Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological Implications of Extracellular Adenosine in Hepatic Ischemia and Reperfusion Injury

The purine nucleoside adenosine is clinically employed in the treatment of supraventricular tachycardia. In addition, it has direct coronary vasodilatory effects, and may influence platelet aggregation. Experimental observations mechanistically link extracellular adenosine to cellular adaptation to hypoxia. Adenosine generation has been implicated in several pathophysiologic processes including angiogenesis, tumor defenses and neurodegeneration. In solid organ transplantation, prolonged tissue ischemia and subsequent reperfusion injury may lead to profound graft dysfunction. Importantly, conditions of limited oxygen availability are associated with increased production of extracellular adenosine and subsequent tissue protection. Within the rapidly expanding field of adenosine biology, several enzymatic steps in adenosine production have been characterized and multiple receptor subtypes have been identified. In this review, we briefly examine the biologic steps involved in adenosine generation and chronicle the current state of adenosine signaling in hepatic ischemia and reperfusion injury.
OPTN/SRTR 2012 Annual Data Report: Pancreas

The number of pancreas transplants has decreased over the past decade, most notably numbers of pancreas after kidney (pak) and pancreas transplant alone (pta) procedures. This decrease may be mitigated in the future when changes to national pancreas allocation policy approved by the Organ Procurement and Transplantation Network Board of Directors in 2010 are implemented. The new policy will combine waiting lists for pak, pta, and simultaneous pancreas‐kidney (spk) transplants), and give equal priority to candidates for all three procedures. This policy change may also eliminate geographic variation in waiting times caused by geographic differences in allocation policy. Deceased donor pancreas donation rates have been declining since 2005, and the donation rate remains low. The outcomes of pancreas grafts are difficult to describe due to lack of a uniform definition of graft failure in the transplant community. However long‐term survival is better for spk versus pak and pta transplants. This may represent the difficulty of detecting rejection in the absence of a simultaneously transplanted kidney. The challenges of pancreas transplant are reflected in high rates of rehospitalization, most occurring within the first 6 months posttransplant. Pancreas transplant is associated with higher incidence of rejection compared with kidney transplant.
OPTN/SRTR 2012 Annual Data Report: Deceased Organ Donation

The status of deceased organ donation is assessed using several metrics, including donation/conversion rate (how often at least one organ is recovered for transplant from an eligible death), organ yield (ratio of observed/expected numbers of organs transplanted), and rate of organs discarded (number of organs discarded divided by the number of organs recovered for transplant). The 2012 donation/conversion rate was 72.5. eligible donors per 100 eligible deaths, slightly lower than the 2011 rate but higher than in previous years. The 2011‐2012 yield ratio varied by donation service area from 0.91 (fewer organs transplanted per donor than expected) to 1.09 (more than expected), and also varied for specific organs. The mean number of organs transplanted per donor in 2012 was 3.02, lower than in 2011 and 2010; this number varied by donation service area from 2.04 to 3.76. The number of organs discarded is calculated by subtracting the number of organs transplanted from the number recovered for transplant; this number is used to calculate the discard rate. The discard rate in 2012 for all organs combined was 0.14 per recovered organ, slightly higher than in 2011 and 2011; it varied by donation service area and organ type.
Invasive Group B Streptococcal Disease in Adults: A Population-Based Study in Metropolitan Atlanta

Objective. —To define the incidence and clinical spectrum of group B streptococcus infection in adults. To characterize groups at increased risk for infection. Design. —Retrospective population-based surveillance of group B streptococcus infections occurring in adults. Patients were identified by review of microbiology records at all surveillance area hospital laboratories. Demographic and clinical data were abstracted from patient medical records. Setting. —Metropolitan Atlanta, Ga, 1982 through 1983. Patients. —We identified 70 adult patients with invasive group B streptococcus infections; 14 infections occurred in pregnant women and 56 in nonpregnant adults. Results. —The annual incidence of group B streptococcus infection in men and nonpregnant women was 2.4 cases per 100 000 population. Incidence increased with age and was higher in blacks than in whites. The case-fatality rate was 32%. Group B streptococcus was most often isolated from blood (71%) and soft tissue (16%). Common clinical presentations included skin and soft-tissue infection (36%), bacteremia without focus (34%), pneumonia (11%), arthritis (9%), and endocarditis (9%). Compared with the general population's risk of infection, the risk of infection in persons with diabetes mellitus was increased 10.5-fold (95% confidence interval [Cl], 7.8 to 14.4); in persons with cancer, it was increased 16.4-fold (95% CI, 11.5 to 23.3). Conclusions. —Group B streptococcus infections cause serious disease in adults as well as in neonates, providing an additional rationale for vaccine development. Determining the incidence of adult disease and groups at greatest risk will help in focusing prevention efforts. ( JAMA . 1991;266:1112-1114)
Do flexible work policies improve parents’ health? A natural experiment based on the UK Millennium Cohort Study

Background There is limited evidence of the impact of policies to promote work–family balance on family health. Exploiting the introduction of the UK Flexible Working Act (2003), we examined whether a policy that grants parents the right to request flexible work influences their health and well-being. Methods Using the UK Millennium Cohort Study, we focus on 6424 mothers employed in 2001–2002, when the cohort child was 9 months old, until their child’s seventh birthday. We used a difference-in-differences (DiD) approach to compare changes in outcomes before and after the policy among mothers most likely to benefit and mothers unlikely to benefit from the policy. Results Flexible working increased in a small group of mothers (n=548) whose employer did not offer work flexibility before the reform (treatment group). By contrast, among mothers whose employer already offered flexible work before the reform (control group, n=5810), there was little change or a slight decline in flexible working. DiD estimates suggest that the policy was associated with an increase in flexible working (37.5 percentage points, 95% CI 32.9 to 41.6), but it had no impact on self-rated health (−1.6 percentage points, 95% CI −4.4 to 1.1), long-term illness (−1.87 percentage points, 95% CI −4.3 to 0.5) or life satisfaction scores (β=0.04, 95% CI −0.08 to 0.16). Conclusion The Flexible Working Act increased flexible working only among a small group of mothers who had not yet the right to request work flexibility, but it had no impact on their health and well-being. Policies promoting work flexibility may require stronger incentives for both parents and employers.
Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic machine perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 [1.11–1.94] to 6.74 [4.15–8.16] mL O2/min kg liver), lactate levels (4.04 [3.70–5.99] to 2.29 [1.20–3.43] mmol/L) and adenosine triphosphate content (45.0 [70.6–87.5] pmol/mg preperfusion to 167.5 [151.5–237.2] pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.
On-chip DC-DC converters for three-dimensional ICs

Guidelines for distributing a buck converter rectifier for application to three-dimensional (3-D) circuits is described. The 3-D rectifier exploits the properties of transmission lines to generate and distribute power supplies to different planes. As compared to a conventional rectifier, the proposed rectifier circuit only requires moderately size capacitors without the use of onchip inductors. A case study in a 0. 18µm CMOS 3-D technology demonstrates the generation of a 1.2 volt power supply delivering 700mA peak current.
De Novo Donor‐Specific HLA Antibodies: Biomarkers of Pancreas Transplant Failure

This study assesses the role of posttransplant HLA antibody monitoring in the surveillance of pancreas transplant recipients. Four hundred thirty‐three pancreas transplants were performed at the Oxford Transplant Centre 2006–2011 (317 simultaneous pancreas kidney [SPK] and 116 isolated pancreas [IP]). HLA antibody monitoring was performed at 0, 6 and 12 months and annually and during clinical events. There was no association between pancreas graft failure and recipient or donor characteristics. Posttransplant antibody status, available for 354 (81.8%) of recipients, demonstrated that 141 (39.8%) developed de novo HLA antibodies, of which 52 (36.9%) were de novo donor‐specific HLA antibodies (DSA) (34 SPK, 18 IP). The development of antibodies to donor HLA, but not to nondonor HLA, was significantly associated with poorer graft outcomes, with 1‐ and 3‐year graft survival inferior in SPK recipients (85.2% vs. 93.5%; 71.8% vs. 90.3%, respectively; log‐rank p = 0.002), and particularly in IP recipients (50.0% vs. 82.9%; 16.7 vs. 79.4%, respectively; log‐rank p = 0.001). In a multivariate analysis, development of de novo DSA emerged as a strong independent predictor of pancreas graft failure (hazard ratio 4.66, p < 0.001). This is the largest study to examine de novo HLA antibodies following pancreas transplantation and clearly defines a high‐risk group in need of specific intervention.
Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage

Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14highCD16−, CD14highCD16low, and CD14lowCD16high. The phenotypes and functions of these subpopulations, including CD16+ monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract in AIDS pathogenesis, we conducted a cross‐sectional study of 54 SIV‐ or SHIV‐infected macaques and 48 uninfected controls. The absolute numbers of monocyte populations were examined in acutely infected animals, chronically infected animals with no detectable plasma virus RNA, chronically infected animals with detectable plasma virus RNA, and animals that died with AIDS. The absolute numbers of CD14highCD16low and CD14lowCD16high monocytes were elevated significantly in acutely infected animals and chronically infected animals with detectable plasma virus RNA compared with uninfected controls. Moreover, a significant, positive correlation was evident between the number of CD14highCD16low or CD14lowCD16high monocytes and plasma viral load in the infected cohort. These data show the dynamic changes of blood monocytes, most notably, CD14highCD16low monocytes during lentiviral infection, which are specific to disease stage.
Mitigating TSV-induced substrate noise in 3-D ICs using GND plugs

Through-silicon vias (TSVs) in 3-D ICs are a major source of substrate noise, causing performance degradation of neighboring active devices. To reduce this noise, we propose using a tungsten-filled ground plug, a TSV-like structure that connects to ground (GND) and that partially or completely extends through the substrate. We evaluate the impact of plug size and placement on noise isolation. We compare the GND plug technique with two other noise mitigation techniques: using a thicker dielectric liner and using a backside ground plane. Our study demonstrates that the GND plug is a superior technology, effective in mitigating TSV-induced substrate noise by an order of magnitude when compared to the other two techniques. The GND plug offers a more practical noise isolation approach than using a backside ground plane. When compared with increased dielectric thickness, the GND plug offers a 33% reduction in foot print and permits a significantly reduced keep out zone.
Functional Outcomes of Face Transplantation

In this study we provide a compilation of functional impairments before and improvements after face transplantation (FT) of five FT recipients of our institution and all FTs reported in current literature. Functional outcome included the ability to smell, breath, eat, speak, grimace and facial sensation. Before FT, all our patients revealed compromised ability to breath, eat, speak, grimace and experience facial sensation. The ability to smell was compromised in two of our five patients. Two patients were dependent on tracheostomy and one on gastrostomy tubes. After FT, all abilities were significantly improved and all patients were independent from artificial air airways and feeding tubes. Including data given in current literature about the other 24 FT recipients in the world, the abilities to smell, eat and feel were enhanced in 100% of cases, while the abilities of breathing, speaking and facial expressions were ameliorated in 93%, 71% and 76% of cases, respectively. All patients that required gastrostomy and 91% of patients depending on tracheostomy were decannulated after FT. Unfortunately, outcomes remain unreported in all other cases and therefore we are unable to comment on improvements.
Efficient region-aware P/G TSV planning for 3D ICs

Power delivery network (PDN) design is one of the most critical challenges in 3D Integrated Circuits (IC) design. In existing studies, to ensure the robustness of the 3D PDN, the number of TSVs was always increased inefficiently to mitigate the IR-drop and power noise. However, the overhead for connections is a crucial obstacle to the development of 3D ICs. Consequently, an efficient TSV topology is needed to reduce the overhead of TSVs while meeting the power supply requirements. The redundant TSVs may introduce more keep-out zones, decrease the core utilization of the chip, and lead to high cost. In this paper, we propose a region-aware TSV planning algorithm which can distribute TSV resources non-evenly over different areas according to their IR-drop constraints separately. This method can use fewer power TSVs to meet the power integrity constraint of the whole chip while guaranteeing the functionality. Furthermore, to ensure the practicability, we also take the whitespace into account. Experimental results show that, the proposed algorithm can save on average 42% and 27% power TSV resources without and with whitespace consideration respectively compared with the evenly TSV planning algorithm.
Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases

Hepatic lymphocytes are enriched in NK and NKT cells that play important roles in antiviral and antitumor defenses and in the pathogenesis of chronic liver disease. In this review, we discuss the differential distribution of NK and NKT cells in mouse, rat, and human livers, the ultrastructural similarities and differences between liver NK and NKT cells, and the regulation of liver NK and NKT cells in a variety of murine liver injury models. We also summarize recent findings about the role of NK and NKT cells in liver injury, fibrosis, and repair. In general, NK and NKT cells accelerate liver injury by producing proinflammatory cytokines and killing hepatocytes. NK cells inhibit liver fibrosis via killing early–activated and senescent–activated stellate cells and producing IFN–γ. In regulating liver fibrosis, NKT cells appear to be less important than NK cells as a result of hepatic NKT cell tolerance. NK cells inhibit liver regeneration by producing IFN–γ and killing hepatocytes; however, the role of NK cells on the proliferation of liver progenitor cells and the role of NKT cells in liver regeneration have been controversial. The emerging roles of NK/NKT cells in chronic human liver disease will also be discussed. Understanding the role of NK and NKT cells in the pathogenesis of chronic liver disease may help us design better therapies to treat patients with this disease.
The Athlete’s Spine—Lumbar Herniated Nucleus Pulposus

Lumbar herniated nucleus pulposus is common among athletes given the physical stresses placed upon the lumbar spine with various athletic activities. Although the natural course is generally favorable with conservative management, the reproducible success of lumbar discectomy provides itself as an alternative treatment option for the athlete. Both conservative and operative management are associated with quick recovery and return to play. This chapter reviews the natural history of lumbar herniated nucleus pulposus, various treatment modalities, and the athlete-specific metrics pertinent to the management of athletes.
Reduced transcript stabilization restricts TNF‐α expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan

Despite the critical role that TNF‐α plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn's disease. We found that in MAP‐infected macrophages, TNF‐α gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF‐α transcription alone could not fully explain the differential TNF‐α mRNA expression, suggesting that there must be a substantial contribution by post‐transcriptional mechanisms. Accordingly, we found reduced TNF‐α mRNA stability in MAP‐infected macrophages. Further comparison of MAP‐ and MS‐infected macrophages revealed that lower TNF‐α mRNA stability combined with lower mRNA and protein expression in MAP‐infected macrophages correlated with lower p38 MAPK phosphorylation. Theses findings were independent of viability of MAP and MS. We demonstrate that the major mycobacterial cell‐wall lipoglycan LM of MAP and MS induced TNF‐α mRNA transcription, but only the MS‐LM induced p38 MAPK‐dependent transcript stabilization. Overall, our data suggest that pathogenic mycobacteria cause weak p38 MAPK activation and TNF‐α mRNA stabilization as a result of their structural cell‐wall components such as LM and thereby, restrict TNF‐α expression in macrophages.
Modulation of human neutrophil survival and antigen expression by activated CD4+ and CD8+ T cells

Neutrophils and T cells often co‐infiltrate pathological tissues, which suggests that these 2 cell types may interact with each other. Over the years, in vitro studies have demonstrated that neutrophils and T cells are capable of modulating each otherˈs responses. However, few studies have examined the cross‐talk between human neutrophils and CD8+ T cells, although murine models clearly show the critical role of their interaction in bacterial infections and cancer. Herein, we evaluated the interaction between human neutrophils and CD8+ T cells in a coculture system using highly purified cell preparations and compared the responses to ones from cocultures of neutrophils and CD4+ T cells. We report that anti‐CD3‐activated CD4+ and more potently, anti‐CD3‐activated CD8+ T cells modulate apoptosis and expression of activation markers by neutrophils, and neutrophils have no or little effect on T cell survival, expression of surface markers, and cytokine release. The observed effects of CD8+ T cells on neutrophils were mainly attributable to the release of TNF‐α, IFN‐γ, and GM‐CSF, and the effects of CD4+ T cells involved IFN‐γ and GM‐CSF production. This study expands our knowledge of the molecular bases, whereby human CD4+ and CD8+ T cells modulate neutrophil survival and antigen expression.
How specificity for self‐peptides shapes the development and function of regulatory T cells

The cataclysmic disease that develops in mice and humans lacking CD4+ T cells expressing the transcription factor Foxp3 has provided abundant evidence that Foxp3+CD4+ Tregs are required to suppress a latent autoreactivity of the immune system. There is also evidence for the existence of tissue‐specific Tregs that can act to suppress regional autoimmune responses, suggesting that Tregs exert their effects, in part, through responding to self‐peptides. However, how the immune system generates a repertoire of Tregs that is designed to recognize and direct regulatory function to self‐peptides is incompletely understood. This review describes studies aimed at determining how T cell recognition of self‐peptide(s) directs Treg formation in the thymus, including discussion of a modified “avidity” model of thymocyte development. Studies aimed at determining how TCR specificity contributes to the ability of Tregs to suppress autoimmune diseases are also discussed.
Pain Characteristics of People with Chronic Fatigue Syndrome

ABSTRACT Objectives: Until now, there has been a lack of fundamental research into the pain experienced in chronic fatigue syndrome [CFS]. The aims of this study were to (1) investigate the pain experiences of people with CFS with a range of disability, and (2) identify specific pain characteristics of people with CFS. Methods: Fifty people were recruited, including 10 people who were severely disabled by CFS [25% Group]. Participants completed a structured interview and a series of pain assessments about their current pain, which included the McGill Pain Questionnaire [MPQ], the Pain Anxiety Symptoms Scale [PASS], and visual analog scales. Results: Muscle pain was the most reported painful symptom [68 percent]. The current pain intensity was 43.2 mm ± 20.8 mm measured on a visual analog scale. The MPQ pain rating index was 23.6 ± 10.8. The PASS total score was 37.9 ± 17.6. Thirty percent [N = 15] of participants reported the cervical spine the location of “most severe” pain, followed by the left and right scapular and right lumbar spine [N = 10 each, 20 percent each]. Further analysis indicated that those people, who were severely disabled by CFS, also experienced significantly more pain [P < 0.05]. Conclusion: The results of this study provide objective data to support anecdotal and clinical reports of pain in people with CFS. Pain in people with CFS should be accepted and treated as seriously as other conditions where pain is a significant symptom. Management strategies need to be tailored to the individual requirements of patients presenting with symptoms of both fatigue and pain.