Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy

Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2gib005Δ8/+) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability.
Expression of AKR1C3 Protein in Human Keloid Skin Tissue

Keloids are among the most noticeable types of scars and may occur as a result of abnormal wound healing. They are formed by deposition of extracellular matrix components and proliferation of fibroblasts [1]. Keloids compose a pathologic condition characterized by the presence of hyalinized collagen bundles and the existence of chronic inflammatory reactions, such as oxidative stress [2]. Keloid scars extend beyond the margin of the original wound compared with hypertrophic scars. Keloids are estimated to occur in about 10% of people [3] and are seen more often in people with highly pigmented skin such as Black and Asian people rather than Caucasian people [4]. The pathophysiological basis of keloids is yet to be completely determined. There have been many ongoing keloid-related studies because keloids cause serious functional and aesthetic problems. However, there are no uniformly successful treatments for keloid scars. Excision and primary repair frequently result in recurrence. It was recently reported that keloid formation is associated with reactive oxygen species (ROS) [3]. According to De Felice et al. [3], significant increases in ROS in keloid tissue fibroblasts are related to oxidative injury and inflammatory reaction. ROS, including superoxide anion (O), hydrogen peroxide (H2O2), and hydroxyl anion (OH), can oxidize and modify intracellular molecules. ROS production is induced either directly by oxidants/ oxidases or by a decrease in antioxidants and related upregulation of oxidative damage-inducible genes [2,5]. ROS can directly destroy both DNA and proteins. ROS play a crucial role in the apoptosis of cells injured by oxidation, especially in inflammatory cells Doo Hyun Nam, DaWoon Lee, Chul Han Kim, Sang Gue Kang, Ho Seong Shin, Young Man Lee
Sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio and non-alcoholic steatohepatitis in patients with biopsy-proven non-alcoholic fatty liver disease

Abstract Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (P interaction = 0·017 for NASH and P interaction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
Aggregating large-scale databases for PubMed author name disambiguation

OBJECTIVE PubMed has suffered from the author ambiguity problem for many years. Existing studies on author name disambiguation (AND) for PubMed only used internal metadata for development. However, some of them are incomplete (eg, a large number of names are only abbreviated and their full names are not available) or less discriminative. To this end, we present a new disambiguation method, namely AggAND, by aggregating information from external databases. MATERIALS AND METHODS We address this issue by exploring Microsoft Academic Graph, Semantic Scholar, and PubMed Knowledge Graph to enhance the built-in name metadata, and extend the internal metadata with some external and more discriminative metadata. RESULTS Experimental results on enhanced name metadata demonstrate comparable performance to 3 author identifier systems, as well as show superiority over the original name metadata. More importantly, our method, AggAND, incorporating both enhanced name and extended metadata, yields F1 scores of 95.80% and 93.71% on 2 datasets and outperforms the state-of-the-art method by a large margin (3.61% and 6.55%, respectively). CONCLUSIONS The feasibility and good performance of our methods not only help better understand the importance of external databases for disambiguation, but also point to a promising direction for future AND studies in which information aggregated from multiple bibliographic databases can be effective in improving disambiguation performance. The methodology shown here can be generalized to broader bibliographic databases beyond PubMed. Our code and data are available online (https://github.com/carmanzhang/PubMed-AND-method).
Is partial ablation appropriate for benign thyroid nodules? A retrospective study with long-term follow-up after microwave ablation

Abstract Objective This retrospective study aimed to investigate the efficacy and safety of partial ablation (PA) for benign thyroid nodules (BTNs) using microwave ablation (MWA) in a long-term follow-up. Materials and methods Between February 2015 and April 2019, 236 patients with 236 BTNs (maximum diameter ≥2 cm) treated with ultrasound-guided MWA were enrolled. Contrast-enhanced ultrasound (CEUS) was performed within 3 d after ablation to determine whether there was residual tissue according to which the patients were assigned PA or complete ablation (CA). The volume reduction ratio (VRR) and complications were evaluated during follow-up. Results Eighty-two patients were enrolled in the PA group, and 154 were enrolled in the CA group. Both groups achieved continuous reductions in nodule volume and increases in VRR within 2 years after ablation. Although the VRR of the PA group at 4 years was lower than that of the CA group (65.54 vs. 95.08%; p<.05), PA still achieved ‘technical efficacy’ with a volume reduction of more than 50%. The complication and side effect rates between the two groups showed no significant difference (p>.05). Conclusions Both PA and CA were safe and effective in reducing the volumes of BTNs in the long-term follow-up. For nodules with a large initial volume and dangerous location, PA with a small amount of residual tissue may be acceptable.
Improved biopharmaceutical attributes of lumefantrine using choline mimicking drug delivery system: preclinical investigation on NK-65 P.berghei murine model

ABSTRACT Background Lumefantrine (LMF) is first-line antimalarial drug, possesses activity against almost all human malarial parasites, but the in vivo activity of this molecule gets thwarted due to its low and inconsistent oral bioavailability (i.e. 4–12%) owing to poor biopharmaceutical attributes. Methods Lumefantrine phospholipid complex (LMF-PC) was prepared by rota-evaporation method following job’s plot technique for the selection of apt stoichiometric ratios. Docking studies were carried out to determine the possible interaction(s) of LMF with phosphatidylcholine analogue. Comparative in vitro physiochemical, solid-state characterization, MTT assay, dose-response on P. falciparum, in vivo efficacy studies including pharmacokinetic and chemosuppression on NK-65 P. berghei infected mice were carried out. Results Aqueous solubility was distinctly improved (i.e. 345 times) with phospholipid complex of LMF. Cytotoxicity studies on Hela and fibroblast cell lines demonstrated safety of LMF-PC with selectivity indices of 4395 and 5139, respectively. IC50 value was reduced almost 2.5 folds. Significant enhancement in Cmax (3.3-folds) and AUC (2.7-folds) of rat plasma levels indicated notable pharmacokinetic superiority of LMF-PC over LMF suspension. Differential leukocytic count and cytokine assay delineated plausible immunoregulatory role of LMF-PC with nearly 98% chemosuppression and over 30 days of post-survival. Conclusion Superior antimalarial efficacy and survival time with full recovery of infected mice revealed through histopathological studies.
Conceptual and analytical overlap between allostatic load and systemic biological aging measures: Analyses from the National Survey of Midlife Development in the United States.

BACKGROUND Indices quantifying allostatic load (AL) and biological aging (BA) have independently received widespread use in epidemiological literature. However, little attention has been paid to their conceptual and quantitative overlap. By reviewing literature utilizing measures of AL and BA, and conducting comparative analysis, we highlight similarities and differences in biological markers employed and approach toward scale construction. Further, we outline opportunities where both types of indices might be improved by adopting methodological features of the other. METHODS Using data from the National Survey of Midlife Development in the United States (N=2,055, age=26-86), we constructed three AL indices: one common literature standard, and two alternative formulations informed by previous work with measures of BA. The performance of AL indices was juxtaposed against two commonly employed BA indices: Klemera-Doubal Method Biological Age and Homeostatic Dysregulation. RESULTS All indices correlated with chronological age. Participants with higher AL and older BA performed worse on tests of physical and subjective functioning. Further, participants with increased life-course risk exposure exhibited higher AL and BA. Notably, alternative AL formulations tended to exhibit effect-sizes equivalent to or larger than those observed for BA measures, and displayed superior mortality prediction. CONCLUSIONS In addition to their conceptual similarity, AL and BA indices also exhibit significant analytical similarity. Further, BA measures are robust to construction using a panel of biomarkers not observed in previous iterations, including carotenoids indexing antioxidant capacity. In turn, AL indices could benefit by adopting the methodological rigor formalized within BA composites, such as applying biomarker down-selection criteria.
Reducing False-Positive Results With Fourth-Generation HIV Testing at a Veterans Affairs Medical Center.

Background In 2006, the Centers for Disease Control and Prevention issued guidelines advocating routine HIV screening for all patients. However, false-positive results are a potential patient care threat for low-risk populations even with accurate screening assays. A reduction in HIV false-positive screening results can potentially be seen by switching from the third-generation to a more sensitive and specific fourth-generation screening assay. Methods We studied the impact on the false-positive screening rate of a change to a fourth-generation assay at a regional US Department of Veteran Affairs Medical Center. HIV screening tests performed by the laboratory from March 1, 2016 to February 28, 2017, prior to implementation of the new assay were compared with fourth-generation HIV screening tests performed from March 1, 2017 to February 28, 2018. Results Of 7,516 third-generation HIV screening tests reviewed, 52 were reactive on the screening assay; 24 were true positives, 28 were false positives. The following year 7,802 fourth-generation HIV screening tests were performed and 23 were reactive on the screening assay; 16 were true positives and 7 were false positives. The positive predictive value for the third-generation test was 46% and 70% for the fourth-generation test. Conclusions There were fewer false-positive results with testing with the more specific fourth- vs third-generation assay (0.09% vs 0.37%, respectively), which was statistically significant (P = .002). This reduction in false-positive screening would reduce the laboratory workload and would save an estimated $3,875 yearly and reduce the adverse effects of false-positive screening results for patients.
Differential Pain Presentations Observed Across Post-Traumatic Stress Disorder Symptom Trajectories After Combat Injury.

OBJECTIVE This study evaluated the association between pain outcomes and post-traumatic stress disorder (PTSD) symptom trajectories after combat-related injury, while adjusting for receipt of regional anesthesia (RA) soon after injury. METHODS The PTSD symptom trajectories of N = 288 combat-injured service members were examined from within a month of injury up to two-years after. Linear mixed-effects models evaluated the association between PTSD symptom trajectories and average pain and pain interference outcomes while adjusting for receipt of RA during combat casualty care. RESULTS Four PTSD trajectories were characterized: resilient, recovering, worsening, and chronic. Differential pain presentations were associated with PTSD symptom trajectories, even after adjusting for receipt of RA. Compared to those with a resilient PTSD symptom trajectory, individuals presenting with chronic PTSD trajectories were estimated to experience average pain scores 2.61 points higher (95% CI: 1.71, 3.14). Participants presenting with worsening (β = 1.42; 95% CI: 0.77, 1.78) and recovering PTSD trajectories (β = 0.65; 95% CI: 0.09, 1.08) were estimated to experience higher average pain scores than participants with resilient PTSD trajectories. Significant differences in pain interference scores were observed across PTSD trajectories. Receiving RA was associated with improved pain up to two years after injury (β =-0.31; 95% CI: -0.90, -0.04), however no statistically significant association was detected between RA and PTSD trajectories. CONCLUSIONS PTSD trajectories were associated with greater pain intensity and interference following combat injury even when accounting for receipt of early RA for pain management. These findings underscore the need to jointly assess pain and PTSD symptoms across the trauma care continuum.
Monitoring of large B-cell lymphoma and T-zone lymphoma in a dog via flow cytometry

A 12-y-old, castrated male Pomeranian dog was presented because of mandibular lymph node (LN) enlargement. Physical examination and a complete blood count revealed generalized lymphadenopathy and moderate lymphocytosis. Fine-needle aspirate cytology revealed expansion of medium lymphocytes in the right mandibular LN and expansion of large lymphocytes in the left popliteal LN. Flow cytometry identified 2 aberrant lymphocyte populations in both LNs, namely a CD5+CD45− T-cell population, and a large CD21+ B-cell population. Flow cytometry of the peripheral blood revealed an identical population of aberrant CD45− T cells. The patient was diagnosed with concurrent T-zone lymphoma and leukemia, and B-cell lymphoma. Multi-agent chemotherapy was instituted, and serial clinical and flow cytometric analysis revealed complete remission of the neoplastic B cells, but persistence of the neoplastic T cells and persistent lymphadenopathy. This case affirms the diagnostic value of flow cytometry and reveals a unique limitation of the RECIST criteria.
Understanding Skin Failure: A Scoping Review

Supplemental digital content is available in the text. ABSTRACT OBJECTIVE To map the use of the term “skin failure” in the literature over time and enhance understanding of this term as it is used in clinical practice. DATA SOURCES The databases searched for published literature included PubMed, Embase, the Cumulative Index for Nursing and Allied Health Literature, and Google Scholar. The search for unpublished literature encompassed two databases, Open Gray and ProQuest Dissertation and Theses. STUDY SELECTION Search terms included “skin failure,” “acute skin failure,” “chronic skin failure,” and “end stage skin. ” All qualitative and quantitative research designs, editorial, opinion pieces, and case studies were included, as well as relevant gray literature. DATA EXTRACTION Data collected included author, title, year of publication, journal name, whether the term “skin failure” was mentioned in the publication and/or in conjunction with other skin injury, study design, study setting, study population, sample size, main focus of the publication, what causes skin failure, skin failure definition, primary study aim, and primary outcome. DATA SYNTHESIS Two main themes of skin failure were identified through this scoping review: the etiology of skin failure and the interchangeable use of definitions. CONCLUSIONS Use of the term “skin failure” has increased significantly over the past 30 years. However, there remains a significant lack of empirical evidence related to skin failure across all healthcare settings. The lack of quality research has resulted in multiple lines of thinking on the cause of skin failure, as well as divergent definitions of the concept. These results illustrate substantial gaps in the current literature and an urgent need to develop a globally agreed-upon definition of skin failure, as well as a better understanding of skin failure etiology.
Does E-learning Improve Plastic Surgery Education?

Purpose E-learning is rapidly growing in medical education, overcoming physical, geographic, and time-related barriers to students. This article critically evaluates the existing research on e-learning in plastic surgery. Methods A systematic review of e-learning in plastic surgery was conducted using the PubMed/MEDLINE, Scopus, and Embase databases. Studies were limited to those written in English and published after 1995 and excluded short communications, letters to the editor, and articles focused on in-person simulation. Results A total of 23 articles were identified. Represented subspecialties include breast, burns, craniofacial/pediatrics, hand, and microsurgery. Most e-learning resources target surgeons and trainees, but a small number are for patients, parents, and referring physicians. Users reported high levels of satisfaction with e-learning and significant gains in knowledge after completion, although there may be more variable satisfaction with teaching technical skills. Two studies showed no differences in knowledge gains from e-learning compared with traditional learning methods. Subgroup analysis showed greater benefit of e-learning for novice learners when evaluated. Surveys of plastic surgeons and trainees showed high interest in and growing utilization of e-learning. Conclusions Research in plastic surgery e-learning shows high user satisfaction and overall improvements in learning outcomes with knowledge gains equivalent to traditional teaching methods and greater benefit in novice learners. Thus, e-learning can serve an important role in plastic surgery education, especially in the current state of social distancing. Future work should aim to define learner preferences and educational needs and better establish how e-learning can augment plastic surgical education, particularly among other teaching methods.
Beneficial and limiting factors in return to work after primary total knee replacement: Patients’ perspective

BACKGROUND: Return to work (RTW) is an important outcome in Total Knee Arthroplasty (TKA). At present, 70–80%of TKA patients return to work within three to six months. OBJECTIVE: What are patients’ perspectives regarding beneficial and limiting factors in RTW after TKA? METHODS: Focus groups were formed in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Three major topics were explored: 1. What was beneficial for RTW after TKA; 2. What was limiting for RTW after TKA; and 3. What additional care would benefit RTW after TKA? RESULTS: Data saturation was reached after four focus groups, comprising 17 participants—nine men and eight women (median age 58, range 52–65). The focus group study identified four main themes that contributed to a successful RTW namely rehabilitation (medical) like post-operative physical therapy, patient characteristics (personal), like motivation to RTW, occupational characteristics (work-related) like build-up in work tasks and medical support (medical) like availability of a walker or crutches. CONCLUSION: According to participants, factors within the following four themes can contribute to a successful return to work: occupational, patient, rehabilitation and medical care. Incorporating these factors into the integrated care pathway for the “young” TKA patients may increase the chances of a successful RTW.