PCOM Library / Archive for "Hot Topics in Research"

Category: Hot Topics in Research

Hot Topics: Keywords Reveal Upcoming Research Trends

Jackie Werner Hot Topics in Research, Research and Scholarly Communication

Generating process of emerging topics in the life sciences

Ohniwa, R. L., & Hibino, A. (2019). Generating process of emerging topics in the life sciences. Scientometrics, https://dx.doi.org/10.1007/s11192-019-03248-z

Clarifying the mechanism of how emerging topics in science and technology research fields are generated is useful for both researchers and agencies to identify potential emerging topics of the future. In the present study, we use bibliometric analyses targeting data of about 30 million published articles from 1970 to 2017 on PubMed, the largest article database in the life science field, to test our hypothesis that existing emerging topics contribute to the generation of new emerging topics in that field. We first collected emerging keywords from medical subject headings attached to each article using our previously reported methodology (Ohniwa et al. in Scientometrics 85(1):111–127, 2010), and performed co-word analyses of each emerging keyword 1-year prior to it becoming an emerging keyword. About 75% of total emerging keywords, at 1-year prior to becoming identified as emerging, co-appeared with other emerging keywords in the same article. Furthermore, most of the keywords co-appeared again at the point when the target keyword was identified as emerging, which is consistent with our hypothesis regarding the mechanism that emerging topics generate emerging topics.

Hot Topics: Long-Held Perception Theory Disproven

Jackie Werner Hot Topics in Research, Otolaryngology

Rapid visual categorization is not guided by early salience-based selection

Tsotsos, J. K., Kotseruba, I., & Wloka, C. (2019). Rapid visual categorization is not guided by early salience-based selection. Plos One, 14(10), e0224306. https://doi.org/10.1371/journal.pone.0224306

The current dominant visual processing paradigm in both human and machine research is the feedforward, layered hierarchy of neural-like processing elements. Within this paradigm, visual saliency is seen by many to have a specific role, namely that of early selection. Early selection is thought to enable very fast visual performance by limiting processing to only the most salient candidate portions of an image. This strategy has led to a plethora of saliency algorithms that have indeed improved processing time efficiency in machine algorithms, which in turn have strengthened the suggestion that human vision also employs a similar early selection strategy. However, at least one set of critical tests of this idea has never been performed with respect to the role of early selection in human vision. How would the best of the current saliency models perform on the stimuli used by experimentalists who first provided evidence for this visual processing paradigm? Would the algorithms really provide correct candidate sub-images to enable fast categorization on those same images? Do humans really need this early selection for their impressive performance? Here, we report on a new series of tests of these questions whose results suggest that it is quite unlikely that such an early selection process has any role in human rapid visual categorization.

Hot Topics: ACE Inhibitors Less Effective for Hypertension

Jackie Werner Family Medicine, Hot Topics in Research, Pharmaceutical Sciences

Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis

Suchard, M. A., Schuemie, M. J., Krumholz, H. M., You, S. C., Chen, R., Pratt, N., . . . Ryan, P. B. (2019). Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: A systematic, multinational, large-scale analysis https://doi.org/10.1016/S0140-6736(19)32317-7

Background

Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice.

Methods

We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested.

Findings

Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75–0·95), hospitalisation for heart failure (0·83, 0·74–0·95), and stroke (0·83, 0·74–0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes.

Interpretation

This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension—in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers.

Hot Topics: Flavored Vapes Hook Teens

Jackie Werner Hot Topics in Research, Pediatrics, Substance Use Disorders

Flavored E-cigarette Use and Progression of Vaping in Adolescents

Leventhal, A. M., Goldenson, N. I., Cho, J., Kirkpatrick, M. G., McConnell, R. S., Stone, M. D., . . . Barrington-Trimis, J. L. (2019). Flavored E-cigarette use and progression of vaping in adolescents. Pediatrics. https://dx.doi.org/10.1542/peds.2019-0789

OBJECTIVES: Electronic cigarettes (e-cigarettes) are available in nontraditional flavors (eg, fruit and candy) that are banned in combustible cigarettes in the United States. Whether adolescent use of e-cigarettes in nontraditional flavors prospectively predicts continuation of vaping and progression to more frequent vaping is unknown.

METHODS: High school students in Los Angeles, California, completed 5 semiannual surveys (2014–2017 [10th grade to 12th grade]). Among past-6-month e-cigarette users at survey waves 1 to 4 (N = 478), e-cigarette flavor (or flavors) used was coded into 2 mutually exclusive categories at each wave (use of ≥1 nontraditional flavors [fruit, candy, sweet or dessert, buttery, blends or combinations, and other] versus exclusive use of tobacco, menthol or mint, or flavorless). Flavor used during waves 1 to 4 was modeled as a time-varying, time-lagged regressor of vaping status and frequency outcomes 6 months later at waves 2 to 5.

RESULTS: Across waves 1 to 4, there were 739 (93.8%) observations of nontraditional-flavor use and 49 (6.2%) observations of exclusive use of tobacco, mint or menthol, or flavorless e-cigarettes. Use of e-cigarettes in nontraditional flavors (versus only tobacco, mint or menthol, or flavorless) was positively associated with vaping continuation (64.3% vs 42.9%; adjusted odds ratio = 3.76 [95% confidence interval 1.20 to 10.31]) and past-30-day number of puffs per nicotine vaping episode (mean: 3.1 [SD 5.5] vs 1.5 [SD 3.8]; adjusted rate ratio = 2.41 [95% confidence interval 1.08 to 5.92]) 6 months later. Flavor used was not associated with the subsequent number of past-30-day vaping days or episodes per day.

CONCLUSIONS: Adolescents who vaped e-cigarettes in nontraditional flavors, compared with those who exclusively vaped tobacco-flavored, mint- or menthol-flavored, or flavorless e-cigarettes, were more likely to continue vaping and take more puffs per vaping occasion 6 months later.

Hot Topics: Stress Influences Circadian Clock

Jackie Werner Hot Topics in Research, Psychology and Psychiatry

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4

Pathak, S. S., Liu, D., Li, T., de Zavalia, N., Zhu, L., Li, J., . . . Cao, R. (2019). The eIF2α kinase GCN2 modulates period and rhythmicity of the circadian clock by translational control of Atf4https://doi.org/10.1016/j.neuron.2019.08.007

The integrated stress response (ISR) is activated in response to diverse stress stimuli to maintain homeostasis in neurons. Central to this process is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Here, we report a critical role for ISR in regulating the mammalian circadian clock. The eIF2α kinase GCN2 rhythmically phosphorylates eIF2α in the suprachiasmatic circadian clock. Increased eIF2α phosphorylation shortens the circadian period in both fibroblasts and mice, whereas reduced eIF2α phosphorylation lengthens the circadian period and impairs circadian rhythmicity in animals. Mechanistically, phosphorylation of eIF2α promotes mRNA translation of Atf4. ATF4 binding motifs are identified in multiple clock genes, including Per2Per3Cry1Cry2, and Clock. ATF4 binds to the TTGCAGCA motif in the Per2 promoter and activates its transcription. Together, these results demonstrate a significant role for ISR in circadian physiology and provide a potential link between dysregulated ISR and circadian dysfunction in brain diseases.

Hot Topics: Determining the Best Option for Broken Hips

Jackie Werner Hot Topics in Research, Orthopedics, Surgery

Total Hip Arthroplasty or Hemiarthroplasty for Hip Fracture

The HEALTH Investigators. (2019). Total hip arthroplasty or hemiarthroplasty for hip fracture. N Engl J Med, https://doi.org/10.1056/NEJMoa1906190

BACKGROUND

Globally, hip fractures are among the top 10 causes of disability in adults. For displaced femoral neck fractures, there remains uncertainty regarding the effect of a total hip arthroplasty as compared with hemiarthroplasty.

METHODS

We randomly assigned 1495 patients who were 50 years of age or older and had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty. All enrolled patients had been able to ambulate without the assistance of another person before the fracture occurred. The trial was conducted in 80 centers in 10 countries. The primary end point was a secondary hip procedure within 24 months of follow-up. Secondary end points included death, serious adverse events, hip-related complications, health-related quality of life, function, and overall health end points.

RESULTS

The primary end point occurred in 57 of 718 patients (7.9%) who were randomly assigned to total hip arthroplasty and 60 of 723 patients (8.3%) who were randomly assigned to hemiarthroplasty (hazard ratio, 0.95; 95% confidence interval [CI], 0.64 to 1.40; P=0.79). Hip instability or dislocation occurred in 34 patients (4.7%) assigned to total hip arthroplasty and 17 patients (2.4%) assigned to hemiarthroplasty (hazard ratio, 2.00; 99% CI, 0.97 to 4.09). Function, as measured with the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, pain score, stiffness score, and function score, modestly favored total hip arthroplasty over hemiarthroplasty. Mortality was similar in the two treatment groups (14.3% among the patients assigned to total hip arthroplasty and 13.1% among those assigned to hemiarthroplasty, P=0.48). Serious adverse events occurred in 300 patients (41.8%) assigned to total hip arthroplasty and in 265 patients (36.7%) assigned to hemiarthroplasty.

CONCLUSIONS

Among independently ambulating patients with displaced femoral neck fractures, the incidence of secondary procedures did not differ significantly between patients who were randomly assigned to undergo total hip arthroplasty and those who were assigned to undergo hemiarthroplasty, and total hip arthroplasty provided a clinically unimportant improvement over hemiarthroplasty in function and quality of life over 24 months.

Hot Topics: Asthma Guidelines Inadequate for Black Children

Jackie Werner Hot Topics in Research, Pediatrics

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Wechsler, M. E., Szefler, S. J., Ortega, V. E., Pongracic, J. A., Chinchilli, V., Lima, J. J., . . . Israel, E. (2019). Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med, 381(13), 1227-1239. https://doi.org/10.1056/NEJMoa1905560

BACKGROUND

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P=0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol–low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P=0.003]; salmeterol–medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P=0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA.


Hot Topics: Advances in Gene Therapy for Vision Loss

Jackie Werner Hot Topics in Research

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Ding, K., Shen, J., Hafiz, Z., Hackett, S. F., Lima, e. S., Khan, M., . . . Campochiaro, P. A. (2019). AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. The Journal of Clinical Investigation, https://doi.org/10.1172/JCI129085

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8.GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti-VEGF Fab and similar suppression of VEGF-induced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE.

Hot Topics: New Factors Could Reverse Arterial Plaque Buildup

Jackie Werner Cardiology, Hot Topics in Research

Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis

Chen, P., Qin, L., Li, G., Wang, Z., Dahlman, J. E., Malagon-Lopez, J., . . . Simons, M. (2019). Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism, http://doi.org/10.1038/s42255-019-0102-3

Atherosclerosis is a progressive vascular disease triggered by interplay between abnormal shear stress and endothelial lipid retention. A combination of these and, potentially, other factors leads to a chronic inflammatory response in the vessel wall, which is thought to be responsible for disease progression characterized by a buildup of atherosclerotic plaques. Yet molecular events responsible for maintenance of plaque inflammation and plaque growth have not been fully defined. Here we show that endothelial transforming growh factor β (TGF-β) signalling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGF-β signalling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. These proinflammatory effects of endothelial TGF-β signalling are in stark contrast with its effects in other cell types and identify it as an important driver of atherosclerotic plaque growth and show the potential of cell-type-specific therapeutic intervention aimed at control of this disease.

Hot Topics: Cannabis Use in Teen Cancer Patients Increasing

Jackie Werner Hot Topics in Research, Oncology

Cannabis Use in Young Adult Cancer Patients

Donovan, K. A., Oberoi-Jassal, R., Chang, Y. D., Rajasekhara, S., Haas, M. F., Randich, A. L., & Portman, D. G. (2019). Cannabis use in young adult cancer patients. Journal of Adolescent and Young Adult Oncologyhttp://doi.org/10.1089/jayao.2019.0039

Background: The use of cannabis by young adult (YA) cancer patients is likely to increase as medical cannabis becomes more available. Clinically relevant data on cannabis use are needed to establish benchmarks for use, to identify patients who are more likely to use cannabis, and to assess outcomes associated with use.

Objective: The current study sought to determine the rate of cannabis use in YA cancer patients ages 18 to 39, identify demographic and clinical correlates of use, and examine differences in moderate-to-severe symptoms between users and nonusers.

Methods: We conducted a retrospective review of objectively measured tetrahydrocannabinol (THC), self-reported cannabis use, and cancer-related symptomatology in YA cancer patients in active treatment referred for comprehensive supportive care.

Results: Approximately 30% of YA cancer patients tested positive for THC on urine drug testing. At the univariate level, cannabis users were more likely to be male, to have a lifetime history of smoking at least 100 cigarettes, and to be more recently diagnosed. Cannabis use was associated with moderate-to-severe symptomatology, including pain, nausea, lack of appetite, constipation, difficulty sleeping, and poorer overall well-being.

Conclusions: YAs referred for comprehensive supportive care may be managing their cancer-related symptoms with cannabis. Further research is needed to better understand patients’ perceptions of cannabis’s therapeutic and adverse effects, in patients who used cannabis before diagnosis, and in patients who commenced use in response to a cancer diagnosis.