Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Circulating Osteopontin Levels With Lower Extremity Arterial Disease in Subjects With Type 2 Diabetes Mellitus: A Cross-Sectional Observational Study

Osteopontin (OPN) is involved in the atherosclerotic and inflammatory process. In this article, we examined the relationship between circulating OPN levels with lower extremity arterial disease (LEAD) in individuals with type 2 diabetes mellitus (T2DM). Seventy individuals with T2DM and 66 individuals without T2DM were recruited. Diagnosis of LEAD was based on the absence of triphasic waveform on the pedal arteries. Plasma OPN levels were determined by Luminex Multiplex immunoassay. LEAD was present in 34 (48.6%) patients with T2DM. In the diabetes cohort, individuals with LEAD had higher plasma OPN concentrations than those without LEAD (geometric mean [95% confidence intervals]; 43.4 [37.5-50.4] vs 26.1 [22.9-29.8] ng/mL, respectively, P < .001). Multivariable analysis showed that presence of LEAD independently associated with higher OPN levels in subjects with T2DM, with marginal statistical significance (P = .049). In both cohorts, plasma OPN concentrations were negatively associated with ankle-brachial index values (P < .05). In the total sample, there was a gradual increase of OPN levels across subgroups with triphasic, biphasic, and monophasic/blunted waveforms (P < .001). In conclusion, plasma OPN levels are associated with the presence and severity of LEAD in subjects with T2DM. Further studies are needed to investigate the role of OPN in the pathogenesis and progression of LEAD.
Fermentation Pattern of Several Carbohydrate Sources Incubated in An in Vitro Semicontinuous System with Inocula From Ruminants Given Either Forage or Concentrate-Based Diets

Simple Summary A sudden change from a milk/forage diet to a high concentrate diet in young ruminants increases the rate and extent of rumen microbial fermentation, leading to digestive problems, such as acidosis. The magnitude of this effect depends on the nature of the ingredients. Six carbohydrate sources were tested: three cereal grains (barley, maize and brown sorghum), as high starch sources of different availability, and three byproducts (sugarbeet pulp, citrus pulp and wheat bran), as sources of either insoluble or soluble fibre. An in vitro semicontinuous incubation system was used to compare the fermentation pattern of substrates incubated with inocula-simulating concentrate or forage diets, under the pH and liquid outflow rate conditions of intensive feeding systems. The magnitude of microbial fermentation was higher with the concentrate than the forage inoculum, and the drop in pH in the first part of incubation was more profound. Among the substrates, citrus pulp had a greater acidification potential and was fermented at a higher extent, followed by wheat bran and barley. In conclusion, the acidification capacity of substrates plays an important role in the environmental conditions, depending on the type of diet given to the ruminant. This in vitro system allows us to compare the substrates under conditions simulating high-concentrate feeding. Abstract The fermentation pattern of several carbohydrate sources and their interaction with the nature of microbial inoculum was studied. Barley (B), maize (M), sorghum, (S), sugarbeet pulp (BP), citrus pulp (CP) and wheat bran (WB) were tested in an in vitro semicontinuous system maintaining poorly buffered conditions from 0 to 6 h, and being gradually buffered to 6.5 from 8 to 24 h to simulate the rumen pH pattern. Rumen fluid inoculum was obtained from lambs fed with either concentrate and barley straw (CI) or alfalfa hay (FI). The extent of fermentation was higher with CI than FI throughout the incubation (p < 0.05). Among the substrates, S, BP and M maintained the highest pH (p < 0.05), whereas CP recorded the lowest pH with both inocula. Similarly, CP recorded the highest gas volume throughout the incubation, followed by WB and B, and S recorded the lowest volume (p < 0.05). On average, the total volatile fatty acid (VFA), as well as lactic acid concentration, was higher with CP than in the other substrates (p < 0.05). The microbial structure was more affected by the animal donor of inoculum than by the substrate. The in vitro semicontinuous system allows for the study of the rumen environment acidification and substrate microbial fermentation under intensive feeding conditions.
The Use of Tranexamic acid (TXA) for The Management of Haemorrhage In Trauma Patients In The Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes.

Tranexamic acid (TXA) is an anti-fibrinolytic agent used to prevent traumatic exsanguination. It was first introduced to clinical practice for the management of patients with bleeding disorders, especially adapted to reduce bleeding in haemophiliacs undergoing oral surgical interventions. TXA exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin. This ultimately prevents fibrinolysis and reduces haemorrhage. Thus, TXA may be well suited for the management of traumatic haemorrhage in the pre-hospital setting.Despite multiplicity of studies on the use of TXA in clinical practice, there is no consensus regarding the use of TXA for the management of haemorrhage in trauma patients in the prehospital environment. Thus, a review on this topic was warranted. An extensive literature search yielded 14 full journal articles which met the inclusion criteria. These articles were thoroughly analysed and the and following themes were identified: "Dose of TXA administration", "Route of TXA administration", "Optimal window of TXA administration", "Safety of TXA use", "Clinical Effectiveness of TXA application" and the "Feasibility of TXA use in the prehospital setting". Overall, to achieve the best possible outcomes, literature supports the use of a loading dose of 1 gram of TXA, followed by 1 gram infusion over 8 hours, given by intravenous administration within a 3 hour window period of traumatic injury. TXA is very effective and safe to use in the pre-hospital setting, and its use is clinically and economically feasible.
Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality after Allogeneic Hematopoietic Cell Transplantation

Background: Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors’ mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantiﬁed. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-speciﬁc mortality. Methods: We calculated conditional survival rates and standardized mortality ratio for overall and cause-speciﬁc mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976–2014. Statistical tests were two-sided. Results: The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% conﬁdence interval [CI] ¼ 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95%
Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM)

Rationale: Glioblastoma is the most frequent, primary brain tumor that is characterized by a highly immunosuppressive tumor microenvironment (TME). The TME plays a key role for tumor biology and the effectiveness of immunotherapies. Composition of the TME correlates with overall survival and governs therapy response. Non invasive assessment of the TME has been notoriously difficult. Methods: We have designed an in vivo imaging approach to non invasively visualize innate immune cell dynamics in the TME in a mouse glioma model by correlated MRI and multiphoton microscopy (MR-MPM) using a bimodal, fluorescently labeled iron oxide nanoparticle (NP). The introduction of Teflon cranial windows instead of conventional Titanium rings dramatically reduced susceptibility artifacts on MRI and allowed longitudinal MR-MPM imaging for innate immune cell tracking in the same animal. Results: We visualized tumor associated macrophage and microglia (TAM) dynamics in the TME and dissect the single steps of NP uptake by blood-born monocytes that give rise to tumor-associated macrophages. Next to peripheral NP-loading, we identified a second route of direct nanoparticle uptake via the disrupted blood-brain barrier to directly label tissue resident TAMs. Conclusion: Our approach allows innate immune cell tracking by MRI and multiphoton microscopy in the same animal to longitudinally investigate innate immune cell dynamics in the TME.
The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor.

BACKGROUND Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C>T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS To determine the frequency of the FII c.1824C>T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C>T variant. Scanning electron microscopy was used to examine the structure of fibrin clots. RESULTS Frequency of the FII c.1824C>T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C>T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION Our data indicate that FII c.1824C>T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C>T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
Evolution of Laparoscopic Donor Nephrectomy Techniques and Outcomes: A Single-Center Experience with More than 1000 Cases

Background Laparoscopic donor nephrectomy (LDN) has evolved and has been established as a surgical standard of care for kidney transplantation. Material/Methods This study retrospectively reviews 1132 patients who underwent 4 different laparoscopic living-donor nephrectomies: hand-assisted laparoscopic nephrectomy (HALDN), pure laparoscopic donor nephrectomy (PLDN), laparoendoscopic single-site plus 1-port donor nephrectomy (LESSOP-DN), and mini laparoscopic donor nephrectomy (MLDN). Results The mean estimated blood loss (EBL) for the HALDN group was meaningfully higher than those of LESSOP-DN and MLDN (57.5±52.2 mL versus 21.0±30.0 mL versus 18.2±28.7 mL) (P<0.001). The EBL for PLDN (53.3±35.3 mL) was also significantly higher than those of LESSOP-DN and MLDN (P<0.001). Length of stay (LOS) for HALDN was longer than that for LESSOP-DN (4.2±1.2 day versus 4.0±1.4 days, P=0.002). There was 1 intraoperative open conversion in the HALDN group and 2 HALDN surgeries that required postoperative exploratory laparotomy. LESSOP-DN had 3 (0.8%) postoperative incisional hernias. For recipients, the results revealed no significant differences between all 4 groups in terms of estimated glomerular filtration rate (eGFR) and the 1-year graft failure rate. Conclusions The LESSOP-DN group was associated with a shorter incision length than those of HALDN and PLDN and shorter LOS than that of HALDN. Recipient results showed no meaningful difference regarding laparoscopic donor nephrectomy technique.
Risk of alzheimer's disease in obstructive sleep apnea patients with or without treatment: Real-world evidence.

OBJECTIVE To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real-world evidence. STUDY DESIGN Retrospective cohort study. METHODS Patients newly diagnosed with OSA during 1997-2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 1:4 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence. RESULTS This study included 3,978 OSA patients and 15,912 non-OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio: 2.12; 95% confidence interval [CI], 1.27-3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation: 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06-0.98). CONCLUSION OSA is independently associated with an increased risk of AD. Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development. LEVEL OF EVIDENCE IV Laryngoscope, 2020.
Consensus statement on the assessment of comorbidities in people living with HIV in Romania.

Introduction The life expectancy of HIV-infected patients has been increased by highly effective therapies. People living with HIV (PLWH) in Romania are exposed to age-related comorbidities occurring earlier than in uninfected individuals. Multidisciplinary care is required to maintain the general health and quality of life in these patients. Currently, the communication among different specialties needs to be enhanced and formalized. Methods A panel consisting of 8 Romanian experts in infectious diseases, cardio-metabolic, bone, and kidney diseases and psychology met in May 2019 in Bucharest Romania to discuss the need to evaluate and monitor the most prevalent comorbidities in PLWH. The meeting resulted in practical guidance on the management of several non-infectious associated diseases. The algorithms were endorsed by the Society for Infectious Diseases and HIV/AIDS, Romania. Results The consensus statement offers practical guidance on how to assess and monitor associated diseases in adult PLWH. The recommendations are grouped for each cluster of comorbidities and are based on international guidelines and clinical experience, including landmarks for referral of PLWH to cardiology, endocrinology, nephrology specialist or clinical psychologist for additional investigations and adequate treatment. Specific indications for diagnosis or treatment were beyond the scope of this consensus. Conclusions Screening for associated diseases and adequate management are required to maintain the overall health status of PLWH. When implemented in clinical practice, the recommended algorithms should be used in addition to diagnosis and treatment guidelines and protocols. The infectious diseases specialist plays a key role in coordinating the overall treatment strategy and working within the multidisciplinary team.
Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

Abstract Background Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. Patients and methods Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. Results Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). Conclusions Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.
HDAC Inhibitor Attenuated Nets Formation Induced by Activated Platelets In Vitro, Partially Through Downregulating Platelet Secretion.

BACKGROUND Accumulating studies in recent years have revealed that platelet activation is an important factor inducing neutrophil extracellular traps (NETs) formation in vivo, while the mechanism of this process is not fully elaborated, restricting its clinical use. Our previous study found that a histone deacetylase inhibitor (HDACi) could attenuate serum H3 elevation in septic mice, which was related to NETs formation, and others found HDAC6 to be involved in platelet activation, indicating that HDACis may attenuate platelet activation and result in reduced NETs formation. METHODS Freshly isolated human platelets were activated by TRAP-6 with or without a HDACi, and secretion of α-granules was evaluated by testing PF4 in the supernatant using ELISA. NETs were induced by coincubating neutrophils with preactivated platelets, quantified by fluorescent intensity (FI) of Sytox green, monitored by live-cell imaging, and qualitatively analyzed by immunofluorescence. MAIN RESULTS An in vitro bioreactive system to induce and monitor NETs formation using platelets and neutrophils was established. The PF4 elevation stimulated by TRAP-6 in the supernatant of platelets was attenuated by the HDACi, and NETs formation that was induced by coincubating neutrophils with the preactivated platelets was decreased in the presence of the HDACi. CONCLUSION The HDACi attenuates NETs formation induced by activated platelets partially by modulating the secretion of platelets.
Statin Drugs Plus Th1 Cytokines Potentiate Apoptosis and Ras Delocalization in Human Breast Cancer Lines and Combine with Dendritic Cell-Based Immunotherapy to Suppress Tumor Growth in a Mouse Model of HER-2pos Disease

A dendritic cell-based, Type 1 Helper T cell (Th1)-polarizing anti-Human Epidermal Growth Factor Receptor-2 (HER-2) vaccine supplied in the neoadjuvant setting eliminates disease in up to 30% of recipients with HER-2-positive (HER-2pos) ductal carcinoma in situ (DCIS). We hypothesized that drugs with low toxicity profiles that target signaling pathways critical for oncogenesis may work in conjunction with vaccine-induced immune effector mechanisms to improve efficacy while minimizing side effects. In this study, a panel of four phenotypically diverse human breast cancer lines were exposed in vitro to the combination of Th1 cytokines Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) and lipophilic statins. This combination was shown to potentiate multiple markers of apoptotic cell death. The combination of statin drugs and Th1 cytokines minimized membrane K-Ras localization while maximizing levels in the cytoplasm, suggesting a possible means by which cytokines and statin drugs might cooperate to maximize cell death. A combined therapy was also tested in vivo through an orthotopic murine model using the neu-transgenic TUBO mammary carcinoma line. We showed that the combination of HER-2 peptide-pulsed dendritic cell (DC)-based immunotherapy and simvastatin, but not single agents, significantly suppressed tumor growth. Consistent with a Th1 cytokine-dependent mechanism, parenterally administered recombinant IFN-γ could substitute for DC-based immunotherapy, likewise inhibiting tumor growth when combined with simvastatin. These studies show that statin drugs can amplify a DC-induced effector mechanism to improve anti-tumor activity.