Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrient‐driven O‐GlcNAc in proteostasis and neurodegeneration

Proteostasis is essential in the mammalian brain where post‐mitotic cells must function for decades to maintain synaptic contacts and memory. The brain is dependent on glucose and other metabolites for proper function and is spared from metabolic deficits even during starvation. In this review, we outline how the nutrient‐sensitive nucleocytoplasmic post‐translational modification O‐linked N‐acetylglucosamine (O‐GlcNAc) regulates protein homeostasis. The O‐GlcNAc modification is highly abundant in the mammalian brain and has been linked to proteopathies, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. C. elegans, Drosophila, and mouse models harboring O‐GlcNAc transferase‐ and O‐GlcNAcase‐knockout alleles have helped define the role O‐GlcNAc plays in development as well as age‐associated neurodegenerative disease. These enzymes add and remove the single monosaccharide from protein serine and threonine residues, respectively. Blocking O‐GlcNAc cycling is detrimental to mammalian brain development and interferes with neurogenesis, neural migration, and proteostasis. Findings in C. elegans and Drosophila model systems indicate that the dynamic turnover of O‐GlcNAc is critical for maintaining levels of key transcriptional regulators responsible for neurodevelopment cell fate decisions. In addition, pathways of autophagy and proteasomal degradation depend on a transcriptional network that is also reliant on O‐GlcNAc cycling. Like the quality control system in the endoplasmic reticulum which uses a ‘mannose timer’ to monitor protein folding, we propose that cytoplasmic proteostasis relies on an ‘O‐GlcNAc timer’ to help regulate the lifetime and fate of nuclear and cytoplasmic proteins. O‐GlcNAc‐dependent developmental alterations impact metabolism and growth of the developing mouse embryo and persist into adulthood. Brain‐selective knockout mouse models will be an important tool for understanding the role of O‐GlcNAc in the physiology of the brain and its susceptibility to neurodegenerative injury.
HAPLOPOOL: improving haplotype frequency estimation through DNA pools and phylogenetic modeling

MOTIVATION The search for genetic variants that are linked to complex diseases such as cancer, Parkinson's;, or Alzheimer's; disease, may lead to better treatments. Since haplotypes can serve as proxies for hidden variants, one method of finding the linked variants is to look for case-control associations between the haplotypes and disease. Finding these associations requires a high-quality estimation of the haplotype frequencies in the population. To this end, we present, HaploPool, a method of estimating haplotype frequencies from blocks of consecutive SNPs. RESULTS HaploPool leverages the efficiency of DNA pools and estimates the population haplotype frequencies from pools of disjoint sets, each containing two or three unrelated individuals. We study the trade-off between pooling efficiency and accuracy of haplotype frequency estimates. For a fixed genotyping budget, HaploPool performs favorably on pools of two individuals as compared with a state-of-the-art non-pooled phasing method, PHASE. Of independent interest, HaploPool can be used to phase non-pooled genotype data with an accuracy approaching that of PHASE. We compared our algorithm to three programs that estimate haplotype frequencies from pooled data. HaploPool is an order of magnitude more efficient (at least six times faster), and considerably more accurate than previous methods. In contrast to previous methods, HaploPool performs well with missing data, genotyping errors and long haplotype blocks (of between 5 and 25 SNPs).
Isolated Anti-HBc and Occult HBV Infection in Dialysis Patients

Background: Occult Hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV-DNA in the liver or serum with undetectable hepatitis B surface antigen (HBsAg). Hemodialysis (HD) patients are at risk of acquiring parenterally transmitted infections. Objectives: The aim of this study was to assess the prevalence of OBI in HD patients. Patients and Methods: A hundred HBsAg negative HD patients were included in this study from main dialysis units in Tehran, Iran. HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc) and liver enzymes levels were examined in all subjects. The presence of HBV-DNA was determined in plasma samples using real-time PCR. Results: A hundredpatients with a mean age of 58.5 ± 16.1 years were enrolled in this study. In total, 56.7% were male and 43.3% female. Anti-HBs, anti-HBc, anti-HCV and anti-HIV were detected in 56.7%, 2%, 5.2% and 1% of patients, respectively. Isolated anti-HBc was detected in 2% of cases. HBV-DNA was detected in 1% of HBsAg negative patients. Conclusions: This study showed a low rate of isolated anti-HBc and occult HBV infection in HD patients. It can be due to improvement of people’s knowledge about HBV transmission routes, HBV vaccination of HD patients and regular surveillance of HBV infection.
Discerning Lived Spirituality: The Reception of Otherness

A previous article focused on an analysis of prominent conceptualizations of spirituality in health care. The encompassing character of those approaches was viewed as problematic because too little attention is paid to the distinctiveness and particularities of spiritual experience. This article argues that the criteria gleaned from the prior analysis provide an impetus for a constructive discernment proposal of lived spirituality. The experience of otherness is provides a central clue to an understanding of spirituality particularly by two key terms, receptivity and transformation, as central characterizations of lived spirituality. These terms are investigated as they embrace operational potential for chaplaincy care. The article concludes with a reflection on chaplaincy care as it relates to spiritual practice.
Characteristics of human large granular lymphocytes and relationship to natural killer and K cells

Recent evidence, has demonstrated an association between a subpopulation of peripheral blood mononuclear cells, morphologically identified as large granular lymphocytes (LGL), and natural killer (NK) activity. We have now evaluated more directly the role of LGL in both NK activity and antibody- dependent cellular cytotoxicity (ADCC), by using highly enriched populations of LGL, obtained by centrifugation of peripheral blood mononuclear cells on Percoll discontinuous density gradients. Both spontaneous and interferon- augmented NK and ADCC activities were exclusively associated with the LGL- enriched, low density fractions. The majority of LGL formed conjugates with NK-susceptible and antibody-coated target cells. Approximately 20 percent of small conventional lymphocytes also formed conjugates with the target cells for NK, but this was not associated with cytotoxic activity. Virtually all LGL were found to have receptors for the Fc portion of IgG (FcγR). The frequency of LGL among blood leukocytes was 2-6 percent. LGL could be enriched to an average purity of 95 percent by combining discontinuous density gradient centrifugation with subsequent adsorptions of the low density fractions on monolayers of immobilized immune complexes. About 50 percent of LGL were found to be FcγR-bearing T cells (T(G)), forming low affinity rosettes with sheep erythrocytes at 4 degrees C. Only 10-20 percent of LGL formed high affinity rosettes with sheep erythrocytes at 29 degrees C. LGL could be enriched to a purity of more than 90 percent by depleting high affinity rosette-forming cells from low density Percoll fractions. LGL were only a subpopulation of T(G) cells, because some lymphocytes with conventional morphology also adhered to the immobilized immune complex monolayers and formed high affinity rosettes with sheep erythrocytes. Separation of these cells from LGL by discontinuous density gradient centrifugation indicated that they are not cytotoxic, suggesting a morphological and functional subdivision of T(G) cells. The verification in this study that virtually all human NK and K cells have a characteristic morphology adds a useful parameter to the monitoring of human lymphocytes, and the ability to purify these cells by simple physical procedures should be invaluable in their further characterization.
Multi-Target Tracking - Linking Identities using Bayesian Network Inference

Multi-target tracking requires locating the targets and labeling their identities. The latter is a challenge when many targets, with indistinct appearances, frequently occlude one another, as in football and surveillance tracking. We present an approach to solving this labeling problem. When isolated, a target can be tracked and its identity maintained. While, if targets interact this is not always the case. This paper assumes a track graph exists, denoting when targets are isolated and describing how they interact. Measures of similarity between isolated tracks are defined. The goal is to associate the identities of the isolated tracks, by exploiting the graph constraints and similarity measures. We formulate this as a Bayesian network inference problem, allowing us to use standard message propagation to find the most probable set of paths in an efficient way. The high complexity inevitable in large problems is gracefully reduced by removing dependency links between tracks. We apply the method to a 10 min sequence of an international football game and compare results to ground truth.
Biliary complications in one hundred adult liver transplantations.

BACKGROUND Biliary complications are a common problem in liver transplantation (LT). METHODS We reviewed 100 consecutive adult LTs, including 10 retransplantations. Ten patients who survived for less than 1 month or developed hepatic artery thrombosis were excluded. Biliobiliary anastomosis was performed with a T-tube (CCT) (n = 25) or without it (CC) (n = 59), or biliodigestive anastomosis (Rouxen-Y) (n = 6) was used. RESULTS Biliary complications (8 anastomotic strictures and 9 bile leakages) occurred in 15 LTs. Surgical treatment was needed for seven strictures and two leakages. Complications tended to be more frequent with CCT than with CC (24% versus 12%). Biliary complications were often accompanied by cytomegalovirus disease and bacterial infections. After a median follow-up time of 5.2 years, total patient survival was 71% for all 100 LTs and 81% for those with biliary complications. CONCLUSIONS Biliary complications are rather frequent after LTs; they are often preceded by infections but can be treated and do not cause excessive mortality. T-tubes are not to be recommended.
Neogenin-mediated Hemojuvelin Shedding Occurs after Hemojuvelin Traffics to the Plasma Membrane*

HFE2 (hemochromatosis type 2 gene) is highly expressed in skeletal muscle and liver hepatocytes. Its encoded protein, hemojuvelin (HJV), is a co-receptor for the bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and enhances the BMP-induced hepcidin expression. Hepcidin is a central iron regulatory hormone predominantly secreted from hepatocytes. HJV also binds neogenin, a membrane protein widely expressed in many tissues. Neogenin is required for the processing and release of HJV from cells. The role that neogenin plays in HJV trafficking was investigated, using HepG2 cells, a human hepatoma cell line. Knockdown of endogenous neogenin markedly suppresses HJV release but has no evident effect on HJV trafficking to the plasma membrane. The addition of a soluble neogenin ectodomain to cells markedly inhibits HJV release, indicating that the HJV shedding is not processed before trafficking to the cell surface. At the plasma membrane it undergoes endocytosis in a dynamin-independent but cholesterol-dependent manner. The additional findings that HJV release is coupled to lysosomal degradation of neogenin and that cholesterol depletion by filipin blocks both HJV endocytosis and HJV release suggest that neogenin-mediated HJV release occurs after the HJV-neogenin complex is internalized from the cell surface.
Endosymbiotic flexibility associates with environmental sensitivity in scleractinian corals

Flexibility in biological systems is seen as an important driver of macro-ecosystem function and stability. Spatially constrained endosymbiotic settings, however, are less studied, although environmental thresholds of symbiotic corals are linked to the function of their endosymbiotic dinoflagellate communities. Symbiotic flexibility is a hypothesized mechanism that corals may exploit to adapt to climate change. This study explores the flexibility of the coral–Symbiodinium symbiosis through quantification of Symbiodinium ITS2 sequence assemblages in a range of coral species and genera. Sequence assemblages are expressed as an index of flexibility incorporating phylogenetic divergence and relative abundance of Symbiodinium sequences recovered from the host. This comparative analysis reveals profound differences in the flexibility of corals for Symbiodinium, thereby classifying corals as generalists or specifists. Generalists such as Acropora and Pocillopora exhibit high intra- and inter-species flexibility in their Symbiodinium assemblages and are some of the most environmentally sensitive corals. Conversely, specifists such as massive Porites colonies exhibit low flexibility, harbour taxonomically narrow Symbiodinium assemblages, and are environmentally resistant corals. Collectively, these findings challenge the paradigm that symbiotic flexibility enhances holobiont resilience. This underscores the need for a deeper examination of the extent and duration of the functional benefits associated with endosymbiotic diversity and flexibility under environmental stress.
Bacterial Community Composition and Extracellular Enzyme Activity in Temperate Streambed Sediment during Drying and Rewetting

Droughts are among the most important disturbance events for stream ecosystems; they not only affect stream hydrology but also the stream biota. Although desiccation of streams is common in Mediterranean regions, phases of dryness in headwaters have been observed more often and for longer periods in extended temperate regions, including Central Europe, reflecting global climate change and enhanced water withdrawal. The effects of desiccation and rewetting on the bacterial community composition and extracellular enzyme activity, a key process in the carbon flow of streams and rivers, were investigated in a typical Central European stream, the Breitenbach (Hesse, Germany). Wet streambed sediment is an important habitat in streams. It was sampled and exposed in the laboratory to different drying scenarios (fast, intermediate, slow) for 13 weeks, followed by rewetting of the sediment from the fast drying scenario via a sediment core perfusion technique for 2 weeks. Bacterial community structure was analyzed using CARD-FISH and TGGE, and extracellular enzyme activity was assessed using fluorogenic model substrates. During desiccation the bacterial community composition shifted toward composition in soil, exhibiting increasing proportions of Actinobacteria and Alphaproteobacteria and decreasing proportions of Bacteroidetes and Betaproteobacteria. Simultaneously the activities of extracellular enzymes decreased, most pronounced with aminopeptidases and less pronounced with enzymes involved in the degradation of polymeric carbohydrates. After rewetting, the general ecosystem functioning, with respect to extracellular enzyme activity, recovered after 10 to 14 days. However, the bacterial community composition had not yet achieved its original composition as in unaffected sediments within this time. Thus, whether the bacterial community eventually recovers completely after these events remains unknown. Perhaps this community undergoes permanent changes, especially after harsh desiccation, followed by loss of the specialized functions of specific groups of bacteria.
Prescription of prosthetic ankle-foot mechanisms after lower limb amputation.

BACKGROUND A correct prosthetic prescription can be derived from adapting the functional benefits of a prosthesis to the functional needs of the prosthetic user. For adequate matching, the functional abilities of the amputees are of value, as well as the technical and functional aspects of the various prosthetic ankle-foot mechanisms. There seems to be no clear clinical consensus on the precise prescription criteria for the various prosthetic ankle-foot mechanisms related to the functional abilities of amputees. OBJECTIVES To obtain information about aspects of prosthetic ankle-foot mechanisms and daily functioning of amputees with a prosthesis, for appropriate prosthetic prescription criteria. SEARCH STRATEGY We searched the Cochrane Musculoskeletal Injuries Group specialised register of trials (April 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2003), MEDLINE (1966 to April 2003), EMBASE (1983 to April 2003), CINAHL (1982 to April 2003) and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA All randomised controlled trials and quasi-randomised controlled trials comparing different prosthetic devices for lower limb amputation in adults. No language restrictions were applied. DATA COLLECTION AND ANALYSIS Two reviewers independently identified potential articles from the literature search. Methodological quality was assessed using a checklist comprising 13 criteria. The reviewers extracted data using pre-defined extraction forms. MAIN RESULTS Twenty-three trials were included, with a total of 217 participants. The methodological quality was moderate. Only one study was of high quality. No classical RCT's were identified, yet, all included studies used cross-over designs allowing sufficient control for confounding. In high activity transfemoral amputees, there is limited evidence for the superiority of the Flex foot during level walking compared with the SACH foot in respect of energy cost and, gait efficiency. This benefit has only been confirmed in transtibial amputees during decline and incline walking and increased walking speeds. REVIEWER'S CONCLUSIONS There is insufficient evidence from high quality comparative studies for the overall superiority of any individual type of prosthetic ankle-foot mechanism. In high activity transfemoral amputees, there is limited evidence for the superiority of the Flex foot during level walking compared with the SACH foot in respect of energy cost and, gait efficiency. This benefit has only been confirmed in transtibial amputees during decline and incline walking and increased walking speeds. In prescribing prosthetic-ankle foot mechanisms for lower-limb amputees, practitioners should take into account availability, patient functional needs, and cost.
Development of a decision support model for screening attention-deficit hyperactivity disorder with actigraph-based measurements of classroom activity

Summary Objective: Questionnaire-based ADHD screening tests may not always be objective or accurate, owing to both subjectivity and prejudice. Despite attempts to develop objective measures to characterize ADHD, no widely applicable index currently exists. The principal aim of this study was to develop a decision support model for ADHD screening by monitoring children’s school activities using a 3-axial actigraph. Methods: Actigraphs were placed on the non-dominant wrists of 153 children for 3 hours, while they were at school. Children who scored high on the questionnaires were clinically examined by child psychiatrists, who then confirmed ADHD. Mean, variance, and ratios of low-level (0.5-1.0G) and high-level (1.6-3.2G) activity were extracted as activity features from 142 children (10 ADHD, 132 non-ADHD). Two decision-tree models were constructed using the C5.0 algorithm: [A] from whole hours (class + playtime) and [B] during classes. Accuracy, sensitivity, and specificity were evaluated. PPV, NPV, likelihood ratio, and AUC were also calculated for evaluation. Results: [Model A] One child without ADHD was misclassified, resulting in an accuracy score of 99.30%. Sensitivity and NPV were 1.0000. Specificity and PPV were 0.992 and 0.803-0.909, respectively. [Model B] Two children without ADHD were misclassified, resulting in an accuracy score of 98.59%. Specificity and PPV were scored at 0.985 and 0.671-0.832, respectively. Conclusion: The selected features were consistent with the findings of previous studies. Objective screening of latent patients with ADHD can be accomplished with a simple watch-like sensor, which is worn for just a few hours while the child attends school. The model proposed herein can be applied to a great many children without heavy cost in time and manpower cost, and would generate valuable results from a public health perspective.
Preparation, cellular uptake and angiogenic suppression of shikonin-containing liposomes in vitro and in vivo

Shikonin has anticancer activity, but it has not yet been applied into clinical use. In the present study, shikonin was prepared using liposomes. We aimed to examine several aspects of sh-L (shikonin-containing liposomes): preparation, angiogenic suppression and cellular uptake through self-fluorescence. Sh-L were prepared using soybean phospholipid and cholesterol to form the membrane and shikonin was encapsulated into the phospholipid membrane. Three liposomes were prepared with shikonin. They had red fluorescence and were analysed using a flow cytometer. Angiogenic suppression of sh-L was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide], Transwell tests, chick CAM (chorioallantoic membrane) and Matrigel™ plug assay. MTT assay showed the median IC50 (inhibitory concentrations) as follows: shikonin, sh-L1 and sh-L2 were 4.99±0.23, 5.81±0.57 and 7.17±0.69 μM, respectively. The inhibition rates of migration were 53.58±7.05, 46.56±4.36 and 41.19±3.59% for 3.15 μM shikonin, sh-L1 and sh-L2, respectively. The results of CAM and Matrigel plug assay demonstrated that shikonin and sh-L can decrease neovascularization. Effect of shikonin was more obvious than sh-L at the same concentration. The results showed that sh-L decreased the toxicity, the rate of inhibition of migration and angiogenic suppression. The cellular uptake of the sh-L could be pictured because of the self-fluorescence. The self-fluorescence will be useful for conducting further research. Sh-L might be an excellent preparation for future clinical application to cancer patients.