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An epidemiologic review of dietary intake studies among American Indians and Alaska Natives: implications for heart disease and cancer risk.

PURPOSE: Dietary factors play an important role in the occurrence of heart disease and cancer. While American Indians and Alaska Natives (AIANs) have unique heart disease and cancer mortality profiles, little is known about the effect of diet on heart disease and cancer risk in these populations. This paper reviews existing nutritional intake data from adult AIANs, and considers the potential impact of diet on heart disease and cancer in these communities. METHODS: A review of the literature was conducted using the Medline database system and other reference materials. Studies documenting nutrient intakes only were included in this review. Studies were limited to those among healthy, non-pregnant adults. RESULTS: A total of twelve reports from 1959 to 1996 were found. Sample sizes for the studies ranged from 20 to 575 subjects. Most studies were done among women, and a variety of nutritional assessment techniques (24 hour recall, food frequency questionnaire, multiple-day food record) were used. Most studies also had limited nutrient intake data, especially for dietary fiber and vitamin E. The majority of studies reported moderately high intakes of fat and saturated fat, and low intakes of polyunsaturated fat and fiber. CONCLUSIONS: Based on the limited data, diet may play an important role in the heterogeneity of heart disease and cancer mortality in AIAN communities. More research is needed to assess the impact of diet on heart disease and cancer risk, including more longitudinal data, and data to assess the validity and reliability of traditional methods of dietary assessment.

Adult

Free radicals and antioxidants in sepsis.

OBJECTIVES: The clinical condition of sepsis is caused by the release of numerous mediators from many cells. The purpose of this review is to describe the results of studies in which the role of free radicals and/or the potential therapeutic value of antioxidants are assessed. DATA SOURCES: The studies described in this review come from a variety of sources, including Med-Line CD-ROM computerized database, Index Medicus, and references identified from the bibliographies of pertinent articles and books. Reports were confined to English language articles from 1966 to 1992. STUDY SELECTION: All retrieved references in which free-radical activity was assessed or antioxidants were measured or administered in sepsis or endotoxemia were included. This selection process encompassed clinical, animal and in vitro cell culture work. DATA EXTRACTION: Cited literature was found in reputable peer-reviewed clinical or basic science journals. DATA SYNTHESIS: Any contradictions in the results of studies are discussed. CONCLUSIONS: There is evidence that free radicals play an important role in the pathogenesis of sepsis. Antioxidant therapy has the potential to protect against such injury. It is suggested that combination therapy, which augments the endogenous antioxidant defenses, is likely to be the best approach.

Animals

Classification and identification of bacteria by Fourier-transform infrared spectroscopy.

This study describes a computer-based technique for classifying and identifying bacterial samples using Fourier-transform infrared spectroscopy (FT-IR) patterns. Classification schemes were tested for selected series of bacterial strains and species from a variety of different genera. Dissimilarities between bacterial IR spectra were calculated using modified correlation coefficients. Dissimilarity matrices were used for cluster analysis, which yielded dendrograms broadly equated with conventional taxonomic classification schemes. Analyses were performed with selected strains of the taxa Staphylococcus, Streptococcus, Clostridium, Legionella and Escherichia coli in particular, and with a database containing 139 bacterial reference spectra. The latter covered a wide range of Gram-negative and Gram-positive bacteria. Unknown specimens could be identified when included in an established cluster analysis. Thirty-six clinical isolates of Staphylococcus aureus and 24 of Streptococcus faecalis were tested and all were assigned to the correct species cluster. It is concluded that: (1) FT-IR patterns can be used to type bacteria; (2) FT-IR provides data which can be treated such that classifications are similar and/or complementary to conventional classification schemes; and (3) FT-IR can be used as an easy and safe method for the rapid identification of clinical isolates.

Antigens, Bacterial

Blinking and the release reflexes: are they clinically useful?

OBJECTIVE: To review the clinical utility of blinking and the release reflexes, palmomental, glabellar, grasp, and snout, as an important part of the bedside neurological examination. DESIGN: Articles published from 1966 to 1993 that addressed blinking or the release reflexes were identified by searching the MEDLINE database. Thirty-seven references provided clinically useful and applicable information. RESULTS: There is controversy regarding the optimal method of clinical elicitation of these reflexes. The release reflexes are frequently seen as an incidental abnormality in the elderly. A positive grasp reflex, especially if asymmetrical, is sensitive but not specific for abnormal brain function. Lack of habituation is more important than the mere presence or absence of a reflex. The brainstem circuits involved in the regulation of blinking and the release reflexes are discussed, as are their abnormalities in a variety of clinical settings. CONCLUSION: Blinking and the release reflexes have clinical utility in the diagnosis and bedside clinical assessment of diseases as diverse as frontal lobe lesions, hydrocephalus, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, falls in the elderly, ageing, HIV-encephalopathy, schizophrenia, tumors in the region of the sylvian aqueduct and recovery from head trauma.

Blinking

Homogeneity of 16S-23S ribosomal intergenic spacer regions of Tropheryma whippelii in Swiss patients with Whipple's disease.

The current genetic strategies used to identify Tropheryma whippelii, the putative agent of Whipple's disease, are based on PCR-mediated amplification of a part of its 16S rRNA gene (16S rDNA). Because there is very little intraspecies variation in these molecules, they are not suitable as targets for epidemiologic investigations. However, the intergenic spacer region between the 16S and 23S rDNAs is usually much more variable and has repeatedly been used for epidemiologic purposes. We have therefore amplified the spacer region of T. whippelii directly from clinical specimens from nine independent Swiss patients with Whipple's disease by PCR with primers complementary to the 3' and 5' ends of the 16S and 23S rDNAs, respectively. The amplicons were directly sequenced and the sequences were compared to the T. whippelii reference sequence in GenBank/EMBL (accession no. X99636). Complete sequence homogeneity was found between the samples from our nine patients; the spacer sequence was also identical to the reference sequence. However, the sequences corresponding to the 3' and 5' ends of the 16S and the 23S rDNAs of T. whippelii, respectively, differed from the respective sequences in GenBank/EMBL. The same sequence found in our patients was then found in a sample from the German patient from which the published sequence had been derived. We conclude that the 16S-23S rDNA spacer region seems to be very conserved in T. whippelii and that the respective reference entry in public databases should be revised.

Actinobacteria

Palliative Mustard operation for transposition of the great arteries: late results after 15-20 years.

OBJECTIVE: To assess the clinical, functional state, and complications late (15-20 years) after palliative Mustard operation. DESIGN: Examination and evaluation of all patients presenting in adolescence and adult life after palliative Mustard operation for transposition of the great arteries and pulmonary vascular disease. SETTING: Grown-up Congenital Heart Unit specialised in the care of adolescents and adults with congenital heart disease, designated as having "quaternary" status within a tertiary referral centre for cardiac diseases. PATIENTS AND METHODS: Database searched for patients referred after palliative Mustard for classic transposition of the great arteries. Ten patients aged 18-31 (mean (SD) 25.9 (5.2)) years with a palliative Mustard operation performed at age 1.7-15 (mean (SD) 9 (4.6)) years were fully evaluated by echocardiography, exercise testing, Holter monitoring, and magnetic resonance imaging or radionuclide ventriculography, or both 15-20 years later. RESULTS: One patient died aged 25 years with biventricular failure (ability index 3/4), haemoptysis, and atrial flutter, eight were well (ability index 2), and one disabled (ability index 3). Arterial oxygen saturation at rest was 85-98% (mean (SD) 93.8 (4)%) decreasing to 59-87% (mean 77 (9.5)%) after limited exercise. Symptomatic arrhythmias occurred in four patients, atrial flutter being the most common, and two had sinus node dysfunction. Significant tricuspid regurgitation occurred in four patients. CONCLUSION: Patients with palliative Mustard operation have a low incidence of symptomatic ventricular dysfunction and despite exercise limitation by hypoxia, continue to live active, near normal lives until their thirties.

Adolescent

A systematic review of the use of computers in the management of hypertension.

STUDY OBJECTIVE: To assess the effect of computers and computer-based clinical decision support systems on the management of hypertension. DESIGN: Systematic review of randomised controlled trials. SETTING: Ambulatory hypertension clinics, community-based health centres, and general practices. PARTICIPANTS: 11,962 patients enrolled in seven trials retrieved from a systematic search (electronic databases, contact with authors, reference lists; no restriction on language). MAIN RESULTS: Individual trials report on a diverse population of patients (newly diagnosed or established hypertensive patients), interventions (computers used for case finding, recall and registration, feedback on quality of blood pressure control and prescribing information), and outcomes (administration, physician performance and blood pressure control). Four of five trials reported an improvement in patient administration using a computer. Two of three trials reported an improvement in physician performance using a computer. Two of six trials. reported an improvement in blood pressure control in patients using a computer. However, positive findings in two trials should be regarded cautiously because of the potential effects of cluster randomisation. CONCLUSIONS: It seems that computers have a favourable effect on the uptake and follow up of patients in hypertension management. The effect of computers on physician knowledge, recording of information, and blood pressure control in patients is less conclusive and further studies are required.

Decision Making, Computer-Assisted

Assessment of bibliographic databases performance in information retrieval for occupational and environmental toxicology.

OBJECTIVE: To determine the efficiency of the major bibliographic databases by assessing the percentage of references among the total literature available that can be retrieved from each database. We also evaluated the best database combinations to carry out an exhaustive search. METHODS: BIOSIS, EMBASE, MEDLINE, NIOSH-TIC, and TOXLINE were searched on two topics: allergy to latex and asbestos and mesothelioma, in the title, abstract, or keywords (textwords). This search was performed for the years 1994 and 1995. All the records were classified by journal and author's name and were verified for each record whether or not it was indexed in each database. Statistical analysis was performed with chi 2 test. RESULTS: 777 articles in 510 issues were found. The efficiency of each database (percentage of articles recovered) and of combinations varied between 11% and 63% for one database and between 42% and 86% for a combination of two databases. The reasons why these differences exist between databases, and within a database, between two different subjects or two different years are reported. CONCLUSION: Firstly, it is not advisable to assert that a bibliography is complete when only one database is searched. Secondly, the efficiency of the databases may be quite different. Finally, it is suggested that the best way to be as exhaustive as possible is to search two or more databases-for example, in EMBASE and TOXLINE, or to a lesser extent EMBASE and MEDLINE. This seems to be the best compromise solution between time consumed for searching and efficiency.

Asbestos

National genomic projects in Asia and Africa: a review.

National genome projects (NGPs) are increasingly shaping precision medicine by improving representation of population-specific genetic diversity. This review compiles findings from NGPs across Asia and Africa, regions that remain underrepresented in global genomic databases despite their extensive demographic and genetic diversity. A total of 53 studies from 24 countries were identified to understand (1) the genomic approach utilized, (2) novel findings that have emerged, and (3) strategies for improving research in these regions. The NGPs implement population-based variome databases (20 NGPs), linear reference genome assemblies (8 NGPs), and graph-based pangenome assemblies (1 NGP). Novel variants ranged between 0.28% (China) and 19.6% (Iran), whereas rare variants accounted for up to 88.9% of the detected variants in the Chinese population. Each NGP documents its country's evolutionary and migration history, which impacts disease frequency and pharmacogenomic variants. Clinically, NGPs revealed strong population stratification in disease-associated and pharmacogenomic variants. For example, the GJB2 rs72474224 hearing-loss variant ranged from 13% in Vietnam and 12% in Hong Kong to 0.0894% in Turkey, while the VKORC1 rs9923231 pharmacogenomic variant reached 89.2% in Taiwan but was 20%-25% in European-related Russian subpopulations. These findings demonstrate that clinically relevant allele frequencies, pathogenicity assessments, and drug-response markers differ substantially across ancestries. This review highlights ongoing efforts and strategies to enhance the representativeness of genomic data through NGPs in Asia and Africa. We also suggest future directions for national projects, including integrating family-based studies, multi-omic data, and standardized pipelines to accelerate discovery and support the equitable implementation of precision medicine.

Humans

Consultation-liaison psychiatry to renal medicine: work with an inpatient unit.

OBJECTIVE: To provide an overview of the work of a liaison psychiatry service to a renal medicine inpatient unit, based on a comprehensive clinical database, in order to provide a basis for comparison with similar units and to identify issues of concern. METHOD: The MICRO-CARES prospective clinical database system was used to obtain data on all patients referred to the Liaison Psychiatry Service, and the hospital clinical database was used to compare referred patients with total Renal Unit admissions in a large, suburban, university-affiliated hospital. RESULTS: Two hundred and ninety-nine inpatient referrals were made in the three years from 1990 to 1992: a referral rate of 17%. There was no bias in referral on age, sex or marital status. Coping problems (27%), depression (20%) and noncompliance (11%) were the most frequent reasons cited. Forty-five per cent of referrals required a pre-dialysis assessment. There was good agreement between consultee and consultant about noncompliance, but poorer agreement about organic brain syndromes, depression, anxiety and alcohol problems. The highest prevalence of DSM-III-R diagnoses was for V Codes (35% of Mental Disorders (23%). Referred patients had a length of stay significantly longer than that of the total admissions (20.5 days +/- 20.6 SD compared with 8.7 +2- 12.5 SD, p < .001). Psychotropic drugs were prescribed in 25% of referrals, and liaison psychiatry staff spent a mean of 181 +/- 148 SD minutes per patient, reflecting the emphasis on psychological management. The systems issues are discussed. CONCLUSIONS: The high level of complex physical/psychiatric comorbidity present and the systemic issues involved suggest that the management of patients in a renal medicine inpatient unit requires a dedicated attachment of a consultant psychiatrist-led, multidisciplinary, liaison psychiatry team which is well trained in psychodynamic issues and is comfortable with the complexity of biological issues which arise. The data provide a reliable basis for comparison with other services.

Adaptation, Psychological

Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy.

PURPOSE: To review the efficacy and safety of electrical and pharmacologic conversion of atrial fibrillation, strategies for maintenance of sinus rhythm, and the importance of antithrombotic therapy. DATA SOURCES: English-language trials were identified from the MEDLINE database through 1995, bibliographic references, Current Contents, textbooks, and recent abstracts. STUDY SELECTION: Randomized trials (including abstracts) were selected. Cohort studies were used if randomized trials were not available. DATA EXTRACTION: Study design and data were extracted from clinical trials. Statistical analysis of combined data was not appropriate, given the marked variations in study designs and study populations. DATA SYNTHESIS: Cardioversion restores sinus rhythm in more than 80% of patients. In atrial fibrillation of recent onset, pharmacologic regiments have a success rate of 40% to 90%. Sinus rhythm at 1 year is maintained in 30% of patients without antiarrhythmic therapy but in 50% of patients with such therapy. The efficacy and safety of antiarrhythmic drugs relative to one another are not established because trials done to date have been small and cases vary. Successful cardioversion and maintenance of sinus rhythm are most predictable when the duration of atrial fibrillation is brief. Warfarin reduces the incidence of ischemic strokes and emboli in patients with nonvalvular atrial fibrillation from 4.5% to 1.4% per year. Aspirin (325 mg/d) appears to be equally effective in patients younger than 75 years of age who do not have hypertension or a history of thromboembolism or recent heart failure. Although warfarin is more effective than aspirin in preventing embolic strokes in patients older than 75 years of age, it may increase the incidence of hemorrhagic stroke and result in a similar rate of disabling stroke. CONCLUSION: Cardioversion remains the preferred method with which to re-establish sinus rhythm. Long-term antiarrhythmic therapy is warranted only if recurrences or initial clinical instability are seen; pro-arrhythmic concerns and potential side effects should guide drug selection. Antithrombotic therapy is indicated for all patients older than 60 years of age and in all patients younger than 60 years of age who have clinical evidence of a primary cardiac disorder.

Algorithms

Antileukotrienes in the treatment of asthma.

PURPOSE: To review the activity in clinical models, the efficacy, and the safety of antileukotrienes as a new class of antiasthma treatment. DATA SOURCES: English-language trials identified from the archival literature, including the MEDLINE database, through 1996; bibliographic references; and textbooks. STUDY SELECTION: Reports from placebo-controlled, double-blind, randomized trials were selected. DATA EXTRACTION: Study designs and results were extracted from the clinical trial reports. Statistical evaluation of combined results was not attempted. DATA SYNTHESIS: The various classes of antileukotrienes have shown activity in clinical models of asthma, including exercise-induced, cold air hyperventilation-induced, allergen-induced, and aspirin-induced bronchoconstriction. In addition, the antileukotrienes partially reverse spontaneous bronchoconstriction in asthmatic persons, an effect additive to that of inhaled beta 2-agonists. Clinical trials of the antileukotrienes have shown clinical benefit, as measured by reductions in asthma symptom scores, improvements in air flow obstruction, and reductions in the rescue use of inhaled beta 2-agonists. Some, but not all, of the antileukotrienes have been shown to cause liver microsomal activation with increases in hepatic aminotransferase levels. CONCLUSIONS: Antileukotrienes are an important new therapy for asthma. Inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneous asthma. These results show that leukotrienes are important mediators of the asthmatic response. In addition, encouraging results have been obtained from clinical trials of antileukotrienes; however, these results do not yet provide guidelines for the optimal clinical use of antileukotrienes in asthma treatment. Such recommendations await the results of further studies.

Animals

Computerized decision support systems in primary care.

Computerized decision support can be passive or active. Passive decision support occurs when a computer facilitates access to relevant patient data or clinical knowledge for interpretation by the physician. Examples include CPR systems and reference texts or literature databases on CD-ROM. Effective passive decision support may ultimately prove to have a significant impact on physician decision making, but its potential to do so has been largely unexplored. Active decision support implies some higher level of information processing, or inference, by the computer. Examples include reminder / alert systems and diagnostic decision support systems. Inference processing in active decision support systems is generally rule-based, but probabilistic inference has been successfully used as well. Reminder systems have been consistently demonstrated to improve dramatically physician guideline compliance, generally by reducing oversight or error. The same potential for large-scale, systematic impact on physician decision-making by diagnostic decision support systems probably does not exist, but these systems may prove to be extremely useful in individual cases. Current applicability of diagnostic decision support systems to primary care is limited by the incompleteness and inaccuracies of the knowledge bases of these systems with respect to primary care. The applicability of computerized decision support in general to primary care is limited by more practical considerations. Widespread computerized decision support will not occur without CPR systems coupled with appropriate data standards and nomenclatures that will permit decision support tools to be accessed effortlessly during the routine process of patient care.

Clinical Medicine

Carbohydrate and alcohol content of 200 oral liquid medications for use in patients receiving ketogenic diets.

OBJECTIVE: The ketogenic diet is used in patients with intractable seizure disorders. To maintain a ketotic state, patients on this diet must maintain a strict low-carbohydrate intake. Because these patients often require medication, and because many pharmaceutical products (especially liquid formulations) contain significant quantities of carbohydrates, it is important that each drug product be evaluated before proceeding with the ketogenic diet. The purpose of this study was to compile the carbohydrate content of oral liquid products for patients on or considering a ketogenic diet. METHODS: A list of 200 oral liquid drug products and their manufacturers was compiled using the Children's Health Care-Minneapolis pharmacy purchasing database, the Physicians' Desk Reference, and previously published lists of oral liquid medications. Manufacturers were contacted either by telephone or by letter and asked specifically about the sucrose, fructose, sorbitol, glycerin, and alcohol content of these liquid formulations. RESULTS: The carbohydrate and alcohol content of 200 oral liquid products was determined and shown in an accompanying table. CONCLUSIONS: Many oral liquid medications contain significant amounts of carbohydrate. Tablet and capsule formulations are preferred when possible. To date, it has been difficult to quantify the carbohydrate content of liquid medications because of unavailability of this information. The carbohydrate content of 200 oral liquid medications is provided here to assist health care practitioners, patients, and care givers in designing drug regimens low in carbohydrates for patients on or considering a ketogenic diet.

Administration, Oral

Assessment of bone density in children with Scheuermann's disease.

Twenty four children with Scheuermann's disease (11 girls and 13 boys) aged 9-18 years measured for bone mineral density. The total skeleton (TB BMD) and lumbar spine (L2-L4 BMD) mineral density were investigated by dual energy X-ray absorptiometry (DEXA). In nine patients with Scheuermann's disease and backache we found lower levels of TB BMD and L2-L4 BMD in comparison with reference population of Lunar database. Osteopenia in these children may be caused by decreased physical activity due to vertebral pain.

Absorptiometry, Photon

A World Wide Web (WWW) server database engine for an organelle database, MitoDat.

We describe a simple database search engine "dbEngine" which may be used to quickly create a searchable database on a World Wide Web (WWW) server. Data may be prepared from spreadsheet programs (such as Excel, etc.) or from tables exported from relationship database systems. This Common Gateway Interface (CGI-BIN) program is used with a WWW server such as available commercially, or from National Center for Supercomputer Algorithms (NCSA) or CERN. Its capabilities include: (i) searching records by combinations of terms connected with ANDs or ORs; (ii) returning search results as hypertext links to other WWW database servers; (iii) mapping lists of literature reference identifiers to the full references; (iv) creating bidirectional hypertext links between pictures and the database. DbEngine has been used to support the MitoDat database (Mendelian and non-Mendelian inheritance associated with the Mitochondrion) on the WWW.

Computer Communication Networks

Risk factors and precipitating neck movements causing vertebrobasilar artery dissection after cervical trauma and spinal manipulation.

STUDY DESIGN: Potential precipitating events and risk factors for vertebrobasilar artery dissection were reviewed in an analysis of the English language literature published before 1993. OBJECTIVES: To assess the literature pertaining to precipitating neck movements and risk factors for vertebrobasilar artery dissection in an attempt to determine whether the incidence of these complications can be minimized. SUMMARY OF BACKGROUND DATA: Vertebrobasilar artery dissection and occlusion leading to brain stem and cerebellar ischemia and infarction are rare but often devastating complications of cervical, manipulation and neck trauma. Although various investigators have suggested potential risk factors and precipitating events, the basis for these suggestions remains unclear. METHODS: A detailed search of the literature using three computerized bibliographic databases was performed to identify English language articles from 1966 to 1993. Literature before 1966 was identified through a hand search of Index Medicus. References of articles obtained by database search were reviewed to identify additional relevant articles. Data presented in all articles meeting the inclusion criteria were summarized. RESULTS: The 367 case reports included in this study describe 160 cases of spontaneous onset, 115 cases of onset after spinal manipulation, 58 cases associated with trivial trauma, and 37 cases caused by major trauma (3 cases were classified in two categories). The nature of the precipitating trauma, neck movement, or type of manipulation that was performed was poorly defined in the literature, and it was not possible to identify a specific neck movement or trauma that would be considered the offending activity in the majority of cases. There were 208 (57%) men and 158 (43%) women (gender data not reported in one case) with an average age of 39.3 +/- 12.9 years. There was an overall prevalence of 13.4% hypertension, 6.5% migraines, 18% use of oral contraception (percent of female patients), and 4.9% smoking. In only isolated cases was specific vascular disease such as fibromuscular hyperplasia noted. CONCLUSIONS: The literature does not assist in the identification of the offending mechanical trauma, neck movement, or type of manipulation precipitating vertebrobasilar artery dissection or the identification of the patient at risk. Thus, given the current status of the literature, it is impossible to advise patients or physicians about how to avoid vertebrobasilar artery dissection when considering cervical manipulation or about specific sports or exercises that result in neck movement or trauma.

Aortic Dissection

Comparative genomics reveals hidden biosynthetic diversity in Streptomyces spp. and metal-dependent regulatory features associated with untapped specialized metabolites.

The genus Streptomyces is one of the richest sources of bioactive natural products; however, a substantial proportion of its biosynthetic gene clusters (BGCs) remain cryptic and their metabolic products are unresolved. Advances in genome mining and computational prediction now enable comprehensive exploration of this hidden biosynthetic repertoire. In this study, whole-genome sequencing and comparative genomic analyses were performed on three three newly isolated Streptomyces strains to evaluate their specialized metabolic potential. Genome assemblies were annotated and systematically analyzed using antiSMASH, DeepBGC, GECCO, and PRISM to identify, cross-validate, and functionally characterize BGCs while predicting their associated secondary metabolite scaffolds. Taxonomic analyses based on Average Nucleotide Identity (ANI), phylogenomics, and BLAST identified the isolates as Streptomyces thinghirensis, Streptomyces novocaesareae, and Streptomyces griseorubens. Applying the consensus framework across the three Streptomyces genomes yielded 43 cryptic BGCs, lacking close similarity to reference BGCs in the MIBiG database, of which 26 were classified as HIGH, 10 as MEDIUM, and 7 as LOW confidence. Notably, numerous BGCs exhibited low abundance to characterized reference clusters, indicating a high potential for previously undescribed biosynthetic pathways and novel metabolite scaffolds. Comparative analyses further revealed strain-specific biosynthetic architectures together with putative metal-responsive regulatory systems; Fur, Zur, and Nur, which were frequently associated with specialized metabolite biosynthetic loci. Collectively, these findings demonstrate the effectiveness of integrated genome-mining strategies for prioritizing cryptic biosynthetic gene clusters and highlight the remarkable biosynthetic potential of newly identified Streptomyces isolates as a source of novel natural products.

comparative genomics