Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts.

BACKGROUND CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time. METHODS Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years. RESULTS At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term-treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group. CONCLUSIONS ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non-AIDS-related events by alleviating this elevation.
Single unit hyperactivity and bursting in the auditory thalamus of awake rats directly correlates with behavioural evidence of tinnitus

Medial geniculate body (MGB) single units recorded from sound‐exposed animals with behavioural evidence of tinnitus exhibits enhanced spontaneous firing and burst properties. MGB units in tinnitus animals exhibit increased rate‐level function slope when driven by broadband noise and tones at the unit's characteristic frequency. Elevated patterns of neuronal activity and altered bursting showed a significant positive correlation with animals’ tinnitus scores.
Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

BACKGROUND Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. METHODS Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. RESULTS Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. CONCLUSIONS Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.
Knowledge Management: An Introduction and Perspective

Leaders of successful organizations are consistently searching for better ways to improve performance and results. Frequent disappointments with past management initiatives have motivated managers to gain new understandings into the underlying, but complex mechanisms ‐ such as knowledge ‐ which govern an enterprise’s effectiveness. Knowledge Management, far from being a management “fad”, is broad, multi‐dimensional and covers most aspects of the enterprise’s activities. To be competitive and successful, experience shows that enterprises must create and sustain a balanced intellectual capital portfolio. They need to set broad priorities and integrate the goals of managing intellectual capital and the corresponding effective knowledge processes. This requires systematic Knowledge Management. With knowledge as the major driving force behind the “economics of ideas”, we can expect that the emphasis on knowledge creation, development, organization and leverage will continue to be the prime focus for improving society.
Would eradication of Helicobacter pylori infection reduce the risk of gastric cancer?

This article reviews the data on the epidemiology of gastric cancer, to determine if treatment of an asymptomatic individual can be justified. It reviews retrospective and prospective case‐control studies of gastric cancer in Italy and other countries. Mucosa‐associated lymphoid tissue lymphoma is associated with Helicobacter pylori infection. The risk of noncardia gastric cancer is higher (4‐fold or greater) in those with H. pylori infection. Although no studies have shown prevention following treatment, erradication of asymptomatic H. pylori infection in an individual in the age group 40 or lower may be expected to reduce the risk of gastric cancer.
Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.

BACKGROUND Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. METHODS We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. RESULTS Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). CONCLUSIONS Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.
ERP and application integration: Exploratory survey

During the 1990s, companies focused on the adoption of enterprise resource planning (ERP) systems to solve integration problems. However, ERP systems automate core business activities without solving underlying business structures and processes. As a result a number of disparate applications often coexist with ERP systems. To better understand ERP and application integration (AI) problems, this paper proposes to identify, analyse and present the problems of ERP systems, as well as examining new approaches for AI. In doing so, a multi‐choice questionnaire has been designed, and was distributed to ERP specialists over the Internet. Responses show that ERP systems amplified the need for integration, as existing systems have to be incorporated with ERP applications. AI securely incorporates functionality from disparate applications, and has shown to lead to the development of new strategic business solutions for enterprises. The results of the research confirm AI as a new means of system integration that adds value by placing business logic in the applications network, thus creating a more dynamic information systems infrastructure.
Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C

Natriuretic peptides (NPs) elicit their effects via multiple NP receptors (including NPR‐A, NPR‐B and NPR‐C, with NPR‐C being relatively poorly understood). We have studied the effects of NPR‐C ablation on cardiac structure, function and arrhythmogenesis using NPR‐C knockout (NPR‐C−/−) mice. NPR‐C−/− mice are characterized by sinoatrial node (SAN) dysfunction and a profound increase in susceptibility to atrial fibrillation. Increased susceptibility to arrhythmias in NPR‐C−/− mice was associated with slowed electrical conduction in the SAN as well as the right and left atria due to enhanced collagen expression and deposition in the atria (structural remodelling), but without changes in action potential morphology (electrical remodelling) in isolated SAN or atrial myocytes. This study demonstrates a critical protective role for NPR‐C in the heart.
The myriad challenges of respiratory fungal infection in cystic fibrosis

Fungal infection in cystic fibrosis (CF) is a recognized challenge, with many areas requiring further investigation. Consensus definitions exist for allergic bronchopulmonary aspergillus in CF, but the full scope of clinically relevant non‐allergic fungal disease in CF—asymptomatic colonization, transient or chronic infection localized to endobronchial mucus plugs or airway tissue, and invasive disease—is yet to be clearly defined. Recent advances in mycological culture and non‐culture identification have expanded the list of both potential pathogens and community commensals in the lower respiratory tract. Here we aim to outline the current understanding of fungal presence in the CF respiratory tract, risk factors for acquiring fungi, host‐pathogen interactions that influence the role of fungi from bystander to pathogen, advances in the diagnostic approaches to isolating and identifying fungi in CF respiratory samples, challenges of classifying clinical phenotypes of CF patients with fungi, and current treatment approaches. Development and validation of biomarkers characteristic of different fungal clinical phenotypes, and controlled trials of antifungal agents in well‐characterized target populations, remain central challenges to surmount and goals to be achieved.
Real-World Sustained Virologic Response Rates of Sofosbuvir-Containing Regimens in Patients Coinfected With Hepatitis C and HIV.

BACKGROUND Patients with hepatitis C virus (HCV) with or without human immunodeficiency virus (HIV) achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens in clinical trials. Real world data on patients coinfected with HCV and HIV treated with SOF-based regimens are lacking. METHODS This observational cohort study included HIV/HCV-coinfected adults with genotype 1 HCV who initiated treatment with a SOF-containing regimen between December 2013 and December 2014 (n = 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was SVR at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events, and side effects. A post hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up. RESULTS In an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (P = .15). However the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (P < .01). In a per protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) vs 57% (16/28) (P < .01). The most commonly reported adverse effects were rash, pruritus, fatigue, and insomnia. One patient who had decompensated cirrhosis prior to treatment initiation died after receiving SMV/SOF. CONCLUSIONS SMV/SOF ± RBV is an effective option with minimal adverse effects for most HIV-positive patients with genotype 1 HCV. SMV should be used with caution in patients with decompensated cirrhosis.
Key success factors in implementation of process-based management: A UK housing association experience

This paper explores the implementation of a process‐based management system within a service organisation that has recently achieved certification of its quality management system to the ISO 9001:2000 requirements. Many academics and business people alike consider process‐based management as a fundamental requirement of certification to ISO 9001:2000 quality management systems. Hence, this paper discusses the definition of a process‐based management system and also considers, through a literature review, theories relating to the topic. Consequently, a theoretical model is proposed that outlines the factors affecting successful implementation of a process‐based management system. The paper demonstrates that the theoretical model has been assessed within a UK housing association enterprise case study organisation. The case study organisation presented in this paper, shows the potential barriers of implementation of a process‐based management system.
Proteomics in human cancer research

Proteomics is now widely employed in the study of cancer. Many laboratories are applying the rapidly emerging technologies to elucidate the underlying mechanisms associated with cancer development, progression, and severity in addition to developing drugs and identifying patients who will benefit most from molecular targeted compounds. Various proteomic approaches are now available for protein separation and identification, and for characterization of the function and structure of candidate proteins. In spite of significant challenges that still exist, proteomics has rapidly expanded to include the discovery of novel biomarkers for early detection, diagnosis and prognostication (clinical application), and for the identification of novel drug targets (pharmaceutical application). To achieve these goals, several innovative technologies including 2‐D‐difference gel electrophoresis, SELDI, multidimensional protein identification technology, isotope‐coded affinity tag, solid‐state and suspension protein array technologies, X‐ray crystallography, NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulation have evolved, and are being used in different combinations. This review provides an overview of the field of proteomics and discusses the key proteomic technologies available to researchers. It also describes some of the important challenges and highlights the current pharmaceutical and clinical applications of proteomics in human cancer research.
Microbial etiology of periodontal disease

Abstract Longitudinal studies with humans indicate that gingivitis is associated with an increased dental plaque mass. Also, prior to the onset of gingivitis, changes in the microflora towards a more complex bacterial composition frequently occur. On the other hand, recent cross sectional cultural studies generally do not reveal clear-cut differences between the composition of the subgingival microflora associated with healthy or inflamed gingivae. Also, some studies have demonstrated an enhanced cell-mediated immune response during the course of gingivitis to a variety of subgingival plaque bacteria. It has also been observed that plaques allowed to form on cleaned teeth for 2 or 3 days do not differ substantially in their microbial composition. However, long-term thorough oral hygiene performed at intervals of 48 h permits maintenance of gingival health, whereas that instituted at intervals of 72 h will lead eventually to gingivitis. Collectively, this evidence supports the concept that the etiology of gingivitis is bacteriologically nonspecific. Thus a large increase in the accumulation of bacteria on the tooth surface per se may have a greater pathogenic effect on the periodontal tissues than the relatively minor and inconsistent shifts in the microbial composition. The transition from gingivitis into periodontitis may be induced by changes in the pathogenic potential of subgingival plaque. Gram-negative rods appear to be specifically associated with periodontitis. A growing body of evidence implicates especially Bacteriodes asaccharolyticus as one of the responsible pathogens. Juvenile periodontitis (periodontosis) seems to be a distinct disease entity. Recent findings suggest abnormalities in peripheral blood polymorphonuclear leucocytes (PMNL) of patients with juvenile periodontitis. The subgingival microflora is different from that associated with periodontitis and the findings so far implicate Actinobacillus actinomycetemcomitans as an important pathogen. The bacterial etiology of acute necrotizing ulcerative gingivitis (ANUG) is still unclear. Satisfactory cultural studies have yet to be performed. The presence of spirochetes in the ulcerative lesions of the junctional epithelium does not necessarily imply that they play an important role in this disease entity. Future research on the bacteriology of periodontal disease should concentrate on longitudinal studies; particular attention should be paid to the change of gingivitis into periodontitis whereby animals as well as humans can be used. Improvements of sampling methods as well as precise and simple identification techniques of microorganisms are required.
Examining the conditions of ERP implementations: lessons learnt from adopters

Purpose – This paper sets out to examine the conditions of enterprise resource planning (ERP) implementations on the basis of research conducted among practitioners dealing with ERP projects.Design/methodology/approach – This paper builds on the research conducted among a few dozen practitioners dealing with ERP projects. The queried respondents include both ERP adopters and experts representing system suppliers. The study discusses how the researched projects were linked with enterprise strategy, how their efficiency was measured and to what extent they defined implementation goals. The analysis takes into consideration various types of projects and success levels achieved.Findings – The results show that adopters experience different conditions depending on the project type. The findings suggest that practitioners should be more focused on the business benefits. The outcome shows that implementers from very complicated projects are more aware of the overwhelming challenge at large, while, on the other h.
The impact of business process orientation on financial and non-financial performance

Purpose – Extensive literature on business process management suggests that organizations could enhance their overall performance by adopting a process view of business. However, there is a lack of empirical research in this field. The purpose of this paper is to investigate the understanding of the process view and process maturity levels in a transition economy and to test the impact of process orientation maturity level on organizational performance.Design/methodology/approach – Empirical investigation combined an exploratory‐confirmatory approach using factor analysis and structural equation modeling.Findings – The investigation confirms the impact of business process orientation on organizational performance in a transition economy. The link is even stronger than in the original investigation. The results show that business process orientation leads to better non‐financial performance and indirectly to better financial performance.Practical implications – The research confirms that business process o.
Neuroproteomics and systems biology‐based discovery of protein biomarkers for traumatic brain injury and clinical validation

The rapidly growing field of neuroproteomics has expanded to track global proteomic changes underlying various neurological conditions such as traumatic brain injury (TBI), stroke, and Alzheimer's disease. TBI remains a major health problem with approximately 2 million incidents occurring annually in the United States, yet no affective treatment is available despite several clinical trials. The absence of brain injury diagnostic biomarkers was identified as a significant road‐block to therapeutic development for brain injury. Recently, the field of neuroproteomics has undertaken major advances in the area of neurotrauma research, where several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers in the field of TBI. One scope of this review is to evaluate the current status of TBI biomarker discovery using neuroproteomics techniques, and at what stage we are at in their clinical validation. In addition, we will discuss the need for strengthening the role of systems biology and its application to the field of neuroproteomics due to its integral role in establishing a comprehensive understanding of specific brain disorder and brain function in general. Finally, to achieve true clinical input of these neuroproteomic findings, these putative biomarkers should be validated using preclinical and clinical samples and linked to clinical diagnostic assays including ELISA or other high‐throughput assays.