Miracle-dz/UniFAR-FTUs huggingface dataset:
Contribution of Neuromuscular Factors to Quadriceps Asymmetry After Anterior Cruciate Ligament Reconstruction.

CONTEXT To quantify quadriceps weakness after anterior cruciate ligament reconstruction (ACLR), researchers have often analyzed only peak torque. However, analyzing other characteristics of the waveform, such as the rate of torque development (RTD), time to peak torque (TTP), and central activation ratio (CAR), can lend insight into the underlying neuromuscular factors that regulate torque development. OBJECTIVE To determine if interlimb neuromuscular asymmetry was present in patients with ACLR at the time of clearance to return to activity. DESIGN Cross-sectional study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 10 individuals serving as controls (6 men, 4 women; age = 23.50 ± 3.44 years, height = 1.73 ± 0.09 m, mass = 71.79 ± 9.91 kg) and 67 patients with ACLR (43 men, 24 women; age = 21.34 ± 5.73 years, height = 1.74 ± 0.11 m, mass = 77.85 ± 16.03 kg, time postsurgery = 7.52 ± 1.36 months) participated. MAIN OUTCOME MEASURE(S) Isokinetic (60°/s) and isometric quadriceps strength were measured. Peak torque, TTP, and RTD were calculated across isometric and isokinetic trials, and CAR was calculated from the isometric trials via the superimposed burst. Repeated-measures analyses of variance were used to compare limbs in the ACLR and control groups. RESULTS No between-limbs differences were detected in the control group ( P > .05). In the ACLR group, the involved limb demonstrated a longer TTP for isokinetic strength ( P = .04; Cohen d effect size [ES] = 0.18; 95% confidence interval [CI] = -0.16, 0.52), lower RTD for isometric ( P < .001; Cohen d ES = 0.73; 95% CI = 0.38, 1.08) and isokinetic ( P < .001; Cohen d ES = 0.84; 95% CI = 0.49, 1.19) strength, lower CAR ( P < .001; Cohen d ES = 0.37; 95% CI = 0.03, 0.71), and lower peak torque for isometric ( P < .001; Cohen d ES = 1.28; 95% CI = 0.91, 1.65) and isokinetic ( P < .001; Cohen d ES = 1.15; 95% CI = 0.78, 1.52) strength. CONCLUSIONS Interlimb asymmetries at return to activity after ACLR appeared to be regulated by several underlying neuromuscular factors. We theorize that interlimb asymmetries in isometric and isokinetic quadriceps strength were associated with changes in muscle architecture. Reduced CAR, TTP, and RTD were also present, indicating a loss of motor-unit recruitment or decrease in firing rate.
From Mitochondria to Disease: Role of the Renin-Angiotensin System

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.
Animal models for the study of hepatitis B virus infection

Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus (HBV) worldwide. Current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.
Research Roadmap for Tuberculosis Transmission Science: Where Do We Go From Here and How Will We Know When We’re There?

Abstract High rates of tuberculosis transmission are driving the ongoing global tuberculosis epidemic, and there is a pressing need for research focused on understanding and, ultimately, halting transmission. The ongoing tuberculosis–human immunodeficiency virus (HIV) coepidemic and rising rates of drug-resistant tuberculosis in parts of the world add further urgency to this work. Success in this research will require a concerted, multidisciplinary effort on the part of tuberculosis scientists, clinicians, programs, and funders and must span the research spectrum from biomedical sciences to the social sciences, public health, epidemiology, cost-effectiveness analyses, and operations research. Heterogeneity of tuberculosis disease, both among individual patients and among communities, poses a substantial challenge to efforts to interrupt transmission. As such, it is likely that effective interventions to stop transmission will require a combination of approaches that will vary across different epidemiologic settings. This research roadmap summarizes key gaps in our current understanding of transmission, as laid out in the preceding articles in this series. We also hope that it will be a call to action for the global tuberculosis community to make a sustained commitment to tuberculosis transmission science. Halting transmission today is an essential step on the path to end tuberculosis tomorrow.
Analytical Application of Lectins

ABSTRACT This review is devoted to the analytical application of carbohydrate-binding proteins called lectins. The nature of lectins and the regularities of their specificity with respect to simple sugars and complex carbohydrate-containing biomolecules are discussed. The main areas of the modern analytical application of lectins are described. Lectin-affinity chromatography, histo- and cytochemical approaches, lectin blotting, microarray, and biosensor technologies as well as microplate analysis are considered in detail. Data on the use of lectins for the detection of cells and microorganisms as well as the study of protein glycosylation are summarized. The large potential of lectins as components of analytical systems used for the identification of glycans and the characteristics of their structure are substantiated.
Selective antigen‐specific CD4+ T‐cell, but not CD8+ T‐ or B‐cell, tolerance corrupts cancer immunotherapy

Self‐tolerance, presumably through lineage‐unbiased elimination of self‐antigen‐specific lymphocytes (CD4+ T, CD8+ T, and B cells), creates a formidable barrier to cancer immunotherapy. In contrast to this prevailing paradigm, we demonstrate that for some antigens, self‐tolerance reflects selective elimination of antigen‐specific CD4+ T cells, but preservation of CD8+ T‐ and B‐cell populations. In mice, antigen‐specific CD4+ T‐cell tolerance restricted CD8+ T‐ and B‐cell responses targeting the endogenous self‐antigen guanylyl cyclase c (GUCY2C) in colorectal cancer. Although selective CD4+ T‐cell tolerance blocked GUCY2C‐specific antitumor immunity and memory responses, it offered a unique solution to the inefficacy of GUCY2C vaccines through recruitment of self‐antigen‐independent CD4+ T‐cell help. Incorporating CD4+ T‐cell epitopes from foreign antigens into vaccines against GUCY2C reconstituted CD4+ T‐cell help, revealing the latent functional capacity of GUCY2C‐specific CD8+ T‐ and B‐cell pools, producing durable antitumor immunity without autoimmunity. Incorporating CD4+ T‐cell epitopes from foreign antigens into vaccines targeting self‐antigens in melanoma (Trp2) and breast cancer (Her2) produced similar results, suggesting selective CD4+ T‐cell tolerance underlies ineffective vaccination against many cancer antigens. Thus, identification of self‐antigens characterized by selective CD4+ T‐cell tolerance and abrogation of such tolerance through self‐antigen‐independent T‐cell help is essential for future immunotherapeutics.
Widespread Genome Reorganization of an Obligate Virus Mutualist

The family Polydnaviridae is of interest because it provides the best example of viruses that have evolved a mutualistic association with their animal hosts. Polydnaviruses in the genus Bracovirus are strictly associated with parasitoid wasps in the family Braconidae, and evolved ∼100 million years ago from a nudivirus. Each wasp species relies on its associated bracovirus to parasitize hosts, while each bracovirus relies on its wasp for vertical transmission. Prior studies establish that bracovirus genomes consist of proviral segments and nudivirus-like replication genes, but how these components are organized in the genomes of wasps is unknown. Here, we sequenced the genome of the wasp Microplitis demolitor to characterize the proviral genome of M. demolitor bracovirus (MdBV). Unlike nudiviruses, bracoviruses produce virions that package multiple circular, double-stranded DNAs. DNA segments packaged into MdBV virions resided in eight dispersed loci in the M. demolitor genome. Each proviral segment was bounded by homologous motifs that guide processing to form mature viral DNAs. Rapid evolution of proviral segments obscured homology between other bracovirus-carrying wasps and MdBV. However, some domains flanking MdBV proviral loci were shared with other species. All MdBV genes previously identified to encode proteins required for replication were identified. Some of these genes resided in a multigene cluster but others, including subunits of the RNA polymerase that transcribes structural genes and integrases that process proviral segments, were widely dispersed in the M. demolitor genome. Overall, our results indicate that genome dispersal is a key feature in the evolution of bracoviruses into mutualists.
Maps From Mud—Using the Multiple Scenario Approach to Reconstruct Land Cover Dynamics From Pollen Records: A Case Study of Two Neolithic Landscapes

Pollen records contain a wide range of information about past land cover, but translation from the pollen diagram to other formats remains a challenge. In this paper, we present LandPolFlow, a software package enabling Multiple Scenario Approach (MSA) based land cover reconstruction from pollen records for specific landscapes. It has two components: a basic Geographic Information System which takes grids of landscape constraints (e.g. topography, geology) and generates possible 'scenarios' of past land cover using a combination of probabilistic and deterministic placement rules to distribute defined plant communities within the landscape, and a pollen dispersal and deposition model which simulates pollen loading at specified points within each scenario and compares that statistically with actual pollen assemblages from the same location. Goodness of fit statistics from multiple pollen site locations are used to identify which scenarios are likely reconstructions of past land cover. We apply this approach to two case studies of Neolithisation in Britain, the first from the Somerset Levels and the second from Mainland, Orkney. Both landscapes contain significant evidence of Neolithic activity, but present contrasting contexts. In Somerset, wet-preserved Neolithic remains such as trackways are abundant, but little dry land settlement archaeology is known, and the pre-Neolithic landscape was extensively wooded. In Orkney, the Neolithic archaeology includes domestic and monumental stone-built structures forming a UNESCO World Heritage Site, and the pre-Neolithic landscape was largely treeless. Existing pollen records were collated from both landscapes and correlated within a new age model framework (presented elsewhere). This allowed pollen data to be grouped into 200 year periods, or “timeslices”, for reconstruction of land cover through time using the MSA. Reconstruction suggests that subtle but clear and persistent impacts of Neolithisation on land cover occurred in both landscapes, with no reduction in impact during periods when archaeological records suggest lower activity levels. By applying the methodology to specific landscapes, we critically evaluate the strengths and weaknesses and identify potential remedies, which we then expand into consideration of how simulation can be incorporated into palynological research practice. We argue that the MSA deserves a place within the palynologist’s standard tool kit.
Osteochondral lesions of the talus

Background and purpose — The frequency of progression of osteoarthritis and persistence of symptoms in untreated osteochondral lesion of the talus (OCL) is not well known. We report the outcome of a nonoperative treatment for symptomatic OCL. Patients and methods — This study included 142 patients with OCLs from 2003 to 2013. The patients did not undergo immobilization and had no restrictions of physical activities. The mean follow-up time was 6 (3–10) years. Initial MRI and CT confirmed OCL and showed lesion size, location, and stage of the lesion. Progression of osteoarthritis was evaluated by standing radiographs. In 83 patients, CT was performed at the final follow-up for analyses of the lesion size. We surveyed patients for limitations of sports activity, and Visual Analogue Scales (VAS), AOFAS, and SF-36 were assessed. Results — No patients had progression of osteoarthritis. The lesion size as determined by CT did not change in 69/83 patients, decreased in 5, and increased in 9. The mean VAS score of the 142 patients decreased from 3.8 to 0.9 (p < 0.001), the mean AOFAS ankle–hindfoot score increased from 86 to 93 (p < 0.001), and the mean SF-36 score increased from 52 to 72 (p < 0.001). Only 9 patients reported limitations of sports activity. The size and location of the lesion did not correlate with any of the outcome scores. Interpretation — Nonoperative treatment can be considered a good option for patients with OCL.
Cigarette Smoking and Risk of Early Natural Menopause

Menopause before 45 years of age affects roughly 5%-10% of women and is associated with a higher risk of adverse health conditions. Although smoking may increase the risk of early menopause, evidence is inconsistent, and data regarding smoking amount, duration, cessation, associated risks, and patterns over time are scant. We analyzed data of 116,429 nurses from the Nurses' Health Study II from 1989 through 2011 and used Cox proportional hazards models to estimate hazard ratios adjusted for confounders. Compared with never-smokers, current smokers (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.71, 2.11) and former smokers (HR = 1.10, 95% CI: 1.00, 1.21) showed an increased risk of early menopause. Increased risks were observed among women who reported current smoking for 11-15 pack-years (HR = 1.72, 95% CI: 1.36, 2.18), 16-20 pack-years (HR = 1.72, 95% CI: 1.38, 2.14), and more than 20 pack-years (HR = 2.42, 95% CI: 2.11, 2.77). Elevated risk was observed in former smokers who reported 11-15 pack-years (HR = 1.29, 95% CI: 1.07, 1.55), 16-20 pack-years (HR = 1.42, 95% CI: 1.13, 1.79), or more than 20 pack-years (HR = 1.54, 95% CI: 1.23, 1.93). Women who smoked 10 or fewer cigarettes/day but quit by age 25 had comparable risk to never-smokers (HR = 1.03, 95% CI: 0.91, 1.17). A dose-response relationship between smoking and early natural menopause risk, as well as reduced risk among quitters, may provide insights into the mechanisms of cigarette smoking in reproductive health.
Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae

The concept that mutations cause aging phenotypes could not be directly tested previously due to inability to identify age‐related mutations in somatic cells and determine their impact on organismal aging. Here, we subjected Saccharomyces cerevisiae to multiple rounds of replicative aging and assessed de novo mutations in daughters of mothers of different age. Mutations did increase with age, but their low numbers, < 1 per lifespan, excluded their causal role in aging. Structural genome changes also had no role. A mutant lacking thiol peroxidases had the mutation rate well above that of wild‐type cells, but this did not correspond to the aging pattern, as old wild‐type cells with few or no mutations were dying, whereas young mutant cells with many more mutations continued dividing. In addition, wild‐type cells lost mitochondrial DNA during aging, whereas shorter‐lived mutant cells preserved it, excluding a causal role of mitochondrial mutations in aging. Thus, DNA mutations do not cause aging in yeast. These findings may apply to other damage types, suggesting a causal role of cumulative damage, as opposed to individual damage types, in organismal aging.
The mitochondrial genome of Iberobaenia (Coleoptera: Iberobaeniidae): first rearrangement of protein-coding genes in the beetles

Abstract The complete mitochondrial genome of the recently discovered beetle family Iberobaeniidae is described and compared with known coleopteran mitogenomes. The mitochondrial sequence was obtained by shotgun metagenomic sequencing using the Illumina Miseq technology and resulted in an average coverage of 130 × and a minimum coverage of 35×. The mitochondrial genome of Iberobaeniidae includes 13 protein-coding genes, 2 rRNAs, 22 tRNAs genes, and 1 putative control region, and showed a unique rearrangement of protein-coding genes. This is the first rearrangement affecting the relative position of protein-coding and ribosomal genes reported for the order Coleoptera.
Relationship between physician-based assessment of disease activity, quality of life, and costs of ulcerative colitis in Poland

Introduction Ulcerative colitis (UC) is an idiopathic inflammatory bowel disorder, which requires lifelong treatment. It generates substantial direct and indirect costs, and significantly affects the quality of life, especially in the active state of the disease. Aim To evaluate the direct and indirect costs of UC as well as to assess disease activity and quality of life reported by patients with UC in Polish settings. Material and methods A questionnaire, cross-sectional study among UC patients as well as physicians involved in the therapy of the patients was conducted. The Clinical Activity Index (CAI) was used to assess disease activity, and the WPAI questionnaire to assess productivity loss. The quality of life was presented as utility calculated using the EQ-5D-3L questionnaire. Indirect costs included absenteeism, presenteeism, and informal care were assessed with the Human Capital Approach and expressed in euros (€). The productivity loss among informal caregivers was valuated with the average wage in Poland. Correlations were presented using the Spearman’s coefficient, and the between-group difference was assessed with Mann-Whitney U-test. Results One hundred and forty-seven patients participated in the study, including 95 working persons. Mean cost of absenteeism and presenteeism was €1615.2 (95% CI: 669.5–2561.0) and €3684.4 (95% CI: 2367.8–5001.1), respectively, per year per patient with a disease in remission. The mean yearly cost of productivity loss due to informal care was estimated to be €256.6 (range: 0.0–532.6). The corresponding values for patients with active disease were: €8,913.3 (95% CI: 6223.3–11,603.3), €4325.1 (95% CI: 2282.4–6367.8), and €2396.1 (95% CI: 402.0–4390.3). The between-group difference in total indirect costs, cost of absenteeism, and cost of informal care was statistically significant (p < 0.05). The average weighted monthly costs of therapy with particular drugs categories (e.g. mesalazine or biologic drugs) differed significantly between active disease or remission patients. The difference in utility values between patients with a disease in remission (0.898 ±0.126) and patients with an active disease (0.646 ±0.302) was statistically significant. Conclusions Our study revealed the social burden of UC and high dependency of direct and indirect costs as well as quality of life on the severity of UC in Poland. The statistically significant differences were identified in total direct and indirect cost, cost of absenteeism, cost of informal care, and health-related quality of life among patients with an active disease compared to patients with a disease in remission.
Simplified Disease Activity Index remission at month 6 is an independent predictor of functional and structural remissions at month 12 during abatacept treatment in patients with rheumatoid arthritis: A multi-center, prospective cohort study in Japan

Abstract Objective: To evaluate association of clinical remission at month 6 with functional and structural remissions at month 12 during abatacept treatment in patients with rheumatoid arthritis (RA). Methods: This 12-month prospective, multicenter cohort study enrolled 168 patients with RA who started abatacept. Outcomes were assessed using composite measures, quality of life indices, and the van der Heijde-modified total Sharp score (mTSS). The logistic regression analysis was applied to identify factors associated with outcomes and their odds ratios (OR) with 95% confidence interval (95% CI). Results: At month 6 and 12, 21.4% and 26.2% of the patients achieved Simplified Disease Activity Index (SDAI) remission (SDAI <3.3), and 40.6% and 41.7% achieved Health Assessment Questionnaire-Disability Index (HAQ-DI <0.5) remission. Among 129 patients whose mTSS progression was evaluated at month 12, 83 (64.3%) achieved structural remission (ΔmTSS ≤0.5 for 12 months). SDAI remission at month 6 was identified as a significant predictor of both functional (OR, 3.732; 95% CI, 1.328–10.489) and structural remissions (OR, 4.301; 95% CI, 1.298–14.243) at month 12 after adjusting for covariates. Conclusions: Aiming for SDAI remission at month 6 is an appropriate strategy to obtain good functional and structural outcomes at month 12.
Accelerated Simplified Swarm Optimization with Exploitation Search Scheme for Data Clustering

Data clustering is commonly employed in many disciplines. The aim of clustering is to partition a set of data into clusters, in which objects within the same cluster are similar and dissimilar to other objects that belong to different clusters. Over the past decade, the evolutionary algorithm has been commonly used to solve clustering problems. This study presents a novel algorithm based on simplified swarm optimization, an emerging population-based stochastic optimization approach with the advantages of simplicity, efficiency, and flexibility. This approach combines variable vibrating search (VVS) and rapid centralized strategy (RCS) in dealing with clustering problem. VVS is an exploitation search scheme that can refine the quality of solutions by searching the extreme points nearby the global best position. RCS is developed to accelerate the convergence rate of the algorithm by using the arithmetic average. To empirically evaluate the performance of the proposed algorithm, experiments are examined using 12 benchmark datasets, and corresponding results are compared with recent works. Results of statistical analysis indicate that the proposed algorithm is competitive in terms of the quality of solutions.