal component analysis of the transcriptome profiles indicated that cells from seven women clustered closely together these women had a less diverse cervicovaginal microbiota than the remaining three women. Expression of genes involved in neutrophil mediated immunity, activation, degranulation, and other immune functions correlated negatively with Gardnerella vaginalis abundance and positively with Lactobacillus iners abundance; microbes previously associated with birth outcome. The finding that neutrophils are the dominant immune cell type in the cervix during pregnancy and that the cervical neutrophil transcriptome of pregnant women may be modified in response to the microbial cervicovaginal environment, or vice versa, establishes the rationale for investigating associations between the innate immune response, cervical shortening and spontaneous preterm birth and the underlying mechanisms.
Grain Size and Heterophase Effects on Mechanical Properties of Mg-Cu Nanoglasses

Tailoring heterogeneities in amorphous alloys is a promising strategy for promoting the strength-ductility synergy. Here, molecular dynamics simulations are performed to investigate the effects of grains size and heterogeneous chemical composition on the mechanical properties of Mg-Cu nanoglasses (NGs). The reduced grain size in single-phase NGs improves the plasticity but at the expense of strength. In addition, the mechanical properties of dual-phase NGs composed of two chemical compositions depend critically upon the fraction of softer phase. In particular, the plasticity is improved for the low fraction of the softer phase, but is deteriorated for the high fraction of the softer phase, which is in striking contrast to the observations of the plasticity improvement reported in the traditional nanostructured metals/alloys. This is because that heterogeneities at the glass-glass interfaces intentionally introduce more stress concentration sites which are easier to accelerate the shear band formation. For an appropriate fraction of heterogeneous composition, a balance among strength and plasticity can be realized, which is useful for the design of novel NGs with high strength and superior ductility.
Pre-stroke Disability and Long-Term Functional Limitations in Stroke Survivors: Findings From More of 12 Years of Follow-Up Across Three International Surveys of Aging

Background Almost 50% of the post-stroke disabled population already have a premorbid disability before stroke. These patients may be offered a different care pathway in the acute and subacute phase than those without pre-morbid disability. Therefore, the aim of this study was to assess the association of the severity of premorbid disability with change of limitations in basic and instrumental activities of daily living (ADL/IADL) 1 year after stroke and over the following decade. Methods Among 3,432 participants from HRS, SHARE and ELSA cohorts with a first stroke, ADL/IADL limitations were measured at 1–2 years prior to stroke, at 1 year post-stroke, and during the chronic phase. Modified Ranking Scale (P-mRS) was used to categorize the participants by level of premorbid disability (1–2 years pre-stroke). Change in ADL/IADL limitations by P-mRS level (0–1, 2–3, and 4–5) was assessed using a piecewise linear mixed model with a breakpoint set at 1 year post-stroke, stratified by median age groups. Results Increase in ADL limitations at 1 year post-stroke was less pronounced in P-mRS ≥2 (p < 0.005). After years of relative stability, limitations of ADL increased for all P-mRS levels (p = 0.003). In those aged ≥75 years at stroke event, the increase was similar irrespective of P-mRS (p = 0.090). There were no significant differences in IADL trajectories between P-mRS levels (p ≥ 0.127). Conclusion These results suggest similar trajectories of functional limitations between P-mRS levels up to 9 years post-stroke, highlighting the possible benefit of including patients with pre-morbid disability to certain treatments during the acute phase.
State Changes During Resting-State (Magneto)encephalographic Studies: The Effect of Drowsiness on Spectral, Connectivity, and Network Analyses

Background A common problem in resting-state neuroimaging studies is that subjects become drowsy or fall asleep. Although this could drastically affect neurophysiological measurements, such as magnetoencephalography (MEG), its specific impact remains understudied. We aimed to systematically investigate how often drowsiness is present during resting-state MEG recordings, and how the state changes alter quantitative estimates of oscillatory activity, functional connectivity, and network topology. Methods About 8-min MEG recordings of 19 healthy subjects, split into ~13-s epochs, were scored for the presence of eyes-open (EO), alert eyes-closed (A-EC), or drowsy eyes-closed (D-EC) states. After projection to source-space, results of spectral, functional connectivity, and network analyses in 6 canonical frequency bands were compared between these states on a global and regional levels. Functional connectivity was analyzed using the phase lag index (PLI) and corrected amplitude envelope correlation (AECc), and network topology was analyzed using the minimum spanning tree (MST). Results Drowsiness was present in >55% of all epochs that did not fulfill the AASM criteria for sleep. There were clear differences in spectral results between the states (A-EC vs. D-EC) and conditions (EO vs. A-EC). The influence of state and condition was far less pronounced for connectivity analyses, with only minimal differences between D-EC and EO in the AECc in the delta band. There were no effects of drowsiness on any of the MST measures. Conclusions Drowsiness during eyes-closed resting-state MEG recordings is present in the majority of epochs, despite the instructions to stay awake. This has considerable influence on spectral properties, but much less so on functional connectivity and network topology. These findings are important for interpreting the results of EEG/MEG studies using spectral analyses in neurological disease, where recordings should be evaluated for the presence of drowsiness. For connectivity analyses or studies on network topology, this seems of far less importance.
A Narrative Review of Postoperative Anticoagulation Therapy for Congenital Cardiac Disease

Congenital heart disease encompasses a range of cardiac birth defects. Some defects require early and complex surgical intervention and post-operative thromboprophylaxis primarily for valve, conduit, and shunt patency. Antiplatelet and anticoagulant management strategies vary considerably and may or may not align with recognized consensus practice guidelines. In addition, newer anticoagulant agents are being increasingly used in children, but these medications are not addressed in most consensus statements. This narrative review evaluated the literature from 2011 through 2021 on the topic of postoperative thromboprophylaxis after congenital heart disease operations. The search was focused on the descriptions and results of pediatric studies for replacement and/or repair of heart valves, shunts, conduits, and other congenital heart disease operations. Wide variability in practice exists and, as was true a decade ago, few randomized controlled trials have been conducted. Aspirin, warfarin, and perioperative heparin remain the most commonly used agents with varying dosing, duration, and monitoring strategies, making comparisons difficult. Only recently have data on direct oral anticoagulants been published in children, suggesting evolving paradigms of care. Our findings highlight the need for more research to strengthen the evidence for standardized thromboprophylaxis strategies.
Heat Accumulation Mechanism of the Gaoyang Carbonatite Geothermal Field, Hebei Province, North China

From 2019 to 2021, we constructed two high-productivity geothermal wells with wellhead temperatures of 109.2 and 123.4°C in the Gaoyang geothermal field. Based on the two wells, it was proved that Gaoyang is a medium-temperature carbonate geothermal field with great development potential. The article reported the latest exploration achievements of deep buried hill geothermal resources in the geothermal field. The productivity of D34 and D35 geothermal wells were evaluated by James end-pressure method: the total flow of steam–water mixture was 234.59–331.92 (t/h), the dryness was 1.36–2.03%, and the single-well power generation potential was 2.10–2.55 MW. Combined with those results, the heat control factors and heat accumulation mechanism of the deep carbonatite geothermal field were confirmed. The westward subduction of the Pacific plate caused obvious damage to the eastern North China Craton and greatly reduced the thickness of the lithosphere and crust. This process facilitated the conduction of mantle-derived heat to shallow crust. Deep strike-slip faults (e.g., Maxi fault) cut through the lithosphere, leading the deep mantle-derived heat and magma to migrate into the crust. The heat accumulated from the depression with low thermal conductivity to the uplift with high thermal conductivity. Groundwater was heated up by deep cycle and convection along faults. The catchment of regional karst groundwater also had a certain effect on the heat accumulation. The Gaoyang geothermal field was formed by these factors.
A 0.65-V process variation and supply noise insensitive ring VCO

ABSTRACT A low-voltage feedforward ring voltage-controlled oscillator (FRVCO) withstanding process variation and supply-voltage noise is proposed in this paper. In this design, the variation of transistors’ threshold voltages and supply voltage noise are detected by a compensating voltage generated circuit, and the load capacitance of the FRVCO is tuned by the compensating voltage to reduce the variation of oscillating frequency. Simulation results demonstrate that the centre oscillating frequency difference between ‘FF’ and ‘SS’ corners is reduced from 38.3% to 1.5% by tuning the voltage from 0 to 650 mV. Moreover, with a supply voltage change of ±0.5%, the frequency variation is smaller than ±0.06%. The 0.65-V 600-MHz FRVCO has been fabricated using the TSMC 130-nm CMOS process.
Performance Comparison and Evaluation of the Routing Protocols for MANETs Using NS3

MANETs (mobile ad hoc networks) contain wireless mobile nodes to construct dynamic networks without the support of fixed infrastructure. Its nodes and hosts are all movable and self-configurable while simultaneously serving as routers to deliver data from sources to their respective destinations. Because routers in MANETs have to cooperate efficiently to meet the performance requirements, routing algorithms play a crucial role in MANET architecture design. In the past, tremendous works have been done on comparison and evaluation of routing algorithms using NS2 (network simulator 2). This paper presents performance evaluations and analyses on the Proactive and Reactive routing protocols using NS3 (network simulator 3), a relatively newer and more advanced version of NS2. This paper will also show simulation results of evaluating the drop rate, throughput, power consumption, and end-to-end delay of MANETs. Lastly, a performance justification of said simulation results will be presented.
Analysis of lateral vehicle position using naturalistic driving data

Traffic crashes have a significant impact on humans lives and the world economy. Understanding crash causation is an important step to prevent crashes from happening. One way of gaining information about crashes and human driver behaviour is through the analysis of naturalistic driving data. Often the challenge arises to generate the maximum information from a given database to answer a certain problem or research question. The thesis covers the research question, of how to analyze large quantities of video material in a quantifiable and efficient way to gain information about the lateral position of a vehicle. The research addresses that problem by developing a tool to extract the lateral vehicle position of a front view video and using reference data to evaluate its performance and sensitivity. A reliable set of CAN-Bus data serves as reference data for the vehicle position. The vehicle position is extracted from the video through multiple image processing steps. Evaluations are performed to assess precision and accuracy of the method. A sensitivity analysis is conducted to determine the impact of providing correct camera parameters. The method is applied to a new data set to ensure versatility. The results show that the method is reliable but highly sensitive to the orientation and position of the camera relative to the vehicle. The overall estimation of the precision shows a systematic error in the measurements caused by the camera parameters. The sensitivity evaluation shows that the height and the roll of the camera have a significant impact on the precision of the method. The developed tool can be used to determine the lateral vehicle position. Tuning of the tool is needed to further improve accuracy and precision of the tool.
Antihypertensive drug treatment in white-coat hypertension: data from the Plaque HYpertension Lipid-Lowering Italian Study

Aim: Little evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection might be indirectly inferred, however, from the blood pressure (BP) effects of treatment as in trials BP reduction is linearly related to outcome reduction. We analyzed the effect of antihypertensive treatment on office and ambulatory BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS). Methods : Office and ambulatory blood pressure were measured in 470 hypertensive patients randomized to fosinopril or hydrochlorothiazide alone or combined with a statin before treatment and at 6 month or yearly intervals during 2.6 years of follow-up. Patients were divided into two groups according to whether before randomization to treatment office and 24-h mean BP were elevated (sustained hypertension) or office BP was elevated but 24-h BP values were normal (WCH). Results : In both sustained hypertension and WCH antihypertensive treatment was associated with an early marked office BP reduction, which persisted virtually unchanged throughout the treatment period. In contrast, 24-h (and day and night) BP showed a marked and persistent treatment-related fall in sustained hypertension but no change in WCH. The results were similar when data were separately analyzed in patients under fosinopril or diuretic, with or without statin treatment. Conclusion : In WCH, antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline. This appears to be unrelated to the type of treatment employed.
COVID-19 IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION: A META-ANALYSIS OF OBSERVATIONAL STUDIES

Objective: A number of studies have indicated a deleterious effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on endothelial function of enrolled subjects, further impairing during post-infectious stage. Endothelial function might indeed have a prognostic role in coronavirus disease-19 (COVID-19). Herein we sought to determine the effect of SARS-CoV-2 on endothelial function as quantified by flow-mediated dilation (FMD). Design and method: We searched the PubMed database from inception till 21st December, 2021, for observational studies assessing the impact of SARS-CoV-2 on endothelial function either in the in-hospital or the outpatient setting. We set as primary efficacy outcome the mean difference in FMD between infected patients and healthy controls. Results: We pooled data from 5 observational studies in a total of 541 enrolled subjects. One study enrolled children, while the rest 4 enrolled adults. Overall, COVID-19 induced a significant decrease in FMD by 3.29% (95% CI; -4.57 to -2.01, I2 = 81%) compared to healthy controls. Conclusions: Despite being preliminary, these results suggest a significant effect of SARS-CoV-2 on endothelial system, leading to significant endothelial dysfunction. Prognostic implications of that effect have to be determined in prospective studies.
Determining the Key Residues for Capsule Production in the GBS CpsA Protein

Streptococcus agalactiae (GBS) is a common bacterium found commensally in the vaginal mucosa of healthy adults. GBS also causes severe infection in neonates, often leading to meningitis, which can cause lifelong health consequences including impaired hearing and seizures. Infection of newborns mainly arises from a colonized mother, either before birth through ascending infection or during labor. Ascending infection, where the bacteria travel to the fetus from the vaginal mucosa, is especially concerning as it can lead to loss of pregnancy or premature birth. The most common method of neonatal GBS disease prevention is antibiotic prophylaxis during delivery, though this method is lacking in safety and application. A promising alternative target for GBS virulence attenuation involves capsular polysaccharide (CPS), which protects GBS from immune recognition and clearance. CPS is regulated by CpsA, a multifunctional protein which is implicated in transcriptional activation, and ligation of CPS to the cell wall via the LytR domain. In this study, a CpsA mutant was created with two amino acid substitutions in the LytR domain which were predicted to decrease LytR functionality. We used microscopy to determine that this mutant induced a change in chain length, as well FL-vancomycin to show that this phenotypic change was not due to a change in cell envelope structure. We measured CPS levels with an ELISA to show that this mutant causes a reduction in CPS level. Finally, we analyzed virulence in zebrafish of bacteria expressing the mutant and found that virulence was increased in WT GBS with this mutant.
Evaluation of Project Risk Assessment Strategies

The risk involved in the construction works is relatively higher than the other works. The biggest challenge is to reduce the risks involved. Risk assessments include identifying risks, analyzing risk and controlling risk qualitatively by various methods. In this study, the Questionnaire checklist method is used to identifying the risk in the construction work, at the Federal Ministry of Works and Housing, Nigeria. Based on this, risk assessment is made to control the risk. There are various factors which affects the occurrence of these risks. All these risk occur during the project life cycle will results in financial loss and even in the stoppage of a particular project. Hence in order to prevent this, proper risk assessment is very important. The purpose of this research is to evaluate various risks factors that could hinder the implementation of projects and the determining the influence of risk avoidance, according to the perception of the employees of the Federal Ministry of Works and Housing. For that, a questionnaire of five point scale was prepared. The study adopted a descriptive survey design and collected data through questionnaires from 212 employees of the Federal Ministry works and Housing through stratified random sampling. Data was analyzed using both descriptive statistics with the help of IBM SPSS Statistics for Windows, Version 25.0. In conclusion, the results indicated that the staff of the Federal Ministry of Works and Housinghad very high opinion with regards to the implementation of risk avoidance strategy and its impact on project implementation (mean = 0.152; std. dev. = 0.33).