Miracle-dz/UniFAR-FTUs huggingface dataset:
OscillococcinumR in patients with influenza-like syndromes: A placebo-controlled double-blind evaluation

Abstract A controlled clinical trial was conducted to assess the effectiveness of OscillococcinumR in the treatment of patients with influenza-like syndromes. 188 patients received the test drug and 184 patients were assigned to the placebo. Data were recorded by the participating physicians at the beginning of the treatment, after 48 hours and after 7–10 days. During the first few days, the patients recorded their rectal temperature twice a day (mornings and evenings), 9 symptoms on a rating scale (cough, catarrh, sore throat, muscle pain, etc.), and use of medication. Recovery was defined as follows: ‘rectal temperature < 37.5°C and no headache or muscle pain’. Effectiveness was defined as a statistically significant greater decrease in symptoms after 48 hours in the verum group or a shorter duration of symptoms in comparison to the placebo group. After 48 hours the symptoms of the patients in the verum group were significantly milder (P=0.023) than in the placebo group. The number of patients with no symptoms was significantly higher in the verum group from the second day onwards (verum: 17.4%, placebo: 6.6%) until the end of the patients’ recording (day 5 in the evening: verum: 73.7%, placebo: 67.7%). The biggest group difference was recorded for the time between the evening of the second day (10.6% more patients with no symptoms) and the morning of the fourth day (10.2% more patients with no symptoms). The clinical trial showed that treatment of influenza-like syndromes with OscillococcinumR has a positive effect on the decline of symptoms and on the duration of the disease.
A Structured Resistive Training Program Improves Muscle Strength and Power in Elderly Persons with Dementia

Abstract The primary aim of this study was to determine if resistive training would increase muscle strength and power in cognitively impaired elderly people. The secondary aim was to assess whether resistive training influenced physical functional abilities. Eight men and women, age range 63-88 years, with a diagnosis of dementia (Mini Mental Status Exam scores that ranged from 13-20), attended and successfully and safely completed a group resistive training program held twice weekly for 12 weeks. In post- versus pre-training comparisons, muscle strength and power were increased for the hip abductor/adductor (p < .01), shoulder press (p < .05), leg extension/curl (p < .01) and chest/back (p < .01) exercises. However, there were no measurable improvements of functional abilities, including balance, the timed chair stand, gait speed or the timed stair climb. This study demonstrates that it is feasible to engage elderly persons with dementia in a structured resistive training program with measurable improvements after 12 weeks in muscle strength and power but not functional abilities.
Fourier transform infrared spectroscopy for inorganic compound speciation.

Work at Battelle Columbus Laboratories has resulted in the development of a methodology that permits the identification of individual inorganic species, even in complex particulate pollutant mixtures. Development of this capability has permitted the identification of various sulfates and oxides obtained from both coaland oil-fired fly ash samples. The analysis technique is based on the sensitivity, stability, and computerized data handling capabilities inherent to Fourier transform infrared systems (FT-IR). In our experience, FT-IR, when combined with proper sample handling, elemental analysis, the use of appropriate reference standards, and a simple separation step, has proven superior to other techniques in the identification of many inorganic compounds. In many cases, the infrared results were verified by also obtaining independent X-ray diffraction (XRD) data on the same sample.
Regulation of STAT pathways and IRF1 during human dendritic cell maturation by TNF‐α and PGE2

Maturation of dendritic cells (DCs) by TLR ligands induces expression of IFN‐β and autocrine activation of IFN‐inducible Stat1‐dependent genes important for DC function. In this study, we analyzed the regulation of STAT signaling during maturation of human DCs by TNF‐α and PGE2, which induced maturation of human DCs comparably with LPS but did not induce detectable IFN‐β production or Stat1 tyrosine phosphorylation. Consistent with these results, TNF‐α and PGE2 did not induce Stat1 DNA binding to a standard Stat1‐binding oligonucleotide. Instead, TNF‐α and PGE2 increased Stat1 serine phosphorylation and Stat4 tyrosine phosphorylation and activated expression of the NF‐κB and Stat1 target gene IFN regulatory factor 1 (IRF1), which contributes to IFN responses. TNF‐α and PGE2 induced a complex that bound an oligonucleotide derived from the IRF1 promoter that contains a STAT‐binding sequence embedded in a larger palindromic sequence, and this complex was recognized by Stat1 antibodies. These results suggest that TNF‐α and PGE2 activate STAT‐mediated components of human DC maturation by alternative pathways to the IFN‐β‐mediated autocrine loop used by TLRs.
Maternal ambient air pollution, preterm birth and markers of fetal growth in Rhode Island: results of a hospital-based linkage study

Background Maternal exposure to ambient air pollution has been associated with higher risk of preterm birth and reduced fetal growth, but heterogeneity among prior studies suggests that additional studies are needed in diverse populations and settings. We examined the associations between maternal ambient air pollution levels, risk of preterm birth and markers of fetal growth in an urban population with relatively low exposure to air pollution. Methods We linked 61 640 mother–infant pairs who delivered at a single hospital in Providence, Rhode Island, from 2002 to 2012 to birth certificate and hospital discharge data. We used spatial-temporal models and stationary monitors to estimate exposure to fine particulate matter (PM2.5) and black carbon (BC) during pregnancy. Using generalised linear models, we evaluated the association between pollutant levels, risk of preterm birth and markers of fetal growth. Results In adjusted models, an IQR (2.5 µg/m3) increase in pregnancy-average PM2.5 was associated with ORs of preterm birth of 1.04 (95% CI 0.94 to 1.15) and 0.86 (0.76 to 0.98) when considering modelled and monitored PM2.5, respectively. An IQR increase in modelled and monitored PM2.5 was associated with a 12.1 g (95% CI −24.2 to –0.1) and 15.9 g (95% CI −31.6 to –0.3) lower birth weight. Results for BC were highly sensitive to choice of exposure metric. Conclusion In a population with relatively low exposures to ambient air pollutants, PM2.5 was associated with reduced birth weight but not with risk of preterm birth.
IgG Response to Intracerebral Xenotransplantation: Specificity and Role in the Rejection of Porcine Neurons

Xenogenic fetal neuroblasts are considered as a potential source of transplantable cells for the treatment of neurodegenerative diseases, but immunological barriers limit their use in the clinic. While considerable work has been performed to decipher the role of the cellular immune response in the rejection of intracerebral xenotransplants, there is much still to learn about the humoral reaction. To this end, the IgG response to the transplantation of fetal porcine neural cells (PNC) into the rat brain was analyzed. Rat sera did not contain preformed antibodies against PNC, but elicited anti‐porcine IgG was clearly detected in the host blood once the graft was rejected. Only the IgG1 and IgG2a subclasses were up‐regulated, suggesting a T‐helper 2 immune response. The main target of these elicited IgG antibodies was porcine neurons, as determined by double labeling in vitro and in vivo. Complement and anti‐porcine IgG were present in the rejecting grafts, suggesting an active role of the host humoral response in graft rejection. This hypothesis was confirmed by the prolonged survival of fetal porcine neurons in the striatum of immunoglobulin‐deficient rats. These data suggest that the prolonged survival of intracerebral xenotransplants relies on the control of both cell‐mediated and humoral immune responses.
Expression of Human CD46 Modulates Inflammation Associated With GalTKO Lung Xenograft Injury

Evaluation of lungs from GalTKO.hCD46 pigs, genetically modified to lack the galactose‐α(1,3)‐galactose epitope (GalTKO) and to express human CD46, a complement regulatory protein, has not previously been described. Physiologic, hematologic and biochemical parameters during perfusion with heparinized fresh human blood were measured for 33 GalTKO.hCD46, GalTKO (n = 16), and WT pig lungs (n = 16), and 12 pig lungs perfused with autologous pig blood. Median GalTKO.hCD46 lung survival was 171 min compared to 120 for GalTKO (p = 0.27) and 10 for WT lungs (p < 0.001). Complement activation, platelet activation and histamine elaboration were significantly reduced during the first 2 h of perfusion in GalTKO.hCD46 lungs compared to GalTKO (ΔC3a at 120′ 812 ± 230 vs. 1412 ± 1047, p = 0.02; ΔCD62P at 120′ 9.8 ± 7.2 vs. 25.4 ± 18.2, p < 0.01; Δhistamine at 60′ 97 ± 62 vs. 189 ± 194, p = 0.03). We conclude that, in addition to significant down‐modulation of complement activation, hCD46 expression in GalTKO lungs diminished platelet and coagulation cascade activation, neutrophil sequestration and histamine release. Because GalTKO.hCD46 lung failure kinetics correlated directly with platelet and neutrophil sequestration, coagulation cascade activation and a rise in histamine levels within the first hour of perfusion, further progress will likely depend upon improved control of these pathways, by rationally targeted additional modifications to pigs and pharmacologic interventions.
Evaluation of Molecular Profiles in Calcineurin Inhibitor Toxicity Post–Kidney Transplant: Input to Chronic Allograft Dysfunction

The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated by: (1) identifying specific CNIT molecular pathways that associate with allograft injury (cross‐sectional study) and (2) assessing the contribution of the identified CNIT signature in the progression to CAD with IF/TA (longitudinal study). Kidney biopsies from well‐selected transplant recipients with histological diagnosis of CNIT (n = 14), acute rejection (n = 13) and CAD with IF/TA (n = 10) were evaluated. Normal allografts (n = 18) were used as controls. To test CNIT contribution to CAD progression, an independent set of biopsies (n = 122) from 61 KT patients collected at 3 and ∼12 months post‐KT (range = 9–18) were evaluated. Patients were classified based on 2‐year post‐KT graft function and histological findings as progressors (n = 30) or nonprogressors to CAD (n = 31). Molecular signatures characterizing CNIT samples were identified. Patients classified as progressors showed an overlap of 7% and 22% with the CNIT signature at 3 and at ∼12 months post‐KT, respectively, while the overlap was <1% and 1% in nonprogressor patients, showing CNIT at the molecular level as a nonimmunological factor involved in the progression to CAD.
Public transport policy, social engagement and mental health in older age: a quasi-experimental evaluation of free bus passes in England

Background Social engagement and social isolation are key determinants of mental health in older age, yet there is limited evidence on how public policies may contribute to reducing isolation, promoting social engagement and improving mental health among older people. This study examines the impact of the introduction of an age-friendly transportation policy, free bus passes, on the mental health of older people in England. Methods We use an instrumental variable (IV) approach that exploits eligibility criteria for free bus passes to estimate the impact of increased public transportation use on depressive symptoms, loneliness, social isolation and social engagement. Results Eligibility for the free bus travel pass was associated with an 8% (95% CI 6.4% to 9.6%) increase in the use of public transportation among older people. The IV model suggests that using public transport reduces depressive symptoms by 0.952 points (95% CI −1.712 to −0.192) on the Center for Epidemiologic Studies Depression Scale. IV models also suggest that using public transport reduces feelings of loneliness (β −0.794, 95% CI −1.528 to −0.061), increases volunteering at least monthly (β 0.237, 95% CI 0.059 to 0.414) and increases having regular contact with children (β 0.480, 95% CI 0.208 to 0.752) and friends (β 0.311, 95% CI 0.109 to 0.513). Conclusion Free bus travel is associated with reductions in depressive symptoms and feelings of loneliness among older people. Transportation policies may increase older people’s social engagement and consequently deliver significant benefits to mental health.
N‐Acylhomoserine lactones are potent neutrophil chemoattractants that act via calcium mobilization and actin remodeling

In gram‐negative bacteria, cell‐cell communication based on HSL QS molecules is known to coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human immune cell behavior. Using a Transwell migration assay, we found that human primary neutrophils are strongly stimulated by 3O‐C12‐HSL and ‐C10‐HSL but not C4‐HSL in a concentration‐dependent manner. Moreover, 3O‐C12‐HSL and ‐C10‐HSL activate PLCγ1 but not ‐γ2, mobilize intracellular calcium, and up‐regulate IP3R. These changes were paralleled by F‐actin accumulation, primarily in the leading edge of neutrophils, as evidenced by phalloidin staining and confocal microscopy. F‐ and G‐actin isolation and quantification by immunoblotting revealed that the F/G‐actin ratio was increased significantly after treatment with all three HSLs. Furthemore, 3O‐C12‐HSL‐ and 3O‐C10‐HSL treatment resulted in phosphorylation of Rac1 and Cdc42. In contrast, C4‐HSL had negligible influence on the phosphorylation status of PLC and Rac1/Cdc42 and failed to attract neutrophils and induce calcium release. The calcium inhibitor thapsigargin, which blocks ER calcium uptake, strongly prevented neutrophil migration toward 3O‐C12‐HSL and ‐C10‐HSL. These findings show that the bacterial QS molecules 3O‐C12‐HSL and ‐C10‐HSL may attract human neutrophils to the sites of bacterial infection and developing biofilms. Indeed, recognition of HSL QS signals by neutrophils may play a critical role in their recruitment during infections.
RIPK3‐Mediated Necroptosis Regulates Cardiac Allograft Rejection

Cell death results in tissue damage and ultimately donor graft rejection and can occur as an active molecular process through apoptotic, necrotic and newly identified receptor interacting protein 1 and 3 kinase (RIPK1/3)‐mediated necroptotic pathways. Necroptosis leads to the release of inflammatory molecules which can activate host immune cells. This pathway has yet to be studied in heart transplantation. We have found that necroptosis was induced in murine cardiac microvascular endothelial cell (MVEC) under anti‐apoptotic condition following tumor necrosis factor alpha treatment. Necroptotic cell death and release of the danger molecule high mobility group box 1 (HMGB1) were inhibited by the RIPK1 inhibiting molecule necrostatin‐1 and by genetic deletion of RIPK3. In addition, tissue necrosis, release of HMGB1 and graft cell infiltrate were attenuated in RIPK3 null heart allografts following transplantation. Finally, a brief sirolimus treatment markedly prolonged RIPK3 null cardiac allograft survival in allogeneic BALB/c recipients as compared to WT C57BL/6 donor grafts (95 ± 5.8 vs. 24 ± 2.6 days, p < 0.05). This study has demonstrated that RIPK1/3 contributes to MVEC death and cardiac allograft survival through necroptotic death and the release of danger molecules. Our results suggest that targeting RIPK‐mediated necroptosis may be an important therapeutic strategy in transplantation.
HMGB1 Is Involved in Chronic Rejection of Cardiac Allograft via Promoting Inflammatory‐Like mDCs

Chronic rejection that leads to diffuse narrowing and occlusion of graft vessels is the most important cause of morbidity and mortality following cardiac transplantation. The role and underlying mechanism of high‐mobility group box 1 (HMGB1), as an established inflammatory mediator in acute rejection, remains poorly understood in chronic rejection. Here, we assessed the effects and mechanisms of HMGB1 on the chronic rejection using single MHC Class II‐mismatched mouse cardiac transplantation model. It was found that HMGB1 was increased accompanying with the development of chronic rejection, while blockade of HMGB1 with specific neutralizing mAb substantially ameliorated chronic rejection‐mediated vasculopathy and fibrosis of allograft, as well as markedly decreased T cell infiltration and production of IL‐17A and interferon‐gamma in allograft and recipient's spleen. Further, anti‐HMGB1 antibody treatment significantly declined the number and frequency of mature dendritic cells (DCs) in allograft and recipient's spleen, especially CD11b+Ly6Chigh matured DCs that share the phenotypes with inflammatory‐DCs. These findings indicate that HMGB1 contributes to chronic rejection, and HMGB1 blockade may be a novel mean to disrupt the proinflammatory loop after heart transplantation.
Alemtuzumab in Lung Transplantation: An Open‐Label, Randomized, Prospective Single Center Study

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post‐TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher‐grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.
Design method of NOR-type comparison circuit in CAM with ground bounce noise considerations

CAM devices generate excessive and simultaneous current through NOR circuits during a comparison operation because of the parallel comparisons for all bits in the CAM. The ground bounce noise can be severe due to the parasitic inductance in the paths to the system ground, such as the metal lines in the CAM power structure, package pins, and system board. The ground bounce noise can cause subtle failures unless carefully considered as a key design parameter. The simultaneous current largely depends on the number of stored bits matching compared data. Traditionally, the NOR circuit in the CAM is perceived to respond faster when the transistors to the ground path in the circuit are active. However, this work shows that this notion can be greatly misleading when the ground bounce effects are not considered. The design method of the comparison cells is newly proposed to meet the optimal CAM evaluation time by simultaneously considering operational speed, extreme case analyses of the NOR circuit, and ground bounce noises. The proposed design method effectively provided the optimal design decision, which could be otherwise misleading if no ground bounce effect is considered. We demonstrated in sample designs that the proper choice of comparison-cell size reduced evaluation time by 54.9% while reducing comparison-cell size by 57.1% when ground bounce effects were considered.
Survival Benefit of Repeat Liver Transplantation in the United States: A Serial MELD Analysis by Hepatitis C Status and Donor Risk Index

Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End‐Stage Liver Disease (MELD) ≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure ≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post‐ReLT graft failure rates were 416 (95% confidence interval [CI] 384–450) and 375 (95% CI 345–407) per 1000 patient‐years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p < 0.001). The MELD for SB from ReLT overall was 21 (21 in non‐HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non‐HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts.
A STATus report on DC development

DCs have a vital role in the immune system by recognizing exogenous or self‐antigens and eliciting appropriate stimulatory or tolerogenic adaptive immune responses. DCs also contribute to human autoimmune disease and, when depleted, to immunodeficiency. Moreover, DCs are being explored for potential use in clinical therapies including cancer treatment. Thus, understanding the molecular mechanisms that regulate DCs is crucial to improving treatments for human immune disease and cancer. DCs constitute a heterogeneous population including plasmacytoid (pDC) and classic (cDC) subsets; however, the majority of DCs residing in lymphoid organs and peripheral tissues in steady state share common progenitor populations, originating with hematopoietic stem cells. Like other hematopoietic lineages, DCs require extracellular factors including cytokines, as well as intrinsic transcription factors, to control lineage specification, commitment, and maturation. Here, we review recent findings on the roles for cytokines and cytokine‐activated STAT transcription factors in DC subset development. We also discuss how cytokines and STATs intersect with lineage‐regulatory transcription factors and how insight into the molecular basis of human disease has revealed transcriptional regulators of DCs. Whereas this is an emerging area with much work remaining, we anticipate that knowledge gained by delineating cytokine and transcription factor mechanisms will enable a better understanding of DC subset diversity, and the potential to manipulate these important immune cells for human benefit.