Miracle-dz/UniFAR-FTUs huggingface dataset:
The correlation between serum growth differentiation factor 15 and malnutrition in patients with end-stage kidney disease on hemodialysis

Abstract Objective Malnutrition commonly occurs in patients undergoing maintenance hemodialysis. Early detection of malnutrition could allow early interventions to prevent later complications. At present, there are not many biomarkers with high predictive value of end-stage kidney disease (ESKD)-related malnutrition, especially for early malnutrition in hemodialysis patients, which needs more in-depth research. Therefore, we performed a cross-sectional study on 97 patients to identify biomarkers for malnutrition in hemodialysis patients. Research Methods & Procedures 7-point subjective global assessment (SGA) was applied to evaluate the nutritional status of patients on hemodialysis. Serum levels of growth differentiation factor 15 (GDF15), albumin, pre-albumin, c-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), hemoglobin, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol were detected before hemodialysis. Logistic analysis and linear regression were used to analyze the association between GDF15 levels and the SGA score after adjustment for basic characteristics and laboratory findings. Results Among the 97 patients on hemodialysis, 51 had malnutrition (SGA < 6). There was no difference between the malnourished and well nourished (SGA ≥ 6) groups for dialysis duration, cholesterol, CRP, TNF-α, and hemoglobin. The malnutrition group had significantly lower grip strength (p < 0.05). GDF15 levels correlated negatively with the SGA score after adjustment for possible confounding factors [rho (male) = -0.312, rho(female)= -0.437;P(male) = 0.0181, P(female) = 0.005], and might contribute to the malnutritional status, the AUCs of GDF15 for malnutrition was 0.697 (p = 0.011) in male and 0.828 (p < 0.001) in female. Conclusions GDF15 is associated with malnutrition according to the SGA score in patients with ESKD on hemodialysis, suggesting that GDF15 might be involved in the pathogenesis of malnutrition patients with ESKD in this setting. Furthermore, GDF15 is likely to be a potential diagnostic biomarker for malnutrition according to the SGA score.
Early intervention in psychosis services: A systematic review and narrative synthesis of barriers and facilitators to seeking access

Abstract Background The duration of untreated psychosis (DUP) continues to be a global priority. Early intervention services were established to reduce treatment delays but have had limited impact. This systematic review examines barriers and facilitators to seeking access to these services, to identify targets for service level change. Methods We conducted a systematic review of relevant databases (PsychINFO, MEDLINE, CINAHL, and PsychARTICLES) using pre-defined search terms for psychosis, early intervention, and barriers and facilitators. Given the majority of qualitative studies, a thematic synthesis rather than meta-analysis was indicated. Results The search yielded 10 studies. Mental health stigma and discrimination predict DUP, compounded by structural barriers which limit the impact of early intervention services on timely access to recommended treatments. Synthesis of the qualitative studies generated three themes: knowledge, relationships, and stigma. Lack of knowledge, absence of supportive relationships (social and professional), and self-stigma constitute significant barriers to seeking access to early intervention services. Conclusions This is the first review of the barriers and facilitators to seeking access to early intervention services. The findings highlight public health and secondary care service targets to expedite access to recommended treatments and thereby reduce the DUP.
Younger and older adults’ memory of past feelings surrounding an election

ABSTRACT People often misremember their past feelings, especially when recalling their prior mood as opposed to their specific emotions in response to events. A previous study also found that the direction of memory errors varies based on feeling type; younger adults overestimated the intensity of prior moods but underestimated the intensity of prior event-specific emotions. This study aimed to replicate these patterns and test whether they vary with age. In doing so, we also tested whether an age-related positivity effect would emerge, such that older adults would be relatively more likely to overestimate past positive feelings and underestimate past negative feelings. Using a sample of American voters, who reported their feelings following the 2020 United States presidential election, we found that both younger and older adults subsequently overestimated the intensity of their past mood in the week following the election but were relatively accurate in recalling the intensity of their prior emotions about the election result. Unexpectedly, among election losers, we also observed an age-related negativity effect in recall for prior mood. When faced with negative real-world events, older adults may not show the same positivity biases that are observed in lab studies.
Lipin‐2 regulates the antiviral and anti‐inflammatory responses to interferon

Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin‐2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT‐1‐dependent manner. Lipin‐2 inhibits viral replication both in vitro and in vivo. Moreover, lipin‐2 also acts as a regulator of inflammation in a viral context by reducing the signaling through TLR3 and the generation of ROS and release of mtDNA that ultimately activate the NLRP3 inflammasome. Inhibitors of mtDNA release from mitochondria restrict IL‐1β production in lipin‐2‐deficient animals in a model of viral infection. Finally, analyses of databases from COVID‐19 patients show that LPIN2 expression levels negatively correlate with the severity of the disease. Overall, these results uncover novel regulatory mechanisms of the IFN response driven by lipin‐2 and open new perspectives for the future management of patients with LPIN2 mutations.
Novel Size‐Based High‐Density Lipoprotein Subspecies and Incident Vascular Events

Background High‐density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size‐based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size‐based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size‐based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi‐Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow‐up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size‐based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.
Extracellular Vesicles Released by Lactobacillus paracasei Mitigate Stress-induced Transcriptional Changes and Depression-like Behavior in Mice

Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of “responses to stress or steroid hormones”, “histone modification”, and “regulating MAPK signaling pathways”. While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.
Clinical and Cognitive Features of Attention Deficit Hyperactivity Disorder with Intellectual Giftedness: A Systematic Review

ABSTRACT A systematic review was carried out on publications from the last 15 years that have studied the effect of intellectual giftedness, defined as IQ > 115, on the clinical and cognitive features of ADHD. Studies indicate that about 15% of people with high IQ meet ADHD criteria. IQ has shown no effect on the pharmacological treatment, and comorbidity does not differ from that of other children with ADHD. High IQ-ADHD, compared to average IQ-ADHD, tends to show less severity in cognitive and behavioral symptoms, as well as a better prognosis; however high IQ may mask ADHD symptoms delaying diagnosis and treatment.
Open MoA: revealing the mechanism of action (MoA) based on network topology and hierarchy

Abstract Motivation Many approaches in systems biology have been applied in drug repositioning due to the increased availability of the omics data and computational biology tools. Using a multi-omics integrated network, which contains information of various biological interactions, could offer a more comprehensive inspective and interpretation for the drug mechanism of action (MoA). Results We developed a computational pipeline for dissecting the hidden MoAs of drugs (Open MoA). Our pipeline computes confidence scores to edges that represent connections between genes/proteins in the integrated network. The interactions showing the highest confidence score could indicate potential drug targets and infer the underlying molecular MoAs. Open MoA was also validated by testing some well-established targets. Additionally, we applied Open MoA to reveal the MoA of a repositioned drug (JNK-IN-5A) that modulates the PKLR expression in HepG2 cells and found STAT1 is the key transcription factor. Overall, Open MoA represents a first-generation tool that could be utilized for predicting the potential MoA of repurposed drugs and dissecting de novo targets for developing effective treatments. Availability and implementation Source code is available at https://github.com/XinmengLiao/Open_MoA.
Machine Learning in Spine Surgery: A Narrative Review

Artificial intelligence and machine learning (ML) can offer revolutionary advances in their application to the field of spine surgery. Within the past 5 years, novel applications of ML have assisted in surgical decision-making, intraoperative imaging and navigation, and optimization of clinical outcomes. ML has the capacity to address many different clinical needs and improve diagnostic and surgical techniques. This review will discuss current applications of ML in the context of spine surgery by breaking down its implementation preoperatively, intraoperatively, and postoperatively. Ethical considerations to ML and challenges in ML implementation must be addressed to maximally benefit patients, spine surgeons, and the healthcare system. Areas for future research in augmented reality and mixed reality, along with limitations in generalizability and bias, will also be highlighted.
Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction: Cost-Effectiveness Analysis of the REVIVED-BCIS2 Trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom. REGISTRATION: URL: https://www.clinicaltrials. gov; Unique identifier: NCT01920048.
A Novel Riboflavin Formulation for Corneal Delivery Without Damaging Epithelial Cells

Purpose This study aimed to evaluate the trans-epithelial permeability enhancement and cell damage caused by a novel riboflavin composition for corneal delivery. Methods We developed a trans-epithelial formulation of riboflavin for corneal delivery using 1,2-dioleoyl-3-dimethylammonium-propane (DODAP) and isostearic acid (ISA). The permeation enhancement was evaluated using an in vitro corneal epithelial cell culture system by measuring the amount of transferred riboflavin with high-performance liquid chromatography. Riboflavin permeation of MedioCROSS TE, a commercially available riboflavin formulation containing benzalkonium chloride, was also evaluated and compared to that of the DODAP/ISA formulation by changing the riboflavin concentration. The trans-epithelial electrical resistance (TEER) was measured after exposure to the samples in an in vitro corneal epithelial cell culture system to assess cytotoxicity. Results The DODAP/ISA formulation demonstrated greater permeation when used together than when each component was used individually. The permeation enhancement effect of the DODAP/ISA formulation was almost the same as that of MedioCROSS TE. However, when a 10-fold higher riboflavin concentration was used in the DODAP/ISA formulation, the permeation enhancement effect surpassed that of MedioCROSS TE. After 24 hours of exposure, the TEER of the DODAP/ISA formulation was higher than that of MedioCROSS TE, indicating that the DODAP/ISA formulation was less cytotoxic than MedioCROSS TE. Conclusions This study indicated that the DODAP/ISA formulation could serve as a less cytotoxic alternative to MedioCROSS TE. Further studies are required to determine the clinical efficacy and safety of the DODAP/ISA formulation in vivo. Translational Relevance This study may provide alternative procedures for corneal collagen crosslinking with less of a cytotoxic effect on corneal epithelial cells.
On the use of the Norwegian Geotechnical Institute's prototype seabed-coupled shear wave vibrator for shallow soil characterization – I. Acquisition and processing of multimodal surface waves

SUMMARY Pure shear wave data are only very rarely acquired for offshore site investigations and exploration. Here, we present details of a novel, seabed-coupled, shear wave vibrator and field data recorded by a densely populated, multicomponent ocean-bottom cable, to improve shallow soil characterization. The prototype shear wave vibrator uses vibroseis technology adopted for marine environments through its instalment on top of a suction anchor, assuring seabed coupling in combination with self-weight penetration. The prototype is depth rated to 1500 m water depth, and can be rotated while installed in the seabed. The philosophy is to acquire fully complementary seismic data to conventional P- and P-to-S-converted waves, in particular for 2-D profiling, VSP (vertical seismic profiling) or monitoring purposes, thereby exploiting advantages of shear waves over compressional waves for determining, for example, anisotropy, small-strain shear modulus and excess pore pressures/effective stress. The source was primarily designed for reservoir depths. However, significant energy is emitted as surface waves, which provide detailedgeotechnicalinformationthroughmappingofshearwavevelocitiesinpotentiallyhigh resolution of the upper soil units. To fully utilize pure shear wave content, a proper analysis of surface waves is paramount, due to the proximity of surface wave propagation speed with shear wave velocities. The experiment was carried out in the northern North Sea in 364 m water depth. Cable dragging was necessary to obtain close receiver spacing (2.5 m effective spacing), with total line length of 600 m. Frequency–waveform transforms reveal both Scholte and Love waves. Up to six surface wave modes are identified, that is, fundamental mode and several higher surface wave modes. The occurrence of these two different dispersive surface wave types with well-resolved higher modes allows for a unique analysis and inversion scheme for highresolution mapping of physical properties in the shallow subsurface as well as anisotropy, which is discussed in an accompanying paper. The data presented in this paper are thus a unique (long and densely populated receiver array allows for multimodal Love and Scholte surface waves from the marine environment) but challenging (marine operations) marine data set.
Effective Acquisition Protocol of Terrestrial Laser Scanning for Underwater Topography in a Steep Mountain Channel

For better risk management, detailed and quantitative measurement of channel and stream‐bed structure is required to understand and predict water and sediment flow in mountain channels. Our previous research demonstrated good performance of green‐wavelength Terrestrial laser scanning (TLS) for measurement of submerged stream‐bed in a steep mountain channel. This paper examines how the acquisition protocol of TLS affects the accuracy of data collected in the mountain channel. First, it was tested whether varying the scanner height, i.e., incident angle affects the data acquisition in terms of point density and accuracy in the pool unit of step‐pool channel. Then, the effect of varying the minimum point spacing on the derived Digital terrain model (DTM) was examined. It was also analyzed whether a combination of multiple TLS data acquired from different directions would improve the accuracy of data compared to data acquired by a single measurement. Furthermore, TLS data were acquired over a cascade unit of the channel and examined whether TLS is capable of capturing reliable underwater data. All the acquired underwater data by TLS were corrected for water refraction and validated using manual surveyed data. The results showed that the accuracy of derived DTM was improved when the scanner height was increased or data was acquired from multiple directions, however, acquiring denser point cloud with a minimum point spacing of 1 mm did not improve the accuracy of the data. Accuracy of TLS measurement in the cascade unit was considerably lower. Special consideration is required for this area.