Tag: nevin manimala

Genomics Proteomics Bioinformatics. 2021 Mar 29:S1672-0229(21)00075-9. doi: 10.1016/j.gpb.2020.05.006. Online ahead of print.

ABSTRACT

Current FDA-approved kinase inhibitors cause diverse adverse effects, some of which are due to the mechanism-independent effects of these drugs. Identifying these mechanism-independent interactions could improve drug safety and support drug repurposing. We have developed iDTPnd (integrated Drug Target Predictor with negative dataset), a computational approach for large-scale discovery of novel targets for known drugs. For a given drug, we construct a positive and a negative structural signature that captures the weakly conserved structural features of drug binding sites. To facilitate assessment of unintended targets, iDTPnd also provides a docking-based interaction score and its statistical significance. We were able to confirm the interaction of sorafenib, imatinib, dasatinib, sunitinib, and pazopanib with their known targets at a sensitivity and specificity of 52% and 55%, respectively. We have validated 10 predicted novel targets by using in vitro experiments. Our results suggest that proteins other than kinases, such as nuclear receptors, cytochrome P450, or MHC Class I molecules can also be physiologically relevant targets of kinase inhibitors. Our method is general and broadly applicable for the identification of protein-small molecule interactions, when sufficient drug-target 3D data are available. The code for constructing the structural signature is available at https://sfb.kaust.edu.sa/Documents/iDTP.zip.

PMID:33794377 | DOI:10.1016/j.gpb.2020.05.006

J Surg Res. 2021 Mar 29;264:76-80. doi: 10.1016/j.jss.2021.01.036. Online ahead of print.

ABSTRACT

BACKGROUND: The emotional toll and financial cost of end-of-life care can be high. Existing literature suggests that medical providers often choose to forego many aggressive interventions and life-prolonging therapies for themselves. To further investigate this phenomenon, we compared how providers make medical decisions for themselves versus for relatives and unrelated patients.

METHODS: Between 2016 and 2019, anonymous surveys were emailed to physicians (attendings, fellows, and residents), nurse practitioners, physician assistances, and nurses at two multifacility tertiary medical centers. Participants were asked to decide how likely they would offer a tracheostomy and feeding gastrostomy to a hypothetical patient with a devastating neurological injury and an uncertain prognosis. Participants were then asked to reconsider their decision if the patient was their own family member or if they themselves were the patient. The Kruskal-Wallis H, Mann-Whitney U, and Tukey tests were used to compare quantitative data. Statistical significance was set at P < 0.05.

RESULTS: Seven hundred seventy-three surveys were completed with a 10% response rate at both institutions. Regardless of professional identity, age, or gender, providers were significantly more likely to recommend a tracheostomy and feeding gastrostomy to an unrelated patient than for themselves. Professional identity and age of the respondent did influence recommendations made to a family member.

CONCLUSIONS: We demonstrate that medical practitioners make different end-of-life care decisions for themselves compared with others. It is worth investigating further why there is such a discrepancy between what medical providers choose for themselves compared with what they recommend for others.

PMID:33794388 | DOI:10.1016/j.jss.2021.01.036

J Surg Res. 2021 Mar 29;264:99-106. doi: 10.1016/j.jss.2021.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: The foundation for a successful academic surgical career begins in medical school. We examined whether attending a top-ranked medical school is correlated with enhanced research productivity and faster career advancement among academic cardiothoracic (CT) surgeons.

MATERIALS AND METHODS: Research profiles and professional histories were obtained from publicly available sources for all CT surgery faculty at accredited US CT surgery teaching hospitals in 2018 (n = 992). We focused on surgeons who completed medical school in the United States during or after 1990, the first-year US News & World Report released its annual medical school research rankings (n = 451). Subanalyses focused on surgeons who completed a research fellowship (n = 299) and those who did not (n = 152).

RESULTS: A total of 124 surgeons (27.5%) attended a US News & World Report top 10 medical school, whereas 327 (72.5%) did not. Surgeons who studied at a top 10 medical school published more articles per year as an attending surgeon (3.2 versus 1.9; P < 0.0001), leading to more total publications (51.5 versus 27.0; P < 0.0001) and a higher H-index (16.0 versus 11.0; P < 0.0001) over a similar career duration (11.0 versus 10.0 y; P = 0.1294). These differences in career-long research productivity were statistically significant regardless of whether the surgeons completed a research fellowship or not. The surgeons in both groups, however, required a similar number of years to reach associate professor rank (P = 0.6993) and full professor rank (P = 0.7811) after starting their first attending job.

CONCLUSIONS: Attending a top-ranked medical school is associated with enhanced future research productivity but not with faster career advancement in academic CT surgery.

PMID:33794390 | DOI:10.1016/j.jss.2021.01.008

Midwifery. 2021 Mar 18;98:102966. doi: 10.1016/j.midw.2021.102966. Online ahead of print.

ABSTRACT

BACKGROUND: Continuity of Care Experiences are a mandated component of Australian midwifery programs leading to registration. Despite research evidence of the benefits of Continuity of Care Experiences for student learning and for women, there is limited evidence on the personal impact of this experience to students. Additionally, there is limited guidance on how to best support students to successfully complete this valuable component of their program.

OBJECTIVE: To identify the emotional, psychological, social and financial costs of undertaking the Continuity of Care Experience component of a midwifery program and to provide information which may lead to educational strategies within CoCE aimed to improve student support and alleviate challenges.

DESIGN: Using surveys and diary entries, a convergent parallel mixed methods approach was used to collect qualitative and quantitative data concurrently. Descriptive statistics were used to analyse financial cost, and clinical, travel and wait times. A constant comparative analysis was used for qualitative data about student’s Continuity of Care Experiences. Integrative analysis was used to reconstruct the two forms of data.

SETTING: Two Australian universities offering Bachelor of Midwifery programs.

PARTICIPANTS: Seventy students completed the demographic survey and 12 students submitted 74 diaries describing 518 episodes of care. There was a response rate of 18% recorded.

FINDINGS: Analysis identified four themes: perception of Continuity of Care Experiences; personal safety; impact on self and family; and professional relationships. The mean time spent per completed experience was 22.20 hours and the mean cost was $367.19. Although students found Continuity of Care Experiences to be a valuable learning experience, they identified numerous factors including time, money, and personal circumstances that impacted on their ability to successfully meet the requirements.

IMPLICATIONS FOR PRACTICE: Continuity of Care Experiences are a highly valuable, but often challenging component of midwifery education in Australia. Using a model of social interdependence, students, educators and maternity care providers may engage better with the process and philosophies of CoCE.

PMID:33794393 | DOI:10.1016/j.midw.2021.102966

Neuroimage. 2021 Mar 29:118009. doi: 10.1016/j.neuroimage.2021.118009. Online ahead of print.

ABSTRACT

Longitudinal non-human primate neuroimaging has the potential to greatly enhance our understanding of primate brain structure and function. Here we describe its specific strengths, compared to both cross-sectional non-human primate neuroimaging and longitudinal human neuroimaging, but also its associated challenges. We elaborate on factors guiding the use of different analytical tools, subject-specific versus age-specific templates for analyses, and issues related to statistical power.

PMID:33794361 | DOI:10.1016/j.neuroimage.2021.118009

Spine J. 2021 Mar 29:S1529-9430(21)00166-2. doi: 10.1016/j.spinee.2021.03.029. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Computer-assisted navigation (CAN) has emerged in spine surgery as an approach to improve patient outcomes. While there is substantial evidence demonstrating improved pedicle screw accuracy in CAN as compared to conventional spinal fusion (CONV), there is limited data regarding clinical outcomes and utilization trends in the United States.

PURPOSE: The purpose of this study was to determine the utilization rates of CAN in the United States, identify patient and hospital trends associated with both techniques, and to compare their results.

STUDY DESIGN: Retrospective review of national database.

PATIENT SAMPLE: Nationwide Inpatient Sample (NIS), United States national database.

OUTCOME MEASURES: CAN utilization, mortality, medical complications, neurologic complications, discharge destination, length of hospital stay, cost of hospital stay.

METHODS: The NIS database was queried to identify patients undergoing spinal fusion with CAN or CONV. CAN and CONV utilization were tracked by year and anatomic location (cervical, thoracic, lumbar/lumbosacral). Patient demographics, hospital characteristics, index length of stay (LOS), and cost of stay (COS) were compared between the cohorts. After multivariate adjustment, index hospitalization clinical outcomes were compared.

RESULTS: 4,275,413 patients underwent spinal fusion surgery during the study period (2004 to 2014). CONV was performed in 98.4% (4,208,068) of cases and CAN was performed in 1.6% (67,345) of cases. The utilization rate of CAN increased from 0.04% in 2004 to 3.3% in 2014. Overall, CAN was performed most commonly in the lumbar/lumbosacral region (70.4%) compared to the cervical (20.4%) or thoracic (9.2%) regions. When normalized to region-specific rates of fusion with any technique, the proportional utilization of CAN was highest in the thoracic spine (2.7%), followed by the lumbar/lumbosacral (2.2%) and cervical (0.9%) regions. CAN utilization was positively correlated with patient factors including increasing age and number of medical comorbidities. Multivariate adjusted clinical outcomes demonstrated that compared to CONV, CAN was associated with a statistically significant decreased risk of mortality (0.28% vs 0.31%, OR=0.67, 95% CI: 0.46-0.97, p=0.035) and increased risk of blood transfusions (9.1% vs 6.7%, OR=1.19, 95% CI: 1.02-1.39, p=0.032). However, there was no difference in risk of neurologic complications. CAN patients had an increased average LOS (4.44 days vs 3.97 days, p<0.0001) and average COS ($34,669.49 vs $26,784.62, p<0.0001) compared to CONV patients.

CONCLUSIONS: CAN utilization increased in the United States from 2004-2014. Use of CAN was proportionately higher in the thoracic and lumbar/lumbosacral regions and in older patients with more comorbidities. Given the continued trend towards increased CAN utilization, large-scale studies are needed to determine the impact of this technology on long-term clinical outcomes.

PMID:33794362 | DOI:10.1016/j.spinee.2021.03.029

J Vasc Interv Radiol. 2021 Mar 29:S1051-0443(21)00934-9. doi: 10.1016/j.jvir.2021.03.530. Online ahead of print.

ABSTRACT

PURPOSE: To determine the ability of prostatic artery embolization (PAE) to achieve freedom from catheterization in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS: This retrospective single-center study was performed between June 2014 and March 2019 in patients with lower urinary tract symptoms (LUTS) related to BPH. PAE was performed in 154 eligible patients, where 76 suffered from spontaneous AUR and had indwelling catheters placed and kept until the procedure because of the failure in the removal of the previous intermittent catheter. Each patient was followed for at least 12 months. The first trial without catheter was performed 3 days after PAE. The successful catheter removal within the first 30 days after PAE was considered as a clinical success. The rate of patients free from catheterization, LUTS relief, prostate volume (PV) and adverse events was recorded.

RESULTS: Clinical success was achieved in 70 (92.1%) patients. The rates of patients free from catheterization were 90.3% (65/72), 83.3% (60/72) and 80.6% (58/72) at 3-, 6-, and 12-month follow-up, respectively. The median period of time from PAE to catheter removal was 10 days. However, 18 patients needed further interventions. The symptom scores revealed a continuous improvement in urinary symptoms. A statistically significant decrease in mean PV was observed at 3 and 12 months compared to its baseline value. No severe adverse events occurred.

CONCLUSION: PAE can achieve freedom from catheterization in patients with AUR caused by BPH.

PMID:33794374 | DOI:10.1016/j.jvir.2021.03.530

Contemp Clin Trials. 2021 Mar 29:106377. doi: 10.1016/j.cct.2021.106377. Online ahead of print.

ABSTRACT

INTRODUCTION: Efficient management of study drug inventory shipments is critical to keep research sites enrolling into multisite clinical treatment trials. A standard manual drug-management process used by the Tuberculosis Trials Consortium (TBTC), did not accommodate import permit approval timelines, shipment transit-times and time-zone differences. We compared a new web-based solution with the manual process, during an international 34-site clinical trial conducted by the TBTC and the AIDS Clinical Trials Group (ACTG); TBTC Study 31/ACTG A5349.

MATERIAL AND METHODS: We developed and implemented a technological solution by integrating logistical and regulatory requirements for drug importation with statistical simulations that estimated stock-out times in an online Drug Management Module (DMM). We measured the average shipment-related drug stock-outs and time to drug availability, to assess the efficiency of the DMM compared to the manual approach.

RESULTS: An Interrupted Time-Series (ITS) analysis showed a 15% [p-value = 0.03; 95% C.I. (-28.8%, -2.0%)] reduction in average shipment-related study drug stock-out after DMM implementation. The DMM streamlined the restocking process at study sites, reducing median transit-time for sites associated with a depot by 2 days [95% C.I. (-3.0, -1.0)]. Under the DMM, study drugs were available for treatment assignment on the day received, compared to one day after receipt under the manual process.

DISCUSSION: The DMM provided TBTC’s Data and Coordinating Center and site staff with more efficient procedures to manage and consistently maintain study drug inventory at enrolling sites. This DMM framework can improve efficiency in future multicenter clinical trials.

TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015.

PMID:33794353 | DOI:10.1016/j.cct.2021.106377

Neuroimage. 2021 Mar 29:118004. doi: 10.1016/j.neuroimage.2021.118004. Online ahead of print.

ABSTRACT

This work presents a single-step deep-learning framework for longitudinal image analysis, coined Segis-Net. To optimally exploit information available in longitudinal data, this method concurrently learns a multi-class segmentation and nonlinear registration. Segmentation and registration are modeled using a convolutional neural network and optimized simultaneously for their mutual benefit. An objective function that optimizes spatial correspondence for the segmented structures across time-points is proposed. We applied Segis-Net to the analysis of white matter tracts from N=8045 longitudinal brain MRI datasets of 3249 elderly individuals. Segis-Net approach showed a significant increase in registration accuracy, spatio-temporal segmentation consistency, and reproducibility compared with two multistage pipelines. This also led to a significant reduction in the sample-size that would be required to achieve the same statistical power in analyzing tract-specific measures. Thus, we expect that Segis-Net can serve as a new reliable tool to support longitudinal imaging studies to investigate macro- and microstructural brain changes over time.

PMID:33794359 | DOI:10.1016/j.neuroimage.2021.118004

Neuroimage. 2021 Mar 29:117996. doi: 10.1016/j.neuroimage.2021.117996. Online ahead of print.

ABSTRACT

Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing functional networks identified by neuroimaging techniques. To aid in functional and structural data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. This anatomical scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM) with 210 primary regions-of-interest (ROIs). The subcortical parcellation and nomenclature reflect those of the 4^th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (Paxinos et al., in preparation), rather than proposing yet another novel atlas. The primary ROIs are organized across six spatial hierarchical scales from small, fine-grained ROIs to broader composites of multiple ROIs, making the SARM suitable for analysis at different resolutions and allowing broader labeling of functional signals when more accurate localization is not possible. As an example application of this atlas, we have included a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques using a visual flickering checkerboard stimulus, identifying and quantifying significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MRI data processing software, such as AFNI, where the atlas has been embedded into the software alongside cortical macaque atlases.

PMID:33794360 | DOI:10.1016/j.neuroimage.2021.117996