Miracle-dz/UniFAR-FTUs huggingface dataset:
Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years.

OBJECTIVE In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period. METHODS Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or > or =2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models. RESULTS The mean +/- SD ages of the progressors and nonprogressors were 64.2 +/- 7.8 years and 63.3 +/- 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by > or =2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean +/- SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 +/- 3.39 units/liter versus 12.62 +/- 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 +/- 2.71 versus 10.82 +/- 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%. CONCLUSION The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.
Translational control of maturation-protein synthesis in phage MS2: a role for the kinetics of RNA folding?

The gene for the maturation (A) protein of the single-stranded RNA coliphage MS2 is preceded by an untranslated leader of 130 nt. Secondary structure of the leader was deduced by phylogenetic comparison and by probing with enzymes and chemicals. The RNA folds into a cloverleaf, i.e., three stem-loop structures enclosed by a long-distance interaction (LDI). This LDI is essential for translational control. Its 3'moiety contains the Shine-Dalgarno region of the A-protein gene, whereas its complement is located 80 nt upstream, i.e., about 30 nt from the 5'-terminus of the RNA chain. Mutational analysis shows that this base pairing represses expression of the A-protein gene. We present a model in which translational starts can only take place on nonequilibrated RNA, in which base pairing between the complementary regions has not yet taken place. We suggest that this pairing is kinetically delayed by the intervening sequence, which contains the three hairpins of the cloverleaf. The model is mainly based on the observation that reducing the length of the intervening sequence reduces expression, whereas increasing the length has the opposite effect. In addition, further stabilization of the LDI by a stronger base pair does not lead to a decrease in A-protein synthesis. Such a decrease is predicted to occur if translation would be controlled by the equilibrium structure of the leader RNA. These and other observations fit a kinetic model of translational control by RNA folding.
Association of Anti-VEGF Injections with Progression of Geographic Atrophy

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.
Electrochemical aptasensor based on proximity-dependent surface hybridization assay for single-step, reusable, sensitive protein detection.

This study developed a novel electrochemical biosensor for single-step detection of proteins based on proximity-dependent surface hybridization assay. This strategy relied on simultaneous recognition of a target molecule by a pair of affinity probes, which was a prerequisite for efficiently promoting the ferrocene-labeled tail sequences of the proximate affinity probe pair to hybridize together with surface-tethered oligonucleotide, thus triggering the redox current of ferrocene at the electrode. The strategy, as a universal methodology for developing high-performance biosensors, was demonstrated using an aptamer probe to a homodimer protein PDGF-BB, and the fabricated aptasensor showed intrinsic high sensitivity, excellent resistance to nonspecific interferences, and ready reusability.
mSin3A/Histone Deacetylase 2- and PRMT5-Containing Brg1 Complex Is Involved in Transcriptional Repression of the Myc Target Gene cad

ABSTRACT The role of hSWI/SNF complexes in transcriptional activation is well characterized; however, little is known about their function in transcriptional repression. We have previously shown that subunits of the mSin3A/histone deacetylase 2 (HDAC2) corepressor complex copurify with hSWI/SNF complexes. Here we show that the type II arginine-specific methyltransferase PRMT5, which is involved in cyclin E repression, can be found in association with Brg1 and hBrm-based hSWI/SNF complexes. We also show that hSWI/SNF-associated PRMT5 can methylate hypoacetylated histones H3 and H4 more efficiently than hyperacetylated histones H3 and H4. Protein-protein interaction studies indicate that PRMT5 and mSin3A interact with the same hSWI/SNF subunits as those targeted by c-Myc. These observations prompted us to examine the expression profile of the c-Myc target genes, carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) and nucleolin (nuc). We found that cad repression is altered in cells that express inactive Brg1 and in cells treated with the HDAC inhibitor depsipeptide. Using chromatin immunoprecipitation assays, we found that Brg1, mSin3A, HDAC2, and PRMT5 are directly recruited to the cad promoter. These results suggest that hSWI/SNF complexes, through their ability to interact with activator and repressor proteins, control expression of genes involved in cell growth and proliferation.
Regulation of the DNA Methyltransferase by the Ras-AP-1 Signaling Pathway (*)

Using deletion analysis and site-specific mutagenesis to map the 5′ regulatory region of the DNA methyltransferase (MeTase) gene, we show that a 106-bp sequence (at −1744 to −1650) bearing three AP-1 sites is responsible for induction of DNA MeTase promoter activity. Using transient cotransfection chloramphenicol acetyltransferase assays in P19 cells, we show that the DNA MeTase promoter is induced by c-Jun or Ha-Ras but not by a dominant negative mutant of Jun, ∂9. The activation of the DNA MeTase promoter by Jun is inhibited in a ligand dependent manner by the glucocorticoid receptor. Stable expression of Ha-Ras in P19 cells results in induction of transcription of the DNA MeTase mRNA as determined by nuclear run-on assays and the steady state levels of DNA MeTase mRNA as determined by an RNase protection assay. These experiments establish a potential molecular link between nodal cellular signaling pathways and the control of expression of the DNA MeTase gene. This provides us with a possible molecular explanation for the hyperactivation of DNA MeTase in many cancer cells and suggests that DNA MeTase is one possible downstream effector of Ras.
Sfrp5 expression and secretion in adipocytes are up‐regulated during differentiation and are negatively correlated with insulin resistance

We have examined the patterns of Sfrp5 (secreted frizzled‐related protein 5) mRNA expression and protein secretion during adipocyte differentiation, and investigated the potential role of Sfrp5 in IR (insulin resistance) in adipocytes. 3T3‐L1 pre‐adipocytes were induced for differentiation, and RT—PCR (reverse transcription—PCR) and ELISA assays were used to determine Sfrp5 mRNA expression and protein secretion. The results showed that with the differentiation and maturity of pre‐adipocytes, transcription and protein secretion of Sfrp5 gradually increased, peaking on the 9th day of differentiation. Sfrp5 mRNA expression in mature adipocytes was decreased by 20, 22 and 32 upon treatment with dexamethasone, insulin and TNF (tumour necrosis factor) respectively, whereas Sfrp5 protein secretion was decreased by 15, 17 and 30%, correspondingly. In contrast, Sfrp5 mRNA expression in mature adipose was increased by 34 and 19% upon treatment with rosiglitazone and metformin respectively, whereas Sfrp5 protein secretion was increased by 10 and 6%, correspondingly. In conclusion, Sfrp5 mRNA expression and protein secretion depend on the differentiation of adipocytes. The dysregulation of Sfrp5 expression and secretion is directly correlated with IR. Up‐regulation of Sfrp5 expression and secretion in adipocytes may be one crucial mechanism by which rosiglitazone and metformin improve insulin sensitivity.
Future perspectives on psychiatry

consider that our field of knowledge is more related to philosophy and social sciences than medicine. It is our impression that this scenario is changing rapidly. Psychiatry is a leading field in many countries, and its prestige is closely related to the scientific achievements in the area. The translational neurosciences as the basis for 21st century psychiatry may help to address many of the challenges raised by our colleagues in their work (6). We cannot call ourselves specialists in neuroscience and, at the same time, call to ourselves the duty of explaining complex human behavior in strictly theoretical terms—as philosophers might. We do not have to convince our colleagues that psychiatry is ‘good’ and that they must think highly of us. What we can do is to focus on our work within medicine and refrain from using psychiatry as a means to provide large explanatory models for human behavior. If we concentrate in our target to help people who suffer from mental disorders using available scientific evidence, our diagnostic and therapeutic achievements shall determine how our colleagues and the community think about us and our work. F. Kapczinski and I. C. Passos Psychiatry, Federal University, UFRGS, Porto Alegre, Brazil and University of Texas at Houston, Houston, TX, USA E-mail: flavio.kapczinski@gmail.com
Real-time detection of moving cast shadows using foreground luminance statistics

This paper presents a robust real-time method for detection of moving cast shadows which employs the assumption of higher interdependence of luminance values for the shadow pixels in larger regions compared to the object pixels. First, a fast modified image differencing technique is used to separate foreground pixels from the background. Next, for a moving window of fixed width scanning the foreground regions, a new measure called Modified Correlation is introduced. The new measure is determined by first computing the correlation between the luminance values of the moving window and luminance values of its neighbouring windows; this correlation is then divided by a robust-to-noise range measured based on the luminance values of the moving window. The modified correlation exhibits abrupt rising transitions as it enters the shadow region from the object region, transitions which can be used to separate object pixels from shadow pixels. Thus, the new method is very effective at suppressing moving cast shadows, while avoiding limiting structures, unrealistic assumptions, the need for a-priori knowledge, and manual selection of critical parameters. An average shadow detection rate of 85.4% and an average shadow discrimination rate of 99.5% over multiple different sequences, higher than those of available methods in the literature, confirm the efficacy of the method. The robustness of the method is examined under different lighting conditions, different target-environment combinations, and sequences with object-shadow occlusion. The proposed method is computationally efficient and suitable for real-time situations.
Modelling the impacts of removing seal predation from Atlantic salmon, Salmo salar, rivers in Scotland: a tool for targeting conflict resolution

Bioenergetics were used to model the potential impacts on adult Atlantic salmon, Salmo salar L. , stocks and rod fisheries of removing harbour seals, Phoca vitulina L. , from three rivers of different scales in the Moray Firth, Scotland, viz: the Spey (large), Conon (medium) and Moriston (small). Overall, seals had the greatest impact on the Moriston, where removal of a single animal could increase cumulative catch by 17% during the fishing season. On the Conon and Spey the impacts were negligible, and resulted in increased catches of 33% in rivers with monthly rod catches £ 10 fish, but declined to 34 fish. The outputs of the models are qualitative, but provide a management tool for targeting action to resolve seal-salmon fishery conflict. Smaller salmon population units, and spring salmon sub-stocks and fisheries in particular, are most vulnerable to predation. The merit of this approach is discussed regarding the management of Special Areas of Conservation for salmon and seals.
Prions: Current Progress in Advanced Research

Incidences of iatrogenic Creutzfeldt–Jakob disease (iCJD) are caused by transplantation of prion-contaminated hormones, cornea and dura mater as well as contact with prioncontaminated medical devices, such as stereotactic electrodes, used in neurosurgery. Because prions are highly resistant and difficult to inactivate, prion contamination is a severe risk when medical instruments are reused after surgical procedures involving suspicious and confirmed cases of patients with prion diseases. Therefore, when high-risk procedures such as cerebral surgery, craniotomy surgery, orthopaedic spinal surgery and ophthalmic surgery are performed for high-risk patients or individuals with prion diseases, it is necessary to appropriately treat the medical devices using scientifically proven prion inactivation methods. In this chapter, we introduce fundamental aspects of prion inactivation methods, looking specifically at the practical issues involved in their implementation. Introduction Prions (proteinaceous infectious particles) are the causative agents of prion diseases, which are also known as transmissible spongiform encephalopathies (TSEs) (Prusiner, 1998). The prion agent of each prion disease is named after the disease itself [e.g. Creutzfeldt–Jakob disease (CJD) agent in CJD of human, chronic wasting disease (CWD) agent in CWD of cervids, scrapie agent in scrapie of sheep and goats, and bovine spongiform encephalopathy (BSE) agent in BSE of cattle]. Among CJD cases, about 85% represent sporadic CJD (sCJD), which is caused by an unknown mechanism, while the remaining 15% is familial CJD (fCJD), which is inherited and caused by mutation of the human prion protein gene. Less than 1% of cases constitute iatrogenic CJD (iCJD), which mainly results from transmission via contaminated tissue grafts (Brown et al., 2006). Concerns have been raised about incidences of iCJD caused by prion-contaminated materials derived from human growth hormone (hGH), pituitary gonadotropin, dura mater and corneal transplants (Aguzzi and Heppner, 2000). It is hoped that the use of
A Case Study on Differential Privacy

Throughout the ages, human beings prefer to keep most things secret and brand this overall state with the title of privacy. Like most significant terms, privacy tends to create controversy regarding the extent of its flexible boundaries, since various technological advancements are slowly leaching away the power people have over their own information. Even as cell phone brands release new upgrades, the ways in which information is communicated has drastically increased, in turn facilitating the techniques in which people’s privacy can be tampered with. Therefore, questioning the methodology by which people can maintain their privacy in the twenty-first century is a validated action undoubtedly conducted by the multitude of the world’s population.Admittedly, data is everywhere. The world has become an explosion of information, and it should not come as a surprise, especially in a time when data storage is cheap and accessible. Various institutions use this data to conduct research, track the behavior of users, recommend products or maintain national security. As a result, corporations’ need for information is growing by the minute. Companies need to know as much as possible about their customers. Nonetheless, how can this be achieved without compromising the privacy of individuals? How can companies provide great features and maintain great privacy? These questions can be answered by a current, anticipated research topic in the field of data privacy: differential privacy. Differential privacy is a branch of statistics that aims to attain the widest range of data while achieving a robust, significant and mathematically accurate definition of privacy.Thus, the objective of this thesis will be describing and analyzing the concept of differential privacy and its properties that lead to the betterment of data privacy. Hence, we will try to study the basic state-of-the-art methods, the model and the challenges of differential privacy.After analyzing the state-of-the-art differential privacy methods, this thesis will focus on an actual case study that is concerned with two types of different datasets which are experimented with one of the methods of differential privacy methods. We design a basic framework that tries to achieves differential privacy guarantee and evaluate the results regarding the level of privacy achieved.
The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature

ABSTRACT Objective: Systematic review of randomized control trials (RCTs) for the effectiveness of pain neuroscience education (PNE) on pain, function, disability, psychosocial factors, movement, and healthcare utilization in individuals with chronic musculoskeletal (MSK) pain. Data Sources: Systematic searches were conducted on 11 databases. Secondary searching (PEARLing) was undertaken, whereby reference lists of the selected articles were reviewed for additional references not identified in the primary search. Study Selection: All experimental RCTs evaluating the effect of PNE on chronic MSK pain were considered for inclusion. Additional Limitations: Studies published in English, published within the last 20 years, and patients older than 18 years. No limitations were set on specific outcome measures. Data Extraction: Data were extracted using the participants, interventions, comparison, and outcomes (PICO) approach. Data Synthesis: Study quality of the 13 RCTs used in this review was assessed by 2 reviewers using the PEDro scale. Narrative summary of results is provided for each study in relation to outcomes measurements and effectiveness. Conclusions: Current evidence supports the use of PNE for chronic MSK disorders in reducing pain and improving patient knowledge of pain, improving function and lowering disability, reducing psychosocial factors, enhancing movement, and minimizing healthcare utilization.
The psa locus is responsible for thermoinducible binding of Yersinia pseudotuberculosis to cultured cells

Yersinia pseudotuberculosis inv mutant strains cured of the virulence plasmid exhibit thermoinducible adhesion to cultured mammalian cells. To identify the genes responsible for this phenotype, Y. pseudotuberculosis homologs of the Y. enterocolitica ail and the Y. pestis psa loci were identified. Mutations in the Y. pseudotuberculosis ail and psa loci were constructed and tested for thermoinducible binding. Results of cellular binding assays indicated that only mutations in psa, not in ail, resulted in defects for thermoinducible binding, with inv yadA psa strains showing no detectable cell adhesion. In addition, an inv psa strain was defective for hemagglutination of sheep erythrocytes, in contrast to an inv psa+ strain which was fully competent for hemagglutination. The introduction of a plasmid containing a 6.7-kb KpnI-ClaI fragment of Y. pseudotuberculosis encompassing the psa locus was sufficient to complement both the cell adhesion and hemagglutination defects of the psa mutant. Results from subcloning and transposon mutagenesis indicated that the complete 6.7-kb region was required for thermoinducible binding and hemagglutination.
Living alone and depression in Chinese older adults

Western literature has repeatedly indicated a strong relationship between living alone and depression among the aged population, however, studies among the Chinese population are scarce. In this paper, we examine whether the association between living alone and depression is independent of health status, social support and financial strain among Chinese older adults, and subsequently assess whether such association persists after adjusting these variables. Cross-sectional data drawn from the Hong Kong Population Census consisting of 2,003 Chinese elderly people aged 60 or over were analyzed. Chi-square tests and logistic regression analyses revealed that living alone results in higher levels of depressive symptoms for older women but not for older men. This relationship remained significant even when socio-demographic variables, health indicators, social support, and financial strains were adjusted; yet, the impact of living alone with depression disappeared when all variables were controlled. In summary, this paper is the first to report that living alone is an independent risk factor contributing to depression among Chinese older women, as well as identifying certain significant factors including social support and health indicators that can affect and explain the link between living alone and depression. Preventive measures and related issues were discussed.