Nevin Manimala

Microb Genom. 2023 Jun;9(6). doi: 10.1099/mgen.0.001028.

ABSTRACT

We delineate the evolutionary plasticity of the ecologically and biotechnologically important genus Streptomyces, by analysing the genomes of 213 species. Streptomycetes genomes demonstrate high levels of internal homology, whereas the genome of their last common ancestor was already complex. Importantly, we identify the species-specific fingerprint proteins that characterize each species. Even among closely related species, we observed high interspecies variability of chromosomal protein-coding genes, species-level core genes, accessory genes and fingerprints. Notably, secondary metabolite biosynthetic gene clusters (smBGCs), carbohydrate-active enzymes (CAZymes) and protein-coding genes bearing the rare TTA codon demonstrate high intraspecies and interspecies variability, which emphasizes the need for strain-specific genomic mining. Highly conserved genes, such as those specifying genus-level core proteins, tend to occur in the central region of the chromosome, whereas those encoding proteins with evolutionarily volatile species-level fingerprints, smBGCs, CAZymes and TTA-codon-bearing genes are often found towards the ends of the linear chromosome. Thus, the chromosomal arms emerge as the part of the genome that is mainly responsible for rapid adaptation at the species and strain level. Finally, we observed a moderate, but statistically significant, correlation between the total number of CAZymes and three categories of smBGCs (siderophores, e-Polylysin and type III lanthipeptides) that are related to competition among bacteria.

PMID:37266990 | DOI:10.1099/mgen.0.001028

JMIR Form Res. 2023 Jun 2;7:e45102. doi: 10.2196/45102.

ABSTRACT

BACKGROUND: Physician burnout is a multibillion-dollar issue in the United States. Despite its prevalence, burnout is difficult to accurately measure. Institutions generally rely on periodic surveys that are subject to recall bias. SMS text message-based surveys or assessments have been used in health care and have the advantage of easy accessibility and high response rates.

OBJECTIVE: In this pilot project, we evaluated the utility of and participant engagement with a simple, longitudinal, and SMS text message-based mental health assessment system for physician-trainees at the study institution. The goal of the SMS text message-based assessment system was to track stress, burnout, empathy, engagement, and work satisfaction levels faced by users in their normal working conditions.

METHODS: Three SMS text message-based questions per week for 5 weeks were sent to each participant. All data received were deidentified. Additionally, each participant had a deidentified personal web page to follow their scores as well as the aggregated scores of all participants over time. A 13-question optional survey was sent at the conclusion of the study to evaluate the usability of the platform. Descriptive statistics were performed.

RESULTS: In all, 81 participants were recruited and answered at least six (mean 14; median 14; range 6-16) questions for a total of 1113 responses. Overall, 10 (17%) out of 59 participants responded “Yes” to having experienced a traumatic experience during the study period. Only 3 participants ever answered being “Not at all satisfied” with their job. The highest number of responses indicating that participants were stressed or burnt out came on day 25 in the 34-day study period. There were mixed levels of concern for the privacy of responses. No substantial correlations were noted between responses and having experienced a traumatic experience during the study period. Furthermore, 12 participants responded to the optional feedback survey, and all either agreed or strongly agreed that the SMS text message-based assessment system was easy to use and the number of texts received was reasonable. None of the 12 respondents indicated that using the SMS text message-based assessment system caused stress.

CONCLUSIONS: Responses demonstrated that SMS text message-based mental health assessments are potentially useful for recording physician-trainee mental health levels in real time with minimal burden, but further study of SMS text message-based mental health assessments should address limitations such as improving response rates and clarifying participants’ sense of privacy when using the SMS text message-based assessment system. The findings of this pilot study can inform the development of institution-wide tools for assessing physician burnout and protecting physicians from occupational stress.

PMID:37266985 | DOI:10.2196/45102

Cardiovasc J Afr. 2023 Jun 2;34:1-8. doi: 10.5830/CVJA-2023-004. Online ahead of print.

ABSTRACT

BACKGROUND: Right atrial longitudinal strain (RALS) is a useful parameter to define right atrial (RA) subclinical dysfunction prior to changes in RA dimension and volume. We sought to establish normal values for RALS in a sub-Saharan African population.

METHODS: This was a retrospective, cross-sectional study from 2017 to 2019 of 100 normal individuals. All echocardiographic measurements were done as per the standard guidelines.

RESULTS: Mean RALS was 32.7 ± 10.5%. The mean RA volume indexed to body surface area was 19.5 ± 5.7 ml/m². There was a negative correlation between RALS and age but it was not statistically significant (r = -0.15, p = 0.129). Males had a tendency towards higher RA volume indexed and RALS measurements compared to females (20.8 ± 6.3 and 18.7 ± 5.2 ml/m², p = 0.07; 34.6 ± 9.6 and 31.4 ± 10.9%, p = 0.141, respectively). Body mass index was an independent predictor of RALS (r = -0.43, p = 0.003).

CONCLUSION: We have provided normative data for RALS in an African population. This study provides a platform for future larger studies on RALS.

PMID:37266978 | DOI:10.5830/CVJA-2023-004

Traffic Inj Prev. 2023 Jun 2:1-8. doi: 10.1080/15389588.2023.2218511. Online ahead of print.

ABSTRACT

OBJECTIVES: The paper aims to examine the interdependent relationship between the usage of the seatbelt restraint system and severities of the driver-injury in single-vehicle crashes.

METHODS: This paper developed a comprehensive joint econometric structure – a joint random parameters binary probit-binary probit model – that allows for the simultaneous examination of injury severity of the driver in a crash, and taking into account the fact that seat belt use can be endogenous to the outcomes of driver injury. The developed model is tested using data on drivers-injury severities involved in single-vehicle crashes in Thailand from 2012-2017.

RESULTS: In terms of the interdependent relationship between seatbelt use status and driver-injury severities, the findings suggest that drivers who do not use seat belts may demonstrate more dangerous or aggressive driving behaviors (such as speeding), subsequently increasing their likelihood of involvement in severe or fatal crashes. Additionally, the result also shows that drivers who are involved in speeding-related crashes are less likely to wear a seatbelt and have a higher risk of sustaining severe and fatal injuries. The findings also reveal that in crashes, drivers who are young, or operating trucks are less likely to be wearing their seat belts. The study also indicates that severe and fatal crashes are associated with factors such as elderly drivers, alcohol involvement, unbelted drivers, fatigue, depressed medians, and barrier medians. Conversely, a crash in a U-turn area, driving a passenger car, pickup truck, or large truck, or colliding with a guardrail reduces the likelihood of severe and fatal injuries.

CONCLUSIONS: Neglecting the hidden endogenous effect in statistical analyses could result in an overestimation of the impact of seat belt usage on crash-injury outcomes. The findings of this study can provide valuable insights for relevant authorities aiming to improve driver safety.

PMID:37266974 | DOI:10.1080/15389588.2023.2218511

JAMA Health Forum. 2023 Jun 2;4(6):e231361. doi: 10.1001/jamahealthforum.2023.1361.

NO ABSTRACT

PMID:37266962 | DOI:10.1001/jamahealthforum.2023.1361

JAMA. 2023 Jun 2. doi: 10.1001/jama.2023.7843. Online ahead of print.

ABSTRACT

IMPORTANCE: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

OBJECTIVE: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

DESIGN, SETTING, AND PARTICIPANTS: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

INTERVENTION: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

MAIN OUTCOMES AND MEASURES: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

RESULTS: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

CONCLUSIONS AND RELEVANCE: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

JAMA Netw Open. 2023 Jun 1;6(6):e2315914. doi: 10.1001/jamanetworkopen.2023.15914.

ABSTRACT

IMPORTANCE: Animal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; however, precise treatment using bisensory (auditory and somatosensory) stimuli can reverse altered neural patterns and lessen tinnitus.

OBJECTIVE: To confirm and extend the findings of a pilot study, which suggested an increased efficacy of bisensory stimulation, to a clinical trial with a greater duration and greater number of participants.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, crossover, single-center randomized clinical trial was conducted from March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System in Ann Arbor, Michigan. Eligibility criteria included bothersome tinnitus (Tinnitus Functional Index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatments in the 6 months prior to the trial. Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment. Results were analyzed using intent-to-treat (ITT) and per protocol (PP) populations.

INTERVENTION: Precisely timed bisensory (combined auditory and somatosensory) treatment was delivered through a portable, custom, take-home device that was provided to each participant for daily, at-home treatments. Group 1 participants received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Group 2 participants received the auditory-only treatment first, followed by a washout phase, and then the bisensory treatment followed by a second washout phase.

MAIN OUTCOMES AND MEASURES: Primary end points were changes in TFI score and tinnitus loudness level from baseline through week 6 and week 12.

RESULTS: Of 337 screened individuals, 99 (mean [SD] age, 47 [12.7] years; 59 males [60%]; 85 with non-Hispanic White [86%] race and ethnicity) were enrolled into the study and randomized to treatment group 1 (n = 49) or group 2 (n = 50). The active but not the control treatment resulted in clinically significant decreases in TFI scores at week 6 of phase 1 (ITT population: -12.0 [95% CI, -16.9 to -7.9] points; P < .001; PP population: -13.2 [95% CI, -16.0 to -10.5] points; P < .001). Decreases in tinnitus loudness level were greater than 6 dB sensation level (SL; >half as loud) at week 6 for the bisensory treatment group, with little effect for the auditory-only treatment control group at week 6 of phase 1 (ITT population: -5.8 [95% CI, -9.5 to -2.2] dB; P = .08; PP population: -7.2 [95% CI, -11.4 to -3.1] dB; P = .03), and up to 11 dB SL at week 12 of phase 2 (ITT population: -10.9 [95% CI, -15.2 to -6.5] dB; P = .001; PP population: -14.1 [95% CI, -18.4 to -9.8] dB; P < .001). Decreased tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect.

CONCLUSIONS AND RELEVANCE: This trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms can result from using an extended treatment duration.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03621735.

PMID:37266943 | DOI:10.1001/jamanetworkopen.2023.15914

JAMA Netw Open. 2023 Jun 1;6(6):e2316094. doi: 10.1001/jamanetworkopen.2023.16094.

ABSTRACT

IMPORTANCE: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

OBJECTIVE: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. The study was conducted at 19 cancer centers with a median (IQR) follow-up of 9.0 (7.7-9.3) years. Included patients were adults (aged ≥18 years) with NPC that was World Health Organization (WHO) histologic grade I to IIb or III, American Joint Committee on Cancer stage IIB or greater, and with or without lymph node involvement.

INTERVENTIONS: Patients received 3 cycles of bevacizumab (15 mg/kg) concurrently with standard cisplatin (100 mg/m2) and RT (69.96 Gy) followed by 3 cycles of adjuvant bevacizumab (15 mg/kg) given concurrently with cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/d).

MAIN OUTCOMES AND MEASURES: The primary end point was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary end points were locoregional progression-free (LRPF) interval, distant metastasis-free (DMF) interval, progression-free survival (PFS), overall survival (OS), and other adverse events. Long-term toxic effects and clinical outcomes were reported due to the limited follow-up in the initial report for this trial and the importance of long-term outcomes when combining bevacizumab with chemoradiation.

RESULTS: Among 46 patients with NPC who were enrolled, 44 patients were analyzed (29 males [65.9%]; 23 Asian [52.3%], 2 Black [4.5%], and 16 White [36.4%]; 38 not Hispanic [86.4%]; median [IQR] age, 48.5 [39.0-56.0] years). There were 33 patients with a Zubrod performance status of 0, indicating that they were fully functional and asymptomatic (75.0%); 32 patients with a WHO histologic grade of IIb or III (72.7%); and 39 patients with stage III or IVB disease (88.6%). Among analyzed patients, 42 individuals received radiation therapy of 69.96 Gy or greater (95.5%; dose range, 65.72-70.00 Gy); 30 patients received 3 cycles of cisplatin (68.2%) with RT, and 31 patients received 3 cycles of bevacizumab with RT (70.5%); this was followed by 3 cycles of adjuvant cisplatin in 21 patients (47.7%), fluorouracil in 24 patients (54.5%), and bevacizumab in 23 patients (52.3%). No grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter. Late grade 3 AEs occurred in 16 patients (36.4%), including 7 patients with dysphagia (15.9%), 6 patients with hearing impairment (13.6%), and 2 patients with dry mouth (4.5%). The 1- and 5-year rates of feeding tube use were 5 of 41 patients (12.2%) and 0 of 27 patients, respectively. There were 19 patients (43.2%) who progressed or died without disease progression (6 patients with locoregional progression [13.6%], 8 patients with distant progression [18.2%], and 5 patients who died without progression [11.4%]). The 5- and 7-year rates were 79.5% (95% CI, 67.6%-91.5%) and 69.7% (95% CI, 55.9%-83.5%) for OS, 61.2% (95% CI, 46.8%-75.6%) and 56.3% (95% CI, 41.5%-71.1%) for PFS, 74.9% (95% CI, 61.4%-86.6%) and 72.3% (95% CI, 58.4%-84.7%) for LRPF interval, and 79.5% (95% CI,66.4%-90.0%) for both times for DMF interval. Among 13 patients who died, death was due to disease in 8 patients (61.5%).

CONCLUSIONS AND RELEVANCE: In this nonrandomized controlled trial, no grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter among patients with NPC receiving bevacizumab combined with chemoradiation. The rate of distant metastasis was low although 89% of patients had stage III to IVB disease, suggesting that further investigation may be warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00408694.

PMID:37266942 | DOI:10.1001/jamanetworkopen.2023.16094

JAMA Netw Open. 2023 Jun 1;6(6):e2316480. doi: 10.1001/jamanetworkopen.2023.16480.

ABSTRACT

IMPORTANCE: Continuous bedside pressure mapping (CBPM) technology can assist in detecting skin areas with excessive interface pressure and inform efficient patient repositioning to prevent the development of pressure injuries (PI).

OBJECTIVE: To evaluate the efficacy of CBPM technology in reducing interface pressure and the incidence of PIs.

DESIGN, SETTING, AND PARTICIPANTS: This parallel, 2-group randomized clinical trial was performed at a tertiary acute care center. The study started to enroll participants in December 2014 and was completed in May 2018. Participants included adults partially or completely dependent for bed mobility. Statistical analysis was performed from September 2018 to December 2022.

INTERVENTION: Nursing staff using visual feedback from CBPM technology for 72 hours.

MAIN OUTCOMES AND MEASURES: Absolute number of sensing points with pressure readings greater than 40 mm Hg, mean interface pressure across all sensing points under a patient’s body, proportion of participants who had pressure readings greater than 40 mm Hg, and pressure-related skin and soft tissue changes.

RESULTS: There were 678 patients recruited. After attrition, 260 allocated to the control group (151 [58.1%] male; mean [SD] age, 61.9 [18.5] years) and 247 in the intervention group (147 [59.5%] male; mean [SD] age, 63.6 [18.1] years) were included in analyses. The absolute number of sensing points with pressures greater than 40 mm Hg were 11 033 in the control group vs 9314 in the intervention group (P = .16). The mean (SD) interface pressure was 6.80 (1.63) mm Hg in the control group vs 6.62 (1.51) mm Hg in the intervention group (P = .18). The proportion of participants who had pressure readings greater than 40 mm Hg was 99.6% in both the control and intervention groups.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial to evaluate the efficacy of CBPM technology in the reduction of interface pressure and the incidence of PIs in a tertiary acute care center, no statistically significant benefit was seen for any of the primary outcomes. These results suggest that longer duration of monitoring and adequately powered studies where CBPM feedback is integrated into a multifaceted intervention to prevent PI are needed.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02325388.

PMID:37266939 | DOI:10.1001/jamanetworkopen.2023.16480

J Vis. 2023 Jun 1;23(6):2. doi: 10.1167/jov.23.6.2.

ABSTRACT

Most studies on the perception of style have used whole scenes/entire paintings; in our study, we isolated a single motif (an apple) to reduce or even eliminate the influence of composition, iconography, and other contextual information. In this article, we empirically address two fundamental questions of the existence (Experiment 1) and description (Experiment 2) of style. We chose 48 cut-outs of mostly Western European paintings (15th to 21st century) that showed apples. In Experiment 1, 415 unique participants completed online triplet similarity tasks. Multidimensional scaling (MDS) reached a nonrandom three-dimensional (3D) embedding, showing that participants are able to judge stylistic differences in a systematic way. We also found a strong correlation between creation year and embedding, both a linear correlation with Dimension 2, and a rotational correlation in the first two dimensions. To interpret the embedding further, in Experiment 2, we fitted three color statistics and nine attribute ratings (glossiness, three-dimensionality, convincingness, brush coarseness, etc.) to the 3D perceptual style space. Results showed that Dimension 1 is associated with spatial attributes (Smoothness, Brushstroke coarseness) and Convincingness, Dimension 2 is related to Hue, and Dimension 3 is related to Chroma. The results suggest that texture and color are two important variables for style perception. By isolating the motifs, we could exclude higher levels of information such as composition and context. Interestingly, the results reinforce previous findings using whole scenes, suggesting that style can already be perceived in sometimes very small fragments of paintings.

PMID:37266933 | DOI:10.1167/jov.23.6.2