Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic Value of D-Dimer and INR in Patients Suspected to Have Prosthetic Valve Dysfunction

Introduction Prosthetic valve dysfunction is a potentially critical complication of heart valve replacement. An easy and quickly applicable diagnostic procedure is required for recognizing the prosthetic valve dysfunction. The purpose of this study was to prospectively define the diagnostic value of D-dimer and INR level in predicting prosthetic valve dysfunction. Methods This cross-sectional study was performed in 70 patients suspected to have prosthetic valve dysfunction admitted to Imam Ali Hospital, affiliated with Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. Cinefluoroscopy, as the gold standard diagnostic test, was used for the diagnosis of prosthetic valve dysfunction in enrolled patients. Two milliliters of blood from each patient were taken into a tube containing sodium citrate anticoagulant. To evaluate D-dimer, the cutoff value was set at 500 ng/ml. Also, to evaluate international normalized ratio (INR), the cutoff value was set at 2. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the serum markers were used to describe predictive properties. Results Of 70 patients, 27 (38.6%) were male and 43 (61.4%) were female, and the mean age was 54.67±15.11 years (range, 18 to 80 years). Of 70 patients, 27 (38.6%) had prosthetic heart valve malfunction demonstrable by fluoroscopy, and 19 patients (27.1%) had D-dimer levels >500 ng/ml. Elevated D-dimer levels (>500 ng/ml) have been indicated to have sensitivity of 70.4%, and hence an NPV of 84.3%, specificity of 100%, PPV of 100%, NLR of 0.3, and the infinity value of PLR for predicting prosthetic valve dysfunction. There was a significant relationship between fluoroscopy and D-dimer test (P=0.001). A kappa coefficient value of 0.745 indicated a substantial agreement between D-dimer and fluoroscopy testing. Mixing test (combination of D-dimer and INR) showed to have 100% sensitivity, and hence a NPV of 69.8%, specificity of 69.8%, PPV of 51.8%, NLR of 1.41, and PLR of 1.44 for predicting prosthetic valve dysfunction. Conclusion D-dimer with moderate sensitivity and high specificity is an ideal marker for the diagnosis of prosthetic valve dysfunction in suspected patients. Enhanced plasma D-dimer level is not by itself diagnostic of a prosthetic valve dysfunction but may alert physicians to refer the patient for more detailed examination, preferably by fluoroscopy. Mixing test with 100% sensitivity can apply as a rule-out test.
The Influence of Exercise Intensity on Psychosocial Outcomes in Musculoskeletal Disorders: A Systematic Review

Context: Psychosocial parameters play an important role in the onset and persistence of chronic musculoskeletal disorders (CMSDs). Exercise therapy is a valuable therapeutic modality as part of CMSD rehabilitation. Hereby, exercise intensity is an important factor regarding changes in pain and disability in multiple CMSDs. However, the impact of exercise intensity on psychosocial outcomes remains poorly explored. Objective: To identify the effects of different modes of exercise intensity on psychosocial outcomes in persons with CMSDs. Data Sources: A systematic search was conducted up to November 2020 using the following databases: PubMed/MEDline, PEDro, Cochrane Library, and Web of Science. Study Selection: Studies reporting exercise therapy in CMSDs with a predefined display of exercise intensity and an evaluation of at least 1 psychosocial outcome were included. Study Design: Systematic review. Level of Evidence: Level 2a. Data Extraction: Data regarding demographics, exercise intensity, and psychosocial outcomes were included in a descriptive analysis. Methodological quality was assessed using the PEDro scale and Critical Appraisal Skills Programme (CASP) checklist. Results: A total of 22 studies, involving 985 participants (with fibromyalgia, chronic low back pain, knee osteoarthritis, psoriatic arthritis, and axial spondyloarthritis) were included (mean PEDro score = 5.77/10). The most common psychosocial outcomes were quality of life (QoL) (n = 15), depression (n = 10), and anxiety (n = 9). QoL improved at any exercise intensity in persons with fibromyalgia. However, persons with fibromyalgia benefit more from exercising at low to moderate intensity regarding anxiety and depression. In contrast, persons with chronic low back pain benefit more from exercising at a higher intensity regarding QoL, anxiety, and depression. Other CMSDs only showed limited or conflicting results regarding the value of certain exercise intensities. Conclusion: Psychosocial outcomes are influenced by the intensity of exercise therapy in fibromyalgia and chronic low back pain, but effects differ across other CMSDs. Future research is necessary to determine the exercise intensity that yields optimal exercise therapy outcomes in specific CMSDs.
Global chromosome rearrangement induced by CRISPR-Cas9 reshapes the genome and transcriptome of human cells

Abstract Chromosome rearrangement plays important roles in development, carcinogenesis and evolution. However, its mechanism and subsequent effects are not fully understood. Large-scale chromosome rearrangement has been performed in the simple eukaryote, wine yeast, but the relative research in mammalian cells remains at the level of individual chromosome rearrangement due to technical limitations. In this study, we used CRISPR-Cas9 to target the highly repetitive human endogenous retrotransposons, LINE-1 and Alu, resulting in a large number of DNA double-strand breaks in the chromosomes. While this operation killed the majority of the cells, we eventually obtained live cell groups. Karyotype analysis and genome re-sequencing proved that we have achieved global chromosome rearrangement (GCR) in human cells. The copy number variations of the GCR genomes showed typical patterns observed in tumor genomes. The ATAC-seq and RNA-seq further revealed that the epigenetic and transcriptomic landscapes were deeply reshaped by GCR. Gene expressions related to p53 pathway, DNA repair, cell cycle and apoptosis were greatly altered to facilitate the cell survival. Our study provided a new application of CRISPR-Cas9 and a practical approach for GCR in complex mammalian genomes.
Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms Using 68Ga-Pentixafor PET

Visual Abstract In recent years, molecular imaging addressing the C-X-C motif chemokine receptor 4 (CXCR4) has increasingly been used in various clinical settings. Here, we aimed to assess radiopharmaceutical uptake and image contrast to determine the most relevant clinical applications for CXCR4-directed imaging. We also investigated the impact of specific activity on scan contrast. Methods: Patients (n = 690) with a variety of neoplasms underwent a total of 777 PET/CT scans with 68Ga-Pentixafor, serving as the CXCR4-specific radioligand. A semiquantitative target lesion analysis was conducted (providing SUVmax and target-to-blood pool ratio [TBR], defined as SUVmax [from target lesion] divided by SUVmean [from blood pool]). The applied specific activity (in MBq/μg) was compared with semiquantitative assessments. Results: Of the 777 scans, 242 did not show discernible uptake in disease sites, leaving 535 PET scans (68.9%) for further analysis. Very high tracer uptake (SUVmax > 12) was found in multiple myeloma (n = 113), followed by adrenocortical carcinoma (n = 30), mantle cell lymphoma (n = 20), adrenocortical adenoma (n = 6), and small cell lung cancer (n = 12). Providing information on image contrast, comparable results for TBR were recorded, with TBR (>8) in multiple myeloma, mantle cell lymphoma, and acute lymphoblastoid leukemia (n = 6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUVmax or TBR (P ≥ 0.612). Conclusion: In this large cohort, 68Ga-Pentixafor demonstrated high image contrast in a variety of neoplasms, particularly for hematologic malignancies, small cell lung cancer, and adrenocortical neoplasms. The present analysis may provide a roadmap for detecting patients who may benefit from CXCR4-targeted therapies.
NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation

Here, Huth et al. investigated the role of components of the nonsense-mediated mRNA decay (NMD) pathway in regulating embryonic stem cell (ESC) differentiation, and show that NMD controls expression levels of the translation initiation factor Eif4a2 and its premature termination codon-encoding isoform (Eif4a2PTC). Their findings expose an intricate link between mRNA homeostasis and mTORC1 activity that must be maintained for normal dynamics of cell state transitions.
EEG Based Dynamic Functional Connectivity Analysis in Mental Workload Tasks With Different Types of Information

The accurate evaluation of operators’ mental workload in human-machine systems plays an important role in ensuring the correct execution of tasks and the safety of operators. However, the performance of cross-task mental workload evaluation based on physiological metrics remains unsatisfactory. To explore the changes in dynamic functional connectivity properties with varying mental workload in different tasks, four mental workload tasks with different types of information were designed and a newly proposed dynamic brain network analysis method based on EEG microstate was applied in this paper. Six microstate topographies labeled as Microstate A-F were obtained to describe the task-state EEG dynamics, which was highly consistent with previous studies. Dynamic brain network analysis revealed that 15 nodes and 68 pairs of connectivity from the Frontal-Parietal region were sensitive to mental workload in all four tasks, indicating that these nodal metrics had potential to effectively evaluate mental workload in the cross-task scenario. The characteristic path length of Microstate D brain network in both Theta and Alpha bands decreased whereas the global efficiency increased significantly when the mental workload became higher, suggesting that the cognitive control network of brain tended to have higher function integration property under high mental workload state. Furthermore, by using a SVM classifier, an averaged classification accuracy of 95.8% for within-task and 80.3% for cross-task mental workload discrimination were achieved. Results implies that it is feasible to evaluate the cross-task mental workload using the dynamic functional connectivity metrics under specific microstate, which provided a new insight for understanding the neural mechanism of mental workload with different types of information.
Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis

Abstract Aims People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF. Methods and results Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64–0.75, direct oral anticoagulant (DOAC) 0.42, 0.33–0.53; mild frailty: VKA 0.52, 0.50–0.54, DOAC 0.57, 0.52–0.63; moderate: VKA 0.54, 0.52–0.56, DOAC 0.57, 0.52–0.63; severe: VKA 0.48, 0.45–0.51, DOAC 0.58, 0.52–0.65], with cumulative incidence function effects greater for DOAC than VKA. Conclusion Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.
Life-Cycle Assessment of Highway Pavement Alternatives in Aspects of Economic, Environmental, and Social Performance

Life-Cycle Assessment of Highway Pavement Alternatives in Aspects of Economic, Environmental, and Social Performance. (August 2012) Zhuting Mao, B.S., Shanghai Normal University Co-Chairs of Advisory Committee, Dr. Kunhee Choi Dr. Edelmiro Escamilla Economic Input Output Life Cycle Assessment (EIO-LCA) provides economic transactions, environmental emissions, and energy use throughout a product’s life cycle based on a dollar amount of the product. A custom EIO-LCA model was conducted to compare three major rigid pavements of Jointed Plain Concrete Pavement (JPCP), Jointed Reinforced Concrete Pavement (JRCP), and Continuously Reinforced Concrete Pavement (CRCP) within the perspective of economic transactions, greenhouse gases, energy use, hazardous waste, toxic releases, water withdrawals, and transportation movements. The analysis results indicate that CRCP be the most cost-efficient and sustainable choice among the selected rigid pavement alternatives as it requires the lowest life-cycle cost and has the least unfavorable impact on environment when compared to the JPCP and JRCP. Potential improvements could be investigated for the processes of cement manufacturing, power generation and supply, ready-mix concrete manufacturing, and
Human discrimination and modeling of high-frequency complex tones shed light on the neural codes for pitch

Accurate pitch perception of harmonic complex tones is widely believed to rely on temporal fine structure information conveyed by the precise phase-locked responses of auditory-nerve fibers. However, accurate pitch perception remains possible even when spectrally resolved harmonics are presented at frequencies beyond the putative limits of neural phase locking, and it is unclear whether residual temporal information, or a coarser rate-place code, underlies this ability. We addressed this question by measuring human pitch discrimination at low and high frequencies for harmonic complex tones, presented either in isolation or in the presence of concurrent complex-tone maskers. We found that concurrent complex-tone maskers impaired performance at both low and high frequencies, although the impairment introduced by adding maskers at high frequencies relative to low frequencies differed between the tested masker types. We then combined simulated auditory-nerve responses to our stimuli with ideal-observer analysis to quantify the extent to which performance was limited by peripheral factors. We found that the worsening of both frequency discrimination and F0 discrimination at high frequencies could be well accounted for (in relative terms) by optimal decoding of all available information at the level of the auditory nerve. A Python package is provided to reproduce these results, and to simulate responses to acoustic stimuli from the three previously published models of the human auditory nerve used in our analyses.
Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure

Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure. This new analytical approach elucidates several differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3, and demonstrates the ability of tissue-level imaging and analysis to generate cell biological mechanistic insights into neural tube closure.
Spontaneous tumor regression following COVID-19 vaccination

Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up to 69% of patients following vaccination with RNA-based COVID-19 vaccines. Tumor regression can occur following an intense immune-inflammatory response and novel strategies to treat cancer rely on manipulating the host immune system. Here, we report spontaneous regression of metastatic salivary gland myoepithelial carcinoma in a patient who experienced grade 3 systemic reactogenicity, following vaccination with the mRNA-1273 COVID-19 vaccine. Histological and immunophenotypic inspection of the postvaccination lung biopsy specimens showed a massive inflammatory infiltrate with scant embedded tumor clusters (<5%). Highly multiplexed imaging mass cytometry showed that the postvaccination lung metastasis samples had remarkable immune cell infiltration, including CD4+ T cells, CD8+ T cells, natural killer cells, B cells, and dendritic cells, which contrasted with very low levels of these cells in the prevaccination primary tumor and lung metastasis samples. CT scans obtained 3, 6, and 9 months after the second vaccine dose demonstrated persistent tumor shrinkage (50%, 67%, and 73% reduction, respectively), suggesting that vaccination stimulated anticancer immunity. Insight: This case suggests that the mRNA-1273 COVID-19 vaccine stimulated anticancer immunity and tumor regression.
Bone Fragment Resorption and Clinical Outcomes of Traumatic Bony Bankart Lesion Treated With Arthroscopic Repair Versus Open Latarjet

Background: Bony Bankart lesions can perpetuate chronic anterior glenohumeral instability. When surgical treatment is pursued, several factors need to be considered to obtain optimal outcomes. Purpose: To (1) quantitatively describe patterns of bone fragment resorption and associated risk factors for developing glenoid bone loss (GBL) and (2) to compare clinical and radiological results of attritional bone loss treated with either the arthroscopic Bankart or the open Latarjet procedure. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis of prospectively collected data was conducted for patients who underwent arthroscopic stabilization (group A1, 10%-20% GBL; group A2, >20% GBL) or open Latarjet (group B, >10% GBL) for recurrent shoulder instability with bony Bankart lesion. Patient characteristics, number of dislocations, and Western Ontario Shoulder Instability Index (WOSI) scores were obtained. Pre- and postoperative computed tomography imaging was used to quantitatively describe patterns of bone fragment resorption. Results: A total of 120 consecutive patients (group A1, 40; group A2, 23; group B, 57) were included in the study, with a mean age of 25.6 years (range, 19-35 years). The average follow-up was 5.0 years for all groups (range, 4.83-5.16 years in group A1, 4.58-5.41 years in group A2, and 4.33-5.67 years in group B). The mean times between dislocation event and surgery were 12.8 months (range, 6-32 months) and 13.6 months (range, 6-38 months) for groups A and B, respectively. Redislocation rates were 7.5% in group A1 versus 13.0% in group A2, and only occurred in patients with ≥13.5% GBL. There were no redislocations for group B (0%). Patients had better WOSI scores in group B (234.1 ± 126.9) than in group A (576.1 ± 224.6) (P < .0001). In group A, smaller preoperative bone fragment size displayed a higher percentage of resorption after surgery (r = −0.64; P < .05). Conclusion: A significant inverse relationship exists between preoperative bone fragment size and percentage of postoperative resorption. Patients treated with arthroscopic bony Bankart repair who had final GBL ≥13.5% had worse outcomes. When planned GBL approaches 13.5% in high-demand patients, a smaller fragment size can result in worse clinical outcomes because of resorption. In these cases, choosing the open Latarjet procedure leads to better clinical results.
Can listening provide a useful clinical estimate of low vision reading parameters?

The purpose of this study was to determine whether a clinician can assess critical print size (CPS) and/or reading fluency by listening to a visually impaired patient reading aloud across a range of print sizes on an MNREAD chart, rather than needing to plot and analyse reading speed data as a function of print size.
Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

INTRODUCTION Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addiction remain unclear. METHODS We developed a novel stop-signal functional magnetic resonance imaging task where the stop-signal reaction time (SSRT-a classical inhibitory control measure) was tested under different salience conditions (modulated by drug, food, threat, or neutral words) in individuals with cocaine use disorder (CUD; n = 26) versus demographically matched healthy control participants (n = 26). RESULTS Despite similarities in drug cue-related SSRT and valence and arousal word ratings between groups, dorsolateral prefrontal cortex (dlPFC) activity was diminished during the successful inhibition of drug versus food cues in CUD and was correlated with lower frequency of recent use, lower craving, and longer abstinence (Z > 3.1, P < 0.05 corrected). DISCUSSION Results suggest altered involvement of cognitive control regions (e.g. dlPFC) during inhibitory control under a drug context, relative to an alternative reinforcer, in CUD. Supporting the iRISA model, these results elucidate the direct impact of drug-related cue reactivity on the neural signature of inhibitory control in drug addiction.
Nonadiabatic Nano-optical Tunneling of Photoelectrons in Plasmonic Near-Fields

Our work demonstrates nonadiabatic tunneling of photoelectrons in the near-field of gold nanostructures, which occurs in the transition region between the multi-photon-induced photoemission and tunneling emission regimes. Measured kinetic energy spectra at higher laser intensities indicates strong-field electron accelaration and recollision, characteristic for the tunneling emission regime. At the same time, constant scaling of the photoelectron current with the intensity has been measured, a trait of the multi-photon-induced photoemission regime. The Keldysh value of γ ≈ 2 for the transition was determined by analyzing the measured photoemission spectra. This value is in good agreement with the results acquired by the numerical solution of the Time-Dependent Schrödinger Equation.