Miracle-dz/UniFAR-FTUs huggingface dataset:
Laxity Testing of the Shoulder

Laxity testing is an important part of the examination of any joint. In the shoulder, it presents unique challenges because of the complexity of the interactions of the glenohumeral and scapulothoracic joints. Many practitioners believe that laxity testing of the shoulder is difficult, and they are unclear about its role in evaluation of patients. The objectives of the various laxity and instability tests differ, but the clinical signs of such tests can provide helpful information about joint stability. This article summarizes the principles of shoulder laxity testing, reviews techniques for measuring shoulder laxity, and evaluates the clinical usefulness of the shoulder laxity tests. Shoulder laxity evaluation can be a valuable element of the shoulder examination in patients with shoulder pain and instability.
Inhibition of Type I Insulin-Like Growth Factor Receptor Signaling Attenuates the Development of Breast Cancer Brain Metastasis

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.
Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug.

BACKGROUND Fibroblasts undergo a morphological transformation to a reactive phenotype in the tumor microenvironment characterized by the expression of proteins such as fibroblast activation protein (FAP), a post-prolyl endopeptidase with expression largely restricted to carcinoma-associated fibroblasts. Thapsigargin (TG) is a highly toxic natural plant product that triggers a rise in intracellular calcium levels and apoptosis. FAP is therefore a provocative target for the activation of prodrugs consisting of a FAP-specific peptide coupled to a potent cytotoxic analog of TG. METHODS The efficacy of FAP-activated peptidyl-TG prodrugs was tested in vitro in cell proliferation assays and effects on intracellular calcium in human cancer cell lines. The effects of FAP-activated prodrugs on tumor growth and host toxicity were tested in Balb-C nude MCF-7 and LNCaP xenograft mice (n = 9-11 per group). P values were calculated using permutation tests based on 50 000 permutations. Mixed effects models were used to account for correlations among replicate measures. All statistical tests were two-sided. RESULTS FAP-activated prodrugs killed human cancer cells at low nanomolar concentrations (MCF-7 cells: IC(50) = 3.5 nM). Amino acid-12ADT analogs from FAP-cleaved prodrugs, but not uncleaved prodrugs, produced a rapid rise in intracellular calcium within minutes of exposure. Immunohistochemical analysis of xenografts exposed to FAP-prodrugs documented stromal-selective cell death of fibroblasts, pericytes, and endothelial cells of sufficient magnitude to inhibit growth of MCF-7 and LNCaP xenografts with minimal systemic toxicity, whereas non-FAP cleavable prodrugs were inactive. MCF-7 and LNCaP xenografts treated with a FAP-activated prodrug had maximal treated-to-control tumor volume ratios of 0.36 (treated: mean = 0.206 mm(3), 95% CI = 0.068 to 0.344 mm(3); control: mean = 0.580 mm(3), 95% CI = 0.267 to 0.893 mm(3)) and 0.24 (treated: mean = 0.131 mm(3), 95% CI = 0.09 to 0.180 mm(3); control: mean = 0.543 mm(3), 95% CI = 0.173 to 0.913 mm(3)), respectively, on day 21 after therapy. CONCLUSIONS This study validates the proteolytic activity of FAP as a target for the activation of a systemically delivered cytotoxic prodrug and demonstrates that targeted killing of cells within the stromal compartment of the tumor microenvironment can produce a therapeutic response.
p-Values for High-Dimensional Regression

Assigning significance in high-dimensional regression is challenging. Most computationally efficient selection algorithms cannot guard against inclusion of noise variables. Asymptotically valid p-values are not available. An exception is a recent proposal by Wasserman and Roeder that splits the data into two parts. The number of variables is then reduced to a manageable size using the first split, while classical variable selection techniques can be applied to the remaining variables, using the data from the second split. This yields asymptotic error control under minimal conditions. This involves a one-time random split of the data, however. Results are sensitive to this arbitrary choice, which amounts to a “p-value lottery” and makes it difficult to reproduce results. Here we show that inference across multiple random splits can be aggregated while maintaining asymptotic control over the inclusion of noise variables. We show that the resulting p-values can be used for control of both family-wise error and false discovery rate. In addition, the proposed aggregation is shown to improve power while reducing the number of falsely selected variables substantially.
Regulation of nitrogenase activity by ammonium chloride in Azospirillum spp

Ammonium chloride (greater than or equal to 0.05 mM) effectively and reversibly inhibited the nitrogenase activity of Azospirillum brasilense, Azospirillum lipoferum and Azospirillum amazonense. The glutamine synthetase inhibitor L-methionine-DL- sulfoximine abolished this "switch-off" in A. lipoferum and A. brasilense, but not in A. amazonense. Azaserine, an inhibitor of glutamate synthase, inhibited nitrogenase activity itself. This provides further evidence for glutamine as a metabolite of regulatory importance in the NH4+ switch-off phenomenon. In A. brasilense and A. lipoferum, a transition period before the complete inhibition of nitrogenase activity after the addition of 1 mM ammonium chloride was observed. The in vitro nitrogenase activity also was decreased after treatment with ammonium. During sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a second dinitrogenase reductase (Fe protein) subunit appeared, which migrated in coincidence with the modified subunit of the inactive Fe protein of the nitrogenase of Rhodospirillum rubrum. After the addition of ammonium 32P was incorporated into this subunit of the Fe protein of A. brasilense. In A. amazonense, the inhibition of nitrogenase activity by ammonium was only partial, and no transition period could be observed. The in vitro nitrogenase activity of ammonium-treated cells was not decreased, and no evidence for a modified Fe protein subunit was found. Nitrogenase extracts of A. amazonense were active and had an Fe protein that migrated as a close double band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β −/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system.
Mapping white matter integrity in elderly people with HIV

People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z‐score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV. Hum Brain Mapp 35:975–992, 2014. © 2013 Wiley Periodicals, Inc.
Does Red Cell Distribution Width Predict Outcome in Traumatic Brain Injury: Comparison to Corticosteroid Randomization After Significant Head Injury

Background Traumatic brain injury (TBI) is a leading cause of death and disability. The role of red cell distribution width (RDW) as a prognostic biomarker for outcome in TBI patients is unknown. Based on the corticosteroid randomization after significant head injury (CRASH) trial database, a prognosis calculator (CRASH) has been developed for outcome prediction in TBI. The objectives of this study are to investigate the association between RDW on day 1 of TBI and outcome, and to compare outcome prediction from RDW to that from CRASH. Methods We performed a retrospective review of patients with TBI and a Glasgow coma scale (GCS) score of 14 or less. Day 1 RDW and CRASH data were extracted. CRASH was calculated for each patient. Outcome was defined as mortality at 14 days and GOS at 6 months, with poor outcome defined as GOS of 1 - 3. Patients were stratified according to RDW values into six groups, and according to CRASH values into six groups. Results A total of 416 patients with TBI were included, with 339 survivors (S) and 77 non-survivors (NS). Compared to survivors, non-survivors were of similar age in years (58 ± 23 vs. 58 ± 23, P = 1.0), had lower GCS scores (5 ± 3 vs. 12 ± 3, P = 0.0001), similar RDW (14.0 ± 1.2 vs. 13.9 ± 1.5, P = 0.6), and higher CRASH values (68 ± 26 vs. 24 ± 22, P = 0.0001). Estimating the receiver-operating characteristic (ROC) area under the curve (AUC) showed that CRASH was a significantly better predictor of mortality compared to RDW (AUC = 0.91 ± 0.01 for CRASH compared to 0.66 ± 0.03 for RDW; P < 0.0001). In addition, CRASH was a better predictor of neurologic outcome compared to RDW (AUC = 0.85 ± 0.02 for CRASH compared to 0.76 ± 0.03 for RDW; P = 0.005). Conclusions CRASH calculator was a strong predictor of mortality in patients with TBI. RDW on day 1 did not differ between survivors and non-survivors, and was a poor predictor of mortality. Both RDW on day 1 and CRASH calculator are good predictors of 6-month outcome in TBI patients, although CRASH calculator remains a better predictor.
Appearance of sialoglycoproteins in encysting cells of Entamoeba histolytica

Amoeba-bacterium cultures of Entamoeba histolytica transferred to a hypoosmotic medium depleted of nutrients changed morphologically and biochemically. The cells ejected grains of rice starch, rounded up, and formed a distinct cell wall that was resistant to detergent, bound the sialic acid-specific lectin from Limulus polyphemus, and became fluorescent with Calcofluor M2R. A subpopulation of these cells displayed more than one nucleus. All these signs are characteristic of encysting cells and were also observed in cysts obtained from a human patient. The morphological changes were accompanied by the appearance of two new glycoproteins with apparent molecular sizes of 100 and 150 kilodaltons which contained sialic acid. Sialic acid has been reported to be absent from trophozoites of Entamoeba species. The presence of this sugar residue on cyst-specific proteins parallels recently reported findings during the encystation of the related reptilian parasite Entamoeba invadens. This may indicate a basic role for sialic acid in the encystation of Entamoeba parasites.
Immobilizing osteogenic growth peptide with and without fibronectin on a titanium surface: effects of loading methods on mesenchymal stem cell differentiation

In this study, to improve the osseointegration of implants, osteogenic growth peptide (OGP) and fibronectin (FN) were loaded within mineral, which was formed on titanium, through adsorption and coprecipitation methods. The release profiles of OGP loaded by either adsorption or coprecipitation and the effects of the loading methods to immobilize OGP with and without FN on rat mesenchymal stem cell (rMSC) osteogenic differentiation were studied. The coprecipitation approach slightly reduced the initial burst release, while the adsorption approach provided a more sustained release. Dual loading of OGP and FN further improved cell attachments compared with either OGP or FN alone. Dually loaded OGP and FN also had a positive impact on rMSC proliferation and osteogenic differentiation. The difference in methods of loading OGP with and without FN also had some effects on osteogenic differentiation. Compared with coprecipitated OGP alone, adsorbed OGP enhanced later differentiation, such as osteocalcin secretion and matrix mineralization. Simultaneously adsorbed OGP and FN led to higher proliferation and higher osteogenic differentiation in both early and late stages compared with sequentially loaded OGP and FN. rMSC culture clearly indicated that simultaneously adsorbed OGP and FN could improve osseointegration, and this treatment represents a potential method for effective surface modification of dental and orthopedic implants.
Synthesis, part of a Special Feature on Ecosystem Services, Governance and Stakeholder Participation Payments for Ecosystem Services in the Context of Adaptation to Climate Change

The concept of payments for ecosystem services (PES) has recently emerged as a promising tool for enhancing or safeguarding the provision of ecosystem services (ES). Although the concept has been extensively scrutinized in terms of its potential positive and negative impacts on the poor in developing countries, less attention has been paid to examining the role of PES in the context of adaptation to climate change. PES has some potential to contribute to adaptation to climate change, but there are also risks that it could undermine adaptation efforts. In order to maximize synergies and minimize trade-offs between PES and adaptation, it is important that the conceptual links between both are made explicit. The present article presents the main conceptual links between PES and adaptation to climate change and suggests ways of making PES pro-poor and pro- adaptation. Drawing upon the concepts of vulnerability, adaptive capacity, and socioecological systems, it is suggested that PES can potentially contribute to adaptation in three main ways: through enhancements in the provision of ecosystem services, by enhancing adaptive capacity in the way PES is designed and implemented, and by providing an incentive mechanism to adopt specific measures for adaptation to climate change. Reflecting on the lessons from the PES and poverty literature, the article suggests ways to make PES pro-poor and pro-adaptation and concludes with further research needs in this area.
The tenth annual MLSP competition: Schizophrenia classification challenge

For the 24th Machine Learning for Signal Processing competition, participants were asked to automatically diagnose schizophrenia using multimodal features derived from MRI scans. The objective of the classification task was to achieve the best possible schizophrenia diagnosis prediction based only on the multimodal features derived from brain MRI scans. A total of 2087 entries from 291 participants with active Kaggle.com accounts were made. Each participant developed a classifier, with optional feature selection, that combined functional and structural magnetic resonance imaging features. Here we review details about the competition setup, the winning strategies, and provide basic analyses of the submitted entries. We conclude with a discussion of the advances made to the neuroimaging and machine learning fields.
A Distributed Fuzzy Associative Classifier for Big Data

Fuzzy associative classification has not been widely analyzed in the literature, although associative classifiers (ACs) have proved to be very effective in different real domain applications. The main reason is that learning fuzzy ACs is a very heavy task, especially when dealing with large datasets. To overcome this drawback, in this paper, we propose an efficient distributed fuzzy associative classification approach based on the MapReduce paradigm. The approach exploits a novel distributed discretizer based on fuzzy entropy for efficiently generating fuzzy partitions of the attributes. Then, a set of candidate fuzzy association rules is generated by employing a distributed fuzzy extension of the well-known FP-Growth algorithm. Finally, this set is pruned by using three purposely adapted types of pruning. We implemented our approach on the popular Hadoop framework. Hadoop allows distributing storage and processing of very large data sets on computer clusters built from commodity hardware. We have performed an extensive experimentation and a detailed analysis of the results using six very large datasets with up to 11 000 000 instances. We have also experimented different types of reasoning methods. Focusing on accuracy, model complexity, computation time, and scalability, we compare the results achieved by our approach with those obtained by two distributed nonfuzzy ACs recently proposed in the literature. We highlight that, although the accuracies result to be comparable, the complexity, evaluated in terms of number of rules, of the classifiers generated by the fuzzy distributed approach is lower than the one of the nonfuzzy classifiers.
Sea-Level Rise and Land Subsidence: Impacts on Flood Projections for the Mekong Delta’s Largest City

The present paper demonstrates that inundation levels in the Mekong Delta’s largest city, Can Tho, are predominantly determined by ocean tides, sea-level rise, and land subsidence. Our analysis of inundation patterns projects that the duration of inundation at an important road in the city will continue to rise from the current total of 72 inundated days per year to 270 days by 2030 and 365 days by 2050. This is attributed to the combined influence of sea-level rise and land subsidence, which causes relative water level rises at a rate of 22.3 mm·yr −1 . People in the Mekong Delta have traditionally lived with floods, and thus there is certain resilience among residents in coping with small floods. At present, daily maximum inundation depth, which is generally shallower than 10 cm on the road, seems to be still manageable; however, our analysis indicates that this will start drastically increasing in the coming decades and reach an average depth of 70 cm by 2050. Effective and well-planned actions to mitigate the effects of land subsidence and sea-level rise are urgently required, otherwise, local inhabitants will encounter an unmanageable increase in inundation depth and duration in the coming decades. This study, which considers both sea-level rise and land subsidence, suggests that inundation depth and duration are projected to rise much faster than those indicated by previous studies, which only consider sea-level rise.
Computation in a Single Neuron: Hodgkin and Huxley Revisited

A spiking neuron computes by transforming a complex dynamical input into a train of action potentials, or spikes. The computation performed by the neuron can be formulated as dimensional reduction, or feature detection, followed by a nonlinear decision function over the low-dimensional space. Generalizations of the reverse correlation technique with white noise input provide a numerical strategy for extracting the relevant low-dimensional features from experimental data, and information theory can be used to evaluate the quality of the low-dimensional approximation. We apply these methods to analyze the simplest biophysically realistic model neuron, the Hodgkin-Huxley (HH) model, using this system to illustrate the general methodological issues. We focus on the features in the stimulus that trigger a spike, explicitly eliminating the effects of interactions between spikes. One can approximate this triggering feature space as a two-dimensional linear subspace in the high-dimensional space of input histories, capturing in this way a substantial fraction of the mutual information between inputs and spike time. We find that an even better approximation, however, is to describe the relevant subspace as two dimensional but curved; in this way, we can capture 90 of the mutual information even at high time resolution. Our analysis provides a new understanding of the computational properties of the HH model. While it is common to approximate neural behavior as integrate and fire, the HH model is not an integrator nor is it well described by a single threshold.
Iron–manganese: New class of metallic degradable biomaterials prepared by powder metallurgy

An Fe–35 wt-%Mn alloy, aimed to be used as a metallic degradable biomaterial for stent applications, was prepared via a powder metallurgy route. The effects of processing conditions on the microstructure, mechanical properties, magnetic susceptibility and corrosion behaviour were investigated and the results were compared to those of the SS316L alloy, a gold standard for stent applications. The Fe35Mn alloy was found to be essentially austenitic with fine MnO particles aligned along the rolling direction. The alloy is ductile with a strength approaching that of wrought SS316L. It exhibits antiferromagnetic behaviour and its magnetic susceptibility is not altered by plastic deformation, providing an excellent MRI compatibility. Its corrosion rate was evaluated in a modified Hank's solution, and found superior to that of pure iron (slow in vivo degradation rate). In conclusion, the mechanical, magnetic and corrosion characteristics of the Fe35Mn alloy are considered suitable for further development of a new class of degradable metallic biomaterials.