Miracle-dz/UniFAR-FTUs huggingface dataset:
Spending and quality after three years of Medicare’s bundled payments for medical conditions: quasi-experimental difference-in-differences study

Abstract Objective To evaluate whether longer term participation in the bundled payments for care initiative (BPCI) for medical conditions in the United States, which held hospitals financially accountable for all spending during an episode of care from hospital admission to 90 days after discharge, was associated with changes in spending, mortality, or health service use. Design Quasi-experimental difference-in-differences analysis. Setting US hospitals participating in bundled payments for acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease (COPD), or pneumonia, and propensity score matched to non-participating hospitals. Participants 238 hospitals participating in the Bundled Payments for Care Improvement initiative (BPCI) and 1415 non-BPCI hospitals. 226 BPCI hospitals were matched to 700 non-BPCI hospitals. Main outcome measures Primary outcomes were total spending on episodes and death 90 days after discharge. Secondary outcomes included spending and use by type of post-acute care. BPCI and non-BPCI hospitals were compared by patient, hospital, and hospital market characteristics. Market characteristics included population size, competitiveness, and post-acute bed supply. Results In the 226 BPCI hospitals, episodes of care totaled 261 163 in the baseline period and 93 562 in the treatment period compared with 211 208 and 78 643 in the 700 matched non-BPCI hospitals, respectively, with small differences in hospital and market characteristics after matching. Differing trends were seen for some patient characteristics (eg, mean age change −0.3 years at BPCI hospitals v non- BPCI hospitals, P<0.001). In the adjusted analysis, participation in BPCI was associated with a decrease in total episode spending (−1.2%, 95% confidence interval −2.3% to −0.2%). Spending on care at skilled nursing facilities decreased (−6.3%, −10.0% to −2.5%) owing to a reduced number of facility days (−6.2%, −9.8% to −2.6%), and home health spending increased (4.4%, 1.4% to 7.5%). Mortality at 90 days did not change (−0.1 percentage points, 95% confidence interval −0.5 to 0.2 percentage points). Conclusions In this longer term evaluation of a large national programme on medical bundled payments in the US, participation in bundles for four common medical conditions was associated with savings at three years. The savings were generated by practice changes that decreased use of high intensity care after hospital discharge without affecting quality, which also suggests that bundles for medical conditions could require multiple years before changes in savings and practice emerge.
Image-Guided Pediatric Surgery Using Indocyanine Green (ICG) Fluorescence in Laparoscopic and Robotic Surgery

Background: Indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) has been recently adopted in pediatric minimally invasive surgery (MIS). This study aimed to report our experience with ICG-guided NIRF in pediatric laparoscopy and robotics and evaluate its usefulness and technique of application in different pediatric pathologies. Methods: ICG technology was adopted in 76 laparoscopic and/or robotic procedures accomplished in a single division of pediatric surgery over a 24-month period (January 2018–2020): 40 (37 laparoscopic, three robotic) left varicocelectomies with intra-operative lymphography; 13 (10 laparoscopic, three robotic) renal procedures: seven partial nephrectomies, three nephrectomies, and three renal cyst deroofings; 12 laparoscopic cholecystectomies; five robotic tumor excisions; three laparoscopic abdominal lymphoma excisions; three thoracoscopic procedures: two lobectomies and one lymph node biopsy for suspected lymphoma. The ICG solution was administered into a peripheral vein in all indications except for varicocele and lymphoma in which it was, respectively, injected into the testis body or the target organ. Regarding the timing of the administration, the ICG solution was administered intra-operatively in all indications except for cholecystectomy in which the ICG injection was performed 15–18 h before surgery. Results: No conversions to open or laparoscopy occurred. No adverse and allergic reactions to ICG or other postoperative complications were reported. Conclusions: Based upon our 2 year experience, we believe that ICG-guided NIRF is a very useful tool in pediatric MIS to perform a true imaged-guided surgery, allowing an easier identification of anatomic structures and an easier surgical performance in difficult cases. The most common applications in pediatric surgery include varicocele repair, difficult cholecystectomy, partial nephrectomy, lymphoma, and tumors excision but further indications will be soon discovered. ICG-enhanced fluorescence was technically easy to apply and safe for the patient reporting no adverse reactions to the product. The main limitation is represented by the specific equipment needed to apply ICG-guided NIRF in laparoscopic procedures, that is not available in all centers whereas the ICG system Firefly® is already integrated into the robotic platform.
CARMAL Is a Long Non-coding RNA Locus That Regulates MFGE8 Expression

Genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) most of them located in non-protein coding regions of the genome. One such locus is the CAD Associated Region between MFGE8 and ABHD2 (CARMA), a ∼18 kb haplotype that was recently shown to regulate vicinal protein coding genes. Here, we further investigate the region by examining a long non-coding RNA gene locus (CARMAL/RP11-326A19.4/AC013565) abutting the CARMA region. Expression-genotype correlation analyses of public databases indicate that CARMAL levels are influenced by CAD associated variants suggesting that it might have cardioprotective functions. We found CARMAL to be stably expressed at relatively low levels and enriched in the cytosol. CARMAL function was investigated by several gene targeting approaches in HEK293T: inactive CRISPR fusion proteins, antisense, overexpression and inactivation by CRISPR-mediated knock-out. Modest increases in CARMAL (3–4×) obtained via CRISPRa using distinct single-guided RNAs did not result in consistent transcriptome effects. By contrast, CARMAL deletion or reduced CARMAL expression via CRISPRi increased MFGE8 levels, suggesting that CARMAL is contributing to reduce MFGE8 expression under basal conditions. While future investigations are required to clarify the mechanism(s) by which CARMAL acts on MFGE8, integrative bioinformatic analyses of the transcriptome of CARMAL deleted cells suggest that this locus may also be involved in leucine metabolism, splicing, transcriptional regulation and Shwachman-Bodian-Diamond syndrome protein function.
Insights Into First Grade Students' Development of Conceptual Numerical Understanding as Drawn From Progression-Based Assessments

Early numeracy has been found to be one of the strongest predictors for later success in learning. Equipping children with a sound conceptual numerical understanding should therefore be a focus of early primary school mathematics. Assessments that are aligned to empirically validated learning progressions can support teachers to understand their students learning better and target instruction accordingly. This study examines numeracy learning of 101 first grade students over the course of one school year using progression-based assessments. Findings show that the students' performance increased significantly over time and that the initial conceptual numerical understanding had a positive effect on the students' learning progress as well as their end of school year performance. Analyzing the performance data based on the levels of the underlying developmental model uncovered an increasing elaboration of conceptual numerical understanding over time, but also individual differences within this process that need to be addressed through targeted intervention.
The Mediating Role of Catastrophizing in the Relationship Between Emotional Clarity and Posttraumatic Stress Symptoms Among Earthquake Survivors in Korea: A Cross-Sectional Study

Difficulties in emotion regulation reportedly contribute to the development and maintenance of PTSD following exposure to natural disasters. Based on the extended process model of emotion regulation, the present study hypothesized that maladaptive emotion regulation strategies will mediate the relationship between emotional clarity and posttraumatic stress symptoms in a sample of earthquake survivors. A total of 195 adult residents of Gyeongju and Pohang, southeastern coastal cities in Korea, who had experienced recent earthquakes participated in an online survey study. They completed questionnaires assessing emotional clarity, emotion regulation, and posttraumatic stress symptoms a year and 10 months after the Gyeongju earthquake and 7 months after the Pohang earthquake. Bootstrapping procedures were used to test for a mediation effect. The results suggest that emotional clarity was indirectly associated with posttraumatic stress symptoms through maladaptive emotion regulation strategies, especially catastrophizing. The findings suggest that individuals with low emotional clarity tend to use maladaptive strategies, catastrophizing in particular, which may contribute to posttraumatic stress symptoms. This may reflect the mechanism underlying emotional clarity and offer suggestions for target of treatment in the management of long-term psychological difficulties in earthquake survivors. Replication of the current results in a sample of patients diagnosed with PTSD is necessary to better understand the development and progression of the disorder, as well as effective interventions for PTSD.
EEG Channel-Selection Method for Epileptic-Seizure Classification Based on Multi-Objective Optimization

We present a multi-objective optimization method for electroencephalographic (EEG) channel selection based on the non-dominated sorting genetic algorithm (NSGA) for epileptic-seizure classification. We tested the method on EEG data of 24 patients from the CHB-MIT public dataset. The procedure starts by decomposing the EEG data from each channel into different frequency bands using the empirical mode decomposition (EMD) or the discrete wavelet transform (DWT), and then for each sub-band four features are extracted; two energy values and two fractal dimension values. The obtained feature vectors are then iteratively tested for solving two unconstrained objectives by NSGA-II or NSGA-III; to maximize classification accuracy and to reduce the number of EEG channels required for epileptic seizure classification. Our results have shown accuracies of up to 1.00 with only one EEG channel. Interestingly, when using all the EEG channels available, lower accuracies were achieved compared to the case when EEG channels were selected by NSGA-II or NSGA-III; i.e., in patient 19 we obtained an accuracy of 0.95 using all the channels and 0.975 using only two channels selected by NSGA-III. The results obtained are encouraging and it has been shown that it is possible to classify epileptic seizures using a few electrodes, which provide evidence for the future development of portable EEG seizure detection devices.
Altered White Matter Structural Network in Frontal and Temporal Lobe Epilepsy: A Graph-Theoretical Study

Temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) are the largest subgroup of partial epilepsy, and focal cortical dysplasias (FCDs) are highly epileptogenic brain lesions and are a frequent cause for antiepileptic drug (AED)-resistant focal epilepsies that mostly occur in the temporal and frontal lobes. We performed a graph-theoretical study based on the diffusion tensor imaging (DTI) data of patients with FLE or TLE caused by FCDs or lesions with high suspicion of FCDs and evaluated their cognitive function by the Chinese version of the Montreal Cognitive Assessment-Basic (MoCA-BC). The construction of the white matter structural network and graph-theoretical analysis was performed by Pipeline for Analysing Brain Diffusion Images (PANDA) and Graph-theoretical Network Analysis (GRETNA). We used the nonparametric analysis of covariance to compare the differences in diffusion metrics, network attributes and nodal attributes among FLE, TLE, and healthy control (HC) groups and then performed post hoc pairwise comparisons. Nonparametric Spearman partial correlation analysis was performed to analyse the correlation of network attributes with the age of onset, duration of disease, and MoCA-BC scores in patients with FLE and TLE. The results showed that the white matter structural network in patients with FLE and TLE was impaired in a more extensive set of regions than the FCD location. The similarities in white matter alterations between FLE and TLE suggested that their epileptogenic network might affect the fronto-temporal white matter tracts and thalamo-occipital connections, which might be responsible for the overlapping cognitive deficits in FLE and TLE. The white matter impairments in patients with FLE were more severe than those in patients with TLE, which might be explained by more affected nodes in the areas of DMN in patients with FLE.
SRC-1 Knockout Exerts No Effect on Amyloid β Deposition in APP/PS1 Mice

Steroid receptor coactivator 1 (SRC-1) is the key coactivator because of its transcriptional activity. Previous studies have shown that SRC-1 is abundant in the hippocampus and has been implicated in cognition. SRC-1 is also related to some major risk factors for Alzheimer’s disease (AD), such as a decline in estrogen and aging, however, whether SRC-1 is involved in the pathogenesis of AD remains unclear. In this study, we established SRC-1 knockout in AD mice by cross breeding SRC-1−/− mutant mice with APP/PS1 transgenic mice, and investigated the expression of some synaptic proteins, the amyloid β (Aβ) deposition, and activation of astrocytes and microglia in the hippocampus of APP/PS1×SRC-1−/− mice. The results showed that SRC-1 knockout neither affects the Aβ plaque and activation of glia, nor changes the expression of synaptic proteins in AD model mice. The above results suggest that the complete deletion of SRC-1 in the embryo exerts no effect on the pathogenesis of APP/PS1 mice. Nevertheless, this study could not eliminate the possible role of SRC-1 in the development of AD due to the lack of observation of other events in AD such as tau hyperphosphorylation and the limitation of the animal model employed.
Higher Bioavailability of Calcium in Chickens With a Novel In-Feed Pharmaceutical Formulation

Egg production and egg shell quality decrease toward the end of the first laying cycle in hens (approximately by week 80). Even so, farmers often choose to work a second cycle with them. Defective egg shell production has been mainly linked to a decrease in gastrointestinal absorption of calcium. Here we studied pharmaceutically-designed modified-release small pellets (FOLAs) containing calcium to improve calcium bioavailability (F). The influence of FOLA alone or with capsicum-oleoresin was studied in a total of 400 Bovans-White hens randomly divided into four groups of 20 laying hens each and with five replicates per group (n = 100) as follows: (1) control group (GC) receiving a diet containing basal levels of 4.1% of calcium-carbonate; (2) group GF treated as GC but with the same dose of calcium-carbonate in FOLA; (3) group GFc5 was treated as GF but with 6 ppm of capsicum-oleoresin (500,000 Scoville Heat Units [SHU]); and (4) group GFc10 treated as GFc5 but with 1,000,000 SHU capsicum-oleoresin. Plasma concentrations of calcium were determined during 5 days at predetermined times sampling more often on days 1 and 5 for blood plasma kinetics of calcium. Relative bioavailability (Fr) values based on the area under the serum calcium concentration vs. time curve (AUC) were obtained and compared to GC. The AUC was statistically different among all groups (P < 0.5), but the GFc10 had the greatest Fr (194%), with serum calcium concentrations ranging from 25.37 to 31.2 μg/dL. Calcium residence time (RT) between GC and GF showed no statistical differences while GFc5 and GFc10 had statistically superior RT values. Simultaneously, the number of shell-less eggs per group and their thickness was evaluated by utilizing the same groups but with 150 hens per group on 6 days. Shell-less eggs decreased to zero in Group GFc10 and produced eggs with the greatest shell thickness from day 2 onwards. The inclusion of calcium-carbonate in the pharmaceutical form FOLA induced higher serum calcium concentrations (GF, GFc5, and GFc10) particularly during the night-phase of the hen's cycle—this coincides with the time at which egg shell formation occurs.
Synthesis and Biological Evaluation of the Anti-Melanogenesis Effect of Coumaric and Caffeic Acid-Conjugated Peptides in Human Melanocytes

Excessive pigmentation and reduced elasticity are the major skin problems that dermatologists and cosmetologists address. Compounds that inhibit melanin production might contribute to improving skin problems. In this study, we investigated whether coumaric acid- and caffeic acid-conjugated peptides might affect alpha-melanocyte stimulating hormone-induced melanin production, tyrosinase activity, and melanin synthesis-related gene expression in SK-MEL-2 human melanoma cells. Coumaric acid and caffeic acid showed no significant cytotoxicity, and they inhibited melanin production. In addition, coumaric acid- and caffeic acid-conjugated peptides suppressed tyrosinase activity more than arbutin, a known tyrosinase inhibitor. Quantitative real-time PCR (qRT-PCR) results also showed that both peptides inhibited the expression of melanin synthesis-related genes, TYR, TYRP1, TYRP2, and MITF. In particular, among the nine conjugated peptides tested, caffeic acid linked to a Gly-Gly-Gly linker and conjugated to the tripeptide, ARP, showed the greatest inhibition of gene expression in the qRT-PCR analysis. These results suggested that the inhibition of melanin exerted by coumaric acid- and caffeic acid-conjugated peptides might provide important information for the development of pigmentation-related skin diseases and cosmetic products.
Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies

The mechanism of epithelial-mesenchymal transition (EMT) consists of the cellular phenotypic transition from epithelial to mesenchymal status. The cells exhibiting EMT exist in cancer stem cell (CSC) population, which is involved in drug resistance. CSCs demonstrating EMT feature remain after cancer treatment, which leads to drug resistance, recurrence, metastasis and malignancy of cancer. In this context, the recent advance of nanotechnology in the medical application has ascended the possibility to target CSCs using nanomedicines. In this review article, we focused on the mechanism of CSCs and EMT, especially into the signaling pathways in EMT, regulation of EMT and CSCs by microRNAs and nanomedicine-based approaches to target CSCs.
Novel Histone Deacetylase Inhibitors and HIV-1 Latency-Reversing Agents Identified by Large-Scale Virtual Screening

Current antiretroviral therapies used for HIV management do not target latent viral reservoirs in humans. The experimental “shock-and-kill” therapeutic approach involves use of latency-reversal agents (LRAs) that reactivate HIV expression in reservoir-containing cells, followed by infected cell elimination through viral or host immune cytopathic effects. Several LRAs that function as histone deacetylase (HDAC) inhibitors are reported to reverse HIV latency in cells and in clinical trials; however, none to date have consistently reduced viral reservoirs in humans, prompting a need to identify new LRAs. Toward this goal, we describe here a virtual screening (VS) approach which uses 14 reported HDAC inhibitors to probe PubChem and identifies 60 LRA candidates. We then show that four screening “hits” including (S)-N-Hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide (compound 15), N-(4-Aminophenyl)heptanamide (16), N-[4-(Heptanoylamino)phenyl]heptanamide (17), and 4-(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-N-(2-hydroxyethyl)butanamide (18) inhibit HDAC activity and/or reverse HIV latency in vitro. This study demonstrates and supports that VS-based approaches can readily identify novel HDAC inhibitors and LRAs, which in turn may help toward inhibitor design and chemical optimization efforts for improved HIV shock-and-kill-based efforts.
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease

Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.
Generalization of the Cover Pebbling Number for Networks

Pebbling can be viewed as a model of resource transportation for networks. We use a graph to denote the network. A pebbling move on a graph consists of the removal of two pebbles from a vertex and the placement of one pebble on an adjacent vertex. The t-pebbling number of a graph G is the minimum number of pebbles so that we can move t pebbles on each vertex of G regardless of the original distribution of pebbles. Let ω be a positive function on V(G); the ω-cover pebbling number of a graph G is the minimum number of pebbles so that we can reach a distribution with at least ω(v) pebbles on v for all v ∈ V(G). In this paper, we give the ω-cover pebbling number of trees for nonnegative function ω, which generalized the t-pebbling number and the traditional weighted cover pebbling number of trees.