Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of residue-residue contact prediction methods: From retrospective to prospective

Sequence-based residue contact prediction plays a crucial role in protein structure reconstruction. In recent years, the combination of evolutionary coupling analysis (ECA) and deep learning (DL) techniques has made tremendous progress for residue contact prediction, thus a comprehensive assessment of current methods based on a large-scale benchmark data set is very needed. In this study, we evaluate 18 contact predictors on 610 non-redundant proteins and 32 CASP13 targets according to a wide range of perspectives. The results show that different methods have different application scenarios: (1) DL methods based on multi-categories of inputs and large training sets are the best choices for low-contact-density proteins such as the intrinsically disordered ones and proteins with shallow multi-sequence alignments (MSAs). (2) With at least 5L (L is sequence length) effective sequences in the MSA, all the methods show the best performance, and methods that rely only on MSA as input can reach comparable achievements as methods that adopt multi-source inputs. (3) For top L/5 and L/2 predictions, DL methods can predict more hydrophobic interactions while ECA methods predict more salt bridges and disulfide bonds. (4) ECA methods can detect more secondary structure interactions, while DL methods can accurately excavate more contact patterns and prune isolated false positives. In general, multi-input DL methods with large training sets dominate current approaches with the best overall performance. Despite the great success of current DL methods must be stated the fact that there is still much room left for further improvement: (1) With shallow MSAs, the performance will be greatly affected. (2) Current methods show lower precisions for inter-domain compared with intra-domain contact predictions, as well as very high imbalances in precisions between intra-domains. (3) Strong prediction similarities between DL methods indicating more feature types and diversified models need to be developed. (4) The runtime of most methods can be further optimized.
Periconceptional folate and gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies

Abstract Objective To examine the relationship between periconceptional folate exposure and risk of gestational diabetes mellitus (GDM). Methods Several electronic databases, including PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Cochrane Library, were searched for all relevant cohort studies by January 2021. Studies on relationship between folate exposure (intake or status) and GDM risk were included. Quality of included studies was assessed using Newcastle-Ottawa Scale. Random effects meta-analysis was performed to estimate overall odds ratio (OR) and 95% confidence intervals (CIs) by Stata software (Stata Corp., College Station, TX). Results Ten cohort studies with 40,244 pregnancies were eligible for quantitative meta-analysis. Significant association was observed between folate exposure and risk of GDM (OR = 1.24, p=.036, 95% CI: 1.01–1.52). Subgroup analysis revealed that periconceptional folate exposure of population in China (OR = 1.35, 95% CI: 1.09–1.67) but not in western countries, folate exposure during pregnancy (OR = 1.49, 95% CI: 1.22–1.81) but not before pregnancy, and internal folate exposure (OR = 1.36, 95% CI: 1.10–1.67), were significantly associated with increased GDM risk. Conclusions Overall, periconceptional folate exposure is positively associated with GDM risk, especially the exposure during pregnancy and exposure in Chinese populations.
Risk factors for delayed radiographic resolution in children with refractory Mycoplasma pneumoniae pneumonia

Objective To determine the risk factors for delayed radiographic resolution in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and explore the most suitable time for interventional bronchoscopy. Methods This retrospective study involved 142 children with RMPP who were admitted to our hospital from 1 January 2015 to 31 December 2017. They were divided into a common resolution group and a delayed resolution group based on their chest radiograph series. Results Among the 142 patients, 67 showed common resolution on chest radiographs and 75 showed delayed resolution. Independent risk factors for delayed resolution were a clinical course of ≥11.5 days before the performance of interventional bronchoscopy, mucus plug formation, corticosteroid resistance, and atelectasis. When bronchoscopy was performed before the disease had been present for <11.5 days, the length of hospitalization, total fever duration, and duration of time until disappearance of coughing were shorter than those in children who underwent bronchoscopy after the disease had been present for ≥11.5 days. Conclusions Corticosteroid resistance, the time to interventional bronchoscopy, atelectasis, and mucus plug formation were associated with delayed resolution on chest radiographs. Performance of interventional bronchoscopy before the clinical course has reached 11.5 days may help alleviate clinical symptoms and improve radiographic resolution.
Enclosing Control for Multiagent Systems With a Moving Target of Unknown Bounded Velocity

This note studies an enclosing control problem for a multiagent system with a moving target of unknown bounded velocity. The objectives are to let each agent move along a circular orbit with a prescribed radius centered at the target and maintain desired spacing from neighboring agents. A distributed controller composed of three parts is designed by only using the relative position information from each agent to the target and its neighbors. The first two parts are designed to achieve target circling and spacing adjustment, respectively. The last part is designed discontinuously to compensate for the unknown bounded velocity of the target. Due to the discontinuously distributed controller, sufficient conditions are given by a nonsmooth analysis. Furthermore, the agents are shown to have order preservation and collision avoidance properties when the target is stationary. The effectiveness of theoretical results is illustrated by simulations.
Association of Aortic Stiffness With Biomarkers of Neuroinflammation, Synaptic Dysfunction, and Neurodegeneration

Objectives To test the hypothesis that increased aortic stiffening is associated with greater CSF evidence of core Alzheimer disease pathology (β-amyloid [Aβ], phosphorylated tau [p-tau]), neurodegeneration (total tau [t-tau]), synaptic dysfunction (neurogranin), neuroaxonal injury (neurofilament light [NFL]), and neuroinflammation (YKL-40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]), we analyzed pulse wave velocity (PWV) data and CSF data among older adults. Methods Participants free of stroke and dementia from the Vanderbilt Memory and Aging Project, an observational community-based study, underwent cardiac magnetic resonance to assess aortic PWV (meters per second) and lumbar puncture to obtain CSF. Linear regressions related aortic PWV to CSF Aβ, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations after adjustment for age, race/ethnicity, education, apolipoprotein (APOE) ε4 status, Framingham Stroke Risk Profile, and cognitive diagnosis. Models were repeated testing PWV interactions with age, diagnosis, APOE ε4, and hypertension on each biomarker. Results One hundred forty-six participants were examined (age 72 ± 6 years). Aortic PWV interacted with age on p-tau (β = 0.31, p = 0.04), t-tau, (β = 2.67, p = 0.05), neurogranin (β = 0.94, p = 0.04), and sTREM2 (β = 20.4, p = 0.05). Among participants >73 years of age, higher aortic PWV related to higher p-tau (β = 2.4, p = 0.03), t-tau (β = 19.3, p = 0.05), neurogranin (β = 8.4, p = 0.01), and YKL-40 concentrations (β = 7,880, p = 0.005). Aortic PWV had modest interactions with diagnosis on neurogranin (β = −10.76, p = 0.03) and hypertension status on YKL-40 (β = 18,020, p < 0.001). Conclusions Among our oldest participants, ≥74 years of age, greater aortic stiffening is associated with in vivo biomarker evidence of neuroinflammation, tau phosphorylation, synaptic dysfunction, and neurodegeneration, but not amyloidosis. Central arterial stiffening may lead to cumulative cerebral microcirculatory damage and reduced blood flow delivery to tissue, resulting in neuroinflammation and neurodegeneration in more advanced age.
Reliability, construct and concurrent validity of a smartphone-based cognition test in multiple sclerosis

Background: Early detection and monitoring of cognitive dysfunction in multiple sclerosis (MS) may be enabled with smartphone-adapted tests that allow frequent measurements in the everyday environment. Objectives: The aim of this study was to determine the reliability, construct and concurrent validity of a smartphone-adapted Symbol Digit Modalities Test (sSDMT). Methods: During a 28-day follow-up, 102 patients with MS and 24 healthy controls (HC) used the MS sherpa® app to perform the sSDMT every 3 days on their own smartphone. Patients performed the Brief International Cognitive Assessment for MS at baseline. Test–retest reliability (intraclass correlation coefficients, ICC), construct validity (group analyses between cognitively impaired (CI), cognitively preserved (CP) and HC for differences) and concurrent validity (correlation coefficients) were assessed. Results: Patients with MS and HC completed an average of 23.2 (SD = 10.0) and 18.3 (SD = 10.2) sSDMT, respectively. sSDMT demonstrated high test–retest reliability (ICCs > 0.8) with a smallest detectable change of 7 points. sSDMT scores were different between CI patients, CP patients and HC (all ps < 0.05). sSDMT correlated modestly with the clinical SDMT (highest r = 0.690), verbal (highest r = 0.516) and visuospatial memory (highest r = 0.599). Conclusion: Self-administered smartphone-adapted SDMT scores were reliable and different between patients who were CI, CP and HC and demonstrated concurrent validity in assessing information processing speed.
OCaMIR—A Noninvasive, Diagnostic Signature for Early-Stage Ovarian Cancer: A Multi-cohort Retrospective and Prospective Study

Purpose: Due to the lack of effective screening approaches and early detection biomarkers, ovarian cancer has the highest mortality rates among gynecologic cancers. Herein, we undertook a systematic biomarker discovery and validation approach to identify microRNA (miRNA) biomarkers for the early detection of ovarian cancer. Experimental Design: During the discovery phase, we performed small RNA sequencing in stage I high-grade serous ovarian cancer (n = 31), which was subsequently validated in multiple, independent data sets (TCGA, n = 543; GSE65819, n = 87). Subsequently, we performed multivariate logistic regression-based training in a serum data set (GSE106817, n = 640), followed by its independent validation in three retrospective data sets (GSE31568, n = 85; GSE113486, n = 140; Czech Republic cohort, n = 192) and one prospective serum cohort (n = 95). In addition, we evaluated the specificity of OCaMIR, by comparing its performance in several other cancers (GSE31568 cohort, n = 369). Results: The OCaMIR demonstrated a robust diagnostic accuracy in the stage I high-grade serous ovarian cancer patients in the discovery cohort (AUC = 0.99), which was consistently reproducible in both stage I (AUC = 0.96) and all stage patients (AUC = 0.89) in the TCGA cohort. Logistic regression-based training and validation of OCaMIR achieved AUC values of 0.89 (GSE106817), 0.85 (GSE31568), 0.86 (GSE113486), and 0.82 (Czech Republic cohort) in the retrospective serum validation cohorts, as well as prospective validation cohort (AUC = 0.92). More importantly, OCaMIR demonstrated a significantly superior diagnostic performance compared with CA125 levels, even in stage I patients, and was more cost-effective, highlighting its potential role for screening and early detection of ovarian cancer. Conclusions: Small RNA sequencing identified a robust noninvasive miRNA signature for early-stage serous ovarian cancer detection.
Narciclasine attenuates sepsis-induced myocardial injury by modulating autophagy

Acute myocardial injury (AMI) is often secondary to sepsis, which is a life-threatening disease associated with severe cardiac inflammation. Narciclasine, a plant alkaloid isolated from different members of the Amaryllidaceae family, has been extensively characterized as an antitumor and anti-inflammatory compound. In addition, autophagy is critical for sepsis-induced myocardial injury. However, the role and mechanism of autophagy by which narciclasine confers cardioprotection are still unclear. The present study aimed to investigate the underlying mechanism by which narciclasine affects the pathogenesis of sepsis-induced myocardial injury. Narciclasine effectively attenuated LPS-induced myocardial inflammation in vitro and in vivo. In addition, narciclasine protected cardiac function and suppressed the expression of inflammatory cytokines in LPS-induced heart tissue. Furthermore, narciclasine upregulated LPS-induced autophagic activity, and the autophagy inhibitor 3-MA abrogated narciclasine-mediated protection against LPS-induced AMI. Importantly, narciclasine exerted an inhibitory effect on the JNK signaling pathway, and JNK activity was tightly associated with narciclasine-induced autophagy and the consequent protective effects during AMI. Taken together, our findings indicate that narciclasine protects against LPS-induced AMI by inducing JNK-dependent autophagic flux; hence, narciclasine may be an effective and novel agent for the clinical treatment of sepsis-induced myocardial injury.
Computed tomography guided tailored approach to transfemoral access in patients undergoing transcatheter aortic valve implantation

Background Transfemoral approach (TFA) is the most common access route for transcatheter aortic valve implantation (TAVI). Percutaneous femoral access (PA) is preferred over the surgical approach (SA), however, may be associated with a higher risk of access site complications. Thus, we aimed to assess outcomes of computed tomography-guided tailored approach to percutaneous and surgical TFA in patients undergoing TAVI. Methods We evaluated data of 158 patients, who underwent TAVI via femoral route between January 2017 and December 2018. In the PA group, vascular closure was performed with the use of two percutaneous suture devices and an additional mechanical seal device. We compared complications rate and outcomes. Results Of the 158 patients (92%; mean age 79.6 years, 60.8% female), in 92 (61%) patients PA was performed and in 66 (39%) patients SA was used. Median (interquartile range) radiation exposure as well as contrast volume dose was higher in the PA group compared to the SA group 614.0 (410.0; 1104.0) mGy vs. 405 (240.5; 658.0) mGy (p < 0.001) and 150.0 (120.0; 180.7) mL vs. 130.0 (100.0; 160.0) mL (p = 0.04), respectively. Bleeding complications were similar in the PA group 11 (12.2%) compared to 5 (8.62%) in the SA group (p = 0.48). Median length of hospital stay was also similar in the PA and the SA group 6.00 (5.00; 8.00) days vs. 6.00 (4.00; 8.00) days, respectively (p = 0.31). Conclusions Computed tomography-guided PA in TAVI may provide comparable procedural outcomes compared to the SA, despite a higher radiation dose and the use of contrast dye, while being less invasive.
Automated Audiometry in Quiet and Simulated Exam Room Noise for Listeners with Normal Hearing and Impaired Hearing

Abstract Background Up to 80% of audiograms could be automated which would allow more time for provision of specialty services. Ideally, automated audiometers would provide accurate results for listeners with impaired hearing as well as normal hearing. Additionally, accurate results should be provided both in controlled environments like a sound-attenuating room but also in test environments that may support greater application when sound-attenuating rooms are unavailable. Otokiosk is an iOS-based system that has been available for clinical use, but there are not yet any published validation studies using this product. Purpose The purpose of this project was to complete a validation study on the OtoKiosk automated audiometry system in quiet and in low-level noise, for listeners with normal hearing and for listeners with impaired hearing. Research Design Pure tone air conduction thresholds were obtained for each participant for three randomized conditions: standard audiometry, automated testing in quiet, and automated testing in noise. Noise, when present, was 35 dBA overall and was designed to emulate an empty medical exam room. Study Sample Participants consisted of 11 adults with hearing loss and 15 adults with normal hearing recruited from the local area. Data Collection and Analysis Thresholds were measured at 500, 1000, 2000, and 4000 Hz using the Otokiosk system that incorporates a modified Hughson-Westlake method. Results were analyzed using descriptive statistics and also by a linear mixed-effects model to compare thresholds obtained in each condition. Results Across condition and participant group 73.6% of thresholds measured with OtoKiosk were within ± 5 dB of the conventionally measured thresholds; 92.8% were within ± 10 dB. On average, differences between tests were small. Pairwise comparisons revealed thresholds were ∼3.5–4 dB better with conventional audiometry than with the mobile application in quiet and in noise. Noise did not affect thresholds measured with OtoKiosk. Conclusions The OtoKiosk automated hearing test measured pure tone air conduction thresholds from 500 - 4000 Hz at slightly higher thresholds than conventional audiometry, but less than the smallest typical 5 dB clinical step-size. Our results suggest OtoKiosk is a reasonable solution for sound booths and exam rooms with low-level background noise.
Automation and integration of a novel restricted single‐isocenter stereotactic body radiotherapy (a‐RESIST) method for synchronous two lung lesions

Abstract Synchronous treatment of two lung lesions using a single‐isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can decrease treatment time and reduce the impact of intrafraction motion. However, alignment of both lesions on a single cone beam CT (CBCT) can prove difficult and may lead to setup errors and unacceptable target coverage loss. A Restricted Single‐Isocenter Stereotactic Body Radiotherapy (RESIST) method was created to minimize setup uncertainties and provide treatment delivery flexibility. RESIST utilizes a single‐isocenter placed at patient’s midline and allows both lesions to be planned separately but treated in the same session. Herein is described a process of automation of this novel RESIST method. Automation of RESIST significantly reduced treatment planning time while maintaining the benefits of RESIST. To demonstrate feasibility, ten patients with two lung lesions previously treated with a single‐isocenter clinical VMAT plan were replanned manually with RESIST (m‐RESIST) and with automated RESIST (a‐RESIST). a‐RESIST method automatically sets isocenter, creates beam geometry, chooses appropriate dose calculation algorithms, and performs VMAT optimization using an in‐house trained knowledge‐based planning model for lung SBRT. Both m‐RESIST and a‐RESIST showed lower dose to normal tissues compared to manually planned clinical VMAT although a‐RESIST provided slightly inferior, but still clinically acceptable, dose conformity and gradient indices. However, a‐RESIST significantly reduced the treatment planning time to less than 20 min and provided a higher dose to the lung tumors. The a‐RESIST method provides guidance for inexperienced planners by standardizing beam geometry and plan optimization using DVH estimates. It produces clinically acceptable two lesions VMAT lung SBRT plans efficiently. We have further validated a‐RESIST on phantom measurement and independent pretreatment dose verification of another four selected 2‐lesions lung SBRT patients and implemented clinically. Further development of a‐RESIST for more than two lung lesions and refining this approach for extracranial oligometastastic abdominal/pelvic SBRT, including development of automated simulated collision detection algorithm, merits future investigation.
Synergistic effects of myogenic cells and fibroblasts on the promotion of engineered tendon regeneration with muscle derived cells

ABSTRACT Aims Tendon development requires the coordinated interaction of muscles and tendons. Muscle-derived cells (MDCs), a mixed cell population containing both myogenic and fibroblastic cell subsets, have been found to be ideal seed cells for tendon regeneration. However, the necessity of these cell types for tendon regeneration has not yet been tested. In this study, we aim to explore the possible synergistic effects of myogenic cells and fibroblasts in engineered tendon regeneration. Methods MDCs were separated into rapidly adhering cell (RAC; fibroblasts) and slowly adhering cell (SAC; myogenic cells) populations. Myogenic- and tenogenic-related molecules were analyzed by immunofluorescent staining, RT-PCR and real-time PCR. The proliferative abilities of MDCs, RACs and SACs were also evaluated. Cell-scaffold constructs were implanted into nude mice, and subsequently evaluated for their histologic, ultrastructure, gene expression, and biomechanical characteristics. Results MDCs have better proliferative activity than RAC and SAC population. RACs could express higher levels of tenogenic-related molecules tenomodulin (TNMD) and scleraxis (SCX) than SACs. Whereas SACs only expressed myogenic-related molecules MyoD. In contrast to the tendons engineered using RACs and SACs, the tendons engineered using MDCs exhibited a relatively more mature and well-organized tissue structure and ultrastructure as well as better mechanical properties. Conclusions Fibroblasts in muscle may be the primary cell population involved in tendon regeneration and that myogenic cells are an important component of the niche and control the fibroblast activity during tendon regeneration. The synergistic effects between fibroblasts and myogenic cells significantly contribute to efficient and effective regeneration of engineered tendons.
Musculoskeletal disorders of older adults: an integrative literature review.

OBJECTIVE to analyze in available scientific literature what problems are caused to the musculoskeletal system of caregivers of older adults in the home environment. METHODS an integrative literature review indexed in the PubMed, CINAHL, Web of Science, SCOPUS, BDENF, LILACS and SciELO databases. RESULTS the sample totaled 17 studies that showed three thematic categories: Care overload for caregivers' health; Caregivers' physical illness; Caregiver self-neglect. CONCLUSION the evidence identified health problems for caregivers of older adults, regarding the musculoskeletal system, demonstrating the importance of considering intervention strategies that provide guidelines for self-care guidelines, in order to prevent musculoskeletal complications resulting from older adults' care activities at home.