DrugBank 6.0: the DrugBank Knowledgebase for 2024.

First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.

Comment on: "Variability in humpback whale songs reveals how individuals can be distinctive when sharing a complex vocal display" [J. Acoust. Soc. Am. 153, 2238-2250 (2023)].

Lamoni, Garland, Allen, Coxon, Noad, and Rendell [(2023). J. Acoust. Soc. Am. 153, 2238-2250] analyzed variations in humpback whale song structure to assess how individual singers can produce distinctive patterns that communicate desirable individual qualities to potential mates. Their analyses revealed that singers rarely produced individually specific sound patterns and that singers varied subjectively distinctive structural features of songs differently across years. These findings provide the strongest evidence to date that singing humpback whales are not varying song structure in ways that reliably reveal individual singers' physical or cognitive characteristics. Surprisingly, the authors appear to reach the opposite conclusion. Objective strategies for quantitatively comparing song properties are crucial for evaluating competing hypotheses regarding the nature and function of humpback whale songs, but the value of such strategies is reduced when the objectivity of the analyses is suspect and when negative evidence is framed as supporting prior beliefs.

Bacterial community analysis of shallow groundwater undergoing sequential anaerobic and aerobic chloroethene biotransformation.

At Department of Energy Site 300, beneficial hydrocarbon cocontaminants and favorable subsurface conditions facilitate sequential reductive dechlorination of trichloroethene (TCE) and rapid oxidation of the resultant cis-dichloroethene (cis-DCE) upon periodic oxygen influx. We assessed the geochemistry and microbial community of groundwater from across the site. Removal of cis-DCE was shown to coincide with oxygen influx in hydrocarbon-containing groundwater near the source area. Principal component analysis of contaminants and inorganic compounds showed that monitoring wells could be differentiated based upon concentrations of TCE, cis-DCE, and nitrate. Structurally similar communities were detected in groundwater from wells containing cis-DCE, high TCE, and low nitrate levels. Bacteria identified by sequencing 16S rRNA genes belonged to seven phylogenetic groups, including Alpha-, Beta-, Gamma- and Deltaproteobacteria, Nitrospira, Firmicutes and Cytophaga-Flexibacter-Bacteroidetes (CFB). Whereas members of the Burkholderiales and CFB group were abundant in all wells (10(4)-10(9) 16S rRNA gene copies L(-1)), quantitative PCR showed that Alphaproteobacteria were elevated (>10(6) L(-1)) only in wells containing hydrocarbon cocontaminants. The study shows that bacterial community structure is related to groundwater geochemistry and that Alphaproteobacteria are enriched in locales where cis-DCE removal occurs.

Sorption and bioreduction of hexavalent uranium at a military facility by the Chesapeake Bay.

Directly adjacent to the Chesapeake Bay lies the Aberdeen Proving Ground, a U.S. Army facility where testing of armor-piercing ammunitions has resulted in the deposition of >70,000 kg of depleted uranium (DU) to local soils and sediments. Results of previous environmental monitoring suggested limited mobilization in the impact area and no transport of DU into the nation's largest estuary. To determine if physical and biological reactions constitute mechanisms involved in limiting contaminant transport, the sorption and biotransformation behavior of the radionuclide was studied using geochemical modeling and laboratory microcosms (500 ppb U(VI) initially). An immediate decline in dissolved U(VI) concentrations was observed under both sterile and non-sterile conditions due to rapid association of U(VI) with natural organic matter in the sediment. Reduction of U(VI) to U(IV) occurred only in non-sterile microcosms. In the non-sterile samples, intrinsic bioreduction of uranium involved bacteria of the order Clostridiales and was only moderately enhanced by the addition of acetate (41% vs. 56% in 121 days). Overall, this study demonstrates that the migration of depleted uranium from the APG site into the Chesapeake Bay may be limited by a combination of processes that include rapid sorption of U(VI) species to natural organic matter, followed by slow, intrinsic bioreduction to U(IV).

Biosequence Similarity Search on the Mercury System.

Biosequence similarity search is an important application in modern molecular biology. Search algorithms aim to identify sets of sequences whose extensional similarity suggests a common evolutionary origin or function. The most widely used similarity search tool for biosequences is BLAST, a program designed to compare query sequences to a database. Here, we present the design of BLASTN, the version of BLAST that searches DNA sequences, on the Mercury system, an architecture that supports high-volume, high-throughput data movement off a data store and into reconfigurable hardware. An important component of application deployment on the Mercury system is the functional decomposition of the application onto both the reconfigurable hardware and the traditional processor. Both the Mercury BLASTN application design and its performance analysis are described.

Residual paralysis at the time of tracheal extubation.

Respiratory and pharyngeal muscle function are impaired during minimal neuromuscular blockade. Tracheal extubation in the presence of residual paresis may contribute to adverse respiratory events. In this investigation, we assessed the incidence and severity of residual neuromuscular block at the time of tracheal extubation. One-hundred-twenty patients presenting for gynecologic or general surgical procedures were enrolled. Neuromuscular blockade was maintained with rocuronium (visual train-of-four [TOF] count of 2) and all subjects were reversed with neostigmine at a TOF count of 2-4. TOF ratios were quantified using acceleromyography immediately before tracheal extubation, after clinicians had determined that complete neuromuscular recovery had occurred using standard clinical criteria (5-s head lift or hand grip, eye opening on command, acceptable negative inspiratory force or vital capacity breath values) and peripheral nerve stimulation (no evidence of fade with TOF or tetanic stimulation). TOF ratios were measured again on arrival to the postanesthesia care unit. Immediately before tracheal extubation, the mean TOF ratio was 0.67 +/- 0.2; among the 120 patients, 70 (58%) had a TOF ratio <0.7 and 105 (88%) had a TOF ratio <0.9. Significantly fewer patients had TOF ratios <0.7 (9 subjects, 8%) and <0.9 (38 subjects, 32%) in the postanesthesia care unit compared with the operating room (P < 0.001). Our results suggest that complete recovery from neuromuscular blockade is rarely present at the time of tracheal extubation.

Bacterial diversity in the bacterioneuston (sea surface microlayer): the bacterioneuston through the looking glass.

The bacterioneuston is defined as the community of bacteria present within the neuston or sea surface microlayer. Bacteria within this layer were sampled using a membrane filter technique and bacterial diversity was compared with that in the underlying pelagic coastal seawater using molecular ecological techniques. 16S rRNA gene libraries of approximately 500 clones were constructed from both bacterioneuston and the pelagic water samples and representative clones from each library were sequenced for comparison of bacterial diversity. The bacterioneuston was found to have a significantly lower bacterial diversity than the pelagic seawater, with only nine clone types (ecotaxa) as opposed to 46 ecotaxa in the pelagic seawater library. Surprisingly, the bacterioneuston clone library was dominated by 16S rRNA gene sequences affiliated to two groups of organisms, Vibrio spp. which accounted for over 68% of clones and Pseudoalteromonas spp. accounting for 21% of the library. The dominance of these two 16S rRNA gene sequence types within the bacterioneuston clone library was confirmed in a subsequent gene probing experiment. 16S rRNA gene probes specific for these groups of bacteria were designed and used to probe new libraries of 1000 clones from both the bacterioneuston and pelagic seawater DNA samples. This revealed that 57% of clones from the bacterioneuston library hybridized to a Vibrio sp.-specific 16S rRNA gene probe and 32% hybridized to a Pseudoalteromonas sp.-specific 16S rRNA gene probe. In contrast, the pelagic seawater library resulted in only 13% and 8% of 16S rRNA gene clones hybridizing to the Vibrio sp. and Pseudoalteromonas sp. probes respectively. Results from this study suggest that the bacterioneuston contains a distinct population of bacteria and warrants further detailed study at the molecular level.

Left ventricular mass in a patient with Carney's complex.

IMPLICATIONS: Carney's complex is characterized by cardiac myxomas, adrenocortical disease, growth hormone-secreting adenomas, and other types of tumors. Its prevalence and incidence are unknown. The anesthesiologist must examine the patient or order tests to exclude cardiac tumors, signs of excess cortisol secretion, acromegaly, and possible peripheral nerve root involvement.

Postanesthesia care unit recovery times and neuromuscular blocking drugs: a prospective study of orthopedic surgical patients randomized to receive pancuronium or rocuronium.

UNLABELLED: In this study, we examined the effect of choice of neuromuscular blocking drug (NMBD) (pancuronium versus rocuronium) on postoperative recovery times and associated adverse outcomes in patients undergoing orthopedic surgical procedures. Seventy patients were randomly allocated to a pancuronium or rocuronium group. On arrival to the postanesthesia care unit (PACU) and again 30 min later, train-of-four ratios were quantified by using acceleromyography. Immediately after acceleromyographic measurements, patients were assessed for signs and symptoms of residual paresis. During the PACU admission, episodes of hypoxemia, nausea, and vomiting were recorded. The time required for patients to meet discharge criteria and the time of actual PACU discharge were noted. Forty percent of patients in the pancuronium group had train-of-four ratios <0.7 on arrival to the PACU, compared with only 5.9% of subjects in the rocuronium group (P < 0.001). Patients in the pancuronium group were more likely to experience symptoms of muscle weakness (blurry vision and generalized weakness; P < 0.001) and hypoxemia (10 patients in the rocuronium group versus 21 patients in the pancuronium group; P = 0.015) during the PACU admission. Significant delays in meeting PACU discharge criteria (50 min [45-60 min] versus 30 min [25-40 min]) and achieving actual discharge (70 min [60-90 min] versus 57.5 min [45-61 min]) were observed when the pancuronium group was compared with the rocuronium group (P < 0.001). In conclusion, our study indicates that PACU recovery times may be prolonged when long-acting NMBDs are used in surgical patients. IMPLICATIONS: Clinical recovery may be delayed in surgical patients administered long-acting neuromuscular blocking drugs. During the postanesthesia care unit admission, patients randomized to receive pancuronium (versus rocuronium) were more likely to exhibit symptoms of muscle weakness, develop hypoxemia, and require more time to meet discharge criteria.