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PubMed2025

Privacy-preserving framework for genomic computations via multi-key homomorphic encryption.

MOTIVATION: The affordability of genome sequencing and the widespread availability of genomic data have opened up new medical possibilities. Nevertheless, they also raise significant concerns regarding privacy due to the sensitive information they encompass. These privacy implications act as barriers to medical research and data availability. Researchers have proposed privacy-preserving techniques to address this, with cryptography-based methods showing the most promise. However, existing cryptography-based designs lack (i) interoperability, (ii) scalability, (iii) a high degree of privacy (i.e. compromise one to have the other), or (iv) multiparty analyses support (as most existing schemes process genomic information of each party individually). Overcoming these limitations is essential to unlocking the full potential of genomic data while ensuring privacy and data utility. Further research and development are needed to advance privacy-preserving techniques in genomics, focusing on achieving interoperability and scalability, preserving data utility, and enabling secure multiparty computation. RESULTS: This study aims to overcome the limitations of current cryptography-based techniques by employing a multi-key homomorphic encryption scheme. By utilizing this scheme, we have developed a comprehensive protocol capable of conducting diverse genomic analyses. Our protocol facilitates interoperability among individual genome processing and enables multiparty tests, analyses of genomic databases, and operations involving multiple databases. Consequently, our approach represents an innovative advancement in secure genomic data processing, offering enhanced protection and privacy measures. AVAILABILITY AND IMPLEMENTATION: All associated code and documentation are available at https://github.com/farahpoor/smkhe.

Computer Security↗
PubMed2006

ExpoFacts--an overview of European exposure factors data.

European exposure factor data have been collected in one centrally available, freely accessible site on the Internet: the ExpoFacts database (http://www.ktl.fi/expofacts/). The process of compiling the database required locating the exposure factor data and evaluating its general applicability and public availability. The scope of the ExpoFacts database covers 30 European countries, often each with its own approach for data generation and publication. The database includes information on food intake, time use, physiology, housing, and demographic parameters, as available. Information included in the database, as well as the challenges in collecting and compiling this information, are summarized. Data were found to be unavailable for ExpoFacts for a number of reasons: (1) data have not been collected, (2) collected data are not published, (3) the publishing format or language makes the data hard to locate and use, (4) copyright restrictions prevent presenting the data in an open access website, or (5) data exist, but are too expensive to acquire. Improving accessibility and harmonization of existing data would enhance the information base for exposure and risk assessments. In addition, the ExpoFacts project demonstrates a successful process for acquiring, storing, and sharing exposure factors data.

Databases, Factual↗
PubMed1994

The DNA damage-inducible dinD gene of Escherichia coli is equivalent to orfY upstream of pyrE.

The DNA damage-inducible gene dinD, originally identified by Kenyon and Walker (C. J. Kenyon and G. C. Walker, Proc. Natl. Acad. Sci. USA 77:2819-2823, 1980) by selection of the dinD::MudI (Ap lac) fusion, is shown here to be equivalent to the open reading frame orfY near pyrE. The evidence for identity between the two genes includes results from P1 transduction, Southern hybridization, and cloning and sequencing of the dinD fusion. No data were obtained that reveal any hints about the function of the dinD gene.

Bacterial Proteins↗
PubMed1996

Identification and characterization of the caiF gene encoding a potential transcriptional activator of carnitine metabolism in Escherichia coli.

Expression of the Escherichia coli caiTABCDE and fixABCX operons involved in carnitine metabolism is induced by both carnitine and anaerobiosis. When cloned into a multicopy plasmid, the 3' region adjacent to the caiTABCDE operon was found to increase levels of carnitine dehydratase activity synthesized from the chromosomal caiB gene. The nucleotide sequence was determined, and it was shown to contain an open reading frame of 393 bp named caiF which is transcribed in the direction opposite that of the cai operon. This open reading frame encodes a protein of 131 amino acids with a predicted molecular mass of 15,438 Da which does not have any significant homology with proteins available in data libraries. In vivo overexpression consistently led to the synthesis of a 16-kDa protein. The caiF gene was transcribed as a monocistronic mRNA under anaerobiosis independently of the presence of carnitine. Primer extension analysis located the start site of transcription to position 82 upstream of the caiF initiation codon. It was preceded by a cyclic AMP receptor protein motif centered at position -41.5. Overproduction of CaiF resulted in the stimulation of transcription of the divergent cai and fix operons in the presence of carnitine. This suggested that CaiF by interacting with carnitine plays the role of an activator, thereby mediating induction of carnitine metabolism. Moreover, CaiF could complement in trans the regulatory defect of laboratory strain MC4100 impaired in the carnitine pathway. Expression of a caiF-lacZ operon fusion was subject to FNR regulator-mediated anaerobic induction and cyclic AMP receptor protein activation. The histone-like protein H-NS and the NarL (plus nitrate) regulator acted as repressors. Because of the multiple controls to which the caiF gene is subjected, it appears to be a key element in the regulation of carnitine metabolism.

Acyltransferases↗
PubMed1992

Dihydrolipoamide dehydrogenase from Haloferax volcanii: gene cloning, complete primary structure, and comparison to other dihydrolipoamide dehydrogenases.

We used the N-terminal amino acid sequence of dihydrolipoamide dehydrogenase from Haloferax volcanii, to design and synthesize two oligonucleotide probes that were used to identify and clone a 4.3 kilobase pair (kbp) fragment from MboI restriction endonuclease digestion of Hf. volcanii genomic DNA. The nucleotide sequence of a 1.5-kbp region of this clone was determined and this revealed an open reading frame that translated into a protein with good homology to dihydrolipoamide dehydrogenase from other sources. The first 48 amino acids were identical with the N-terminal sequence data obtained from the purified protein. The complete primary structure of the halophilic dihydrolipoamide dehydrogenase was analyzed in terms of its homologies to dihydrolipoamide dehydrogenases from other sources and its molecular adaptations to high intracellular ionic strength.

Amino Acid Sequence↗
PubMed1992

The nucleotide sequence between genes 31 and 30 of bacteriophage T4.

The nucleotide sequence of the 2994 bp T4 phage DNA fragment between genes 31 and 30 is presented. The fragment contains 7 complete open reading frames in the direction of early transcription and two early promoters, PE128.6 and PE128.2, which we show to cause difficulties in cloning DNA from this genomic region. Our data complete the nucleotide sequence and the organization of genes in the genomic region between T4 genes 31 and 30.

Amino Acid Sequence↗
PubMed1996

Body dysmorphic disorder: diagnosis and treatment of imagined ugliness.

Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect in appearance, has been described for more than a century and reported around the world. However, this distressing and impairing disorder often goes undiagnosed, even though available data suggest that it is relatively common. Virtually any body part can be the focus of concern, with preoccupations most often involving the hair, nose, or skin. Most patients engage in excessive and repetitive behaviors such as mirror checking, skin picking, and reassurance seeking. Insight is generally poor, and many patients are frankly delusional. Most patients experience significant impairment in functioning, and suicide attempts are relatively common. Although the majority of patients with BDD seek often costly nonpsychiatric treatment-most often, surgical or dermatologic-such treatment usually appears to be unsuccessful. In contrast, preliminary data from open studies suggest that the serotonin reuptake inhibitors are often, and perhaps preferentially, effective for BDD. Augmentation, combination, and switching strategies may be useful in treatment-resistant cases. Preliminary data suggest that cognitive-behavioral strategies using exposure and response prevention may also be effective. Investigation of all aspects of this understudied disorder, including controlled treatment trials, is greatly needed.

Adult↗
PubMedDate not supplied

Open bite: a review of etiology and management.

Diagnosis and treatment of open bite malocclusion challenges pediatric dentists who attempt to intercept this malocclusion at an early age. This article updates clinicians on the causes and cures of anterior open bite based on clinical data. Patients with open bite malocclusion can be diagnosed clinically and cephalometrically, however, diagnosis should be viewed in the context of the skeletal and dental structure. Accurate classification of this malocclusion requires experience and training. Simple open bite during the exchange of primary to permanent dentition usually resolves without treatment. Complex open bites that extend farther into the premolar and molar regions, and those that do not resolve by the end of the mixed dentition years may require orthodontic and/or surgical intervention. Vertical malocclusion develops as a result of the interaction of many different etiologic factors including thumb and finger sucking, lip and tongue habits, airway obstruction, and true skeletal growth abnormalities. Treatment for open bite ranges from observation or simple habit control to complex surgical procedures. Successful identification of the etiology improves the chances of treatment success. Vertical growth is the last dimension to be completed, therefore treatment may appear to be successful at one point and fail later. Some treatment may be prolonged, if begun early. Long-term clinical outcomes are needed to determine treatment effectiveness and clinicians should consider the cost-effectiveness of these early initiated and protracted plans.

Behavior Therapy↗
PubMed2002

Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)--technique and first results.

Exact pretherapeutic lymph node staging of lung cancer is of special importance for selecting patients for neoadjuvant therapy or for video-assisted thoracoscopic resection. Staging is usually performed by computerized tomography scan and mediastinoscopy. However, these methods do not reach the accuracy of open nodal dissection. Therefore, we developed a technique of radical video-assisted mediastinoscopic lymphadenectomy (VAMLA). In a prospective study, all VAMLA procedures were documented. Lymph nodes were counted and compared to open lymphadenectomy. In 40/46 patients, radical paratracheal and subcarinal dissection was achieved by VAMLA. An average number of 20.7 (5-60, SD 11.1) nodes was gained. This is comparable to our data from open lymphadenectomy.

Adult↗
PubMed2006

Early treatment of skeletal open-bite malocclusion.

DATA SOURCES: Studies were identified by searching the Cochrane Controlled Clinical Trials Register and Medline. STUDY SELECTION: Randomised clinical trials (RCT), prospective and retrospective studies that had concurrent untreated as well as normal controls, and clinical trials that compared at least two treatment strategies but did not have any untreated or normal control group were included. The following were excluded: case series; descriptive studies; case reports; studies concerning treatment in the permanent dentition/ adult patients, surgically assisted treatment, treatment combined with extractions, treatment with full-fixed appliances; and discussion or debate articles. DATA EXTRACTION AND SYNTHESIS: Year of publication, study design, materials, dropouts, measurements, treatment time, success rate, decrease of open bite and divergence, side effects, costs, and authors' conclusions were recorded. Two independent reviewers assessed the articles independently and a quality evaluation and qualitative summary were performed. RESULTS: A total of 1049 articles were identified of which seven were included in the review. No RCT of early treatment of anterior open bite have been performed. Two controlled clinical trials of early anterior open bite were identified, and these both indicated the effectiveness of treatment in the mixed dentition with headgear or functional appliances (or both). Most of the studies had serious problems with lack of power because of small sample size, bias and confounding variables; lack of method-error analysis or blinding in measurements; and deficient or lack of statistical methods. CONCLUSIONS: The quality of the studies was insufficient to allow any evidence-based conclusions to be drawn. RCT of sufficient sample size are still needed to determine which treatment is the most effective for early correction of skeletal open bite. Future studies should also include the assessment of long-term stability as well as an analysis of the cost and side-effects of the interventions.

Comment↗
PubMed1995

DNA sequence analysis of a 13 kbp fragment of the left arm of yeast chromosome XV containing seven new open reading frames.

The sequence of a 13 kbp fragment located in the vicinity of the left telomere of chromosome XV (cosmid pEOA179) has been determined. Seven new open reading frames (ORFs) encoding polypeptides longer than 100 residues have been found (AOB629, AOA342, AOC231, AOE555, AOE236, AOA236 and AOE1045). Three of them show no identity with proteins deposited in the data banks. ORF AOB629 (629 amino acids) has some similarity with previously described ferric reductases from Saccharomyces cerevisiae and Schizosaccharomyces pombe. ORF AOA342 encodes a polypeptide reminiscent of dihydroflavonol-4-reductases from a number of plant species. AOE236 displays a high level of identity when compared with peroxisomal membrane proteins previously cloned from the methylotrophic yeast Candida boidinii. Finally, AOE1045 encodes a large protein (1045 residues) with some identity with a hypothetical 147 kDa protein identified during the sequencing of Caenorhabditis elegans chromosome 3.

Amino Acid Sequence↗
PubMed1991

Molecular cloning and characterisation of the 22-kilodalton adult Schistosoma mansoni antigen recognised by antibodies from mice protectively vaccinated with isolated tegumental surface membranes.

A cDNA clone from an adult Schistosoma mansoni lambda gt11 expression library (A12) encoding an antigenic polypeptide of 22 kDa is described. A12 is 797 bp long and has one open reading frame encoding a protein of 190 amino acids which does not contain a signal sequence or membrane anchor motif and has no homologies with any sequences on the currently available data bases. Its product (sm22.6) is recognised by antibodies from mice protectively vaccinated with purified adult S. mansoni tegumental membranes and by serum from S. mansoni-infected Brazilians. It is present in all post-snail life cycle stages except the egg, is not sex-specific, and is found in 9 species of Schistosoma, but not in a range of other helminths. Data are presented which suggest that sm22.6 is a soluble, peripheral membrane protein.

Amidohydrolases↗
PubMed1999

ATP synthase of yeast mitochondria. Isolation of subunit j and disruption of the ATP18 gene.

The subunit composition of the mitochondrial ATP synthase from Saccharomyces cerevisiae was analyzed using blue native gel electrophoresis and high resolution SDS-polyacrylamide gel electrophoresis. We report here the identification of a novel subunit of molecular mass of 6,687 Da, termed subunit j (Su j). An open reading frame of 127 base pairs (ATP18), which encodes for Su j, was identified on chromosome XIII. Su j does not display sequence similarity to ATP synthase subunits from other organisms. Data base searches, however, identified a potential homolog from Schizosaccharomyces pombe with 51% identity to Su j of S. cerevisiae. Su j, a small protein of 59 amino acid residues, has the characteristics of an integral inner membrane protein with a single transmembrane segment. Deletion of the ATP18 gene encoding Su j led to a strain (Deltasu j) completely deficient in oligomycin-sensitive ATPase activity and unable to grow on nonfermentable carbon sources. The presence of Su j is required for the stable expression of subunits 6 and f of the F0 membrane sector. In the absence of Su j, spontaneously arising rho- cells were observed that lacked also ubiquinol-cytochrome c reductase and cytochrome c oxidase activities. We conclude that Su j is a novel and essential subunit of yeast ATP synthase.

Amino Acid Sequence↗
PubMed2005

Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762].

BACKGROUND: Although serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed. METHODS: We undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks. RESULTS: There was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p < 0.0001; placebo, n = 21, p = 0.001) with 40% (n = 8) of quetiapine and 47.6% (n = 10) of placebo treated subjects being classified as responders. Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period (p = .636). Similarly quetiapine failed to separate from placebo in the subgroup of subjects (n = 10) with co-morbid tics. Quetiapine was generally well tolerated. CONCLUSIONS: In this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations.

Adolescent↗
PubMed1998

Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias.

OBJECTIVE: To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias. DATA SOURCES: A MEDLINE search (January 1960-April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: Open and controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available. DATA SYNTHESIS: Atorvastatin is a recent hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10-80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10-80 mg/d lowered LDL-C by 35-61% and triglyceride (TG) concentrations by 14-45%. In comparative trials, atorvastatin 10-80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20-40% and TG concentrations by approximately 10-30%. In pooled placebo-controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin, erythromycin, or azole antifungals. CONCLUSIONS: Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (> 1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (> 70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.

Animals↗
PubMed2002

Trauma in children and adolescents: risk and treatment of psychiatric sequelae.

The recent wave of terrorism affecting the United States and other countries raises concerns about the welfare of children and adolescents. This review is designed to address such concerns by summarizing data from two scientific areas. First, a series of recent studies examine psychiatric outcomes over time in children exposed to various forms of trauma. This review summarizes data on the various psychiatric consequences of childhood exposure to trauma, with specific emphasis on identifying factors that predict psychiatric outcome. Prior studies suggest that level of exposure, evidence of psychopathology before trauma exposure, and disruption in social support networks consistently emerge as strong predictors of psychopathology following exposure to trauma. Hence, clinicians might monitor children exposed to trauma most closely when they present with these risk factors. Second, a series of randomized controlled trials documents the beneficial effects of cognitive behavioral therapy (CBT) in children exposed to sexual abuse. When combined with other data from open studies and controlled trials in nontraumatized children, these studies suggest that CBT represents a logical therapeutic option for children developing anxiety symptoms following the recent wave of terrorism. In terms of psychopharmacological treatments, data from randomized controlled trials in traumatized children have not been generated, but recent studies in other groups of children exhibiting symptoms of anxiety or depression suggest the utility of selective serotonin reuptake inhibitors.

Child↗