Miracle-dz/UniFAR-FTUs huggingface dataset:
A retrospective study of a nurse residency program and reports of job satisfaction, organizational commitment, and turnover

The aging population in the United States and greater access to healthcare due to recent legislative reforms will result in an increased demand for registered nurses. However, meeting this demand will challenge healthcare organizations due to an aging nursing workforce that will be retiring, a lack of new nurses entering the profession due to lack of employment opportunities related to the current macroeconomic environment, and the lack of capacity to produce nursing graduates. Furthermore, reported turnover rates of newly graduated registered nurses range from 18 to 60% during the first year of employment. Healthcare organizations implementing structured nurse residency programs have reported success in stemming the tide of new graduate turnover. However, there is a lack of empirical evidence in the nurse residency literature regarding variables that have been shown to decrease turnover of registered nurses.
Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis.

BACKGROUND To determine the efficacy of immunoglobulin free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) as an adjuvant treatment to chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM). METHODS Sixty-seven patients with dialysis-dependent renal failure secondary to MM were treated with HCO-HD and chemotherapy. RESULTS The population was predominantly male (62.7%) with new presentation MM (75%) and did not have a history of chronic kidney disease (84%). The mean serum creatinine at presentation was 662 (SD = 349) μmol/L and of the 56.7% of patients who had a renal biopsy, 86.7% had cast nephropathy as the principal diagnosis. Eighty-five percent of patients were treated with a chemotherapy regime consisting of dexamethasone in combination with a novel agent (bortezomib or thalidomide). The median number of HCO-HD sessions was 11 (range 3-45), 97% received an extended dialysis regime. Seventy-six percent of the population had a sustained reduction in serum FLC concentrations by Day 12, of these 71% subsequently became independent of dialysis. In total, 63% of population became independent of dialysis. Factors which predicted independence of dialysis were the degree of FLC reduction at Days 12 (P = 0.002) and 21 (P = 0.005) and the time to initiating HCO-HD (P = 0.006). CONCLUSION The combination of extended HCO-HD and chemotherapy resulted in sustained reductions in serum FLC concentrations in the majority of patients and a high rate of independence of dialysis.
Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry

The kinetic folding of ribonuclease H was studied by hydrogen exchange (HX) pulse labeling with analysis by an advanced fragment separation mass spectrometry technology. The results show that folding proceeds through distinct intermediates in a stepwise pathway that sequentially incorporates cooperative native-like structural elements to build the native protein. Each step is seen as a concerted transition of one or more segments from an HX-unprotected to an HX-protected state. Deconvolution of the data to near amino acid resolution shows that each step corresponds to the folding of a secondary structural element of the native protein, termed a “foldon. ” Each folded segment is retained through subsequent steps of foldon addition, revealing a stepwise buildup of the native structure via a single dominant pathway. Analysis of the pertinent literature suggests that this model is consistent with experimental results for many proteins and some current theoretical results. Two biophysical principles appear to dictate this behavior. The principle of cooperativity determines the central role of native-like foldon units. An interaction principle termed “sequential stabilization” based on native-like interfoldon interactions orders the pathway.
Crop manuring and intensive land management by Europe’s first farmers

The spread of farming from western Asia to Europe had profound long-term social and ecological impacts, but identification of the specific nature of Neolithic land management practices and the dietary contribution of early crops has been problematic. Here, we present previously undescribed stable isotope determinations of charred cereals and pulses from 13 Neolithic sites across Europe (dating ca. 5900–2400 cal B.C.), which show that early farmers used livestock manure and water management to enhance crop yields. Intensive manuring inextricably linked plant cultivation and animal herding and contributed to the remarkable resilience of these combined practices across diverse climatic zones. Critically, our findings suggest that commonly applied paleodietary interpretations of human and herbivore δ15N values have systematically underestimated the contribution of crop-derived protein to early farmer diets.
Modern management of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim‐sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene‐replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life‐threatening infections.
Früherkennung und klinische Relevanz - Insulinresistenz und Atherosklerose

P atienten mit manifestem Typ2-Diabetes, aber auch Patienten mit einer gestörten Glukosetoleranz weisen ein mindestens zweibis dreifach erhöhtes Risiko für kardiovaskuläre Ereignisse auf als die gesunde, nichtdiabetische Bevölkerung, so die FraminghamStudie, die bereits 1979 publiziert wurde. Eine weitere Arbeit, die diesen Sachverhalt stützt, erschien 1985: Uusitupa et al. zeigten an neu diagnostizierten Typ-2-Diabetikern, dass diese im Vergleich zur Normalbevölkerung bereits ein 1,7fach erhöhtes Risiko für zurückliegende Myokardinfarkte für Männer, und ein sogar 4,4faches Risiko für Frauen aufwiesen (23, 24). Insgesamt hatten etwa 50% der 133 untersuchten Patienten bereits manifeste makrooder mikrovaskuläre Veränderungen. Auch der Qualität der Stoffwechseleinstellung kommt eine relevante prognostische Bedeutung zu, so das Ergebnis großer longitudinaler Interventionsstudien, wie der UKPDS1, die den Einfluss der Stoffwechseleinstellung bzw. die Art der antidiabetischen Therapie und das Auftreten kardiovaskulärer Ereignisse untersuchte. Demnach ist eine Reduktion des HbA1c um einen Prozentpunkt mit einer Reduktion der makrovaskulären Komplikationen wie Myokardinfarkt um 14% verbunden. Mikroangiopathische Veränderungen verringerten sich sogar um 37%. Die auffällige Differenz in den Erfolgsraten zwischen makround mikrovaskulären Veränderungen spricht dafür, dass bei Diabetikern eine optimale Einstellung des Blutzuckerspiegels allein nicht ausreicht, um das makrovaskuläre Risiko deutlich zu senken. Hier muss therapeutisch ein multimodaler Ansatz gewählt werden.
Proton transfer through the water gossamer

The diffusion of protons through water is understood within the framework of the Grotthuss mechanism, which requires that they undergo structural diffusion in a stepwise manner throughout the water network. Despite long study, this picture oversimplifies and neglects the complexity of the supramolecular structure of water. We use first-principles simulations and demonstrate that the currently accepted picture of proton diffusion is in need of revision. We show that proton and hydroxide diffusion occurs through periods of intense activity involving concerted proton hopping followed by periods of rest. The picture that emerges is that proton transfer is a multiscale and multidynamical process involving a broader distribution of pathways and timescales than currently assumed. To rationalize these phenomena, we look at the 3D water network as a distribution of closed directed rings, which reveals the presence of medium-range directional correlations in the liquid. One of the natural consequences of this feature is that both the hydronium and hydroxide ion are decorated with proton wires. These wires serve as conduits for long proton jumps over several hydrogen bonds.
Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma

A growing number of agents targeting ligand-induced Wnt/β-catenin signaling are being developed for cancer therapy. However, clinical development of these molecules is challenging because of the lack of a genetic strategy to identify human tumors dependent on ligand-induced Wnt/β-catenin signaling. Ubiquitin E3 ligase ring finger 43 (RNF43) has been suggested as a negative regulator of Wnt signaling, and mutations of RNF43 have been identified in various tumors, including cystic pancreatic tumors. However, loss of function study of RNF43 in cell culture has not been conducted, and the functional significance of RNF43 mutations in cancer is unknown. Here, we show that RNF43 inhibits Wnt/β-catenin signaling by reducing the membrane level of Frizzled in pancreatic cancer cells, serving as a negative feedback mechanism. Inhibition of endogenous Wnt/β-catenin signaling increased the cell surface level of Frizzled. A panel of 39 pancreatic cancer cell lines was tested for Wnt dependency using LGK974, a selective Porcupine inhibitor being examined in a phase 1 clinical trial. Strikingly, all LGK974-sensitive lines carried inactivating mutations of RNF43. Inhibition of Wnt secretion, depletion of β-catenin, or expression of wild-type RNF43 blocked proliferation of RNF43 mutant but not RNF43–wild-type pancreatic cancer cells. LGK974 inhibited proliferation and induced differentiation of RNF43-mutant pancreatic adenocarcinoma xenograft models. Our data suggest that mutational inactivation of RNF43 in pancreatic adenocarcinoma confers Wnt dependency, and the presence of RNF43 mutations could be used as a predictive biomarker for patient selection supporting the clinical development of Wnt inhibitors in subtypes of cancer.
Cord blood stem cell transplantation for haemoglobinopathies

Despite improvements in supportive care, patients with β‐thalassaemia major or sickle cell disease (SCD) may benefit from haematopoietic stem cell transplantation at some point during their lives. Human leucocyte antigen (HLA)‐matched sibling bone marrow donors are not always available and alternative sources of stem cells have been sought, including related and unrelated donor cord blood transplants (CBT). The outcome of CBT from related donors for the treatment of both thalassaemia major and SCD is now approaching that for bone marrow transplantation, with around 90% of patients surviving disease‐free. The main complication is graft rejection, which may be reduced by increasing pretransplant immune suppression. Transplant‐related mortality following HLA‐identical matched related donor CBT is extremely low but is significant in the small series of unrelated and/or mis‐matched donor CBT. The principal limitation to extending the use of CB stem cells for the cure of haemoglobinopathies is the need to better understand the mechanisms of action and optimal conditioning regimens used to secure long‐term engraftment while minimizing morbidity and mortality. Further biological studies and clinical trials are needed to address this aim.
SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling

The mammalian target of rapamycin (mTOR) plays an important role in controlling islet β-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5′ adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain. In this study, we investigated a role of the kinase in regulating pancreatic β-cell morphology and function as a mediator of mTOR complex 1 (mTORC1) signaling. We show that global SAD-A deletion leads to defective glucose-stimulated insulin secretion and petite islets, which are reminiscent of the defects in mice with global deletion of ribosomal protein S6 kinase 1, a downstream target of mTORC1. Consistent with these findings, selective deletion of SAD-A in pancreas decreased islet β-cell size, whereas SAD-A overexpression significantly increased the size of mouse insulinomas cell lines β-cells. In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet β-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Moreover, the 5′-untranslated region of SAD-A mRNA is highly structured and requires mTORC1 signaling for its translation initiation. Together, these findings identified SAD-A as a unique pancreas-specific effector protein of mTORC1 signaling.
Graphene‐Enabled Superior and Tunable Photomechanical Actuation in Liquid Crystalline Elastomer Nanocomposites

Programmable photoactuation enabled by graphene: Graphene sheets aligned in liquid crystalline elastomers are capable of absorbing near-infrared light. They thereafter act as nanoheaters and provide thermally conductive pathways to trigger the nematic-to-isotropic transition of elastomers, leading to macroscopic mechanical deformation of nanocomposites. Large strain, high actuation force, high initial sensitivity, fast reversible response, and long cyclability are concurrently achieved in nanocomposites.
Proteomics of Peripheral Leukocytes in Patients with Elevated Serum Levels of PSA

Abstract : During this second year of research, we have modified patient recruitment protocols for a greater sample acquisition rate, and initiated studies in mouse models of prostate cancer. This will allow us to reduce the influence of genetic heterogeneity observed in human populations, and increase our confidence that observed differences in protein levels are the result of a malignant process. From collected patient samples, we now are able to isolate CD4+ T-lymphocytes and monocytes at high yield and high purity, and analyze them by mass spectrometry. We have observed a total of 1190 proteins from monocytes by two or more peptides from these samples. At this early stage, there are numerous proteins which could become candidates for discriminating between prostate cancer and benign prostate diseases in the setting of an elevated PSA. However, the main task in the coming year will be the analysis of a much larger number of samples, in order to achieve statistical significance.
Inferring relative numbers of human leucocyte genome replications

Genome duplication inevitably results in replication errors. A priori, the more times a genome is copied, the greater the average number of replication errors. This principle could be used to ‘count’ mitotic divisions. Although somatic mutations are rare, cytosine methylation is also copied after DNA replication, but measurably increases with aging at certain CpG rich sequences in mitotic tissues, such as the colon. To further test whether such age‐related methylation represents replication errors, these CpG rich ‘clock’ sequences were measured in leucocytes. Leucocytes within an individual have identical chronological ages (time since birth) but their mitotic ages (numbers of divisions since the zygote) may differ. Neutrophils, B‐lymphocytes, and red cell progenitors are produced from relatively quiescent stem cells throughout life, but T‐lymphocyte production largely ceases after puberty when the thymus disappears. However, T‐lymphocyte genomes may continue to replicate throughout life in response to immunological stimulation. Consistent with this biology, clock methylation significantly increased with aging for T‐lymphocyte genomes, but no significant increase was measured in other cell populations. Moreover, this methylation was greater in genomes isolated from their corresponding neoplastic populations. These studies tentatively support the hypothesis that methylation at certain CpG rich sequences in leucocytes could record their mitotic ages.
Handbook on animal-assisted therapy. Theoretical foundations and guidelines for practice

This introductory chapter provides readers not only with a basic foundation to appreciate and understand this unique kinship with all living creatures but also to discover the roots to the overwhelming growing interest in animal-assisted intervention (AAI). The chapter should also help solidify and clarify how the benefits witnessed within this unique bond have prompted numerous professionals to become more curious about the advantages of animal-assisted interventions. It is apparent that dogs have been bred to coexist with their human counterparts and have filled many roles including herding, guarding, hunting, fishing and being our best friend (Clutton-Brock, 1995). Dogs have also been widely used as service animals, supporting the quality of life of people in need. There have been increasing insights into science’s current understanding of dog behavior and cognition. Perhaps one of the strongest insights that she discusses pertains to dogs’ ability to understand our behaviors (Hare, 2007; Hare et al., 2002). Horowitz (2009) explains that dogs’
The relationship between jumping performance and isokinetic strength of hip and knee extensors and ankle plantar flexors

The purpose of this study was to examine the relationship between vertical jumping performance and isokinetic moment of force of knee extensors, hip extensors and ankle plantar flexors in adult males. Twenty-nine males performed squat and counter movement jumps on an Egrojump device. The peak jumping height and the total work (height x body mass) were used as indicators of vertical jump performance. The subjects also performed three submaximal and three maximal isokinetic efforts of the hip extensors, knee extensors and ankle plantarflexors at angular velocities of 60, 120 and 180°. s -1 on Cybex Norm Dynamometer. Pearson's product correlation tests indicated that there was a significant (p 0.05). Multiple regression analysis indicated that linear combinations of isokinetic torques accounted for 38% and 42% of the countermovement and squat jumping height variance, respectively. In contrast, regression models using isokinetic torques could predict jumping work accounting for 75% (counter movement jump) and 69% (squat jump) of the variance. The above results indicate that there is a moderate to high relationship between isokinetic knee and hip extension torques and vertical jump performance parameters, especially when jumping height is multiplied by subject's body weight. Furthermore, it appears that when using a linear combination of isokinetic torques from hip and knee joint muscle groups the multiple relationship between isokinetic tests and jumping performance is higher.
Humoral signalling compounds in remote ischaemic preconditioning of the kidney, a role for the opioid receptor.

BACKGROUND Renal ischaemia-reperfusion injury (IRI) is a common clinical problem associated with significant mortality and morbidity. One strategy to reduce this damage is remote ischaemic preconditioning (RIPC), in which brief ischaemia of a limb protects the kidney against a prolonged ischaemic insult. The mechanism of renal RIPC has not yet been elucidated. Here, we address the gap in our understanding of renal RIPC signalling, using a rat model of renal IRI and RIPC by brief hind limb ischaemia. METHODS Rats were treated with either no RIPC, RIPC+vehicle or RIPC+ an inhibitor or antagonist of one of the following candidate signalling molecules: noradrenalin, cannabinoids, glucocorticoids, inducible nitric oxide synthase, calcitonin gene-related peptide, ganglion-mediated signalling, haem oxygenase and free radicals. Subsequently, the animals underwent 25 min of renal ischaemia and 2 days of reperfusion, after which renal function and damage were assessed. RESULTS RIPC by three 4 min cycles of hind limb ischaemia effectively reduced renal IRI. Pre-treatment with the opioid receptor antagonist naloxone completely blocked this protective effect, when compared with animals treated with RIPC+vehicle; serum creatinine and urea increased (307.8±43.7 versus 169.5±16.7 µmol/L and 42.2±4.9 versus 27.6±2.2 mmol/L, respectively), as did the renal histological damage (score 4.2±0.7 versus 2.8±0.5) and expression of kidney injury molecule-1 (KIM-1; relative-fold increase in mRNA expression 164±18 versus 304±33). All other antagonists were without effect. CONCLUSIONS Renal RIPC by brief hind limb ischaemia may be the result of endorphin release from the hind limb. The importance of opioid signalling in renal RIPC provides vital clues for its successful translation to the clinical setting.
High-Oleic Ground Beef, Exercise, and Risk Factors for Cardiovascular Disease in Men and Postmenopausal Women

High-Oleic Ground Beef, Exercise, and Risk Factors for Cardiovascular Disease in Men and Postmenopausal Women. (December 2010) Linda Anne Gilmore, B.S., Texas A&M University Chair of Advisory Committee: Dr. Stephen B. Smith Sixty-six percent of the ground beef consumed in the U.S. contains 16-30% fat by weight, and at the retail level, ground beef fat varies widely with regards to saturated, monounsaturated and trans-fatty acid content. Through two independent studies the effect of fatty acid composition of ground beef on selected cardiovascular disease risk indicators was evaluated. In the first study, 27 free-living normocholesterolemic men completed a threeway crossover dietary intervention. Subjects consumed five, 114-g ground beef patties per week for 5 wk with intervening 4-wk washout periods. Patties contained 24% total fat with monounsaturated fatty acid:saturated fatty acid (MUFA:SFA) of either 0.71 (lowMUFA, pasture-fed), 0.83 (mid-MUFA, short-term corn-fed), or 1.10 (high-MUFA, longterm corn-fed). Blood was collected from each subject before and at the end of each diet period. Overall, the ground beef interventions decreased plasma insulin, HDL2, and HDL3 particle diameter and α-linolenic acid (18:2 (n-3)), and increased plasma arachidonic (20:4(n-6)). The greatest increase in HDL cholesterol from baseline (0.07 mmol/L) was after the high-MUFA ground beef intervention. An increase from baseline in LDL particle diameter (0.5 nm) occurred after the midand high-MUFA interventions.