Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges in Longer-Term Mechanical Support of Fontan Circulation in Sheep

Single ventricle congenital heart defects are usually palliated with the end result of a Fontan circulation. Despite improving results, this circulation is still associated with long-term failure. We previously developed an animal model of mechanical cavopulmonary circulation support that was successful in the acute and mid-term period. In the current study, we evaluated longer support durations in five Western-breed sheep. Through a right thoracotomy we instituted mechanical support from the inferior vena cava to the pulmonary artery, using a Heartmate II axial flow pump (Thoratec Corp., Pleasanton, CA). Postoperatively, the animals were anticoagulated with heparin iv. Hemodynamics, pump flow, anticoagulation, and hepatic and renal function were monitored daily. All animals survived the operation. Signs of moderate liver and kidney injury in general reversed quickly. Two animals had a fatal pump thrombosis. When anticoagulation was effective, hemodynamics and pump flow were maintained to normal values. Effective anticoagulation was difficult to achieve because of the high variability in response to heparin. Survival up to 18 days was accomplished. This study is the longest reported survival of animals with a mechanically assisted cavopulmonary circulation. The performance of the Thoratec Heartmate II has been good, but the issue of effective anticoagulation has not yet been solved.
Large‐scale neural model validation of partial correlation analysis for effective connectivity investigation in functional MRI

Recent studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large‐scale functional brain networks. In a previous study, we advocated that data‐driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large‐scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Function of Ech Hydrogenase in Ferredoxin-Dependent, Membrane-Bound Electron Transport in Methanosarcina mazei

ABSTRACT Reduced ferredoxin is an intermediate in the methylotrophic and aceticlastic pathway of methanogenesis and donates electrons to membrane-integral proteins, which transfer electrons to the heterodisulfide reductase. A ferredoxin interaction has been observed previously for the Ech hydrogenase. Here we present a detailed analysis of a Methanosarcina mazei Δech mutant which shows decreased ferredoxin-dependent membrane-bound electron transport activity, a lower growth rate, and faster substrate consumption. Evidence is presented that a second protein whose identity is unknown oxidizes reduced ferredoxin, indicating an involvement in methanogenesis from methylated C1 compounds.
CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

BACKGROUND The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. METHODS Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients). RESULTS The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab. CONCLUSIONS The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.
Effect of Operator and Optical Defocus on the Variability of Pattern Electroretinogram Optimized for Glaucoma Detection (PERGLA)

PurposeTo evaluate the effect of operator and optical defocus on the variability of pattern electroretinogram optimized for glaucoma detection (PERGLA). MethodsTwo different operators obtained 2 PERGLA recordings each from 10 healthy participants (5 women, mean age 32.1±10.3 y). In addition, one of the operators obtained recordings in which corrective lenses of various diopters (±0.5, ±1, ±2, and ±3) were used to generate optical defocus in both eyes. The effect of operator on PERGLA amplitude and phase variability was determined using a single nested variance components' analysis model and by using Bland-Altman plots. One-way analysis of variance (ANOVA) was used to determine the effect of optical defocus on amplitude and phase. ResultsDifferences in measurements between operators accounted for approximately 26.6% and 18.2% of the total variance for amplitude and phase, respectively. Results were confirmed by the use of Bland-Altman plots. ANOVA identified a significant effect of defocus on mean amplitude (F=2.65, P=0.01), but not phase (F=1.02, P=0.42). ConclusionsMeasurements obtained by different operators can result in significant differences in PERGLA amplitude. In addition, although optical defocus leads to a decrease in PERGLA amplitude by reducing visual acuity, this can be avoided by obtaining J1 or better vision before testing.
Emotional Modulation of the Ability to Inhibit a Prepotent Response During Childhood

The present study examined the bottom-up influence of emotional context on response inhibition, an issue that remains largely unstudied in children. Thus, 62 participants, aged from 6 to 13 years old, were assessed with three stop signal tasks: one with circles, one with neutral faces, and one with emotional faces (happy and sad). Results showed that emotional context altered response inhibition ability in childhood. However, no interaction between age and emotional influence on response inhibition was found. Positive emotions were recognized faster than negative emotions, but the valence did not have a significant influence on response inhibition abilities.
Insulin‐like growth factor binding protein‐4 (IGFBP‐4) is a novel anti‐angiogenic and anti‐tumorigenic mediator secreted by dibutyryl cyclic AMP (dB‐cAMP)‐differentiated glioblastoma cells

cAMP has been shown to reverse the transformed phenotype of various cancer cells. Human glioblastoma U87MG cells exposed to 500 μM dB‐cAMP for 6 days showed reduced proliferation, attenuated invasiveness, and inability to induce angiogenic responses in human brain endothelial cells (HBECs) grown in Matrigel™. VEGF was the principal mediator of angiogenic actions of U87MG conditioned media (CM), since VEGF neutralizing antibody completely inhibited U87MG‐induced angiogenic responses and no detectable levels of IGF, bFGF, and PlGF were found in U87MG CM. VEGF release was induced (∼20%) in dB‐cAMP‐treated U87MG cells, suggesting a simultaneous induction of anti‐angiogenic mediators. Down‐stream effectors of dB‐cAMP actions in U87MG were investigated by microarray gene expression analysis. Detected increases in differentiation genes, staniocalcin‐1 and Wnt‐5a, and angiogenesis‐related genes, PAI‐1, SPARC, IGFBP‐4, IGFBP‐7, PAPP‐A, and PRSS‐11 in dB‐cAMP‐treated U87MG cells were validated by real‐time PCR, Western blot, and/or ELISA. A subsequent series of experiments identified IGFBP‐4 as the principal anti‐angiogenic mediator secreted by glioblastoma cells in response to dB‐cAMP. Human recombinant IGFBP‐4 inhibited the angiogenic response of HBEC induced by U87MG CM, whereas anti‐human IGFBP‐4 antibody restored the pro‐angiogenic activity of dB‐cAMP‐treated U87MG CM. Since neither U87MG nor HBEC cells secreted detectable levels of IGF‐I, and there are no known cellular IGFBP‐4 receptors, the anti‐angiogenic effect of IGFBP‐4 was likely IGF‐I‐independent and indirect. IGFBP‐4 also antagonized angiogenic effects of VEGF165, PlGF, and bFGF, and reduced U87MG colony formation in soft‐agar. IGFBP‐4 is a novel dB‐cAMP‐induced anti‐angiogenic and anti‐tumorigenic mediator that may be a promising candidate for glioblastoma therapy. © 2006 Wiley‐Liss, Inc.
Research on the Relationship Between High-Commitment Work Systems and Employees’ Unethical Pro-organizational Behavior: The Moderating Role of Balanced Reciprocity Beliefs

Based on the social exchange theory, this paper explores the indirect impact of high-commitment work systems on employees’ unethical pro-organizational behavior. Through the analysis of multisource data from 139 companies (including 139 human resource managers and 966 employees), a multilevel structuring equation model is used to verify the study’s hypotheses. The research results show the following findings: (1) High-commitment work systems are significantly positively related to employees’ unethical pro-organizational behavior. (2) High-commitment work systems have indirect effects on the employees’ unethical pro-organizational behavior through the relational psychological contract. The relational psychological contract plays a mediating role in this process. (3) Employees’ balanced reciprocity beliefs significantly enhance the positive effect of relational psychological contracts on employees’ unethical pro-organizational behavior. It can also positively moderate the mediating effect of high-commitment work systems that affect employees’ unethical pro-organizational behavior via relational psychological contract.
Prostaglandin E2 differentially regulates contraction and structural reorganization of anchored collagen gels by human adult and fetal dermal fibroblasts

Contraction and remodeling of granulation tissue by fibroblasts is a crucial component of dermal wound healing. Postnatal wounds heal with imperfect repair and scar formation, whereas tissue repair in fetal wounds is regenerative. Prostaglandin E2 (PGE2) modulates the behavior of fibroblasts in the wound bed. This study was designed to investigate the mechanism by which PGE2 regulates an in vitro model of granulation tissue, anchored collagen gels, by human adult and fetal dermal fibroblasts. We hypothesized that PGE2 differentially regulates contraction and remodeling of anchored collagen gels by these fibroblast phenotypes. These results indicate that once tension was generated, fetal fibroblasts exerted lower contractile forces resulting in less collagen contraction. This coincided with less prominent stress fibers, yet fetal fibroblasts were able to substantially remodel the collagen architecture. This mechanism was differentially modulated by PGE2 and was mimicked with a PGE2 receptor agonist, indicating a cyclic adenosine monophosphate (cAMP)‐dependent mechanism through the EP2 receptor. However, direct up‐regulation of cAMP led to decreases in contraction and remodeling by both fibroblast phenotypes indicating an altered signaling pathway. Therefore, targeting cAMP via the EP2 receptor could potentially decrease adult fibroblast contractile forces to the levels of the fetal fibroblast phenotype in order to decrease dermal scarring.
Associations Between Interindividual Differences, Expectations and Placebo and Nocebo Effects in Itch

Introduction: Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent. Methods: The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; n = 92) or negative VSs (Studies 2+3; n = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses. Results: The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower. Conclusion: Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.
Physical map of the Salmonella typhimurium histidine transport operon: correlation with the genetic map

A detailed restriction map of a 12.4-kilobase EcoRI fragment of Salmonella typhimurium deoxyribonucleic acid (DNA) containing the entire histidine transport operon and the argT gene is presented. Subclones of specific regions of the transport operon of S. typhimurium were constructed in plasmid vectors. An accurate correlation between the restriction map and the location of genetically defined deletions was obtained by hybridizing restriction digests of chromosomal DNA from strains carrying each deletion with cloned transport operon DNA as a probe. These data were used to position the histidine transport genes on the cloned 12.4-kilobase fragment of DNA.
THYMINELESS DEATH IN BACILLUS MEGATERIUM

Wachsman, J. T. (University of Illinois, Urbana), S. Kemp, and L. Hogg. Thymineless death in Bacillus megaterium. J. Bacteriol. 87:1079–1086. 1964. —Strain KM:T−, a thymine auxotroph of Bacillus megaterium strain KM, rapidly loses the ability to multiply when incubated in the absence of thymine, on an otherwise sufficient medium. At 37 C, there is a lag of approximately 60 min, prior to the onset of exponential death (decrease of 1 decade per 50 min). The extent of the decrease in viable count varies from 4 to 5 decades after 5 hr of starvation. The cells die more slowly at 30 C (decrease of 1 decade per 120 min) after a lag of approximately 90 min. Thymine starvation permits substantial net ribonucleic acid (RNA) and protein synthesis, but only slight deoxyribonucleic acid synthesis. In contrast with the changes occurring at 30 C, thymineless death at 37 C is eventually accompanied by a rapid hydrolysis of RNA and by cell lysis. Chloramphenicol inhibits thymineless death at 37 C. Strain T−R1, a derivative of strain KM:T−, undergoes a very low rate of thymineless death at 37 C (decrease of 1 decade per 240 min). Neither hydrolysis of RNA nor cell lysis occurs during 8 hr of thymine starvation. Strain KM:T−H− (doubly auxotrophic for thymidine and histidine) requires histidine for maximal thymineless death at 37 C. Preincubation of this strain on the basal medium supplemented with thymidine alone enables the population to become increasingly immune to subsequent thymineless death.
Vitamin D3 supplementation in healthy adults: a comparison between capsule and oral spray solution as a method of delivery in a wintertime, randomised, open-label, cross-over study

Abstract Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays – a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31–49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd 29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.
Different Levels of DNA Methylation Detected in Human Sperms after Morphological Selection Using High Magnification Microscopy

Objective. To analyze DNA methylation levels between two groups of spermatozoa taken from the same sample, following morphological selection by high magnification (HM) at 6100x microscopy. A prospective study was conducted and studied 876 spermatozoa from 10 randomly selected men. Sperm morphology was characterized at HM according to criteria previously established. High-scoring Score 6 and low-scoring Score 0 sperm were selected. Sperm DNA methylation level was assessed using an immunoassay method targeting 5-methylcytosine residues by fluorescence microscopy with imaging analysis system to detect DNA methylation in single spermatozoon. Results. In total, 448 S6 spermatozoa and 428 S0 spermatozoa were analyzed. A strong relationship was found between sperm DNA methylation levels and sperm morphology observed at HM. Sperm DNA methylation level in the S6 group was significantly lower compared with that in the S0 group (p < 10−6), OR = 2.4; and p < 0.001, as determined using the Wilcoxon test. Conclusion. Differences in DNA methylation levels are associated with sperm morphology variations as observed at HM, which allows spermatozoa with abnormal levels to be discarded and ultimately decrease birth defects, malformations, and epigenetic diseases that may be transmitted from sperm to offspring in ICSI.
Progressive tumor features accompany epithelial–mesenchymal transition induced in mitochondrial DNA–depleted cells

The growth of LNCaP, a human prostate adenocarcinoma cell line, and MCF‐7, a human breast adenocarcinoma cell line, is initially hormone dependent. We previously demonstrated that LNρ0‐8 and MCFρ0, derived from LNCaP and MCF‐7 by depleting mitochondrial DNA (mtDNA), exhibited hormone‐independent growth that led to progressed phenotypes. Here, we demonstrate that LNρ0‐8 and MCFρ0 have invasive characters as evaluated by the ability of invasion through the extracellular matrix (ECM) in vitro. In addition, the induction of vimentin and the repression of E‐cadherin expression in ρ0 cells indicate that they are mesenchymal cells. Since LNρ0‐8 and MCFρ0 were derived from epithelial cancer cell lines, LNCaP and MCF‐7 must have lost epithelial features and gained the mesenchymal phenotype by epithelial‐mesenchymal transition (EMT) during the mtDNA depletion. In the ρ0 cell lines, the Raf/MAPK signaling cascade was highly activated together with the expressions of transforming growth factor‐beta (TGF‐β) and type I TGF‐β receptor (TGF‐βRI). EMT requires cooperation of TGF‐β signaling with activation of the Raf/MAPK cascade, suggesting that EMT was induced in mtDNA depleted cells resulting in the acquisition of progressive tumor features, such as higher invasiveness and loss of hormone dependent growth. Our results indicate that decreasing mtDNA content induces EMT, enabling the progressive phenotypes observed in cancer. (Cancer Sci 2008; 99: 1584–1588)
Documentation of Care and Prospective Payment: One Hospital's Experience

Hospitals are now being reimbursed by Diagnosis Related Group (DRG) for Medicare patients. The Johns Hopkins Hospital has worked successfully under this system for the past 5 years, with cost increases being maintained well below the national average. Allowable revenue varies considerably by diagnosis depending on such factors as secondary diagnoses, procedure, and patient age. Failure to document accurately may result in substantial loss of hospital income. More worrisome is the use of data by outside agencies to evaluate quality of care. Recent reports of mortality rates for surgery in Maryland hospitals and of permanent pacemaker use are illustrative. Conclusions were inaccurate because of inadequate documentation of diagnoses and procedures by physicians and inaccurate coding by quality assurance coordinators. Surgeons need to be aware that in the prospective payment era, accurate and complete documentation is essential and that their data are likely to be used for purposes other than monitoring fiscal performance.