Miracle-dz/UniFAR-FTUs huggingface dataset:
ABO antibody and complement depletion by immunoadsorption combined with membrane filtration--a randomized, controlled, cross-over trial.

BACKGROUND Potent antibody depletion techniques have paved the way to successful ABO-incompatible transplantation. Considering its efficiency regarding IgG removal, the use of non-antigen-specific semi-selective immunoadsorption (IA) has been advocated. One attractive strategy to overcome the caveat of incomplete IgM depletion and to interfere with complement activation could be the adjunctive use of membrane filtration (MF) to enhance the removal of macromolecules. METHODS To investigate the depletion efficiency of semi-selective IA plus MF, we conducted a randomized, controlled, cross-over trial including patients on regular IA treatment for indications outside recipient desensitization. According to the results of sample size calculation, 14 subjects were enrolled. Two treatment sequences, a single session of IA plus MF followed by IA alone after ≥7 days (and vice versa), were analysed. RESULTS IA plus MF markedly enhanced the median per cent reduction of ABO-specific IgM determined by flow cytometry (primary end point; 59 versus 23%, P < 0.001) and haemagglutination (2 versus 1 titre steps, P < 0.001), respectively. Combined treatment also substantially lowered C1q concentrations (86 versus 58% reduction, P < 0.001) and the functionality of classical complement as reflected by impaired in vitro C3 activation capability. IgG was strongly reduced without any additional effect of MF. CONCLUSIONS We demonstrate that the innovative strategy of combining MF with semi-selective IA may substantially increase IgM elimination and affect classical complement activation. Our findings suggest that this new treatment concept could be an efficient strategy for recipient desensitization in ABO- and HLA-incompatible transplantation.
Clinical significance of multi-frequency bioimpedance spectroscopy in peritoneal dialysis patients: independent predictor of patient survival.

BACKGROUND It is becoming increasingly evident that the accurate assessment of hydration status is critical to care of a dialysis patient. Using the Body Composition Monitor, different parameters (overhydration (OH), extra-cellular water/total body water (ECW/TBW) or OH/ECW) have been proposed to indicate hydration status. We wished to determine which parameter (if any) was most predictive of all-cause mortality, and if this was independent of nutritional indices. METHODS We performed a single-centre retrospective analysis of prospectively collected data of all peritoneal dialysis (PD) patients between 1 January 2008 and 30 March 2012. Record review was undertaken to establish patient survival, clinical and demographic data. Follow-up was continued even after PD technique failure (transfer to haemodialysis) and transplantation. RESULTS The study included 529 patients. OH index (OH and OH/ECW) was the independent predictor of mortality in multi-variate analysis. ECW/TBW as a continuous variable was not associated with increased risk of death. In contrast, patients that were severely overhydrated (highest 33%) had hazard ratios (HRs) that were statistically significant irrespective of the parameter used to define hydration. Using OH, severely overhydrated patients had an HR of 1.83 [95% confidence interval (CI) 1.19-2.82, P < 0.01], OH/ECW: 2.09 (95% CI 1.36-3.20, P < 0.001) and ECW/TBW: 2.05 (95% CI 1.31-3.22, P < 0.005). CONCLUSIONS Our results also indicated that there was no influence of body mass index (BMI) on the hydration parameter OH/ECW. OH/ECW remained an independent predictor of mortality when the BMI and lean tissue index were included in multivariate model. However, it remains to be determined if correcting the OH status of a patient will lead to improvement in mortality.
Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12

Significance Autophagy-related (ATG)12 is a ubiquitin-like protein essential to autophagy. It has been known for years that ATG12 is conjugated to the structural protein ATG5 and that the resulting protein–protein conjugate acts like an E3 enzyme that facilitates the attachment of the LC3 ubiquitin-like protein to a lipid molecule, phosphatidylethanolamine. However, the exact role of ATG12 in the E3 complex and the significance of ATG12 being a ubiquitin-like protein have remained elusive. We show that ATG12 binds to a short peptide region of the E2 enzyme ATG3 and describe the structural details of this interaction. This work establishes ATG12 as the ATG3 recruitment factor and explains how ATG12 uses its ubiquitin-like fold for binding to the ATG3 peptide. The autophagic ubiquitin-like protein (ublp) autophagy-related (ATG)12 is a component of the ATG12∼ATG5–ATG16L1 E3 complex that promotes lipid conjugation of members of the LC3 ublp family. A role of ATG12 in the E3 complex is to recruit the E2 enzyme ATG3. Here we report the identification of the ATG12 binding sequence in the flexible region of human ATG3 and the crystal structure of the minimal E3 complexed with the identified binding fragment of ATG3. The structure shows that 13 residues of the ATG3 fragment form a short β-strand followed by an α-helix on a surface area that is exclusive to ATG12. Mutational analyses of ATG3 confirm that four residues whose side chains make contacts with ATG12 are important for E3 interaction as well as LC3 lipidation. Conservation of these four critical residues is high in metazoan organisms and plants but lower in fungi. A structural comparison reveals that the ATG3 binding surface on ATG12 contains a hydrophobic pocket corresponding to the binding pocket of LC3 that accommodates the leucine of the LC3-interacting region motif. These findings establish the mechanism of ATG3 recruitment by ATG12 in higher eukaryotes and place ATG12 among the members of signaling ublps that bind liner sequences.
Angiogenic mediators of the angiopoietin system are highly expressed by CD10‐positive lymphoma cells in angioimmunoblastic T‐cell lymphoma

Angioimmunoblastic T‐cell lymphoma (AILT) is a malignant disease of peripheral T‐cell origin that is characterized by a prominent proliferation of high endothelial venules in the lymph node. To investigate angiogenic mechanisms in AILT we measured the angiogenic mediator gene expression levels in the lymph nodes of 54 non‐Hodgkin lymphoma patients, by immunostaining and quantitative reverse transcription polymerase chain reaction. Angiogenic mediators angiopoietin (Ang) 1 (ANGPT1), Ang2 (ANGPT2) and their receptor, Tie2 (TEK), vascular endothelial growth factor (VEGF; VEGFA) and its receptor, VEGFR2 (KDR), and hepatocyte growth factor (HGF) and its receptor, c‐Met (MET) were all more highly expressed in AILT lymph nodes (16 cases) than in B‐cell lymphomas (24 cases). Moreover, significantly higher Ang1 and Tie2 expression was detected in AILT cases with CD10‐positive neoplastic T‐cells by comparison with unspecified peripheral T‐cell lymphoma (14 cases). Immunostaining confirmed the expression of Ang1 and VEGF by both neoplastic T‐cells and follicular dendritic cells. These results suggest that the angiopoietin system may play an important role in the development of high vascularity in AILT lymph nodes. Consequently, as neoplastic T‐cells and follicular dendritic cells are both increased in AILT and may represent an important source of angiogenic mediators, targeting these cells with anti‐angiogenic strategies might represent a novel therapy for AILT.
Crack‐Defined Electronic Nanogaps

Achieving near-atomic-scale electronic nanogaps in a reliable and scalable manner will facilitate fundamental advances in molecular detection, plasmonics, and nanoelectronics. Here, a method is shown for realizing crack-defined nanogaps separating TiN electrodes, allowing parallel and scalable fabrication of arrays of sub-10 nm electronic nanogaps featuring individually defined gap widths.
Room temperature hyperpolarization of nuclear spins in bulk

Significance Nuclear spins are only slightly aligned even in the strong magnetic fields of superconducting magnets because the magnetic energy of nuclear spin is much smaller than thermal energy. This is the major reason for the low sensitivity of NMR spectroscopy. Using electron spins in thermal equilibrium, which have 660 times higher magnetic energy, the sensitivity can be enhanced by at most this factor through a method called dynamic nuclear polarization. Utilizing photo-excited nonthermalized electrons instead, we demonstrate an enhancement factor of 250,000 at room temperature, which can be applied to a wide range of fields including NMR, MRI, and physics. Dynamic nuclear polarization (DNP), a means of transferring spin polarization from electrons to nuclei, can enhance the nuclear spin polarization (hence the NMR sensitivity) in bulk materials at most 660 times for 1H spins, using electron spins in thermal equilibrium as polarizing agents. By using electron spins in photo-excited triplet states instead, DNP can overcome the above limit. We demonstrate a 1H spin polarization of 34%, which gives an enhancement factor of 250,000 in 0.40 T, while maintaining a bulk sample (∼0.6 mg, ∼0.7 × 0.7 × 1 mm3) containing >1019 1H spins at room temperature. Room temperature hyperpolarization achieved with DNP using photo-excited triplet electrons has potentials to be applied to a wide range of fields, including NMR spectroscopy and MRI as well as fundamental physics.
Geomechanical behavior of the reservoir and caprock system at the In Salah CO2 storage project

Significance In Salah is one of the largest carbon capture and storage projects to date and has played a central role in demonstrating the feasibility of onshore sequestration of CO2 in deep saline aquifers. The unique field experience at In Salah provides a valuable case study in managing commercial-scale CO2 injections. In particular, the current work highlights the importance of geomechanics and integrated monitoring in understanding field behavior and managing storage risk. Almost 4 million metric tons of CO2 were injected at the In Salah CO2 storage site between 2004 and 2011. Storage integrity at the site is provided by a 950-m-thick caprock that sits above the injection interval. This caprock consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity. Monitoring observations at the site indirectly suggest that pressure, and probably CO2, have migrated upward into the lower portion of the caprock. Although there are no indications that the overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the system. Several hypotheses have been put forward to explain the measured pressure, seismic, and surface deformation behavior. These include fault leakage, flow through preexisting fractures, and the possibility that injection pressures induced hydraulic fractures. This work evaluates these hypotheses in light of the available data. We suggest that the simplest and most likely explanation for the observations is that a portion of the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. There are no indications, however, that the overall storage complex has been compromised, and several independent data sets demonstrate that CO2 is contained in the confinement zone.
Prevalence and cardiovascular risk profile of chronic kidney disease in Italy: results of the 2008-12 National Health Examination Survey.

BACKGROUND National surveys in countries outside Europe have reported a high prevalence (11-13%) of chronic kidney disease (CKD). Studies in Europe have provided a variable prevalence likely due to differences in study design, including age and extent of geographic areas, equation used to evaluate estimated glomerular filtration rate (eGFR) and CKD stages examined. METHODS The 2008-12 National Health Examination Survey in Italy randomly extracted samples from the general population aged 35-79 years, stratified by age and gender, from the resident list of each Italian region (440 persons/1.5 million of residents). We estimated the prevalence of CKD by means of urinary albumin : creatinine ratio and eGFR (CKD-EPI equation-enzymatic assay of serum creatinine). Cardiovascular (CV) risk profile was also evaluated. RESULTS Three thousand eight hundred and forty-eight men and 3704 women were examined. In the whole population, mean age was 57 ± 12 and 56 ± 12 years in men and women, respectively; hypertension was prevalent in men and women, respectively (56 and 43%) and the same held true for overweight (48 and 33%), obesity (26 and 27%), diabetes (14 and 9%) and smoking (21 and 18%), whereas CV disease was less frequent (9 and 6%). Overall, the prevalence of CKD (95% confidence interval) was 7.05% (6.48-7.65). Early stages constituted 59% of the CKD population [Stage G1-2 A2-3: 4.16% (3.71-4.61) and Stage G3-5: 2.89% (2.51-3.26)]. At multivariate regression analysis, age, obesity, hypertension, diabetes, CV disease and smoking were all independent correlates of CKD. CONCLUSIONS CKD has a relatively lower prevalence in Italy, in particular for advanced stages, when compared with similar national surveys outside Europe. This occurs despite older age and unfavourable CV risk profile of the whole population.
HHV‐6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV‐6 and fatal CMV pneumonitis

Two patients with the characteristic high human herpesvirus 6 (HHV‐6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV‐6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV‐6 DNA was detected at high levels throughout the organs with the exception of donor‐derived haematopoietic tissue. In individuals with chromosomal integration, HHV‐6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.
O uso da fitoterapia no cuidado de crianças com até cinco anos em área central e periférica da cidade de São Paulo

This research evaluated the use of phytotherapy in children who attend a Health Center in an urban area and a Health Center in the suburbs of Sao Paulo city. This is an exploratory and descriptive study with 120 mothers who attend two Health Centers (60 mothers in the urban area and another 60 in the suburbs), during December 2001. After receiving approval from the Ethics Committee, the mothers were individually interviewed and it was confirmed that 79 (66%) of them frequently used chamomile, fennel and peppermint for the intestinal cramps, flu symptoms and to calm their children down. Directions on how and what to use was provided mainly by parents and grandparents (57%) and no great differences could be found in the use of herbs in the two areas of Sao Paulo.
Bone marrow cells from patients with Shwachman‐Diamond syndrome abnormally express genes involved in ribosome biogenesis and RNA processing

Shwachman‐Diamond Syndrome (SDS) is a multi‐system genetic disorder with bone marrow failure. SBDS, the gene associated with SDS, has been postulated to play a role in ribosome biogenesis and RNA processing, but its functions are still unknown. To study whether these pathways are interrupted when Sbds protein is lost, we studied the expression of related genes in patient SBDS−/− cells by an oligonucleotide microarray. We first analysed ribosomal protein (RP) genes, which are normally co‐regulated. In SDS, 27 of the 85 RP genes were downregulated. Among the downregulated RP genes, seven are known to be associated with the inhibition of apoptosis. RPS27L, which mediates p53‐dependent induction of apoptosis, was the only upregulated RP gene. Interestingly, several genes involved in RP mRNA transcription were downregulated without affecting the expression of genes involved in mRNA degradation, suggesting that the downregulation of the RP gene expression might be at the transcriptional level. Importantly we also found dysregulation of multiple genes involved in rRNA transcription and pre‐rRNA processing. We conclude that SDS marrow cells exhibit major dysregulation of RP, RNA processing and RNA transcription genes.
Interfacial Design of Mixed Matrix Membranes for Improved Gas Separation Performance

High-performance metal-organic framework (MOF)/polyimide (PI) mixed matrix membranes (MMMs) are fabricated by a facile strategy by designing the MOF/PI matrix interface via poly dopamine coating. The overall separation performance of the designed MMMs surpasses the state-of-the-art 2008 Robeson upper bound for the H2 /CH4 and H2 /N2 gas pairs and approaches the 2008 upper bound for the O2 /N2 gas pair.
Effect of Robot and Screen Agent Recommendations on Human Decision-Making

Two-dimensional (2D) character agents that have a human-like appearance are being developed. In the future, such agents will be able to interact with their users in a natural and friendly manner through speech recognition, synthesized speech, andaction displays. In addition, robots or robotic companions that have a three-dimensional (3D) physical body are attracting attention as
The predictability of molecular evolution during functional innovation

Significance Understanding the genetic changes that underlie phenotypic functional innovations is a fundamental goal in evolutionary biology, giving insight into species’ past, present, and future evolutionary trajectories. One important unresolved question is whether such genetic changes typically affect protein expression or protein structure. Here we use large-scale laboratory evolution with bacteria to quantify the types of genetic changes that occur during functional innovation. We show that whether these changes affect protein expression or protein structure depends on which cellular functions are being selected upon. We then show that changes affecting protein expression occur in qualitatively different sets of genes from changes affecting protein structure. These results show that using functional knowledge it is possible to predict the course of evolution. Determining the molecular changes that give rise to functional innovations is a major unresolved problem in biology. The paucity of examples has served as a significant hindrance in furthering our understanding of this process. Here we used experimental evolution with the bacterium Escherichia coli to quantify the molecular changes underlying functional innovation in 68 independent instances ranging over 22 different metabolic functions. Using whole-genome sequencing, we show that the relative contribution of regulatory and structural mutations depends on the cellular context of the metabolic function. In addition, we find that regulatory mutations affect genes that act in pathways relevant to the novel function, whereas structural mutations affect genes that act in unrelated pathways. Finally, we use population genetic modeling to show that the relative contributions of regulatory and structural mutations during functional innovation may be affected by population size. These results provide a predictive framework for the molecular basis of evolutionary innovation, which is essential for anticipating future evolutionary trajectories in the face of rapid environmental change.
Levels of non‐transferrin‐bound iron as an index of iron overload in patients with thalassaemia intermedia

Non‐transferrin‐bound iron (NTBI) was evaluated as an index of iron overload in a cross‐sectional randomised study in 74 non‐transfused patients with thalassaemia intermedia (TI). Mean NTBI (2·92 ± 3·43 μmol/l), serum ferritin (1023 ± 780 ng/ml) and liver iron concentration (LIC; 9·0 ± 7·4 mg Fe/g dry weight) were increased above reference‐range levels. Significant positive correlations occurred between mean NTBI and LIC (Pearson correlation 0·36; P = 0·002) and serum ferritin (Pearson correlation 0·421; P < 0·0001); with higher levels observed in splenectomised patients. NTBI assessment has potential as a simple reliable approach to determining iron status in TI.
Repairable Woven Carbon Fiber Composites with Full Recyclability Enabled by Malleable Polyimine Networks

Carbon-fiber reinforced composites are prepared using catalyst-free malleable polyimine networks as binders. An energy neutral closed-loop recycling process has been developed, enabling recovery of 100% of the imine components and carbon fibers in their original form. Polyimine films made using >21% recycled content exhibit no loss of mechanical performance, therefore indicating all of the thermoset composite material can be recycled and reused for the same purpose.
Solid-state electron transport via cytochrome c depends on electronic coupling to electrodes and across the protein

Significance How well a protein conducts electrical current depends on both the chemical nature of the protein and its contacts to the electrodes between which currents are carried. Investigating conduction via protein monolayers, we find that covalent binding to electrodes doubles room temperature conduction and halves its thermal activation energy. At low temperatures, where transport is by tunneling, covalent binding increases conduction up to 10-fold. To examine the electrical conduction across the protein, we used seven different cytochrome c mutants with surface-exposed cysteine, providing distinct electrode–heme orientations and distances. Remarkably, currents do not depend on the electrodes’ separation distance as set by a given protein binding orientation but rather on the distance between the heme and one of the electrodes. Electronic coupling to electrodes, Γ, as well as that across the examined molecules, H, is critical for solid-state electron transport (ETp) across proteins. Assessing the importance of each of these couplings helps to understand the mechanism of electron flow across molecules. We provide here experimental evidence for the importance of both couplings for solid-state ETp across the electron-mediating protein cytochrome c (CytC), measured in a monolayer configuration. Currents via CytC are temperature-independent between 30 and ∼130 K, consistent with tunneling by superexchange, and thermally activated at higher temperatures, ascribed to steady-state hopping. Covalent protein–electrode binding significantly increases Γ, as currents across CytC mutants, bound covalently to the electrode via a cysteine thiolate, are higher than those through electrostatically adsorbed CytC. Covalent binding also reduces the thermal activation energy, Ea, of the ETp by more than a factor of two. The importance of H was examined by using a series of seven CytC mutants with cysteine residues at different surface positions, yielding distinct electrode–protein(–heme) orientations and separation distances. We find that, in general, mutants with electrode-proximal heme have lower Ea values (from high-temperature data) and higher conductance at low temperatures (in the temperature-independent regime) than those with a distal heme. We conclude that ETp across these mutants depends on the distance between the heme group and the top or bottom electrode, rather than on the total separation distance between electrodes (protein width).