Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Comprehensive analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources
PubMed1997

Growth mechanism of the (110) face of tetragonal lysozyme crystals.

The measured macroscopic growth rates of the (110) face of tetragonal lysozyme show an unexpectedly complex dependence on the supersaturation. In earlier studies it has been shown that an aggregate growth unit could account for experimental growth-rate trends. In particular molecular packing and interactions in the growth of the crystal were favored by completion of the helices along the 4(3) axes. In this study the molecular orientations of the possible growth units and the molecular growth mechanism were identified. This indicated that growth was a two-step process: aggregate growth units corresponding to the 4(3) helix are first formed in the bulk solution by stronger intermolecular bonds and then attached to the crystal face by weaker bonds. A more comprehensive analysis of the measured (110) growth rates was also undertaken. They were compared with the predicted growth rates from several dislocation and two-dimensional nucleation growth models, employing tetramer and octamer growth units in polydisperse solutions and monomer units in monodisperse solutions. The calculations consistently showed that the measured growth rates followed the expected model relations with octamer growth units, in agreement with the predictions from the molecular level analyses.

Journal Article↗
PubMed2000

Thermal stability of Clostridium pasteurianum rubredoxin: deconvoluting the contributions of the metal site and the protein.

To provide a framework for understanding the hyperthermostability of some rubredoxins, a comprehensive analysis of the thermally induced denaturation of rubredoxin (Rd) from the mesophile, Clostridium pasteurianum was undertaken. Rds with three different metals in its M(SCys)4 site (M = Fe3+/2+, Zn2+, or Cd2+) were examined. Kinetics of metal ion release were monitored anaerobically at several fixed temperatures between 40 and 100 degrees C, and during progressive heating of the iron-containing protein. Both methods gave a thermal stability of metal binding in the order Fe2+ << Fe3+ < Zn2+ < Cd2+. The temperature at which half of the iron was released from the protein in temperature ramp experiments was 69 degrees C for Fe2+ Rd and 83 degrees C for Fe3+ Rd. Temperature-dependent changes in the protein structure were monitored by differential scanning calorimetry, tryptophan fluorescence, binding of a fluorescent hydrophobic probe, and 1H NMR. Major but reversible structural changes, consisting of swelling of the hydrophobic core and opening of a loop region, were found to occur at temperatures (50-70 degrees C) much lower than those required for loss of the metal ion. For the three divalent metal ions, the results suggest that the onset of the reversible, lower-temperature structural changes is dependent on the size of the MS4 site, whereas the final, irreversible loss of metal ion is dependent on the inherent M-SCys bond strength. In the case of Fe3+ Rd, stoichiometric Fe3+/cysteine-ligand redox chemistry also occurs during metal ion loss. The results indicate that thermally induced unfolding of the native Cp Rd must surmount a significant kinetic barrier caused by stabilizing interactions both within the protein and within the M(SCys)4 site.

Bacterial Proteins↗
PubMed2026

Upcycling Vegetable Waste Into Functional Food Ingredients via Synergistic Microbial Engineering and Artificial Intelligence.

The escalating generation of global vegetable waste represents a critical loss of bioactive resources, necessitating a paradigm shift from passive disposal to active nutrient upcycling. However, the industrial conversion of this heterogeneous biomass into standardized functional food ingredients is currently impeded by significant techno-economic barriers, primarily structural recalcitrance, compositional inconsistency, and the presence of toxic fermentation inhibitors. This review provides a comprehensive analysis of the synergistic application of microbial engineering and artificial intelligence (AI) to resolve these bioprocessing bottlenecks within a food-to-food closed-loop framework (as shown in the graphical abstract). We evaluate recent advances in engineering food-grade microbial chassis (e.g., Saccharomyces cerevisiae and Escherichia coli) to enhance lignocellulose degradation and stress tolerance. Concurrently, we examine the integration of AI across the entire value chain, covering deep learning-based rational enzyme design, genome-scale metabolic modeling, and intelligent process control for precision fermentation. Current evidence demonstrates that the hardware-software coupling of engineered strains and AI algorithms significantly enhances conversion efficiency and process robustness. Key findings highlight that AI-driven Design-Build-Test-Learn cycles facilitate the de novo creation of enzymes with superior kinetics and strains with adaptive stress response capabilities against toxins. Moreover, dynamic digital twin models effectively mitigate the impact of substrate variability, ensuring the batch-to-batch consistency required for food applications. We conclude that this data-driven synergistic paradigm is pivotal for establishing a resilient circular bioeconomy, enabling the reliable bioconversion of waste into high-value single-cell proteins, natural flavor additives, and sustainable packaging materials.

Artificial Intelligence↗
PubMed2024

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

INTRODUCTION: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism. METHODS: Ten patients with leg ulcers were included from the LETS-PAD study, in which patients with lipoprotein-controlled PAD underwent LA. Serum samples collected at baseline and 1&#x2009;month after LA were analyzed for proteomic changes. RESULTS: Six patients exhibited ulcer epithelialization and skin perfusion pressure improvement. Proteomic analysis identified 2033 proteins. Fifty-five proteins showed significant differences. B-cell lymphoma protein-2 associated X (BAX) and C-X-C motif chemokine 10 (CXCL10) were downregulated. CONCLUSION: Serum BAX and CXCL10 levels significantly decreased after LA, which may be involved in the ulcer epithelialization mechanism of LA, which potentially acts through angiogenesis promotion.

Humans↗
PubMed2026

Meiotic Origins of Non-Mosaic Klinefelter Syndrome (47, XXY): Mechanisms, Dimorphism, and Emerging Genetic Susceptibility.

BACKGROUND: Non-mosaic Klinefelter syndrome (47,XXY) arises from sex-specific meiotic mechanisms leading to nondisjunction during gametogenesis. In maternal cases, errors occur predominantly during meiosis I, frequently involving X chromosomes that lack crossovers or exhibit crossovers outside optimal chromosomal locations; this nondisjunction is further exacerbated by advancing maternal age and the subsequent deterioration of cohesins. Conversely, paternal 47,XXY stems primarily from the failure of obligate recombination within the pseudoautosomal region, which is critical for accurate XY segregation. OBJECTIVE: Drawing on the latest literature, this review transitions from a descriptive account of non-mosaic Klinefelter syndrome (nKS) toward a comprehensive analysis of mechanistic and genomic evidence, establishing a unified framework of sex-specific meiotic vulnerability. METHODS: We synthesized recent findings from forward genetic approaches in mouse models with data from human observational and reverse-genetic studies, delineating an updated view of the established and putative mechanisms that modulate sex chromosome segregation. RESULTS: We frame XX and XY nondisjunction as a genetically modulated process rather than a purely stochastic event. The integrated evidence supports a unified framework in which maternal and paternal mechanisms converge primarily on meiotic recombination failure but differ in timing, chromosomal context, and genetic modulation. CONCLUSIONS: From a clinical standpoint, identifying the molecular drivers of sex chromosome aneuploidy will enhance genetic counseling and risk stratification. Such insights are poised to facilitate informed reproductive decision-making and timely therapeutic support, ultimately reducing the burden of nKS comorbidities and improving patients' quality of life.

aneuploidy↗
PubMed2004

Match makers and deal breakers: analyses of assortative mating in newlywed couples.

We conducted a comprehensive analysis of assortative mating (i.e., the similarity between wives and husbands on a given characteristic) in a newlywed sample. These newlyweds showed (a) strong similarity in age, religiousness, and political orientation; (b) moderate similarity in education and verbal intelligence; (c) modest similarity in values; and (d) little similarity in matrix reasoning, self- and spouse-rated personality, emotional experience and expression, and attachment. Further analyses established that similarity was not simply due to background variables such as age and education and reflected initial assortment (i.e., similarity at the time of marriage) rather than convergence (i.e., increasing similarity with time). Finally, marital satisfaction primarily was a function of the rater's own traits and showed little relation to spousal similarity.

Adult↗
PubMed2004

Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique.

Specific interactions between transcription factors and cis-acting DNA sequence motifs are primary events for the transcriptional regulation. Many regulatory elements appear to diverge from the most optimal recognition sequences. To evaluate affinities of a transcription factor to various suboptimal sequences, we have developed a new detection method based on the surface plasmon resonance (SPR) imaging technique. Transcription factor MafG and its recognition sequence MARE (Maf recognition elements) were adopted to evaluate the new method. We modified DNA immobilization procedure on to the gold chip, so that a double-stranded DNA array was successfully fabricated. We further found that a hydrophilic flexible spacer composed of the poly (ethylene glycol) moiety between DNA and alkanethiol self-assembled monolayers on the surface is effective for preventing nonspecific adsorption and facilitating specific binding of MafG. Multiple interaction profiles between MafG and six of MARE-related sequences were observed by the SPR imaging technique. The kinetic values obtained by SPR imaging showed very good correlation with those obtained from electrophoretic gel mobility shift assays, although absolute values were deviated from each other. These results demonstrate that the double-stranded DNA array fabricated with the modified multistep procedure can be applied for the comprehensive analysis of the transcription factor-DNA interaction.

Binding Sites↗
PubMed2005

Characterization of HIV-1 Gag-specific T cell responses in chronically infected Indian population.

India is at the epicentre of the global HIV/AIDS epidemic in South-east Asia, predominated by subtype C infections. It is important to characterize HIV-1-specific T cell responses in this particular population with the aim of identifying protective correlates of immunity to control HIV-1 infection. In this study, we performed a comprehensive analysis of the breadth and magnitude of T cell responses directed at HIV-1 subtype C Gag, one of the most conserved HIV-1 proteins. The study population consisted of antiretroviral naive, chronic HIV-1 subtype C-infected individuals at various stages of infection. We used recent advanced techniques such as enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining to quantify the total CD4(+) and CD8(+) T cell response to HIV-1 gag at single peptide level, regardless of HLA haplotype of the infected individual. The p24-Gag was identified as the most frequently recognized subunit protein with the greatest magnitude of CD4(+) and CD8(+) T cell responses. Stronger and broader CD8 T cell responses were recognized, contrasting with the weaker and narrower CD4 T cell responses with regard to Gag protein subunits. The magnitude of the HIV-specific interferon (IFN)-gamma responses was observed to be higher than the corresponding interleukin (IL)-2 response, indicating the persistence of antigenic load in chronically infected Indian population due to the probable dysfunction of HIV-specific, IFN-gamma-secreting CD8 T cells in absence of IL-2 help.

Adult↗
PubMed2006

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Adenoma↗
PubMed2004

Expression, by functional proteomics, of spontaneous tolerance in rat orthotopic liver transplantation.

Orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, such as DA (RT1a) to PVG (RT1c), without immunosuppressive drugs could completely overcome major histocompatibility complex barriers. Although other organs transplanted in a similar fashion within the same combination have been promptly rejected, 60 day post-OLT serum (POD 60) has been proven competent in rapidly reversing the established rejection in animal models. In order to understand the functional role of tolerogenic serum proteins and their involvement with immune response regulation, a comprehensive analysis surveying global changes in complex OLT systems by proteomic techniques was applied. The results display the varying protein expressions in sera extracted from naïve and transplanted animals on POD 60 with regard to immunosuppression. Among these proteins, haptoglobin (Hp) which is related to inhibition of T-cell proliferation was found to be up-regulated following OLT. In addition, the transcriptional expression level and intracellular localization of Hp correlated with the immune events. Hp also exhibited a strong in vitro immunosuppressive effect on the mixed lymphocyte reaction. In conclusion, the presence of Hp may play an important role in modulating the spontaneous tolerance of liver transplantation. Furthermore, the serum proteome map could provide guidance with respect to discovering potential protein targets in OLT tolerance and eventually prolong hepatic allograft survival in the future.

Amino Acid Sequence↗
PubMed1996

Preventing sleep problems in infants: a randomized controlled trial.

In the pre-school years sleep problems are one of the most common subjects on which parents seek advice from health professionals. In the majority of cases a sleepless child causes significant stress within the family, and if parents do not obtain sufficient sleep this can have a detrimental effect on their physical and emotional well-being. In a small number of cases a child who wakes frequently and will not settle back to sleep may be at risk of physical abuse. In recent years it has been suggested that it may be possible to prevent sleep problems developing by providing parents with advice in the post-natal period. Parents have stated that they find this type of intervention helpful, however, there has been no attempt to establish whether a preventive approach is effective. The aim of this research was to evaluate the efficacy of health education in reducing the incidence of sleep problems. Adopting an experimental approach, participants were randomly allocated to a control group or an intervention group. Parental knowledge of sleep and settling behaviour was manipulated when the children in the intervention group were 3 months old. The sleeping behaviour of the infants in both groups was compared 6 months later, when the children were 9 months old. Data was collected from 86 families in the intervention group and 83 families in the control group. A comprehensive analysis of the sleeping behaviour demonstrated that a significantly smaller percentage of babies in the intervention group had settling and night-waking difficulties than in the control group.

Child Behavior Disorders↗
PubMed2006

Vision, leadership and partnership: how to enhance the nursing and midwifery contribution to research and development.

AIM: This paper reports an evaluation of nursing and midwifery research and development activity in Northern Ireland. BACKGROUND: Research and development is integral to the quality of patient care. Nurses and midwives have an important contribution to make and, whilst the professional landscape has changed significantly, with improved funding and productivity, there remains much room for improvement. To advance this agenda it is necessary to evaluate progress across the spectrum of research and development activity. The policy literature gives examples of the methods by which this can be achieved, but there is less evidence about evaluation criteria, or the methods by which research and development progress is assessed at organizational, national and international levels. METHOD: A comprehensive analysis of the literature was undertaken to develop a 'Research and Development Best Practice Framework'. This was then used as the basis for structured interviews with 32 organizational leads for three main stakeholder groups: health and care providers (n = 20), education providers (n = 7) and funders of research and development (n = 5). Data collection was from March to November 2004. FINDINGS: Despite general recognition of its value, only a minority of organizations had an up-to-date corporate strategy that included nursing and midwifery research and development. There was considerable variability in the systems, support structures, capacity and productivity of nurses and midwives throughout these organizations. In most, no-one had sole responsibility for leading the professional research and development agenda but, where such leadership was in place, improved outcomes were apparent. Building effective partnerships for research and development and forward planning through developing an organizational strategy were also key indicators of success. CONCLUSION: Our findings confirm progress, but also reinforce the need to develop a clear vision, enhance leadership potential and forge effective partnerships to advance the research and development agenda in nursing and midwifery.

Attitude of Health Personnel↗
PubMed2006

Beyond 'faith-based medicine' and EBM.

RATIONALE, AIMS AND OBJECTIVES: Longstanding debate on evidence-based medicine (EBM) may have reached a critical saturation point. I briefly report on systematic reviews on the recurring themes in the critical literature. In this context, some criticisms to EBM are substantial and enduring, although convincing arguments to contrast unresolved issues have yet to be produced. Nonetheless, few changes have been adopted and conservative attitudes persist in EBM. Despite its 'success', implementation in practice has been inexorably overshadowed leading to paradoxical shortcomings. This controversial scenario offers a formidable occasion to gain needed insight. The aim of this paper is to attempt a comprehensive analysis by reframing a number of key concerns, while furnishing pragmatic, interdisciplinary solutions for these deep-rooted dilemmas. In the interests of all stakeholders, I seek to promote a concerted effort to resolve conflict and build consensus. METHODS: This paper explores a strategically unifying vision of primary care, based on current understanding of practice patterns, having a research-friendly 'common ground' where practitioners' information needs may be met. In addition, an analysis of existing problems identifies underlying 'root causes'. Moreover, I expediently reframe crucial matters by focusing on EBM, more than as a paradigm, as an organisation, hence amenable to a variety of cross-disciplinary analyses and solutions. Finally, recent state-of-the-art reviews on implementation and dissemination research are cited for the pertinent implications for study design and practice. RESULTS: Present policies and influential testimonials on behalf of EBM encounter the pitfalls of hindering learning and progress through defensive attitudes and mechanisms. Current study designs and evaluation criteria must strive to adapt to real-world settings, rather than vice versa. CONCLUSIONS: The arguments exposed herein alter the terms of the debate on EBM and may outline a basis for initiatives with conflict-resolution and consensus-building scopes.

Consensus↗
PubMed2005

Future trends of HCV-related cirrhosis and hepatocellular carcinoma under the currently available treatments.

SUMMARY: The epidemic of hepatitis C virus (HCV) infection is a major public health issue. We conducted a comprehensive analysis to estimate future HCV-related morbidity and mortality, using a model which is the first to take into account currently available treatments. We reconstructed the incident infections per year in the past that progressed to chronic hepatitis C (CHC) in Greece. Then, the natural history of the disease was simulated in subcohorts of newly infected subjects in the presence or absence of treatment using yearly estimates of the number of treated patients obtained from national databases. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, hepatocellular carcinoma (HCC) and mortality were obtained up to 2030. The current proportion of naïve CHC patients receiving treatment in Greece is 1.2% per year. Treatment of 1.2-10% of naïve CHC patients per year would reduce the cumulative number of incident cirrhosis and HCC cases from 2002 to 2030 by 10.8-39.4% and 12.8-39.8%, respectively and decrease the number of prevalent cirrhosis and HCC cases in 2030 by approximately 17-48% compared with the number estimated under the assumption of no treatment. Approximately 17 cirrhosis cases or six HCC cases or 10 premature deaths would be prevented for every 100 treated patients. However, the prevalent cirrhotic/HCC cases because of HCV and HCV-related deaths would not plateau until 2030. Despite the introduction of effective treatment, HCV-related morbidity and mortality will likely increase during the next 20-30 years in Greece. Intensive primary prevention efforts coupled with increased access to the currently available treatments are necessary to control the chronic consequences of HCV epidemic.

Carcinoma, Hepatocellular↗
PubMed1981

Review of psychometric features of the Medical School Learning Environment Survey.

Growing concern over the stresses imposed on medical students by their undergraduate educational programme has led to a proliferation of surveys designed to measure students' global perceptions of the medical school as a learning environment. The present study aimed at a comprehensive analysis of the psychometric features of a recently-introduced questionnaire. Students at four Australian medical schools completed the Medical School Learning Environment Survey (Marshall, 1978). Data on the retest reliability, internal consistency and factorial validity of the MSLES are presented. Its potential usefulness for future evaluations within and between medical schools is discussed.

Australia↗
PubMed2005

The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae.

The pilin antigenic variation (Av) system of Neisseria gonorrhoeae (Gc) mediates unidirectional DNA recombination from silent gene copies into the pilin expression locus. A DNA sequencing assay was developed to accurately measure pilin Av in a population of Gc strain FA1090 arising from a defined pilin progenitor under non-selective culture conditions. This assay employs a piliated parental Gc variant with a recA allele whose promoter is replaced by lac-regulatory elements, allowing for controlled induction of pilin Av. From this assay, the frequency of pilin Av was measured as 0.13 recombination events per cell, with a corresponding rate of pilin Av of 4x10(-3) events per cell per generation. Most pilin variants retained the parental piliation phenotype, providing the first comprehensive analysis of piliated variants arising from a piliated progenitor. Sequence analysis of pilin variants revealed that a subset of possible recombination events predominated, which differed between piliated and non-piliated progeny. Pilin Av exhibits the highest reported frequency of any pathogenic gene conversion system and can account for the extensive pilin variation detected during human infection.

Antigenic Variation↗
PubMed2005

Cell wall integrity is dependent on the PKC1 signal transduction pathway in Cryptococcus neoformans.

Cell wall biogenesis and integrity are crucial for fungal growth, pathogenesis and survival, and are attractive targets for antifungal therapy. In this study, we identify, delete and analyse mutant strains for 10 genes involved in the PKC1 signal transduction pathway and its regulation in Cryptococcus neoformans. The kinases Bck1 and Mkk2 are critical for maintaining integrity, and deletion of each of these causes severe phenotypes different from each other. In stark contrast to results seen in Saccharomyces cerevisiae, a deletion in LRG1 has severe repercussions for the cell, and one in ROM2 has little effect. Also surprisingly, the phosphatase Ppg1 is crucial for cell integrity. These data indicate that the mechanisms of maintaining cell integrity differ between the two fungi. Deletions in SSD1 and PUF4, potential alternative regulators of cell integrity, also exhibit phenotypes. This is the first comprehensive analysis examining genes involved the maintenance of cell integrity in C. neoformans and sets the foundation for future biochemical and virulence studies.

Animals↗
PubMed2006

A family of oligopeptide transporters is required for growth of Candida albicans on proteins.

The human fungal pathogen Candida albicans can use proteins as the sole source of nitrogen for growth. The secretion of aspartic proteinases, which have been shown to contribute to virulence of C. albicans, allows the fungus to digest host proteins to produce peptides that must be taken up into the cell by specific transporters. To understand in more detail how C. albicans utilizes proteins as a nitrogen source, we undertook a comprehensive analysis of oligopeptide transporters encoded in the C. albicans genome. We identified eight OPT genes encoding putative oligopeptide transporters, almost all of which are represented by polymorphic alleles in strain SC5314. Expression of these genes was differentially induced when C. albicans was grown in YCB-BSA medium, which contains bovine serum albumin as the sole nitrogen source. Whereas deletion of single OPT genes in strain SC5314 did not affect its ability to utilize proteins as a nitrogen source, opt123delta triple mutants had a severe growth defect in YCB-BSA which was rescued by reintroduction of a single copy of OPT1, OPT2 or OPT3. In addition, forced expression of OPT4 or OPT5 under control of the ADH1 promoter also restored growth of an opt123delta mutant, demonstrating that at least OPT1-OPT5 encode functional peptide transporters. The various oligopeptide transporters differ in their substrate preferences, as shown by the ability of strains expressing specific OPT genes to grow on peptides of defined length and sequence. We present evidence that in addition to the known role of oligopeptide transporters in the uptake of tetra- and pentapeptides these proteins can also transport longer peptides up to at least eight amino acids in length, ensuring an efficient utilization of the various peptides produced via endoproteolytic digestion of proteins by the secreted aspartic proteinases. As even transporters encoded by polymorphic alleles of a single gene exhibited differences in their efficiency to take up specific peptides, the oligopeptide transporters represent an example for how the evolution of gene families containing differentially expressed and functionally optimized members increases the nutritional versatility and, presumably, the adaptation of C. albicans to different host niches.

Biological Transport↗