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GDAP: a web tool for genome-wide protein disulfide bond prediction.

The Genomic Disulfide Analysis Program (GDAP) provides web access to computationally predicted protein disulfide bonds for over one hundred microbial genomes, including both bacterial and achaeal species. In the GDAP process, sequences of unknown structure are mapped, when possible, to known homologous Protein Data Bank (PDB) structures, after which specific distance criteria are applied to predict disulfide bonds. GDAP also accepts user-supplied protein sequences and subsequently queries the PDB sequence database for the best matches, scans for possible disulfide bonds and returns the results to the client. These predictions are useful for a variety of applications and have previously been used to show a dramatic preference in certain thermophilic archaea and bacteria for disulfide bonds within intracellular proteins. Given the central role these stabilizing, covalent bonds play in such organisms, the predictions available from GDAP provide a rich data source for designing site-directed mutants with more stable thermal profiles. The GDAP web application is a gateway to this information and can be used to understand the role disulfide bonds play in protein stability both in these unusual organisms and in sequences of interest to the individual researcher. The prediction server can be accessed at http://www.doe-mbi.ucla.edu/Services/GDAP.

Archaeal Proteins↗

MotifViz: an analysis and visualization tool for motif discovery.

Detecting overrepresented known transcription factor binding motifs in a set of promoter sequences of co-regulated genes has become an important approach to deciphering transcriptional regulatory mechanisms. In this paper, we present an interactive web server, MotifViz, for three motif discovery programs, Clover, Rover and Motifish, covering most available flavors of algorithms for achieving this goal. For comparison, we have also implemented the simple motif-matching program Possum. MotifViz provides uniform and intuitive input and output formats for all four programs. It can be accessed at http://biowulf.bu.edu/MotifViz.

Algorithms↗

How many clones need to be sequenced from a single forensic or ancient DNA sample in order to determine a reliable consensus sequence?

Forensic and ancient DNA (aDNA) extracts are mixtures of endogenous aDNA, existing in more or less damaged state, and contaminant DNA. To obtain the true aDNA sequence, it is not sufficient to generate a single direct sequence of the mixture, even where the authentic aDNA is the most abundant (e.g. 25% or more) in the component mixture. Only bacterial cloning can elucidate the components of this mixture. We calculate the number of clones that need to be sampled (for various mixture ratios) in order to be confident (at various levels of confidence) to have identified the major component. We demonstrate that to be >95% confident of identifying the most abundant sequence present at 70% in the ancient sample, 20 clones must be sampled. We make recommendations and offer a free-access web-based program, which constructs the most reliable consensus sequence from the user's input clone sequences and analyses the confidence limits for each nucleotide position and for the whole consensus sequence. Accepted authentication methods must be employed in order to assess the authenticity and endogeneity of the resulting consensus sequences (e.g. quantification and replication by another laboratory, blind testing, amelogenin sex versus morphological sex, the effective use of controls, etc.) and determine whether they are indeed aDNA.

Cloning, Molecular↗

Psychological distress among homeless adults.

Recent studies have reported a high prevalence of mental illness among the homeless. As part of a community-based survey of 529 homeless adults, we developed and tested a model to increase our understanding of the factors related to their psychological distress. Using a previously validated and reliable scale of perceived psychological distress, we found that homeless adults were more likely to report psychological distress than the general population (80% vs. 49%). Distress levels were not associated with most demographic or homeless characteristics or general appearance. However, distress was related to unemployment, greater cigarette and alcohol use, worse physical health, fewer social supports, and perceived barriers to obtaining needed medical care. Since mental, physical, and social health are strongly related among homeless adults, alleviating distress among them may be most effectively done by implementing a broad-based health services package coupled with employment programs provided in an accessible service delivery setting.

Adaptation, Psychological↗

Implementing a total joint registry using personal digital assistants. A proof of concept.

The PalmPilot Data Entry System with CaptureWare was developed to collect information, such as quality-of-life surveys and standardized orthopaedic clinical evaluations, on a PalmPilot personal digital assistant (PDA). The user downloads this information directly from the PDA into a Microsoft Access Database where software programs analyze the information. Before this technology was available, manual information entry into the database from paper forms was required. This necessitated the expense of data-entry personnel and resulted in a paper quagmire. The PDA system eliminates both these problems. This article discusses general PDA use in the medical field, then describes the PalmPilot Data Entry System experience for one firm, Orthopaedic Associates, Ltd. The firm is a community-based practice, with 4 orthopaedic surgeons who have used the system for 6 months. The PDA Data Entry System was inexpensive and easy to use and, overwhelmingly, generated positive response from patients, nurses, and physicians.

Arthroplasty, Replacement↗

Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients.

PURPOSE: Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years. METHODS: Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission. RESULTS: Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035). CONCLUSION: A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.

Aged↗

Number of oral contraceptive pill packages dispensed, method continuation, and costs.

OBJECTIVE: To estimate the effect of the number of cycles of oral contraceptive pills (OCPs) dispensed per visit on method continuation, pill wastage, use of services, and health care costs. METHODS: We used paid claims data for 82,319 women dispensed OCPs through the California Family PACT (Planning, Access, Care, and Treatment) Program in January 2003 to examine contraceptive continuation and service use. RESULTS: Women who received 13 cycles at their first visit in January 2003 received 14.5 cycles over the course of 2003 compared with 9.0 cycles among women receiving three cycles at first visit. When client characteristics are controlled, women who received 13 cycles were 28% more likely to have OCPs on hand and twice as likely to have sufficient OCP cycles for 15 months of continuous use compared with women who received three cycles. Oral contraceptive pill wastage was higher among women initially dispensed 13 cycles (6.5% of the cycles dispensed) than among women who received three cycles (2% of cycles). Despite having one fewer clinician visit, women dispensed 13 cycles were more likely to receive Pap and Chlamydia tests and less likely to have a pregnancy test than women initially dispensed fewer cycles. Over the course of the year, Family PACT paid 99 US dollars more for women who received three cycles and 44 US dollars more for women who received only one cycle than it did for women who received 13 cycles at their first visits of 2003. CONCLUSION: Dispensing a year's supply of OCP cycles to women is associated with higher method continuation and lower costs than dispensing fewer cycles per visit. LEVEL OF EVIDENCE: II-2.

Adult↗

Long-term psychological outcome for non-treatment-seeking earthquake survivors in Turkey.

This study examined the incidence of posttraumatic stress disorder (PTSD) and depression in 586 earthquake survivors living in prefabricated housing sites a mean of 20 months after the 1999 earthquake in Turkey. The estimated rates of PTSD and major depression were 39% and 18%, respectively. More severe PTSD symptoms related to greater fear during the earthquake, female gender, older age, participation in rescue work, having been trapped under rubble, and personal history of psychiatric illness. More severe depression symptoms related to older age, loss of close ones, single marital status, past psychiatric illness, previous trauma experience, female gender, and family history of psychiatric illness. These findings suggest that catastrophic earthquakes have long-term psychological consequences, particularly for survivors with high levels of trauma exposure. These findings lend further support to the need for long-term mental health care policies for earthquake survivors. Outreach service delivery programs are needed to access non-treatment-seeking survivors with chronic PTSD.

Adult↗

Creating a web application that combines Framingham risk with Electron Beam CT Coronary Calcium Score to calculate a new event risk.

The Electron Beam CT (EBT) Coronary Calcium Score (CCS) is an independent predictor of coronary events and adds incremental information to standard risk factors. How to use this information was uncertain. To assist our referring physicians in utilizing this test, a web based calculator was created that combines the Framingham score risk with the EBT CCS risk to obtain a new risk for cardiac events. To create this calculator, CCS breakpoints of 0, 80, 400, and 600 were selected; and from these breakpoints, 5 ranges of calcium scores: 0, 1-80, 81-400, 401-600, and >600 were defined. Bayes theorem was used to derive equations for the combined Framingham score risk and calcium score range risk for each CCS range. The sensitivity and specificity of each of these CCS breakpoints for the prediction of events was derived from prospective studies. These equations were then translated into a JavaScript program that could be accessed from a web browser. This calculator can be easily used to restratify many individuals classified as low, intermediate, or even high risk according to the Framingham risk score system into a different risk group, allowing more appropriate matching of intervention intensity with absolute cardiovascular event risk.

Bayes Theorem↗

Artificial Intelligence for Colorectal Surgeons-Part II: Research Applications, Challenges in Adoption, and Practical Resources.

BACKGROUND: This is part II of a 2-part series examining artificial intelligence in colorectal surgery. Part I established foundational concepts and clinical applications. Implementation, however, requires understanding research methodologies, available resources, and the specific challenges currently limiting widespread adoption. These topics are the focus of part II. OBJECTIVE: To examine artificial intelligence's transformation of surgical research, provide practical implementation resources, address adoption challenges, and explore future directions in colorectal surgery. METHODS: Comprehensive literature review focusing on artificial intelligence research methodology, implementation barriers, educational resources, and emerging technologies relevant to colorectal surgeons. RESULTS: Artificial intelligence streamlines clinical trial design through predictive modeling and natural language processing, reducing enrollment challenges that contribute to failed or inadequate trial accrual. Machine learning enables heterogeneity analysis within clinical trials, identifying treatment-responsive subgroups. Foundation models unlock analysis of unstructured electronic health record data at scale. Professional societies and universities offer specialized artificial intelligence education programs, with open-access data sets facilitating research participation. However, implementation faces multifaceted challenges: technical infrastructure demands, with real-time processing requiring dedicated graphics processing unit clusters; regulatory frameworks struggling with continuously evolving algorithms; undefined liability distribution for artificial intelligence-assisted decisions; algorithmic bias risking health care disparities; and the "black box" problem limiting clinical trust. Economic barriers include substantial initial costs without clear reimbursement pathways. Future directions include multimodal artificial intelligence integrating imaging, genomics, and histopathology; cognitive robotic systems with real-time decision support; digital twin technology for patient-specific surgical simulation; and global surgical artificial intelligence networks enabling distributed learning across institutions. CONCLUSIONS: Although artificial intelligence offers transformative potential for colorectal surgery research and practice, successful implementation requires addressing technical, regulatory, ethical, and economic challenges. The surgeon's evolving role demands both traditional expertise and computational fluency. Future advances in multimodal integration, autonomous systems, and global collaboration will fundamentally reshape surgical practice but will require thoughtful implementation prioritizing patient benefit and clinical value.

Humans↗

Microcomputer statistics packages for biomedical scientists.

1. There are hundreds of commercially available microcomputer statistics packages, ranging from the very cheap and elementary to the very expensive and complex, and from the very general to the very specialized. This review covers only those that appear to be popular with biomedical investigators who deal with fairly small sets of data but may wish to use relatively complex analytical techniques. 2. It is highly desirable, if not essential, that biomedical investigators who use microcomputer statistics packages have access to a spreadsheet program. These provide sample statistics and simple statistical analyses but, more importantly, they are often the best way of entering data into the files of the statistics packages proper. 3. A vital component of any statistics package is its manual. This should be easy to follow, but at the same time it must provide full documentation of, and references to, precisely how the various statistical tests are performed. 4. Some packages are elementary and offer only a narrow range of test procedures (mini-packages). Some are designed to be used as statistical libraries and programming tools for professional statisticians. Between these extremes are the general purpose packages (mid-range, maxi- and supermaxi-packages) that constitute the main body of this review. 5. All the packages reviewed have some shortcomings or flaws. It is argued that the ideal package for biomedical investigators should have the following features: (i) it should provide a wide range of test procedures for analysing continuous, rank-ordered, and categorical data; (ii) the way in which these tests are carried out should be clearly stated in the manual; and (iii) lastly, although not unimportantly, the package should be easy to use. 6. It is recommended that biomedical investigators purchase a package that provides many more statistical routines than they use in their everyday practice. Provided the manual is a good one and the package itself has no serious flaws, this is an excellent stimulus to continuing education in statistical techniques.

Humans↗

Injury mortality in adults 25-64 years of age: implications for prevention.

The aim of this retrospective study was to identify major categories of death from injury in the age range 25 to 64 years and their potential for prevention. We analysed the Victorian Coroner's database of deaths from injury for the three years from 1989-90 to 1991-92. The major causes of death were suicide (39.9 per cent) and transport-related injury (30.2 per cent). Males accounted for 75.4 per cent of injury deaths. The highest mortality rate was in the youngest age group, 25 to 29 years. Deaths from injury in the study age range accounted for slightly more than half of all deaths from injury in Victoria, although this age group had a lower mortality rate than other age groups. Specific issues for prevention programs include reduction of access to carbon monoxide car emissions and prevention of transport-related injury to motor vehicle occupants. Data reliability issues identified in this study have implications for refinements of the Victorian Coroner's database and hence for the National Coronial Information System currently under development.

Adult↗

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.

BACKGROUND: Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. METHODS: The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. RESULTS: Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. CONCLUSIONS: These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor delays in children with FAS may be related to specific neurobehavioral deficits that affect fine motor skills. The findings support the concept of an FASD continuum in some areas of motor development.

Adaptation, Psychological↗

Design dependent loss of telemetry: uplink telemetry hold.

Bidirectional telemetry in cardiac pacing is the ability of the programmer to communicate with the pacemaker and vice versa. It is an essential capability if one is to interrogate the pacemaker as to its programmed parameters and to access the diagnostic capabilities incorporated in the present generation pacemakers. Pacemaker to programmer telemetry capability was lost in two Medtronic SymbiosR pacemakers due to a design eccentricity termed "uplink telemetry hold". It is initiated by a complex sequence of spontaneous sensed and internal timing events, once activated it cannot be reversed in the clinical setting. It is potentially dangerous in that the subsequent application of a magnet over the pacemaker can result in total output inhibition. The initiating sequence of events included activation of the "cancel magnet" command. If that command is not activated, "uplink telemetry hold" cannot occur. Once telemetry uplink hold does occur, the pulse generator should be replaced.

Equipment Design↗

Repeated DNA sequences of Aegilops markgrafii (Greuter) Hammer var. markgrafii: cloning, sequencing and analysis of distribution in Poaceae species.

Total DNA of Aegilops markgrafii (Greuter) Hammer var. markgrafii was shot gun cloned. From all the recombinants containing repetitive sequences 1-2% hybridized preferentially with the Ae. markgrafii genome and were almost absent in wheat. The cloned sequences are disperse distributed over the Aegilops chromosomes and show the typical features of eukaryotic repetitive DNA. Five specific probes were tested for their applicability in a screening program on 68 Poaceae accessions.

Base Sequence↗

Repressive effect of Sp1 on the C/EBPalpha gene promoter: role in adipocyte differentiation.

Expression of C/EBPalpha is required for differentiation of 3T3-L1 preadipocytes into adipocytes. Previous investigations indicated that transcription of the C/EBPalpha gene is sequentially activated during differentiation, initially by C/EBPbeta and C/EBPdelta and later by C/EBPalpha (autoactivation). These events are mediated by a C/EBP regulatory element in the promoter of the C/EBPalpha gene. This article presents evidence that members of the Sp family, notably Sp1, act repressively on the C/EBPalpha promoter prior to the induction of differentiation. Sp1 was shown to bind to a GC box at the 5' end of the C/EBP regulatory element in the C/EBPalpha promoter and, in so doing, to competitively prevent binding to and transactivation of the promoter by the C/EBPs. One of the differentiation inducers methylisobutylxanthine (a cAMP phosphodiesterase inhibitor) or Forskolin, both of which increase the cellular cAMP level, causes down-regulation of Sp1. This decrease in Sp1 level early in the differentiation program appears to facilitate access of C/EBPbeta and/or C/EBPdelta to the C/EBP regulatory element and, thereby, derepression of the C/EBPalpha gene.

3T3 Cells↗

Building national electronic medical record systems via the World Wide Web.

Electronic medical record systems (EMRSs) currently do not lend themselves easily to cross-institutional clinical care and research. Unique system designs coupled with a lack of standards have led to this difficulty. The authors have designed a preliminary EMRS architecture (W3-EMRS) that exploits the multiplatform, multiprotocol, client-server technology of the World Wide Web. The architecture abstracts the clinical information model and the visual presentation away from the underlying EMRS. As a result, computation upon data elements of the EMRS and their presentation are no longer tied to the underlying EMRS structures. The architecture is intended to enable implementation of programs that provide uniform access to multiple, heterogeneous legacy EMRSs. The authors have implemented an initial prototype of W3-EMRS that accesses the database of the Boston Children's Hospital Clinician's Workstation.

Boston↗