Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Time-Invariance Properties of Upper Limb Synergies

In this paper, we present a novel approach to dynamically describe human upper limb trajectories, addressing the question on whether and to which extent synergistic multi-joint behavior is observed and preserved over time evolution and across subjects. To this goal, we performed experiments to collect human upper limb joint angle trajectories and organized them in a dataset of daily living tasks. We then characterized the upper limb poses at each time frame through a technique that we named repeated-principal component analysis (R-PCA). We found that, although there is no strong evidence on the predominance of one principal component (PC) over the others, the subspace identified by the first three PCs takes into account most of the motion variability. We evaluated the stability of these results over time, showing that during the reaching phase, there is a strong consistency of these findings across participants. In other words, our results suggest that there is a time-invariant low-dimensional approximation of upper limb kinematics, which can be used to define a suitable reduced dimensionality control space for upper limb robotic devices in motion phases.
Cartilage tissue engineering combining microspheroid building blocks and microneedle arrays

ABSTRACT Purpose: Scaffold-free cartilage tissue engineering circumvents issues with scaffold seeding, potential toxicity response, and impaired host integration. However, precisely controlling and maintaining a scaffold-free construct shape have been challenging. We explored the feasibility of microneedle arrays to print tissue using cellular microspheroids as building blocks. Materials and Methods: Human embryonic-derived mesenchymal stem cells or infrapatellar fat pad mesenchymal stem cells were used to create microspheroids of 500 µm in diameter, which were assembled on microneedle arrays in a predefined arrangement using a robotic system under computer vision. Microspheroids on microneedles were cultured to permit fusion into a tissue construct. Infrapatellar fat pad mesenchymal stem cell constructs were either implanted into chondral defects created in human osteoarthritic cartilage explants or maintained on the microneedle array for 3 weeks. Embryonic-derived mesenchymal stem cell constructs were designed to be press-fit into 3 mm subchondral defects in New Zealand White rabbits and maintained for up to 8 weeks to assess retention, early tissue repair, and more mature cartilage regeneration. Results: Microspheroids of both cell types fused together in culture to form neotissues of predefined shape and size. Infrapatellar fat pad mesenchymal stem cell neotissues expressed high levels of chondrogenic genes and integrated with the surrounding osteoarthritic host cartilage. Embryonic-derived mesenchymal stem cell constructs generated chondrogenic neotissue in vivo as early as 2 weeks and more mature tissue by 8 weeks with increased glycosaminoglycan deposition. Conclusions: We constructed defined scaffold-free shapes by bioprinting and fusing microspheroids. Proof of concept was shown in the repair of ex vivo osteoarthritic human cartilage and in vivo rabbit osteochondral (OC) defects.
Degenerative Disc Disease: What's in a Name?

STUDY DESIGN A systematic search and review OBJECTIVE. : To investigate the term, degenerative disc disease, to elucidate its current usage and inform clinical, research, and policy recommendations. SUMMARY OF BACKGROUND DATA Degenerative disc disease has long been a dominant concept in common, painful spinal disorders. Yet, despite its pervasiveness and important clinical consequences and controversies, there has not been a systematic examination of its use and meaning in the scientific literature. METHODS We conducted a systematic search of publications using the term degenerative disc disease from 2007 through 2017 in Ovid MEDLINE (R), Embase, CINAHL and Scopus. Two investigators independently reviewed all publications in the primary sample. Publication and author identifiers, and qualitative study descriptors were extracted. Finally, the definition of degenerative disc disease was placed in one of eight categories. Data were summarized using descriptive statistics. RESULTS Degenerative disc disease appeared in the titles of 402 publications in the primary sample and increased in frequency by 189% from the first to the last three years of the decade. No single definition was used in the majority of publications, and most frequently the term was used without any definition provided (30.1%). In other cases, degenerative disc disease specifically included radiculopathy or myelopathy (14.4%), or only back or neck pain (5.5%), or was equated with disc degeneration regardless of the presence of symptoms (15.4%), or with discogenic pain or disc degeneration as a presumed cause of axial pain (12.7%). Another 7.2% comprised a mix of broad ranging findings and diagnoses. The most notable differences in definitions occurred between surgeons and other disciplines, and when applied to cervical vs. lumbar regions. CONCLUSIONS Despite longstanding use and important consequences, degenerative disc disease represents an underdeveloped concept, with greatly varying, disparate definitions documented. Such inconsistencies challenge clear, accurate communication in medicine and science, create confusion and misconceptions among clinicians, patients and others, and hinder the advancement of related knowledge. LEVEL OF EVIDENCE 4.
Oxidation‐induced destabilization of the fibrinogen αC‐domain dimer investigated by molecular dynamics simulations

Upon activation, fibrinogen is converted to insoluble fibrin, which assembles into long strings called protofibrils. These aggregate laterally to form a fibrin matrix that stabilizes a blood clot. Lateral aggregation of protofibrils is mediated by the αC domain, a partially structured fragment located in a disordered region of fibrinogen. Polymerization of αC domains links multiple fibrin molecules with each other enabling the formation of thick fibrin fibers and a fibrin matrix that is stable but can also be digested by enzymes. However, oxidizing agents produced during the inflammatory response have been shown to cause thinner fibrin fibers resulting in denser clots, which are harder to proteolyze and pose the risk of deep vein thrombosis and lung embolism. Oxidation of Met476 located within the αC domain is thought to hinder its ability to polymerize disrupting the lateral aggregation of protofibrils and leading to the observed thinner fibers. How αC domains assemble into polymers is still unclear and yet this knowledge would shed light on the mechanism through which oxidation weakens the lateral aggregation of protofibrils. This study used temperature replica exchange molecular dynamics simulations to investigate the αC‐domain dimer and how this is affected by oxidation of Met476. Analysis of the trajectories revealed that multiple stable binding modes were sampled between two αC domains while oxidation decreased the likelihood of dimer formation. Furthermore, the side chain of Met476 was observed to act as a docking spot for the binding and this function was impaired by its conversion to methionine sulfoxide.
Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice

Abstract Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated. Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated. Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group. Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1β (IL-1β), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1β (MIP-1β), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups. Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.
Prescription Drug Spending and Medication Adherence Among Medicare Beneficiaries with Heart Failure.

BACKGROUND Evidence suggests that cost sharing adversely affects appropriate prescription drug use for chronic disorders. However, few studies have evaluated this effect in heart failure (HF), the most common cause of hospitalization in Medicare. OBJECTIVE To determine whether spending on HF pharmacotherapy by Medicare Part D enrollees was associated with prescription refill adherence. METHODS This correlational study used pooled data from the 2010-2012 Medicare Current Beneficiary Survey (MCBS). The analysis sample consisted of community-dwelling MCBS participants with self-reported HF and continuous Part D coverage during the year of participation. 3 drug classes were analyzed independently: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). 1,448 weighted participant-year records (derived from 964 individuals) met the inclusion criteria, of which 846 (58%) were included for beta-blockers, 633 (44%) for ACE inhibitors, and 229 (16%) for ARBs. Spending was measured by average out-of-pocket payment for the relevant prescription, standardized to a 30-day supply, as a percentage of average monthly income. Adherence was measured by the medication possession ratio (MPR): total days supplied for all but the last refill divided by number of days between the first and last fills of the year. RESULTS Accounting for sampling weights, the median (interquartile range) monthly income was $1,472 ($949-$2,466), and average percentage of monthly income spent on a 30-day medication supply was 0.22% for beta-blockers, 0.19% for ACE inhibitors, and 0.90% for ARBs. Mean MPR was 88.9% for beta-blockers, 88.5% for ACE inhibitors, and 90.4% for ARBs. Risk-adjusted models showed that percentage of income spent on a beta-blocker prescription was directly associated with odds of nonadherence (MPR < 80%), odds ratio = 1.38, 95% CI = 1.01-1.89, P = 0.045, and inversely associated with beta-blocker MPR, B = -4.17, SE = 1.23, P = 0.001. No such association was observed for ACE inhibitors or ARBs. CONCLUSIONS Price sensitivity was evident for beta-blockers but not for antiangiotensin drugs, despite very low out-of-pocket costs and high adherence. This study is relevant to value-based pricing of HF management drugs in Part D plans. DISCLOSURES No outside funding supported this study. Butler has served as a paid consultant or advisor on unrelated projects for Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3, Innolife, Janssen, Medtronic, Merck, Novartis, Relypsa, Stealth Peptide, SC Pharma, Vifor, and ZS Pharma. The other authors have no potential conflicts of interest to declare. An early version of this paper was presented as a poster at Sigma Theta Tau International's 28th Nursing Research Congress; July 27-31, 2017; Dublin, Ireland.
Vectors with autonomy: what distinguishes animal‐mediated nutrient transport from abiotic vectors?

Animal movements are important drivers of nutrient redistribution that can affect primary productivity and biodiversity across various spatial scales. Recent work indicates that incorporating these movements into ecosystem models can enhance our ability to predict the spatio‐temporal distribution of nutrients. However, the role of animal behaviour in animal‐mediated nutrient transport (i.e. active subsidies) remains under‐explored. Here we review the current literature on active subsidies to show how the behaviour of active subsidy agents makes them both ecologically important and qualitatively distinct from abiotic processes (i.e. passive subsidies). We first propose that animal movement patterns can create similar ecological effects (i.e. press and pulse disturbances) in recipient ecosystems, which can be equal in magnitude to or greater than those of passive subsidies. We then highlight three key behavioural features distinguishing active subsidies. First, organisms can transport nutrients counter‐directionally to abiotic forces and potential energy gradients (e.g. upstream). Second, unlike passive subsidies, organisms respond to the patterns of nutrients that they generate. Third, animal agents interact with each other. The latter two features can form positive‐ or negative‐feedback loops, creating patterns in space or time that can reinforce nutrient hotspots in places of mass aggregations and/or create lasting impacts within ecosystems. Because human‐driven changes can affect both the space‐use of active subsidy species and their composition at both population (i.e. individual variation) and community levels (i.e. species interactions), predicting patterns in nutrient flows under future modified environmental conditions depends on understanding the behavioural mechanisms that underlie active subsidies and variation among agents' contributions. We conclude by advocating for the integration of animal behaviour, animal movement data, and individual variation into future conservation efforts in order to provide more accurate and realistic assessments of changing ecosystem function.
High sensitivity Troponin-I levels in asymptomatic hemodialysis patients

Abstract Reduction in renal clearance and removal by hemodialysis adversely affect the level and utility of high-sensitivity troponin I (hsTnI) for diagnosis of acute myocardial infarction (AMI) in hemodialysis (HD) patients. Furthermore, HD process itself might cause undesirable myocardial injury and enhance post HD hsTnI levels. This comparative cross-sectional study was conducted to compare the hsTnI levels between 100 asymptomatic HD patients and their 107 matched non-chronic kidney disease (CKD) population. The hsTnI levels in HD group were higher than non-CKD group [median (IQR): 54.3 (20.6–152.7) vs. 18 (6.2–66.1) ng/L, p < . 001)]. The hsTnI levels reduced after HD process from 54.3 (20.6–152.7) ng/L in pre-HD to 27.1 (12.3–91.4) ng/L in post-HD (p = .015). Of interest, 25% of HD patients had increment of hsTnI after HD and might represent HD-induced myocardial injury. The significant risk factors were high hemoglobin level and high blood flow rate. In conclusion, the baseline hsTnI levels in asymptomatic HD patients were higher than non-CKD population. The dynamic change of hsTnI over time would be essential for the diagnosis of AMI. Certain numbers of asymptomatic HD patients had HD-induced silent myocardial injury and should be aggressively investigated to prevent further cardiovascular mortality.
Association Between Visfatin and Hepatic Steatosis in the General Population During Long-Term Follow-Up

Abstract The aim of this study was to investigate any association between the adipose tissue-derived protein, visfatin, and non-alcoholic fatty liver disease (NAFLD) and its potential long-term impact on hepatic steatosis. A cross-sectional study including 2429 randomly selected subjects was performed in 2002. Later, 403 subjects were re-evaluated in 2013. Serum visfatin concentrations were determined by sandwich enzyme-linked immunosorbent assay. Phenotyping included abdominal ultrasonography, anthropometric data, and laboratory investigations. No association was found between circulating visfatin levels and the presence of NAFLD at baseline (2002: p=0.0967) or during follow-up (2013: p=0.1312). However, a significant increase in visfatin levels in relation to the level of steatosis was seen during follow-up (p<0.0001). During the more than 10-year follow-up, the metabolic status of the study subjects worsened, with a significant increase in body mass index (BMI) (p<0.0001), waist-to-hip ratio (p<0.0001), triglycerides (TG) (p<0.0001), low-density lipoprotein (p=0.0305), homeostasis model assessment (p<0.0001), and presence of diabetes (p<0.0001). This change was accompanied by an increase in serum visfatin levels, which showed a weak correlation with BMI (p<0.0001, r=0.27586) and presence of diabetes (p<0.0043, r=0.14188). A statistically significant correlation between leucocyte numbers and serum visfatin concentration (p<0.0001, r=0.25615) was found. We found no association between visfatin levels and the presence or absence of NAFLD or the degree of hepatic fatty infiltration at baseline. There was a strong correlation between serum visfatin concentrations and the number of leucocytes, which may suggest a proinflammatory role for visfatin.
Mammalian Target of Rapamycin Complex 1 Signaling Is Required for the Dedifferentiation From Biliary Cell to Bipotential Progenitor Cell in Zebrafish Liver Regeneration

The liver has a high regenerative capacity. Upon two‐thirds partial hepatectomy, the hepatocytes proliferate and contribute to liver regeneration. After severe liver injury, when the proliferation of residual hepatocytes is blocked, the biliary epithelial cells (BECs) lose their morphology and express hepatoblast and endoderm markers, dedifferentiate into bipotential progenitor cells (BP‐PCs), then proliferate and redifferentiate into mature hepatocytes. Little is known about the mechanisms involved in the formation of BP‐PCs after extreme liver injury. Using a zebrafish liver extreme injury model, we found that mammalian target of rapamycin complex 1 (mTORC1) signaling regulated dedifferentiation of BECs and proliferation of BP‐PCs. mTORC1 signaling was up‐regulated in BECs during extreme hepatocyte ablation and continuously expressed in later liver regeneration. Inhibition of mTORC1 by early chemical treatment before hepatocyte ablation blocked the dedifferentiation from BECs into BP‐PCs. Late mTORC1 inhibition after liver injury reduced the proliferation of BP‐PC‐derived hepatocytes and BECs but did not affect BP‐PC redifferentiation. mTOR and raptor mutants exhibited defects in BEC transdifferentiation including dedifferentiation, BP‐PC proliferation, and redifferentiation, similar to the chemical inhibition. Conclusion: mTORC1 signaling governs BEC‐driven liver regeneration by regulating the dedifferentiation of BECs and the proliferation of BP‐PC‐derived hepatocytes and BECs.
Effects of functional communication interventions for people with primary progressive aphasia and their caregivers: a systematic review

Abstract Objectives: Primary progressive aphasia (PPA) is a language led dementia characterised by progressive speech and language difficulties. Impairment focused PPA interventions that seek to remediate, alleviate or improve symptoms, dominate the research literature. Yet speech and language therapists (SLTs) report prioritising functional communication interventions (FCIs), which target engagement in an activity and participation in life situations. This systematic review investigates the research literature on FCIs for PPA to identify the key components of these interventions and their effectiveness. Method: A systematic search of databases identified 19 studies published between 1998 and 2018. Data were extracted from the articles using the Intervention Taxonomy adaptation (ITAX). Results: Results show that the two most common components of FCIs are to build on communication strategies people currently use, and to practise these strategies with a communication partner. There are variations in the interventions, such as location and dosage. All 19 studies report improvements, of which eight report statistically significant results. Forty-two different measures are used across the 19 studies. Conclusion: This study highlights that building on existing strategies and practising these with a CP, are key components of FCIs for people with PPA, yet there remains a lack of clarity around optimal dosage. Further rigorous research using a core set of outcome measures is a priority in this area.
Altered regulation of the transport of RNA from nucleus to cytoplasm in rat hepatoma cells.

Summary RNA base sequences that are restricted to the nucleus in normal rat liver are found in the cytoplasm in azo dye-induced primary hepatomas. Some of these RNA9s are present in the cytoplasm of 19-day fetal liver and of liver regenerating 2.5 hr after 30% hepatectomy. No RNA9s were found to be restricted to the nucleus in the tumor cells, suggesting that the mechanism of selective transport of RNA between nucleus and cytoplasm may be lost during malignant transformation. This migration of RNA out of the tumor cell nucleus is an early effect of the carcinogen, appearing in a significant fraction of the liver cells after the animals were fed a diet containing 0.06% 3′-methyl-4-dimethylaminoazobenzene for only 6 days. Liver cells of rats fed the noncarcinogenic analog aminoazobenzene have nucleus-restricted RNA equivalent to that of normal liver.
A study of deep learning approaches for medication and adverse drug event extraction from clinical text

OBJECTIVE This article presents our approaches to extraction of medications and associated adverse drug events (ADEs) from clinical documents, which is the second track of the 2018 National NLP Clinical Challenges (n2c2) shared task. MATERIALS AND METHODS The clinical corpus used in this study was from the MIMIC-III database and the organizers annotated 303 documents for training and 202 for testing. Our system consists of 2 components: a named entity recognition (NER) and a relation classification (RC) component. For each component, we implemented deep learning-based approaches (eg, BI-LSTM-CRF) and compared them with traditional machine learning approaches, namely, conditional random fields for NER and support vector machines for RC, respectively. In addition, we developed a deep learning-based joint model that recognizes ADEs and their relations to medications in 1 step using a sequence labeling approach. To further improve the performance, we also investigated different ensemble approaches to generating optimal performance by combining outputs from multiple approaches. RESULTS Our best-performing systems achieved F1 scores of 93.45% for NER, 96.30% for RC, and 89.05% for end-to-end evaluation, which ranked #2, #1, and #1 among all participants, respectively. Additional evaluations show that the deep learning-based approaches did outperform traditional machine learning algorithms in both NER and RC. The joint model that simultaneously recognizes ADEs and their relations to medications also achieved the best performance on RC, indicating its promise for relation extraction. CONCLUSION In this study, we developed deep learning approaches for extracting medications and their attributes such as ADEs, and demonstrated its superior performance compared with traditional machine learning algorithms, indicating its uses in broader NER and RC tasks in the medical domain.
Impact of different intraoperative CO2 pressure levels (8 and 15 mmHg) during laparoscopic hysterectomy performed due to benign uterine pathologies on postoperative pain and arterial pCO2: a prospective randomised controlled clinical trial

To compare the effects of two different intraoperative CO2 pressures (8 and 15 mmHg) during laparoscopic hysterectomy for benign uterine pathologies in terms of postoperative abdominal and shoulder pain, laparoscopy‐mediated vegetative alterations, pain medication requirement, arterial CO2 pressure (pCO2), surgical parameters, and safety.