Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction versus aetiology: common pitfalls and how to avoid them: Clinical Epidemiology in Nephrology

Abstract Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre‐existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand. In both scientific and clinical practice, however, the two are often confused, resulting in poor‐quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls.
Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5

Significance Many cancer-associated variants have been found in the 8q24.21 region harboring enhancer activity. However, the functional mechanism of the variants is not clear due to the lack of protein-coding genes in the region and no significant correlation with the nearest oncogene MYC. We identified long noncoding RNAs (lncRNAs) named cancer-associated region long noncoding RNAs (CARLos) in the 8q24.21 region. Interestingly, we found that the cancer-associated variant rs6983267 regulating the enhancer activity is significantly associated with the expression of one of the lncRNAs CARLo-5 and that CARLo-5 has an oncogenic function. By showing direct interaction between the enhancer region and active regulatory region of the CARLo-5 promoter, we provide a regulatory mechanism of cancer susceptibility caused by the cancer-associated variants. The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here we report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, we demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, our data provide a key of the mystery of the 8q24 gene desert.
Prevalencia del síndrome metabólico en pacientes diabéticos

History: the different definitions of the Metabolic Syndrome of the past ten years, have led to confusions. In October 2005, the American Heart Association (AHA) made some modifications to optimize the use of the National Cholesterol Education programs Adult Treatment Panel III Report (ATPIII) criteria in the daily clinical practice. Objective: determine the prevalence of the Metabolic Syndrome as defined by the ATPIII compared to the AHA2005 definition in the patients of a third level care institution, diabetes clinic. Material and methods: a cross sectional study. 249 clinical histories between January 2004 and september 2005 were reviewed. The population under study was described and the prevalence of the metabolic syndrome, according to the ATPII and AHA criteria was estimated. Results: the prevalence of the Metabolic Syndrome according to the ATPIII criteria, was 72, 69% (men 63, 83%, women 78, 06%), whilst using the AHA criteria it was 96, 77% (men 95, 74%, women 96, 77%). 100% of obese and diabetic patients have metabolic syndrome according to the AHA criteria. Conclusions: the population studied presents a high prevalence of Metabolic Syndrome taking into account the ATPIII and AHA criteria. Not all diabetic patients have that conditions, however, all diabetic and obese patients show this syndrome. Both criteria are clinically easy to apply but the AAHA criteria identify a higher proportion of patients with this pathology.
PHYTO-PHARMACOGNOSTICAL STUDY OF MUNDI (Sphaeranthus indicus Linn.)

Mundi( Sphaeranthus indicus Linn.) is a popularly used drug in the texts of Ayurveda. Whole plant is used in therapeutic conditions like Krimi, Apachi, Yoniroga etc. Hence phyto-pharmacognostic standardization forms the base to start any research. Methods: Authentified, matured, fresh plants were collected and both macro-microscopic characters were documented. Chemical study included physico-chemical screening, preliminary phytochemical test and HPTLC. Results: Pharmacognostic study of leaf showed anisocytic and anomocytic stomata on upper and lower surface respectively and stem part showed unicellular, multicellular, glandular , eglandular types of trichomes. Physicochemical standards and presence of protein, flavanoids, triterpenoid compounds as secondary metabolites, serve as qualitative data related to this drug. Conclusion: The results obtained will prove as standard reference for identification and distinguish it from any admixture. Keywords: ( Mundi , Sphaeranthus indicus , phyto-pharmacognostic, vein-islet number HPTLC)
The population-level costs of immunosuppression medications for the treatment of glomerulonephritis are increasing over time due to changing patterns of practice

Background Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013. The primary outcome (mean IS medication cost per treated patient each year) was evaluated for trends over time. Results The cohort included 2983 GN patients followed for a mean of 5.7 years. The yearly per-patient medication cost increased 6.8-fold from $205 to $1394 (P < 0.001), with significant increases of 3.5-11.7-fold in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, focal segmental glomerulosclerosis, lupus nephritis, minimal change disease and membranous nephropathy (P ≤ 0.004), but no change in immunoglobulin A (IgA) nephropathy. The cost of mycophenolate mofetil, calcineurin inhibitors and rituximab increased significantly (P < 0.001) such that in 2000 they accounted for 17.6% of medication costs and were used by 2.2% of patients, which increased to 94.5% and 44.6%, respectively, in 2013. The costs of azathioprine, cyclophosphamide and prednisone increased only slightly or decreased. Patterns of drug use and contribution to cost varied by type of GN. Conclusions These are the first population-level estimates of the IS treatment costs for GN, and demonstrate a striking increase due to changing practice patterns from older, cheaper medications to newer, more expensive therapies. These results provide important information to guide future health policy strategies and cost-effectiveness research in glomerular diseases.
Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease

Background Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD). Methods This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years). The enrolled CKD patients were randomly assigned (1:1) to two different nutritional treatment arms: (i) 3 months of free diet (FD), 6 months of VLPD, 3 months of FD and 6 months of MD; and (ii) 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD. Blood levels of lysine (Lys) and homocitrulline (Hcit) and their ratio were used as markers of cyanate levels. Due to a lack of pre-existing data on the potential effects of different dietary regimens and in light of the exploratory nature of the study, no formal sample size estimation was carried out. Results At study completion, lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus and parathyroid hormone, but higher serum levels of bicarbonate and haemoglobin, were noted with MD and VLPD. When compared with FD, both MD and VLPD were also associated with a decrease in serum Hcit levels and Hcit/Lys ratios (P < 0.001). Notably, reductions in urea levels correlated with substantial reductions in Hcit levels (R2 = 0.16 and 0.17 for VLPD and MD, respectively). Conclusion In conclusion, nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation.
Long term outcome of patients with steroid‐refractory acute intestinal graft versus host disease after treatment with pentostatin

ment with 5-azacytidine. Leukemia, 21, 1937–1944. Ushmorov, A. , Leithäuser, F. , Sakk, O. , Weinhaüsel, A. , Popov, S.W. , Möller, P. & Wirth, T. (2006) Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood, 107, 2493–2500. Voso, M.T. , Santini, V. , Finelli, C. , Musto, P., Pogliani, E. , Angelucci, E. , Fioritoni, G. , Alimena, G. , Maurillo, L. , Cortelezzi, A. , Buccisano, F. , Gobbi, M. , Borin, L. , Di Tucci, A. , Zini, G. , Petti, M.C. , Martinelli, G. , Fabiani, E. , Fazi, P., Vignetti, M. , Piciocchi, A. , Liso, V. , Amadori, S. & Leone, G. (2009) Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. Clincal Cancer Research, 15, 5002–5007.
Albumin Carriers for Cancer Theranostics: A Conventional Platform with New Promise

Theranostic nanoplatforms with integrated diagnostic and therapeutic functions, aiming at imaging‐guided therapy to improve treatment planning, as well as combination therapy to enhance treatment efficacy, have received tremendous attention in recent years. Among numerous types of functional nanomaterials explored in this field, protein‐based nanocarriers with inherent biocompatibility have also been selected as building blocks to construct multifunctional theranostic platforms. In particular, albumin, which has been extensively used as drug‐delivery carriers for decades, has shown great new promise in the construction of novel imaging and therapeutic nanoagents, as demonstrated by a number of recent studies. IHere, the motivations of using albumins to build up nanoscale theranostics are discussed, and the latest progress/future perspectives in this direction are summarized.
A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non‐Hodgkin lymphoma risk

Genetic variation in immune‐related genes may play a role in the development of non‐Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population‐based case‐control studies (1946 cases and 1808 controls). Gene‐based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per‐allele odds ratio = 1·15, 95% confidence interval = 1·05–1·27; Ptrend = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.
The Global Burden of Disease

This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors;. generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age sex and region provided by demographers;. provide methodologies for and assessments of aggregate disease burden that combine--into the Disability-Adjusted Life Year or DALY measure--burden from premature mortality with that from living with disability; and.use historical trends in main determinants to project mortality and disease burden forward to 2020. " This first volume includes chapters summarizing results from the project as a whole. (EXCERPT)
Layer Engineering of 2D Semiconductor Junctions

A new concept for junction fabrication by connecting multiple regions with varying layer thicknesses, based on the thickness dependence, is demonstrated. This type of junction is only possible in super-thin-layered 2D materials, and exhibits similar characteristics as p-n junctions. Rectification and photovoltaic effects are observed in chemically homogeneous MoSe2 junctions between domains of different thicknesses.
The savvy dental hygienist: 4 facts about the Bank of Mom and Dad

Bill and Carly are both in their early 60s. Bill is a diesel mechanic and Carly a dental hygienist. They have three children: Julie, age 29; Megan, age 26; and Samuel, age 24. Julie just finished and MBA program after living at home while waitressing for five years after college. She has a local placement with a good salary, yet plans to live one more year at home while attacking $150,000 in student loans.
Tough Physical Double‐Network Hydrogels Based on Amphiphilic Triblock Copolymers

A series of physical double-network hydrogels is synthesized based on an amphiphilic triblock copolymer. The gel, which contains strong hydrophobic domains and sacrificial dynamic bonds of hydrogen bonds, is stiff and tough, and even stiffens in concentrated saline solution. Furthermore, due to its supramolecular structure, the gel features improved self-healing and self-recovery abilities.
A Late Neolithic Case of Pott's Disease from Hungary

The aim of this study was to present classic bone lesions caused by tuberculosis, as seen in a Late Neolithic–Early Copper Age osteoarchaeological sample deriving from the site of Alsonyek-Bataszek (the western part of Hungary from the 5th millennium bc). In one particular case of an adult male skeleton, vertebral bodies' destruction, collapse, ankylosis and marked angulation in the lower thoracic and the upper lumbal region of the vertebral column were observed. The collapse resulted in a severe gibbus formation. The paleopathological analysis was carried out using morphological observation supported by radiological analyses. The results from this study increase our knowledge of the early occurrence of skeletal tuberculosis in past populations. Copyright © 2012 John Wiley & Sons, Ltd.
Acceptor End‐Capped Oligomeric Conjugated Molecules with Broadened Absorption and Enhanced Extinction Coefficients for High‐Efficiency Organic Solar Cells

Acceptor end-capping of oligomeric conjugated molecules is found to be an effective strategy for simultaneous spectral broadening, extinction coefficient enhancement, and energy level optimization, resulting in profoundly enhanced power conversion efficiencies (of 9.25% and 8.91%) compared to the original oligomers. This strategy is effective in overcoming the absorption disadvantage of oligomers and small molecules due to conjugation limitation.
Non‐pharmacological management interventions for COPD: an overview of Cochrane systematic reviews

This is the protocol for a review and there is no abstract. The objectives are as follows: To a) summarise the evidence, b) identify gaps in the evidence base and c) describe elements of non-pharmacological, non-surgical and non-device interventions for the management of COPD using a standardised taxonomy for disease management adapted from the American Heart Association (Krumholz 2006).
Inhibition of Tumor Promotion in Mouse Skin by 1α,25-Dihydroxyvitamin D3

: 1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, was found to inhibit the promotional phase of 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in female Sencar mice. Topical application of 1 alpha,25-(OH)2D3 once a week at a dose of 1 micrograms or less, a tolerable dose from hypercalcemia, dose dependently inhibited tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). When 1 micrograms of 1 alpha,25(OH)2D3 was applied 30 min before 5 micrograms of TPA, the times required for 50 and 100% tumor incidence were delayed about 2.5 and 7 weeks, respectively, and the number of tumors per mouse was decreased by 25-30%. This inhibitory effect was more pronounced when examined by a two-stage promotion protocol, in which a single application of 5 micrograms of TPA (Stage I) was followed by repeated applications of 5 micrograms of mezerein once a week for 19 weeks (Stage II). When 1 alpha,25(OH)2D3 at 1 micrograms was applied at Stage I + II or Stage II, tumor formation was markedly suppressed, resulting in decrease of about 70-80% in the incidence and 87-90% in the number of tumors per mouse. Application of 1 alpha,25(OH)2D3 at Stage I only did not inhibit tumor formation, indicating that 1 alpha,25(OH)2D3 specifically inhibited Stage II promotion. These results are in good agreement with the previous and present findings that 1 alpha,25(OH)2D3 inhibited induction of epidermal ornithine decarboxylase by TPA and mezerein. The possibility that 1 alpha,25(OH)2D3 suppressed tumor promotion by killing initiated cells rather than inhibiting promotion was ruled out by an experiment in which TPA was applied to the 1 alpha,25(OH)2D3 alone-treated animals.
A cellular solution to an information-processing problem

Significance Cell-surface signaling receptors are organized into different architectures that have been arrived at multiple times in diverse contexts. To understand the trade-offs that lead to these architectures, we pose the generic information-processing problem of identifying the optimal strategy for distributed mobile noisy sensors to faithfully “read” an incoming signal that varies in space–time. This involves balancing two opposing requirements: clustering noisy sensors to reduce statistical error and spreading sensors to enhance spatial coverage, resulting in a phase transition that explains the frequent reemergence of a set of architectures. Our results extend to a variety of engineering and communication applications that involve mobile and distributed sensing, and suggest that biology might offer solutions to hard optimization problems that arise in these applications. Signaling receptors on the cell surface are mobile and have evolved to efficiently sense and process mechanical or chemical information. We pose the problem of identifying the optimal strategy for placing a collection of distributed and mobile sensors to faithfully estimate a signal that varies in space and time. The optimal strategy has to balance two opposing objectives: the need to locally assemble sensors to reduce estimation noise and the need to spread them to reduce spatial error. This results in a phase transition in the space of strategies as a function of sensor density and efficiency. We show that these optimal strategies have been arrived at multiple times in diverse cell biology contexts, including the stationary lattice architecture of receptors on the bacterial cell surface and the active clustering of cell-surface signaling receptors in metazoan cells.
Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection

Significance Patients homozygous for the C-C chemokine receptor type 5 (CCR5) gene with 32-bp deletions (Δ32) are resistant to HIV infection. Using the piggyBac technology plus transcription activator-like effector nucleases or clustered regularly interspaced short palindromic repeats-Cas9, the authors report, to our knowledge, for the first time in induced pluripotent stem cells (iPSCs) the efficient and seamless derivation of a homozygous CCR5Δ32 mutation, exactly mimicking the natural mutation. Monocytes and macrophages differentiated from these mutated iPSCs in vitro are resistant to HIV infection. This approach can be applied in the future toward the functional cure of HIV infection. The findings are also of great interest to researchers in many fields who wish to correct or introduce mutations in specific genes. Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9–mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.