Miracle-dz/UniFAR-FTUs huggingface dataset:
Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy

ABSTRACT In this study, we examined the peripheral blood (PB) central memory (TCM) CD4+ T cell subsets designated peripheral T follicular helper cells (pTfh cells) and non-pTfh cells to assess HIV permissiveness and persistence. Purified pTfh and non-pTfh cells from healthy HIV-negative donors were tested for HIV permissiveness using green fluorescent protein (GFP)-expressing HIV-1NL4-3/Ba-L, followed by viral reactivation using beads coated with anti-CD3/anti-CD28 monoclonal antibodies. The role of pTfh cells in HIV persistence was analyzed in 12 chronically HIV-1 infected patients before and 48 weeks after initiation of raltegravir-containing combination antiretroviral therapy (cART). Total cellular HIV-1 DNA and episomes containing two copies of the viral long terminal repeat (2LTR circles) were analyzed in using droplet digital PCR in the purified pTfh and non-pTfh cells. Activation-inducible HIV p24 expression was determined by flow cytometry. Results indicate that pTfh cells, in particular PD1+ pTfh cells, showed greater permissiveness for HIV infection than non-pTfh cells. At week 48 on cART, HIV DNA levels were unchanged from pre-cART levels, although a significant decrease in 2LTR circles was observed in both cell subsets. Inducible HIV p24 expression was higher in pTfh cells than in non-pTfh cells, with the highest frequencies in the PD1+ CXCR3− pTfh cell subset. Frequencies of HLADR+ CD38+ activated CD4 T cells correlated with 2LTR circles in pTfh and non-pTfh cells at both time points and with p24+ cells at entry. In conclusion, among CD4 TCM cells in PB of aviremic patients on cART, pTfh cells, in particular the PD1+ CXCR3− subset, constitute a major HIV reservoir that is sustained by ongoing residual immune activation. The inducible HIV p24 assay is useful for monitoring HIV reservoirs in defined CD4 T cell subsets. IMPORTANCE Identification of the type and nature of the cellular compartments of circulating HIV reservoirs is important for targeting of HIV cure strategies. In lymph nodes (LN), a subset of CD4 T cells called T follicular helper (Tfh) cells are preferentially infected by HIV. Central memory (TCM) CD4 T cells are the major cellular reservoir for HIV in peripheral blood and contain a subset of CD4 TCM cells expressing chemokine receptor CXCR5 similar in function to LN Tfh cells termed peripheral Tfh (pTfh) cells. We found that the circulating pTfh cells are highly susceptible to HIV infection and that in HIV-infected patients, HIV persists in these cells following plasma virus suppression with potent cART. These pTfh cells, which constitute a subset of TCM CD4 T cells, can be readily monitored in peripheral blood to assess HIV persistence.
The reform of medical education in Iran

In order to investigate the path of medical education in Iran, indicators of medical education were searched from 1970 to 1994. There have been rises in the number of educational institutions from 10 to 46; student admissions in programmes of medical sciences from 1387 to 18141; medical student admissions from 632 to 3630; teaching staff from 1573 to 7979; and teachingbed to student ratio from 1.05 to 2.08. The numbers of students in clinical specialty and MS degrees have increased, and various programmes in clinical subspecialty and PhD degrees have been initiated. The quality of medical education has improved with increasing field and ambulatory care training, with more emphasis on teaching preventive medicine and a significant rise in the research activities. Most qualitative and quantitative progress has been achieved following the establishment of a joint Ministry of Health and Medical Education in 1985. The results of this review demonstrate the success of Iran in upgrading medical education by the unification of health services and medical education in one ministry.
Impact of mode of delivery on neonatal complications: Trends between 1997 and 2005

Objective. This study examined whether rates of selected neonatal complications vary by mode of delivery and whether these rates are changing as a result of the increasing cesarean delivery rate. Method. Birth certificates in New Jersey from 1997 to 2005 were matched to hospital discharge records for mothers and newborns. Results. In New Jersey, the total cesarean section rate for 2005 was 35.3%, a relative increase of 46% since 1997 (from 24.2%). Rates of transient tachypnea of the newborn (TTN) and respiratory distress syndrome (RDS), regardless of mode of delivery, increased between 1997 and 2005 from 3.3 to 3.9% and 2.1 to 2.4%, respectively. Newborn injuries declined sharply (from 4.1 to 2.6%), whereas intra-ventricular hemorrhage (IVH) rates remained stable. The rates of RDS, TTN and IVH were highest for cesarean delivery without trial of labor, while the rate of injuries was highest for instrumental vaginal delivery. Conclusion. Neonatal complication rates varied by mode of delivery and decreased with gestational age.
Shortening the course of antibiotic treatment in the intensive care unit

Effective antimicrobial stewardship is an increasingly important concern for healthcare providers globally. Antibiotics are frequently prescribed for patients who develop sepsis in the intensive care unit and traditionally courses are prolonged, with uncertain benefit and probable harm. There is little evidence to support many guidelines recommending between 10 and 14 days, and a number of studies suggest substantially shorter courses of less than 7 days may suffice. Safely reducing course length is likely to depend on a number of preconditions, including thorough eradication of any septic foci; optimization of serum antibiotic concentrations, particularly when there is physiological derangement; and use of novel biomarkers such as procalcitonin. The critical care environment is well suited to this aim as patients are closely monitored. With these measures in place, it is reasonable to believe short antibiotic courses can safely be used for the majority of intensive care infections.
Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib

Purpose: Non–small cell lung cancers carrying activating mutations in the gene for the epidermal growth factor receptor (EGFR) are highly sensitive to EGFR-specific tyrosine kinase inhibitors. However, most patients who initially respond subsequently experience disease progression while still on treatment. Part of this “acquired resistance” is attributable to a secondary mutation resulting in threonine to methionine at codon 790 (T790M) of EGFR. Experimental Design: We sequenced exons 18 to 21 of the EGFR gene to look for secondary mutations in tumors with acquired resistance to gefitinib in 14 patients with adenocarcinomas. Subcloning or cycleave PCR was used in addition to normal sequencing to increase the sensitivity of the assay. We also looked for T790M in pretreatment samples from 52 patients who were treated with gefitinib. We also looked for secondary KRAS gene mutations because tumors with KRAS mutations are generally resistant to tyrosine kinase inhibitors. Results: Seven of 14 tumors had a secondary T790M mutation. There were no other novel secondary mutations. We detected no T790M mutations in pretreatment specimens from available five tumors among these seven tumors. Patients with T790M tended to be women, never smokers, and carrying deletion mutations, but the T790M was not associated with the duration of gefitinib administration. None of the tumors had an acquired mutation in the KRAS gene. Conclusions: A secondary T790M mutation of EGFR accounted for half the tumors with acquired resistance to gefitinib in Japanese patients. Other drug-resistant secondary mutations are uncommon in the EGFR gene.
Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis

When fused with the protein transduction domain (PTD) derived from the human immunodeficiency virus TAT protein, proteins can cross the blood–brain barrier and cell membrane and transfer into several tissues, including the brain, making protein therapy feasible for various neurological disorders. We have constructed a powerful antiapoptotic modified Bcl‐XL protein (originally constructed from Bcl‐XL) fused with PTD derived from TAT (TAT‐modified Bcl‐XL), and, to examine its clinical effectiveness in a mouse model of familial amyotrophic lateral sclerosis (ALS), transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation were treated by intrathecal infusion of TAT‐modified Bcl‐XL. We demonstrate that intrathecally infused TAT‐fused protein was effectively transferred into spinal cord neurons, including motor neurons, and that intrathecal infusion of TAT‐modified Bcl‐XL delayed disease onset, prolonged survival, and improved motor performance. Histological studies show an attenuation of motor neuron loss and a decrease in the number of cleaved caspase 9‐, cleaved caspase 3‐, and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive cells in the lumbar cords of TAT‐modified Bcl‐XL‐treated G93A mice. Our results indicate that intrathecal protein therapy using a TAT‐fused protein is an effective clinical tool for the treatment of ALS. © 2008 Wiley‐Liss, Inc.
The Small Subunit AroB of Arsenite Oxidase

Here, we describe the characterization of the [2Fe-2S] clusters of arsenite oxidases from Rhizobium sp. NT-26 and Ralstonia sp. 22. Both reduced Rieske proteins feature EPR signals similar to their homologs from Rieske-cyt b complexes, with g values at 2.027, 1.88, and 1.77. Redox titrations in a range of pH values showed that both [2Fe-2S] centers have constant Em values up to pH 8 at ∼+210 mV. Above this pH value, the Em values of both centers are pH-dependent, similar to what is observed for the Rieske-cyt b complexes. The redox properties of these two proteins, together with the low Em value (+160 mV) of the Alcaligenes faecalis arsenite oxidase Rieske (confirmed herein), are in line with the structural determinants observed in the primary sequences, which have previously been deduced from the study of Rieske-cyt b complexes. Since the published Em value of the Chloroflexus aurantiacus Rieske (+100 mV) is in conflict with this sequence analysis, we re-analyzed membrane samples of this organism and obtain a new value (+200 mV). Arsenite oxidase activity was affected by quinols and quinol analogs, which is similar to what is found with the Rieske-cyt b complexes. Together, these results show that the Rieske protein of arsenite oxidase shares numerous properties with its counterpart in the Rieske-cyt b complex. However, two cysteine residues, strictly conserved in the Rieske-cyt b-Rieske and considered to be crucial for its function, are not conserved in the arsenite oxidase counterpart. We discuss the role of these residues.
Chemodenitrification in the cryoecosystem of Lake Vida, Victoria Valley, Antarctica

Lake Vida, in the Victoria Valley of East Antarctica, is frozen, yet harbors liquid brine (~20% salt, >6 times seawater) intercalated in the ice below 16 m. The brine has been isolated from the surface for several thousand years. The brine conditions (permanently dark, −13.4 °C, lack of O2, and pH of 6.2) and geochemistry are highly unusual. For example, nitrous oxide (N2O) is present at a concentration among the highest reported for an aquatic environment. Only a minor 17O anomaly was observed in N2O, indicating that this gas was predominantly formed in the lake. In contrast, the 17O anomaly in nitrate ( NO3− ) in Lake Vida brine indicates that approximately half or more of the NO3− present is derived from atmospheric deposition. Lake Vida brine was incubated in the presence of 15N‐enriched substrates for 40 days. We did not detect microbial nitrification, dissimilatory reduction of NO3− to ammonium ( NH4+ ), anaerobic ammonium oxidation, or denitrification of N2O under the conditions tested. In the presence of 15N‐enriched nitrite ( NO2− ), both N2 and N2O exhibited substantial 15N enrichments; however, isotopic enrichment declined with time, which is unexpected. Additions of 15N– NO2− alone and in the presence of HgCl2 and ZnCl2 to aged brine at −13 °C resulted in linear increases in the δ15N of N2O with time. As HgCl2 and ZnCl2 are effective biocides, we interpret N2O production in the aged brine to be the result of chemodenitrification. With this understanding, we interpret our results from the field incubations as the result of chemodenitrification stimulated by the addition of 15N‐enriched NO2− and ZnCl2 and determined rates of N2O and N2 production of 4.11–41.18 and 0.55–1.75 nmol L−1 day−1, respectively. If these rates are representative of natural production, the current concentration of N2O in Lake Vida could have been reached between 6 and 465 years. Thus, chemodenitrification alone is sufficient to explain the high levels of N2O present in Lake Vida.
Prevention of mandibular third molar extraction-associated periodontal defects: a comparative study.

BACKGROUND Extraction of deep-impacted mandibular third molars may lead to periodontal defects at the distal surface of the adjacent second molar. The purpose of this study was to compare the ability of three regenerative approaches to prevent third molar extraction-related periodontal defects. METHODS Forty-five patients with bilateral osseous or soft tissue-impacted lower third molars were selected to participate in the study. Inclusion criteria were the presence of a pocket that was located distally to the mandibular second molar with a probing depth (PD) >or=7 mm and with a probing clinical attachment level (CAL) >or=6 mm. Ninety third molar impactions were used and were randomly assigned to three equal treatment groups (30 each): bovine porous bone mineral (BPBM) alone, BPBM plus collagen membrane (CM), and an untreated control group. Clinical and radiographic measurements were recorded at 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months after the surgery. RESULTS BPBM or BPBM + CM resulted in a significant reduction in PD and gain in CAL compared to the control group at all time points. BPBM + CM had the best outcome for the prevention of a second-molar periodontal defect. CONCLUSION The application of BPBM, with or without a collagen membrane, can be a viable and stable treatment to alleviate the periodontal defects that are often associated with impacted mandibular third molar extractions.
Effects of Propofol on Cyclic Strain-induced Endothelin-1 Expression in Human Umbilical Vein Endothelial Cells

Background:Propofol is one of the most popular intravenous induction agents of general anesthesia. Experimental results revealed that propofol exerted hypotensive and antioxidative effects. However, the intracellular mechanism of propofol remains to be delineated. The aims of this study were to test the hypothesis that propofol may alter strain-induced endothelin-1 (ET-1) secretion and nitric oxide production, and to identify the putative underlying signaling pathways in human umbilical vein endothelial cells. Methods:Cultured human umbilical vein endothelial cells were exposed to cyclic strain in the presence of propofol, and ET-1 expression was examined by Northern blotting and enzyme-linked immunosorbent assay kit. Activation of extracellular signal-regulated protein kinase, endothelial nitric oxide synthase, and protein kinase B were assessed by Western blot analysis. Results:The authors show that propofol inhibits strain-induced ET-1 expression, strain-increased reactive oxygen species formation, and extracellular signal-regulated protein kinase phosphorylation. On the contrary, nitric oxide production, endothelial nitric oxide synthase activity, and protein kinase B phosphorylation were enhanced by propofol treatment. Furthermore, in the presence of PTIO, a nitric oxide scavenger, and KT5823, a specific inhibitor of cyclic guanosine monophosphate-dependent protein kinase, the inhibitory effect of propofol on strain-induced extracellular signal-regulated protein kinase phosphorylation and ET-1 release was reversed. Conclusions:The authors demonstrate for the first time that propofol inhibits strain-induced ET-1 secretion and enhances strain-increased nitric oxide production in human umbilical vein endothelial cells. Thus, this study delivers important new insight into the molecular pathways that may contribute to the proposed hypotensive effects of propofol in the cardiovascular system.
Outcome analysis for patients with elevated serum tumor markers at postchemotherapy retroperitoneal lymph node dissection.

PURPOSE To evaluate the therapeutic benefit of postchemotherapy retroperitoneal lymph node dissection (PCRPLND) in patients with persistently elevated serum tumor markers. PATIENTS AND METHODS One hundred fourteen patients with metastatic germ cell cancer with elevated serum tumor markers after first-line (50 patients) or second-line chemotherapy (64 patients) who underwent PCRPLND between 1977 and 2000 with a minimum follow-up of 2-years were included in this retrospective study. RESULTS The 5-year overall survival was 53.9%. Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months. Fifty-three patients died of disease, with a medium time to death of 8.0 months. Mean preoperative serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betaHCG) levels were 483 ng/mL and 555 mU/mL, respectively, with no difference in 5-year survival (P = .2). Retroperitoneal pathology revealed germ cell cancer in 53.5% of patients, teratoma in 34.2% of patients, and fibrosis in 12.2% of patients, with 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P < .0001). Predictors of retroperitoneal pathology included an increasing serum AFP or betaHCG, betaHCG more than 100 ng/mL, redo retroperitoneal lymph node dissection (RPLND), and second-line chemotherapy. Poor prognostic variables by multivariable analysis included betaHCG status, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. CONCLUSION A subset of patients with elevated serum tumor markers after chemotherapy is curable with surgery. The prognostic factors predictive of outcome in this analysis include an increasing betaHCG, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. These factors, along with clinical and surgical experience, should aid in determining the appropriate integration of surgery and chemotherapy in this population.
Weight loss at high altitude: pathophysiology and practical implications

Climbers at high altitude (>5000 m) lose weight. This impairs performance and safety, but the mechanisms are not entirely due to an imbalance between energy intake and expenditure. There is some evidence of carbohydrate malabsorption, but there are also changes in fat metabolism and total body water. This paper considers the physiological control of weight and then discusses the changes in each parameter before addressing the practical implications.
Insulitis in type 1 (insulin‐dependent) diabetes mellitus in man—macrophages, lymphocytes, and interferon‐γ containing cells

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon‐γ in inflamed islets (insulitis) of patients with type 1 (insulindependent) diabetes. Autopsy pancreases of 12 patients who had died of recent‐onset type 1 diabetes and one prediabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9·7:1 and approximately 40 per cent of the lymphocytes contained interferon‐γ. Interferon‐γ release in the insulitis process may be involved in the pathogensis of type 1 diabetes.
Non-conductive film underfill for 3D integration of 20 pm-thick LSI wafers with fine Cu-TSVs

The beneficial role played by non-conductive film (NCF) under-fill (UF) compared with the conventional capillary under fill (CUF) is meticulously investigated for the reliability issues in high-density 3D-integration at die/wafer-level. The NCF with co-efficient of thermal expansion (CTE) value of 35 ppm/°C tremendously reduces the local deformation of 20 μm-thick three-dimensionally (3D)-stacked LSI die/wafer. This reduces the local mechanical stress in thinned 3D-LSI by nearly 5 times as against the CUF with the CTE value of 60-70 ppm/C. Both μ-RS and μ-XRD data showed only ~250 MPa of tensile stress on the back surface of 20 μm-thick stacked die/wafer with NCFUF, whereas it was more than five-times larger (~1400 MPa) for CUF. μ-XRD data illustrates that the cause for residual stress in the bump-space region and above the μ-bump are respectively due to the lattice tilt and change in lattice space.
Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors

ABSTRACT Elite suppressors (ES) are human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml without treatment. The observation that the HLA-B*57 allele is overrepresented in these patients implies that HIV-1-specific CD8+ T cells play a key role in suppressing viral replication. We have previously shown that while CD8+ T-cell escape mutations are rarely seen in proviral Gag sequences in resting CD4+ T cells from peripheral blood, they are present in every clone amplified from the low levels of free virus in the plasma of HLA-B*57+ ES. In this study, we compared the pattern of mutations in Nef sequences amplified from peripheral blood CD4+ T cells and from plasma virus. We show that Nef mutations are present in plasma virus but are rare in the cellular sequences and provide evidence that these plasma Nef variants represent novel escape mutants. The results provide further evidence of CD8+ T-cell-mediated selective pressure on plasma virus in ES and suggest that there must be ongoing HIV-1 replication in spite of the very low viral loads seen for these patients.
Empirical Analysis of the Relationship between Industrial Performance and Macroeconomic Factors in Ghana

The conscious attempt to ascertain the wide range of macroeconomic factors that drive industrial production in Ghana necessitated this study. The main purpose of this study is to ascertain the impact that macroeconomic factors have on industrial performanc e in Ghana over the period 1980 to 2013. The Autoregressive Distributed Lag Model was employed to examine the long run and the short run dynamics of macroeconomic factors and industrial output. The study found cointegration relationship between industrial output and the macroeconomic factors. The results indicated that the major macroeconomic factors that affect industrial performance in Ghana are lending rate (+), inflation (+), employment (+) and government expenditure (+). Based on the findings, the stud y recommends that the government of Ghana should stabilize the macroeconomic environment of Ghana in order to achieve industrial growth and development.