Miracle-dz/UniFAR-FTUs huggingface dataset:
Narrowing of Human Influenza A Virus-Specific T Cell Receptor α and β Repertoires with Increasing Age

ABSTRACT Alterations in memory CD8 T cell responses may contribute to the high morbidity and mortality caused by seasonal influenza A virus (IAV) infections in older individuals. We questioned whether memory CD8 responses to this nonpersistent virus, to which recurrent exposure with new strains is common, changed over time with increasing age. Here, we show a direct correlation between increasing age and narrowing of the HLA-A2-restricted IAV Vα and Vβ T cell repertoires specific to M1 residues 58 to 66 (M158–66), which simultaneously lead to oligoclonal expansions, including the usage of a single identical VA12-JA29 clonotype in all eight older donors. The Vα repertoire of older individuals also had longer CDR3 regions with increased usage of G/A runs, whose molecular flexibility may enhance T cell receptor (TCR) promiscuity. Collectively, these results suggest that CD8 memory T cell responses to nonpersistent viruses like IAV in humans are dynamic, and with aging there is a reduced diversity but a preferential retention of T cell repertoires with features of enhanced cross-reactivity. IMPORTANCE With increasing age, the immune system undergoes drastic changes, and older individuals have declined resistance to infections. Vaccinations become less effective, and infection with influenza A virus in older individuals is associated with higher morbidity and mortality. Here, we questioned whether T cell responses directed against the highly conserved HLA-A2-restricted M158–66 peptide of IAV evolves with increasing age. Specifically, we postulated that CD8 T cell repertoires narrow with recurrent exposure and may thus be less efficient in response to new infections with new strains of IAV. Detailed analyses of the VA and VB TCR repertoires simultaneously showed a direct correlation between increasing age and narrowing of the TCR repertoire. Features of the TCRs indicated potentially enhanced cross-reactivity in all older donors. In summary, T cell repertoire analysis in older individuals may be useful as one of the predictors of protection after vaccination.
Fertility regulation among women in rural communities around Jimma, Western Ethiopia

A cross-sectional study was conducted in April 1998 with the an objective to identify the awareness and practice of family planning among women living around Jimma Town. A pre-tested questionnaire was administered to a total of 863 women in reproductive age. Besides, a total of 11 Focus Group Discussion (FGD) sessions were held with a total of 101 women in eight panels. Findings showed that 41.7% of women respondents have heard about family planning, the main source being husbands and health facilities. The majority (93.8%) believed that "it is God that decides when to become pregnant and the number of children to bear". Current use of contraceptive among married women was found to be only 7.0% of which 65.0% use the pill. Age and educational status were found to have significant association with contraceptive non-use. Unlike many studies that concluded men's disapproval as reason for not using family planning services, it was found that men rather were sources of family planning information and the finding from FGD did also show that husbands remain neutral about their wives use of contraceptive. FGD outcomes are in congruence with survey results. God was found to be an ultimate decision-maker concerning their reproductive matters. Besides, it did clearly come out that discussants felt that they lacked sufficient information about family planning. It was concluded from this study that even in areas closer to major urban towns, awareness of women about reproductive services like family planning is far below from what is expected. Thus, it calls for enhancing collaborative effort to reach the wider majority of women. (Ethiopian Journal of Health Development, 2000, 14(2): 117-126)
The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons

ABSTRACT The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1. We next generated HSV-1 with the same pUS9 arginine residues mutated to asparagine (HSV-1pUS9KBDM) and then restored them being to arginine (HSV-1pUS9KBDR). The two mutated viruses were analyzed initially in a zosteriform model of recurrent cutaneous infection. The primary skin lesion scores were identical in severity and kinetics, and there were no differences in viral load at dorsal root ganglionic (DRG) neurons at day 4 postinfection (p.i.) for both viruses. In contrast, HSV-1pUS9KBDM showed a partial reduction in secondary skin lesions at day 8 p.i. compared to the level for HSV-1pUS9KBDR. The use of rat DRG neuronal cultures in a microfluidic chamber system showed both a reduction in anterograde axonal transport and spread from axons to nonneuronal cells for HSV-1pUS9KBDM. Therefore, the basic domain of pUS9 contributes to anterograde axonal transport and spread of HSV-1 from neurons to the skin through recruitment of kinesin-1. IMPORTANCE Herpes simplex virus 1 and 2 cause genital herpes, blindness, encephalitis, and occasionally neonatal deaths. There is also increasing evidence that sexually transmitted genital herpes increases HIV acquisition, and the reactivation of HSV increases HIV replication and transmission. New antiviral strategies are required to control resistant viruses and to block HSV spread, thereby reducing HIV acquisition and transmission. These aims will be facilitated through understanding how HSV is transported down nerves and into skin. In this study, we have defined how a key viral protein plays a role in both axonal transport and spread of the virus from nerve cells to the skin.
Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

ABSTRACT Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.
Variation und Eignung von physiologischen Merkmalen des Glukosetoleranztestes für die indirekte Eigenleistungsprüfung von Jungbullen

Abstract. Title of the paper: Variation and suitability of physiological indicators of the glucose tolerance test for the indirectly evaluation of young bulls The parameters of glucose tolerance test are suitable for an additional recommendation for the valuation of the breeding bulls before the start of test could be given. This show the Variation, the genetic determination and the mean correlations between physiological indicator and estimated breeding value by 0.40 to 0.50. The offspring's breeding value is suitable equivalent examined physiological indicators. These relationships are affected by factors such as experimental conditions, age and nutritional State of animals.
A Control Reconfiguration Strategy for Post-Sensor FTC in Induction Motor-Based EVs

This paper deals with experimental validation of a reconfiguration strategy for sensor fault-tolerant control (FTC) in induction-motor-based electric vehicles (EVs). The proposed active FTC system is illustrated using two control techniques: indirect field-oriented control (IFOC) in the case of healthy sensors and speed control with slip regulation (SCSR) in the case of failed current sensors. The main objective behind the reconfiguration strategy is to achieve a short and smooth transition when switching from a controller using a healthy sensor to another sensorless controller in the case of a sensor failure. The proposed FTC approach performances are experimentally evaluated on a 7.5-kW induction motor drive.
Ibrutinib in Waldenström macroglobulinemia: latest evidence and clinical experience

Ibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events.
Bizarre Parosteal Osteochondromatous Proliferation of Long Bones: Two New Cases and Literature Study

In research on tumors of mesenchymal origin, although the type localized in the short, tubular bones has been evaluated in detail, there have been no reports to date regarding the clinical, radiological and treatment characteristics of the type localized in the long bones. In this study, Nora’s lesions localized in the long bones were investigated in terms of their characteristics and behavior. An extensive literature review was performed using PubMed, MEDLINE (1983 - 2012) and Google Scholar. Search terms included ‘‘bizarre parosteal osteochondromatous proliferation’’ (BPOP) and ‘‘Nora’s lesion’’. The literature search yielded 88 articles and a total of 43 patients. The median age of the cases was 26 years. BPOP occurred with equal frequency in men and women. The most frequent sites of involvement were the femur (25%) and the ulna (23%). Plain radiographs of 20 cases were available, but only a small number of cases had CTs (n = 11) and MRIs (n = 12) performed. It was determined that 66% of the lesions led to cortical changes, while 23.5% led to medullary invasion or soft tissue infiltration. As to treatments, “simple excision” (intralesional) was performed on seven lesions, marginal resection was performed in nine patients, wide resection was performed in two patients, “shark-bite” surgery was performed in one patient and “shave excision” was performed in one patient. The mean follow-up period was 30.9 months. Local recurrence rate was 18.75%. Clinically and in terms of radiological images, we believe that this lesion observed in the long bones consists of four phases: stages I, II, III and IV. We believe this type of lesion demonstrates no spontaneous recovery, and that it is a progressive lesion involving cortical destruction and medullary infiltration. As such, we consider marginal resection to be the appropriate technique for treating this lesion. J Med Cases. 2014;5(6):315-325 doi: http://dx.doi. org/ 10.14740 / jmc1624w
Vaccinia Virus Requires Glutamine but Not Glucose for Efficient Replication

ABSTRACT Viruses require host cell metabolism to provide the necessary energy and biosynthetic precursors for successful viral replication. Vaccinia virus (VACV) is a member of the Poxviridae family, and its use as a vaccine enabled the eradication of variola virus, the etiologic agent of smallpox. A global metabolic screen of VACV-infected primary human foreskin fibroblasts suggested that glutamine metabolism is altered during infection. Glutamine and glucose represent the two main carbon sources for mammalian cells. Depriving VACV-infected cells of exogenous glutamine led to a substantial decrease in infectious virus production, whereas starving infected cells of exogenous glucose had no significant impact on replication. Viral yield in glutamine-deprived cells or in cells treated with an inhibitor of glutaminolysis, the pathway of glutamine catabolism, could be rescued by the addition of multiple tricarboxylic acid (TCA) cycle intermediates. Thus, VACV infection induces a metabolic alteration to fully rely on glutamine to anaplerotically maintain the TCA cycle. VACV protein synthesis, but not viral transcription, was decreased in glutamine-deprived cells, which corresponded with a dramatic reduction in all VACV morphogenetic intermediates. This study reveals the unique carbon utilization program implemented during poxvirus infection and provides a potential metabolic pathway to target viral replication. IMPORTANCE Viruses are dependent on the metabolic machinery of the host cell to supply the energy and molecular building blocks needed for critical processes including genome replication, viral protein synthesis, and membrane production. This study investigates how vaccinia virus (VACV) infection alters global cellular metabolism, providing the first metabolomic analysis for a member of the poxvirus family. Unlike most viruses examined to date, VACV does not activate glycolysis, and exogenous glucose is not required for maximal virus production. Instead, VACV requires exogenous glutamine for efficient replication, and inhibition of glutamine metabolism effectively blocks VACV protein synthesis. This study defines a major metabolic perturbation essential for the replication of a poxvirus and may lead to the discovery of novel antiviral therapies based on metabolic inhibitors.
Recanalization after intravenous thrombolysis

Background: To evaluate the time course of major vessel recanalization under IV thrombolysis in relation to functional outcome in acute ischemic stroke. Methods: A total of 99 patients with an acute anterior circulation vessel occlusion who underwent IV thrombolysis were included. All patients had a standardized admission and follow-up procedure. Color-coded duplex sonography was performed on admission, 30 minutes after thrombolysis, and at 6 and 24 hours after onset of symptoms. Recanalization was classified as complete, partial, and absent. Functional outcome was rated with the modified Rankin Scale on day 30. Results: Complete recanalization occurred significantly more frequently in patients with multiple branch occlusions compared to those with mainstem occlusion (OR 5.33; 95% CI, 2.18 to 13.05; p < 0.0001) and was associated with lower NIH Stroke Scale (NIHSS) scores (p < 0.001). Not the specific time point of recanalization at 6 or 24 hours after stroke onset, but recanalization per se within 24 hours (OR 7.8; 95% CI 2.2 to 28.2; p = 0.002) was significantly associated with a favorable outcome. Multivariate analysis revealed recanalization at any time within 24 hours and NIHSS scores on days 1 and 7 together explaining 75% of the functional outcome variance 30 days after stroke. Conclusions: Complete recanalization up to 24 hours after stroke onset is significantly associated with the short-term clinical course and functional outcome 30 days after acute stroke.
Pharmacological treatments for osteoporosis in very elderly people

Only a few randomized controlled trials investigating antiosteoporotic agents with fracture endpoints have included participants over the age of 80 years. The pivotal trial with alendronic acid had an upper age range of 80 years, although a separate trial that showed a significant reduction in nonvertebral fractures included some participants up to age of 84 years. Risedronate and zoledronic acid are the only bisphosphonates to show a significant reduction in new vertebral, hip and nonvertebral fractures during a 3-year period in those over 80 years of age. In addition, zoledronic acid was associated with a reduction in the rate of new clinical fractures and improved survival in elderly subjects after hip fracture. More recently, denosumab was found to significantly reduce the risk of new radiographic vertebral, hip and nonvertebral fractures in women up to the age of 89 years with osteoporosis. Strontium ranelate and teriparatide have shown fracture reductions in populations that have included subjects over the age of 80 years. There has been evidence to show that a combination of calcium and vitamin D reduces nonvertebral fracture in older populations. The role of vitamin D alone is less clear, although there is the suggestion that it may be effective at higher doses. The burden of osteoporosis is unquestionably rising within our ageing population. More emphasis is therefore required on researching the benefits of these pharmacological agents in very elderly people.
Antecedents to adoption of classroom-based AIDS education in secondary schools

This paper describes the results of a cross-sectional survey of 956 Dutch secondary school teachers. It explores the determinants of adoption of classroom-based AIDS education. The results showed that teachers decision making was most strongly related to highly specific adoption-related beliefs (outcome beliefs subjective norms self-efficacy). Adoption was additionally related to more generic dispositions (sense of responsibility and sexual morality) and environmental conditions (school policy and frequency of collegial interaction about HIV instruction). Past experience with AIDS education appeared to be positively associated with teachers intentions and related determinants. It is concluded that additional support needs to address teachers anticipated ideological and practical constraints both by mass media interventions and responsive in-person assistance. (authors)
Iterative Joint Estimation Procedure for Channel and Frequency Offset in Multi-Antenna OFDM Systems With an Insufficient Cyclic Prefix

This paper addresses a strategy to improve the joint channel and frequency offset (FO) estimation in multi-antenna systems, widely known as multiple-input-multiple-output orthogonal frequency-division multiplexing (MIMO-OFDM), in the presence of intersymbol interference (ISI) and intercarrier interference (ICI) occasioned by an insufficient cyclic prefix (CP). The enhancement is attained by the use of an iterative joint estimation procedure (IJEP) that successively cancels the interferences located in the preamble of the OFDM frame, which is used for the joint estimation and initially contains the interferences due to a CP shorter than the channel length. The IJEP requires at certain steps a proper iterative interference cancellation algorithm, which makes use of an initial FO compensation and channel estimation obtained due to the use of a symmetric sequence in the preamble. After the iterative cancellation of interferences, the procedure performs an additional joint channel and FO estimation whose mean square error converges to the Cramer-Rao bound (CRB). Later on, this subsequent joint estimation permits the removal of the interferences in the data part of the frame, which are also due to an insufficient CP, in the same iterative fashion but saving iterations compared with the use of other estimation strategies. The appraisal of the procedure has been performed by assessing the convergence of the simulated estimators to the CRB as a function of the number of iterations. Additionally, simulations for the evaluation of the bit error rate (BER) have been carried out to probe how the utilization of the proposed IJEP clearly improves the performance of the system. It is concluded that, with a reduced number of iterations in the preamble, the IJEP converges to the theoretical bounds, thus reducing the disturbances caused by a hard wireless channel or a deliberately insufficient CP. Therefore, this eases the interference cancellation in the data part, leading to an improvement in the BER that approximates to the ideal case of a sufficient CP and, consequently, an improvement in the computational cost of the whole procedure that has been analyzed.
Conserved Molecular Signatures in gp120 Are Associated with the Genetic Bottleneck during Simian Immunodeficiency Virus (SIV), SIV-Human Immunodeficiency Virus (SHIV), and HIV Type 1 (HIV-1) Transmission

ABSTRACT Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of “signature” sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. IMPORTANCE The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites are under selection in HIV. Our findings suggest that the signature residues are involved in increasing the transmissibility of infecting viruses; therefore, they are potential targets for developing a vaccine or other protective measures. A recent study identified the same T/F signature motif but interpreted it as an effect of neutralization resistance. Here, we show that the T/F motif has broader functional significance beyond neutralization sensitivity, because it is present in nonimmune subjects. Also, a vaccine regimen popular in animal trials might have increased the transmission of variants with otherwise low transmission fitness. Our observations might explain why many animal vaccine trials have not faithfully predicted outcomes in human vaccine trials and suggest that current practices in vaccine design need to be reexamined accordingly.