Miracle-dz/UniFAR-FTUs huggingface dataset:
[Role and related mechanisms of liasr two-component system in acid tolerance and biofilm formation of Streptococcus mutans].

Objective: To investigate the role and related mechanisms of the LiaSR two-component system in acid tolerance and biofilm formation abilities of Streptococcus mutans (Sm) 593. Methods: The growth curves of various Sm strains in pH=5.5 brian heart infusion (BHI) medium were analyzed. And colony forming unit (CFU) was also performed to evaluate the acid tolerance of Sm. Laurdan probe, H+-K+adenosine triphosphate (ATP)ase activity analysis kit, proton permeability assay and real-time fluorescence quantitative PCR (RT-qPCR) were conducted to detect the acid tolerant mechanisms of LiaSR two-component system in Sm. Crystal violet staining, CFU, SYTOX probe and anthrone-sulfuric method were used to analyze the properties and structures of the Sm biofilms. RT-qPCR was conducted to detect the expression levels of underlying regulated genes. Results: The growth of mutants in acidic BHI were inhibited (P<0.05). The acid tolerance of mutants significantly decreased compared to the wild-type strain (P<0.05). In mutants, the activity of H+-ATPase (917.06±59.53 and 469.53±47.65) were elevated by 7.22-folds and 3.70-folds compared to the wild-type strain (127.00±50.71) (P<0.001, P<0.001) and the encoded gene atpD (3.39±0.21 and 1.94±0.17) were also elevated by 3.39-folds and 1.94-folds compared to the wild-type strain (1.00±0.15) (P<0.001, P=0.001). The fluidity of mutants (0.18±0.04 and 0.18±0.05) reduced significantly compared to the wild-type strain (0.08±0.05) (P=0.006, P=0.003) and the expression levels of fabM gene were decreased in mutants (0.52±0.11 and 0.57±0.05) by 1/2 (P=0.014, P=0.022). In liaR deletion mutant, the increased proton permeability (4.76±0.01) can also be observed (P<0.001). The total amount of the biofilms of three Sm didn't show significant differences (P>0.05). But the number of viable bacteria of mutants' biofilms were decreased [Sm 593: (1.20±2.80)×107 CFU/ml; Sm ΔliaS: (2.95±1.13)×107 CFU/ml; Sm ΔliaR: (7.25±1.60)×107 CFU/ml] (P=0.001, P=0.024). 18.00-folds and 6.50-folds increases of eDNA could be observed in mutants' biofilms (128.73±15.65 and 46.38±5.52) compared to the wild-type strain (7.16±3.62) (P<0.001, P=0.003). Water-soluble exopolysaccharides could be found up-regulated in liaS deletion mutant (138.73±10.12) (P=0.003) along with the expression level of gtfC gene (1.65±0.39) (P=0.014). The expression level of gtfD were elevated by 47.43-folds and 16.90-folds in mutants (47.43±8.32 and 16.90±3.40) (P<0.001, P=0.01). Conclusions: The LiaSR two-component system can promote the expression of fabM gene and increase the fluidity of Sm which contributes to acid tolerance. The LiaR can also decrease the proton permeability and restrict the entrance of H+. The LiaSR two-component system can negatively regulate the production of the extracellular matrix in Sm biofilm.
SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks

Abstract Silencers are repressive cis-regulatory elements that play crucial roles in transcriptional regulation. Experimental methods for identifying silencers are always costly and time-consuming. Computational methods, which relies on genomic sequence features, have been introduced as alternative approaches. However, silencers do not have significant epigenomic signature. Therefore, we explore a new way to computationally identify silencers, by incorporating chromatin structural information. We propose the SilenceREIN method, which focuses on finding silencers on anchors of chromatin loops. By using graph neural networks, we extracted chromatin structural information from a regulatory element interaction network. SilenceREIN integrated the chromatin structural information with linear genomic signatures to find silencers. The predictive performance of SilenceREIN is comparable or better than other states-of-the-art methods. We performed a genome-wide scanning to systematically find silencers in human genome. Results suggest that silencers are widespread on anchors of chromatin loops. In addition, enrichment analysis of transcription factor binding motif support our prediction results. As far as we can tell, this is the first attempt to incorporate chromatin structural information in finding silencers. All datasets and source codes of SilenceREIN have been deposited in a GitHub repository (https://github.com/JianHPan/SilenceREIN).
Financial Performance of Accountable Care Organizations: A 5-Year National Empirical Analysis

Goals: Of 513 accountable care organizations (ACOs) participating in the Medicare Shared Savings Program (MSSP) in 2020, 67% generated a positive shared savings of approximately $2.3 billion. This research aimed to examine their financial performance trends and drivers over time. Methods: The unit of analysis was the ACO in each year of the study period from 2016 to 2020. The dependent variable was the ACOs' total shared savings earned annually per beneficiary. The independent variables included ACO age, risk model, clinician staffing type, and provider type (hybrid, hospital-led, or physician-led). Covariates were the average risk score among beneficiaries, payer type, and calendar year. The Centers for Medicare & Medicaid Services (CMS) public use files (PUFs) and a commercial healthcare data aggregator were the data sources. Results: ACOs' earned shared savings grew annually by 35%, while the proportions of ACOs with positive shared savings grew by 21%. For 1-year increase in ACO age, an additional $0.57 of shared savings per beneficiary was observed. ACOs with two-sided risk contracting were associated with an average marginal increase of $109 in shared savings per beneficiary compared to ACOs with one-sided risk contracting. Primary care physicians were associated with the greatest increase in earned shared savings per beneficiary. In contrast, nurse practitioners/physician assistants/clinical nurse specialists were associated with a reduction in earned shared savings. Under a one-sided risk model, hospital-led ACOs were associated with $18 higher average shared savings earning per beneficiary compared to hybrid ACOs, while physician-led ACOs were associated with lower average saved shared earnings per beneficiary at –$2 compared to hybrid ACOs. Provider-type results were not statistically significant at the 5% nominal level. No statistically significant differences were observed between provider types under a two-sided risk model. Practical Applications: For all ACO provider types, building broader primary care provider networks was correlated with positive financial results. Future research should examine whether ACOs are conducting specific preventive screenings for cancer or monitoring conditions such as diabetes, hypertension, heart disease, obesity, mental disorders, and joint disorders. Such studies may answer health policy and strategy questions about the effects of incentives for improved ACO performance in serving a healthier population.
Proper Indication of Decompressive Craniectomy for the Patients with Massive Brain Edema after Intra-arterial Thrombectomy

Objective Numerous studies have indicated that early decompressive craniectomy (DC) for patients with major infarction can be life-saving and enhance neurological outcomes. However, most of these studies were conducted by neurologists before the advent of intra-arterial thrombectomy (IA-Tx). This study aims to determine whether neurological status significantly impacts the final clinical outcome of patients who underwent DC following IA-Tx in major infarction. Methods This analysis included 67 patients with major anterior circulation major infarction who underwent DC after IA-Tx, with or without intravenous tissue plasminogen activator. We retrospectively reviewed the medical records, radiological findings, and compared the neurological outcomes based on the “surgical time window” and neurological status at the time of surgery. Results For patients treated with DC following IA-Tx, a Glasgow coma scale (GCS) score of 7 was the lowest score correlated with a favorable outcome (p=0.013). Favorable outcomes were significantly associated with successful recanalization after IA-Tx (p=0.001) and perfusion/diffusion (P/D)-mismatch evident on magnetic resonance imaging performed immediately prior to IA-Tx (p=0.007). However, the surgical time window (within 36 hours, p=0.389; within 48 hours, p=0.283) did not correlate with neurological outcomes. Conclusion To date, early DC surgery after major infarction is crucial for patient outcomes. However, this study suggests that the indication for DC following IA-Tx should include neurological status (GCS ≤7), as some patients treated with early DC without considering the neurological status may undergo unnecessary surgery. Recanalization of the occluded vessel and P/D-mismatch are important for long-term neurological outcomes.
Hybrid de novo genome assembly of the sexually dimorphic Lady Amherst’s pheasant

Abstract Pheasants are an important group of birds, valued for their economic benefit as poultry birds, game birds, and as ornamental species for their plumage. Lady Amherst’s pheasant Chrysolophus amherstiae is an ornamental species, valued for its elaborate and beautiful plumage. In this study, we present a high-quality de novo hybrid genome assembly of C. amherstiae. Previous attempts to sequence the genome of this species resulted in draft-level assemblies, which are not available in the public domain. Using a combination of Illumina short reads and Oxford Nanopore’s long-reads, we assembled a high-quality genome of N50 ~3.9 Mb and near complete BUSCO assessment. We observed a correlation between effective population size and past climatic conditions, with an increase in population size during the warm interglacial periods. We further observed significant fluctuations in genes involved with the immune system and visual perception. C. amherstiae is a highly dimorphic species, and significant fluctuations in gene families involved in immune response, visual perception, among others, suggesting a role of mate choice and sexual selection in the evolution and maintenance of exaggerated traits in the males.
Pleural Carcinoembryonic Antigen and Maximum Standardized Uptake Value as Predictive Indicators of Visceral Pleural Invasion in Clinical T1N0M0 Lung Adenocarcinoma

Background Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma. Methods A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group. Results ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14–7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90–14.50; p=0.001) were significant risk factors for VPI in the pleural contact group. Conclusion In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.
Effects of contextualized emotional conflict control on domain-general conflict control: fMRI evidence of neural network reconfiguration

Abstract Domain-general conflict control refers to the cognitive process in which individuals suppress task-irrelevant information and extract task-relevant information. It supports both effective implementation of cognitive conflict control and emotional conflict control. The present study employed functional magnetic resonance imaging and adopted an emotional valence conflict task and the arrow version of the flanker task to induce contextualized emotional conflicts and cognitive conflicts, respectively. The results from the conjunction analysis showed that the multitasking-related activity in the pre-supplementary motor area, bilateral dorsal premotor cortices, the left posterior intraparietal sulcus (IPS), the left anterior IPS and the right inferior occipital gyrus represents common subprocesses for emotional and cognitive conflict control, either in parallel or in close succession. These brain regions were used as nodes in the domain-general conflict control network. The results from the analyses on the brain network connectivity patterns revealed that emotional conflict control reconfigures the domain-general conflict control network in a connective way as evidenced by different communication and stronger connectivity among the domain-general conflict control network. Together, these findings offer the first empirical-based elaboration on the brain network underpinning emotional conflict control and how it reconfigures the domain-general conflict control network in interactive ways.
Relationship between the risk of falling and prescribed medication in community-dwelling elderly subjects.

Abstract Introduction: The riskof falling increases with age. A third of the population over 65 has one or more falls per year. Objetive: to know the relationship between drug prescription and falls in the elderly. Materials and Methods: a study was carried out through a community intervention in individuals ≥ 70 years of age. Results: The sample was composed of 249 participants, 160 women (64%), with a mean age of 74.47years (SD 5.33). During the 12 months prior to the study, themean of falls per person was 0.5 (SD 0.94), the mean of the risk factors was 2.73 (SD 1.4) and the mean of the medication prescribed was 4.2 (SD 3.0). The percentage of the reduction of falls after the study was 12%. The amount of medication prescribed correlated with the incidence of falls before and after the study, r=0.193, p=0.002 y r2=0.170, p=0.009 respectively. Prior to the ,study, the individuals who were prescribed betablockers -and antidepressants, had a fall incidence of 0.74 (SD 1.14) and 1.22 (SD 1.09), respectively, however after the intervention there was no relationship between drug prescription and falls. Conclusions: the fall prevention community program was effective since it prevented the negative effects of medication on falls. An interdisciplinary community intervention reduces the global incidence of falls and the incidence of falls related to some specific medication.
Hypometria of saccadic eye movements to targets in rapid circular motion

Saccades to objects moving on a straight trajectory take the velocity of the object into account. However, it is not known whether saccades can compensate for curved trajectories, nor is it known how they are affected by high target speeds. In Experiment 1, participants made a saccade in a delayed saccade task to a target moving in a circular trajectory. Surprisingly, saccades to high-speed moving targets were severely hypometric, with gains of only ∼55% for trajectories of the largest angular speed (2 revolutions per second) and eccentricity (12°). They also had unusually low peak velocities. In Experiment 2, the target jumped along a circular path around a central fixation point. Hypometria was still severe, except for very large jumps. Experiment 3 was like Experiment 1, except that a landmark was positioned on the trajectory of the target, and participants were instructed to make a saccade to the landmark or to its memorized location. This ameliorated hypometria considerably. Given the delayed nature of the tasks of Experiments 1 and 2, participants had considerable time to program a voluntary saccade to a location on the trajectory, if not to the rapidly moving target itself. Nevertheless, the abnormal saccade properties indicate that motor programming was compromised. These results indicate that motor output can be inextricably bound to sensory input to its detriment, even during a highly voluntary motor act; that apparent motion can produce this behavior; and that such abnormal saccades can be “rescued” by the presence of a stable visual goal.
Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus

Background Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.
Exploring Regional Disparities in Heart Failure Epidemiology and Outcomes: A Comprehensive Study Across Geographical Regions in Türkiye

Background: Heart failure (HF) is a common condition that affects 1-3% of the general population. Its prevalence exhibits notable international and intranational disparities, partly explained by socioeconomic status, religion, ethnic diversity, and geographic factors. A comprehensive understanding of the epidemiological symptoms of HF in different regions of Türkiye has yet to be revealed. Aims: To examine epidemiological data from 2016 to 2022, focusing on crucial patient characteristics and geographical regions, to determine the incidence and prevalence of HF in Türkiye across seven diverse geographical regions. Study Design: A nationwide population-based retrospective cohort study. Methods: The comprehensive National Electronic Database of the Turkish Ministry of Health was used in this study to obtain data that covers the whole Turkish population from January 1, 2016, to December 31, 2022. The International Classification of Diseases-10 (ICD-10) codes were used to identify adults with HF (n = 2,701,099) and associated comorbidities. Türkiye is divided into seven geographically distinct regions. Epidemiological characteristics and survival data of these regions were analyzed separately. All-cause mortality was set as the primary outcome. Results: In , the total estimated prevalence of adult patients with HF is 2.939%, ranging from 2.442% in Southeastern Anatolia to 4.382% in the Black Sea Region. Except for the Eastern Anatolia Region, the three most often reported comorbidities were hypertension, dyslipidemia, and anxiety disorders. The rates of prescribing guideline-directed medical therapy (GDMT) for HF and other medications varied significantly. GDMT prescription rates were lowest in the Eastern Anatolia Region (82.6% for beta-blockers, 48.7% for RASi, 31.8% for mineralocorticoid receptor antagonists, and 9.4% for SGLT2i). The Mediterranean and Aegean regions had the highest median N-terminal brain natriuretic peptide (NT-proBNP) levels of 1,990,0 pg/ml (518.0-6,636,0) and 1,441,0 pg/ml (363.0-5,000,0), respectively. From 2016 to 2022, 915,897 (33.9%) of 2,701,099 patients died. The Eastern Anatolia Region had the lowest all-cause mortality rate of 26.5%, whereas the Black Sea Region had the highest all-cause mortality rate of 35.3%. Conclusion: Our real-world analysis revealed geographic disparities in HF characteristics, such as decreased mortality in socioeconomically challenged regions. Higher stress susceptibility in developed regions may increase the likelihood of adverse outcomes.
Homozygous Loss of CDKN2 in Primary Cutaneous CD8(+) Lymphoma NOS

Abstract: Primary cutaneous acral CD8(+) lymphoma (AL) has been accepted as primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder in the revised WHO and updated WHO-EORTC lymphoma classifications. Commonly arising on the ears and comprising a clonal cytotoxic CD8+ T-cell infiltrate, almost all cases follow an indolent clinical course. A single aggressive case reported in the literature had a deletion at the CDKN2 locus at 9p21. We report an atypical CD8+ T-cell proliferation arising on the chest of an elderly man who had some similarities to AL but with a very high proliferation rate, absent p16 protein expression, and homozygous loss of the CDKN2 locus using FISH analysis. A diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL NOS) was preferred. Analyses of 4 cases of AL demonstrated often low p16 protein expression but intact CDKN2 loci. This case raises the problems of the boundaries between AL and PTCL NOS, and a possible role in the loss of p16 function in pathogenesis.
4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats

Methods Thirty-five rats were randomly divided into five groups: sham, IR, IR + 100 mg kg−1 PBA, IR + 200 mg kg−1 PBA, and IR + placebo. After sacrifice, we assessed serum biochemical variables, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS). The expression levels of Abcc (2 and 5), Abcg2, Abcf2, Ire1-α, and Perk genes were measured with a quantitative real-time polymerase chain reaction. Results Serum biochemical variables, MPO, MDA, TAS, and TOS levels of the PBA groups (especially in the low dose group) were lower than in the IR and placebo group (P < 0.05). Histological tissue damage in the IR group was more severe than in the PBA groups. Ire1-α and Perk expression levels were significantly lower in the PBA groups than the IR group (P < 0.001). Abcc (2 and 5) and Abcg2 expression levels were significantly lower in the IR group than in the sham and PBA groups (P < 0.001, P < 0.035, and P < 0.009, respectively). Conclusions The use of PBA significantly positively affected IR injury, which makes PBA a candidate treatment to reduce liver IR.