Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanically stimulated biomarkers signal cartilage changes over 5 years consistent with disease progression in medial knee osteoarthritis patients

Using serum biomarkers to assess osteoarthritis (OA) disease state and risks of progression remain challenging. This study tested the hypothesis that changes to serum biomarkers in response to a mechanical stimulus in patients with medial knee OA signal cartilage thickness changes 5 years later. Specifically, serum concentrations of a collagen degradation marker (C1,2C) and a chondroitin sulfate synthesis marker (CS846) were measured 0.5 and 5.5 hours after a 30‐min walk in 16 patients. Regional cartilage thickness changes measured from magnetic resonance images obtained at study entry and at 5‐year follow‐up were tested for correlations with baseline biomarker changes after mechanical stimulus, and for differences between groups stratified based on whether biomarker levels increased or decreased. Results showed that an increase in the degradation biomarker C1,2C correlated with cartilage thinning of the lateral tibia (R = −0.63, p = 0.009), whereas an increase in the synthesis marker CS846 correlated with cartilage thickening of the lateral femur (R = 0.76, p = 0.001). Changes in C1,2C and CS846 were correlated (R2 = 0.28, p = 0.037). Subjects with increased C1,2C had greater (p = 0.05) medial tibial cartilage thinning than those with decreased C1,2C. In conclusion, the mechanical stimulus appeared to metabolically link the biomarker responses where biomarker increases signaled more active OA disease states. The findings of medial cartilage thinning for patients with increases in the degradation marker and correlation of cartilage thickening in the less involved lateral femur with increases in the synthetic marker were consistent with progression of medial compartment OA. Thus, the mechanical stimulus facilitated assessing OA disease states using serum biomarkers. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:891–897, 2018.
Low Risk of High-Grade Dysplasia or Esophageal Adenocarcinoma Among Patients With Barrett's Esophagus Less Than 1 cm (Irregular Z Line) Within 5 Years of Index Endoscopy.

BACKGROUND & AIMS Many patients with a < 1 cm segment of columnar metaplasia in the distal esophagus, also called an irregular Z line, are encountered. These patients, often referred to as patients with Barrett's esophagus (BE), are enrolled in surveillance programs. However, little is known about their risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). We aimed to determine the incidence of HGD and EAC in patients with irregular Z line with intestinal metaplasia. METHODS We performed a prospective, multicenter cohort study of patients who underwent endoscopic examination for BE at tertiary care referral centers in the United States and Europe. We analyzed data from 1791 patients (mean age, 56 ± 17 years) found to have non-dysplastic BE at the index endoscopy and after 1 year or more of follow-up. Patients were followed for a median of 5.9 years (interquartile range, 3.1-8.3 years). We calculated rates of progression to HGD or EAC between groups of patients with irregular Z line (n = 167) and those with BE of ≥ 1 cm (n = 1624). RESULTS A higher proportion of patients in the irregular Z-line group were female (26.3%) than in the BE group (14.8% female BE) (P <.001). A lower proportion of patients in the irregular Z-line group were smokers (33.5%) than in the BE group (52.6% smokers). None of the patients with irregular Z line developed HGD or EAC during a median follow-up period of 4.8 years (interquartile range, 3.2-8.3 years). All 71 incident cases of HGD or EAC developed in patients with BE of ≥1 cm in length. On multivariate analysis, patients with irregular Z line and patients with BE of ≥ 1 cm did not differ significantly in age, race, or duration of follow-up. CONCLUSIONS In a prospective, multicenter cohort study, we found that patients with irregular Z line do not develop HGD or esophageal cancer within 5 years after index endoscopy.
Where Is the Evidence? A Systematic Review of Shared Decision Making and Patient Outcomes

Background. Despite widespread advocacy for shared decision making (SDM), the empirical evidence regarding its effectiveness to improve patient outcomes has not been systematically reviewed. The purpose of this study was to systematically review the empirical evidence linking patient outcomes and SDM, when the decision-making process has been explicitly measured, and to identify under what measurement perspectives SDM is associated with which types of patient outcomes (affective-cognitive, behavioral, and health). Data Sources. PubMed (through December 2012) and hand search of article bibliographies. Study Selection. Studies were included if they empirically 1) measured SDM in the context of a patient-clinician interaction and 2) evaluated the relationship between SDM and at least 1 patient outcome. Data Extraction. Study results were categorized by SDM measurement perspective (patient-reported, clinician-reported, or observer-rated) and outcome type (affective-cognitive, behavioral, or health). Data Synthesis. Thirty-nine studies met inclusion criteria. Thirty-three used patient-reported measures of SDM, 6 used observer-rated measures, and 2 used clinician-reported measures. Ninety-seven unique patient outcomes were assessed; 51% affective-cognitive, 28% behavioral, and 21% health. Only 43% of assessments (n = 42) found a significant and positive relationship between SDM and the patient outcome. This proportion varied by SDM measurement perspective and outcome category. It was found that 52% of outcomes assessed with patient-reported SDM were significant and positive, compared with 21% with observer-rated and 0% with clinician-reported SDM. Regardless of measurement perspective, SDM was most likely to be associated with affective-cognitive patient outcomes (54%), compared with 37% of behavioral and 25% of health outcomes. Limitations. The relatively small number of studies precludes meta-analysis. Because the study inclusion and exclusion criteria required both an empirical measure of SDM and an assessment of the association between that measure and a patient outcome, most included studies were observational in design. Conclusions. SDM, when perceived by patients as occurring, tends to result in improved affective-cognitive outcomes. Evidence is lacking for the association between empirical measures of SDM and patient behavioral and health outcomes.
Early Detection of Hepatocellular Carcinoma After Treatment With Direct-Acting Antivirals: Selection Bias or Biologically Plausible?

Marcia Cruz-Correa, Section Editor David Schwartz, Section Editor 65 66 STAFF OF CONTRIBUTORS 67 68 69 70 71 72 73 74 75 Joseph Anderson, White River Junction, VT Johanna L. Chan, Houston, TX Matthew A. Ciorba, St. Louis, MO Massimo Colombo, Milan, Italy Gregory A. Cote, Charleston, SC Evan S. Dellon, Chapel Hill, NC Alex Ford, Leeds, United Kingdom Lauren B. Gerson, San Francisco, CA David S. Goldberg, Philadelphia, PA Samir Gupta, San Diego, CA
Shoulder and arm muscle activity during elastic band exercises performed in a hospital bed

ABSTRACT Objective: Muscle atrophy is a common side-effect of bed rest during hospitalization. However, resistance training may minimize or even prevent these complications. Therefore, we evaluated the efficiency of four upper-body elastic resistance exercises that could be performed while lying or sitting in a hospital bed. Methods: Twenty-two healthy subjects performed three repetitions of each exercise in a supine and seated position with a perceived intensity of 3 (low) and 8 (high) on the Borg CR10 Scale. Surface electromyography was collected from 12 shoulder and arm muscles (e.g. trapezius, deltoideus, and biceps brachii), and normalized to a maximal voluntary isometric contraction (nEMG). Results: During all exercises performed at high intensity, moderate (>40%) to high (>60%) levels of nEMG were found for the majority of the analysed muscles, e.g. deltoideus (from 37% to 69%, median 57.5%), trapezius (from 43% to 66%, median 51%), and infraspinatus (from 54% to 66%, median 59%), with the exception of pectoralis major (from 29% to 47%, median 39.5%) and latissimus dorsi (from 15% to 22%, median 18.5%). No significant differences were found between the supine and seated positions for any of the exercises. Conclusion: This study showed that high levels of shoulder and arm muscle activity can be achieved while lying or sitting in a hospital bed using appropriate exercises with elastic bands. The data presented here can be used by physiotherapists as a guideline for selecting suitable and effective strengthening exercises during in-hospital rehabilitation to counteract bed-rest related muscle atrophy in the upper body.
Inferring infection hazard in wildlife populations by linking data across individual and population scales

Abstract Our ability to infer unobservable disease‐dynamic processes such as force of infection (infection hazard for susceptible hosts) has transformed our understanding of disease transmission mechanisms and capacity to predict disease dynamics. Conventional methods for inferring FOI estimate a time‐averaged value and are based on population‐level processes. Because many pathogens exhibit epidemic cycling and FOI is the result of processes acting across the scales of individuals and populations, a flexible framework that extends to epidemic dynamics and links within‐host processes to FOI is needed. Specifically, within‐host antibody kinetics in wildlife hosts can be short‐lived and produce patterns that are repeatable across individuals, suggesting individual‐level antibody concentrations could be used to infer time since infection and hence FOI. Using simulations and case studies (influenza A in lesser snow geese and Yersinia pestis in coyotes), we argue that with careful experimental and surveillance design, the population‐level FOI signal can be recovered from individual‐level antibody kinetics, despite substantial individual‐level variation. In addition to improving inference, the cross‐scale quantitative antibody approach we describe can reveal insights into drivers of individual‐based variation in disease response, and the role of poorly understood processes such as secondary infections, in population‐level dynamics of disease.
IMPACT OF FORMULATION INGREDIENTS ON QUALITY OF THE PARENTERAL PRODUCTS

Excipients are the integral part of pharmaceutical products development to achieve desired product profile. This review discusses the role of such excipients as well as the impact of formulation ingredient on quality of the parenteral product. The role of excipients such as bulking agents, buffering agents, tonicity modifiers, antimicrobial agents, surfactants and co-solvents as well as their impact on the quality of the products has also been discussed. Development of parenteral preparations typically requires specific consideration on the type and quality of excipients used. Excipients play a critical role in the creation of medicines, helping to preserve the efficacy, safety and stability of active pharmaceutical ingredients and ensuring that they delivered their promised benefits to patients. A careful choice of excipients is crucial for the development of effective and innovative pharmaceuticals. In spite of proper excipients selection, judicious use during formulation manufacturing process based on their critical properties is also important to avoid negative effects such as loss of drug solubility, activity and stability. To deliver parenteral drugs to the final consumer, with intact product quality has remained a prime concern for every parenteral drug manufacturer.
Genomic sequencing-based mutational enrichment analysis identifies motility genes in a genetically intractable gut microbe

Significance There is broad interest in the role microbial communities play in human health. Although DNA-sequencing technologies enabled a broad assessment of microbial diversity and genomic content, our understanding of the molecular mechanisms underlying microbe–microbe and microbe–host interactions has proceeded much more slowly because only a small fraction of microbes are amenable to molecular genetic manipulation. We describe a method, independent of recombinant DNA tools, to perform genetic analysis in any cultivatable microbial species. We identified determinants of motility in a member of the vertebrate microbiome, the Firmicutes Exiguobacterium acetylicum, and experimentally determined a role for motility in animal colonization by this previously uncharacterized commensal bacteria that is important for host nutrient homeostasis. A major roadblock to understanding how microbes in the gastrointestinal tract colonize and influence the physiology of their hosts is our inability to genetically manipulate new bacterial species and experimentally assess the function of their genes. We describe the application of population-based genomic sequencing after chemical mutagenesis to map bacterial genes responsible for motility in Exiguobacterium acetylicum, a representative intestinal Firmicutes bacterium that is intractable to molecular genetic manipulation. We derived strong associations between mutations in 57 E. acetylicum genes and impaired motility. Surprisingly, less than half of these genes were annotated as motility-related based on sequence homologies. We confirmed the genetic link between individual mutations and loss of motility for several of these genes by performing a large-scale analysis of spontaneous suppressor mutations. In the process, we reannotated genes belonging to a broad family of diguanylate cyclases and phosphodiesterases to highlight their specific role in motility and assigned functions to uncharacterized genes. Furthermore, we generated isogenic strains that allowed us to establish that Exiguobacterium motility is important for the colonization of its vertebrate host. These results indicate that genetic dissection of a complex trait, functional annotation of new genes, and the generation of mutant strains to define the role of genes in complex environments can be accomplished in bacteria without the development of species-specific molecular genetic tools.
Extensive Microbial and Functional Diversity within the Chicken Cecal Microbiome

Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, including the ceca. We have carried out deep microbial community profiling of the microbiota in twenty cecal samples via 16S rRNA gene sequences and an in-depth metagenomics analysis of a single cecal microbiota. We recovered 699 phylotypes, over half of which appear to represent previously unknown species. We obtained 648,251 environmental gene tags (EGTs), the majority of which represent new species. These were binned into over two-dozen draft genomes, which included Campylobacter jejuni and Helicobacter pullorum. We found numerous polysaccharide- and oligosaccharide-degrading enzymes encoding within the metagenome, some of which appeared to be part of polysaccharide utilization systems with genetic evidence for the co-ordination of polysaccharide degradation with sugar transport and utilization. The cecal metagenome encodes several fermentation pathways leading to the production of short-chain fatty acids, including some with novel features. We found a dozen uptake hydrogenases encoded in the metagenome and speculate that these provide major hydrogen sinks within this microbial community and might explain the high abundance of several genera within this microbiome, including Campylobacter, Helicobacter and Megamonas.
Tollip or Not Tollip: What Are the Evolving Questions behind It?

Tollip plays an important role in the interleukin-1 receptor IL-1R and Toll pathways. As a modulator of the immune pathway, it indirectly controls the amount of antimicrobial peptides. This could indicate a vital step in maintaining animal immune systems and preventing infection. Evolutionary questions are crucial to understanding the conservation and functioning of the biochemical pathways like the Tollip-mediated one. Through an analysis of 36 sequences of the Tollip protein from different animal taxa, downloaded from Kyoto Encyclopedia of Genes and Genomes (KEGG) databank, we inferred diverse evolutionary parameters, such as molecular selection and structure conservation, by analyzing residue by residue, beyond the canonical parameters to this type of study, as maximum likelihood trees. We found that Tollip presented different trends in its evolving history. In primates, the protein is becoming more unstable, just the opposite is observed in the arthropod group. The most interesting finding was the concentration of positively selected residues at amino terminal ends. Some observed topological incongruences in maximum likelihood trees of complete and curated Tollip data sets could be explained through horizontal transfers, evidenced by recombination detection. These results suggest that there is more to be researched and understood about this protein.
Mosaic and Concerted Evolution in the Visual System of Birds

Two main models have been proposed to explain how the relative size of neural structures varies through evolution. In the mosaic evolution model, individual brain structures vary in size independently of each other, whereas in the concerted evolution model developmental constraints result in different parts of the brain varying in size in a coordinated manner. Several studies have shown variation of the relative size of individual nuclei in the vertebrate brain, but it is currently not known if nuclei belonging to the same functional pathway vary independently of each other or in a concerted manner. The visual system of birds offers an ideal opportunity to specifically test which of the two models apply to an entire sensory pathway. Here, we examine the relative size of 9 different visual nuclei across 98 species of birds. This includes data on interspecific variation in the cytoarchitecture and relative size of the isthmal nuclei, which has not been previously reported. We also use a combination of statistical analyses, phylogenetically corrected principal component analysis and evolutionary rates of change on the absolute and relative size of the nine nuclei, to test if visual nuclei evolved in a concerted or mosaic manner. Our results strongly indicate a combination of mosaic and concerted evolution (in the relative size of nine nuclei) within the avian visual system. Specifically, the relative size of the isthmal nuclei and parts of the tectofugal pathway covary across species in a concerted fashion, whereas the relative volume of the other visual nuclei measured vary independently of one another, such as that predicted by the mosaic model. Our results suggest the covariation of different neural structures depends not only on the functional connectivity of each nucleus, but also on the diversity of afferents and efferents of each nucleus.
High performance analysis of big spatial data

Every year research institutions produce petabytes of data. Yet, only a small percent of the data is readily accessible for analysis. Terra Populus acts as the bridge between big data sources and researchers. Researchers are provided convenient web applications that allow them to access, analyze, and tabulate different datasets under a common platform. Terra Populus is developing three unique applications. The first application, Paragon, is a prototype parallel spatial database, which aims to extend the functionality of PostgreSQL and PostGIS onto multinode systems. Terra Populus' Tabulator application employs Parquet on Spark to build dynamic queries for analyzing large population survey data. The last application, Terra Explorer, is an exploratory analysis tool for visualizing the spatial datasets within the repository.
Reward Sensitivity and Waiting Impulsivity: Shift towards Reward Valuation away from Action Control

Abstract Background Impulsivity and reward expectancy are commonly interrelated. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess human waiting impulsivity using a novel translational task, the 4-Choice Serial Reaction Time task, and the relationship with reward cues. Methods Healthy volunteers (n=29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1), or no reward. Waiting impulsivity was tested with the 4-Choice Serial Reaction Time task. Results For high reward prospects (£5, no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex and lower supplementary motor area activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with orbitofrontal cortex and greater subgenual cingulate connectivity with anterior insula, but decreased connectivity with regions implicated in action selection and preparation. Conclusion These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction.
A Uniaxial Testing Approach for Consistent Failure in Vascular Tissues.

Although uniaxial tensile testing is commonly used to evaluate failure properties of vascular tissue, there is no established protocol for specimen shape or gripping method. Large percentages of specimens are reported to fail near the clamp and can potentially confound the studies, or, if discarded will result in sample waste. The objective of this study is to identify sample geometry and clamping conditions that can achieve consistent failure in the mid-region of small arterial specimens, even for vessels from older individuals. Failure location was assessed in 17 dogbone specimens from human cerebral and sheep carotid arteries using soft inserts. For comparison with commonly used protocols, an additional 22 rectangular samples were tested using either sandpaper or foam tape inserts. Mid-sample failure was achieved in 94% of the dogbone specimens, while only 14% of the rectangular samples failed in the mid-region, the other 86% failing close to the clamps. Additionally, we found mid-region failure was more likely to be abrupt, caused by cracking or necking. In contrast, clamp failure was more likely to be gradual and included a delamination mode not seen in mid-region failure. Hence, this work provides an approach that can be used to obtain consistent mid-specimen failure, avoiding confounding clamp related artifacts. Furthermore, with consistent mid-region failure, studies can be designed to image the failure process in small vascular samples providing valuable quantitative information about changes to collagen and elastin structure during the failure process.