bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of cervical dynamic and static imbalance models and preliminary study on the mechanism of cervical degeneration in rats
Authors: Li Haibo , Yin Jianjian , Huang Yongjing , Xu Nanwei , Chen Liang , Nong Luming
Published: August 2019

This study aimed to observe dynamically the changes of x-ray, histomorphology appearance and serum inflammatory cytokines of cervical degenerative disease in rat models and to discuss the mechanism of cervical degeneration. Sixty Sprague Dawley rats were randomised into test ( n = 45) and control ( n = 15) groups, which were randomly subdivided into three groups corresponding to 1, 3 and 6 mo post operation. At the corresponding postoperative stage, cervical x-ray films were acquired, and intervertebral disc space and intervertebral foramen size were measured. Some serum inflammatory cytokines from all rats were quantitatively determined. Then, the morphological change in cervical intervertebral disc specimens stained with hematoxylin and eosin was observed. The results were analysed and compared among groups. Compared to the control group, the cervical x-ray and histomorphology appearance of rats in the test group showed varying degrees of degeneration. Furthermore, the serum IL-1β, TNF-α and IL-10 in the test group increased significantly at the corresponding postoperative stage ( P < 0.05, P < 0.01 and P < 0.001, respectively) compared to the control group. This model of cervical disc degeneration can accelerate imaging and histological degeneration, but it may be accompanied by changes in serum inflammatory cytokines levels.
UPLC-MS Analysis of Cannabis sativa Using Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabinolic Acid (THCA) as Marker Compounds: Inhibition of Breast Cancer Cell Survival and Progression
Authors: Bala Asis , Rademan Sunelle , Kevin Khorommbi Ndivhuwo , Maharaj Vinesh , Matsabisa Motlalepula G.
Published: August 2019

Cannabis sativa L. extracts were characterized by ultra performance liquid chromatography-mass spectrometry (UPLC-MS) using tetrahydrocannabinol (THC), cannabidiol (CBD), and tetrahydrocannabinolic acid (THCA) as marker compounds. The inhibitory effects of various extracts were determined on the survival and progression of highly metastatic breast cancer cells. A higher amount of CBD was found in the dichloromethane extract, and this was found to be effective in inhibiting breast cancer cell growth in vitro and in angiogenesis. Collectively, it may be concluded that CBD, THC, and THCA in the African variety of C. sativa can be used as marker compounds in UPLC-MS analysis. The ability of the plant to inhibit breast cancer cell survival and progression may affirm the traditional use of the drug as an anticancer agent.
Designing technology tools to support engagement in mindfulness-based interventions: an analysis of teacher and student experiences
Authors: Parsons Christine E. , Jensen Kasper L. , Roepstorff Andreas , Fjorback Lone O. , Linehan Conor
Published: August 2019

Standard mindfulness-based interventions have significant at-home assignments of formal mindfulness practice as a key component. Engagement with formal home practice has been correlated with treatment outcomes, but participants often complete less than the assigned amounts. Here, we explore the requirements for technology tools that can support and encourage home practice, in a way that is appropriate and consistent with the core principles of mindfulness-based interventions. Interviews were held with a group of five highly experienced mindfulness teachers and a group of five participants who had previously completed an eight-week course. Data was subjected to thematic analysis. A key finding was that providing teachers with information on how students practice could support communication around difficulties with home practice. We also identified questions around the appropriateness of adapting the course in response to participant difficulties and participant preferences. Both teachers and students made numerous suggestions for ways to augment their training using technology, such as via practice reminders and provision of teacher-specific content. Finally, a major design issue for technology developers is how to support participants in reflecting on their experiences of mindfulness practice, and subsequent learning, but not to critically evaluate their practice.
Antitumor activity of enzymatically hydrolyzed Ganoderma lucidum polysaccharide on U14 cervical carcinoma–bearing mice
Authors: Kong Min , Yao Yao , Zhang Hongmei
Published: August 2019

Polysaccharides from Ganoderma lucidum have been demonstrated to possess diverse biological activities. Despite lots of studies on the biological activities of Ganoderma lucidum polysaccharide (GLP), little is known regarding the medicinal potential of low–molecular weight enzymatically hydrolyzed Ganoderma lucidum polysaccharide (EGLP). EGLP was prepared by enzymatic degradation and its potential effects in U14 cervical tumor–bearing mice were evaluated. Both GLP and EGLP delayed tumor growth of the tumor xenograft. The EGLP was superior to native polysaccharide. Moreover, EGLP treatment could effectively protect the immune organs of U14 cervical carcinoma–bearing mice. In addition, the EGLP treatment ameliorated oxidative stress as compared with cyclophosphamide (CTX). Compared with the MC group, the expression of Bcl-2 and COX-2 was obviously decreased by EGLP treatment, whereas the expression of Bax and cleaved caspase-3 was obviously increased. These results indicated that EGLP showed stronger antitumor activity with lower toxic effects and had the potential to be a novel antitumor agent.
Inhibition of histone deacetylase protects the damaged cataract via regulating the NF-κB pathway in cultured lens epithelial cells
Authors: Liu Jun , Yin Yan
Published: August 2019

Induction of oxidative damage by the activation of histone deacetylase (HDAC) is an integral event that causes major membrane damage of ocular tissues and leads to the pathogenesis of cataract. It is elucidated that nuclear factor-κB is a mediator in the process of cataract development. However, studies on the role played by epigenetic proteins in regulating cataract pathogenesis are limited. Hence, in the current investigation, ARPE-19 human retinal epithelial cells were used as an experimental model to elucidate the role of HDAC inhibition and its mechanism behind the cataract pathogenesis. ARPE-19 cells were exposed to H2O2, with and without Trichostatin A (TSA), a pan-HDAC inhibitor, and maintained along with control cells without any treatment. On exposure to H2O2, cells were susceptible to oxidative stress as it is evident from the reduced expression levels of superoxide dismutase (SOD), catalase, and GSH levels. Simultaneously, H2O2-exposed cells showed the nuclear translocation of NF-κB with the activation of inflammatory cytokines such as CXCL1 and IL-6. In addition, the mRNA expression analysis revealed that the GADD45α, COX-2, MCP-1, and ICAM-1 expressions were increased in H2O2 group. Moreover, the activity of HDAC was increased to 2-fold with a significant reduction in the histone acetyltransferase (HAT) activity in cells that were maintained under oxidative conditions. However, TSA was able to inhibit the critical cytokines’ expression with attenuated HDAC activity and limited NF-κB translocation. Furthermore, pre-treatment of TSA significantly suppressed the transcript levels of up-regulated inflammatory markers in cells. Together, these findings offer new insight into the role of HDACs in regulating cellular processes involved in the pathogenesis of cataract as well as the potential use of HDAC inhibitors as therapeutics for controlling the disease progression.
Evaluation of the effectiveness of letrozole in the treatment of experimentally modeled endometriosis in rats
Authors: Yarmolinskaya Maria , Molotkov Arsenii
Published: August 2019

The necessity of finding new drugs for the treatment of endometriosis is stipulated by significant number of recurrences, side effects, and high cost of treatment. Increased activity of aromatase in endometrioid heterotopies is revealed. That is why, aromatase inhibitors may be effective in the treatment of endometriosis. In this study, endometriosis was modeled in rats by autotransplantation of uterine fragments to peritoneum, which was supplemented by ovariectomy and ethinylestradiol replacement therapy. After 14 ± 2 days, laboratory animals underwent laparoscopy to measure formed heterotopies and then the rats were divided into two groups. Nine animals were receiving letrozole (0.5 mg/kg/day) therapy for 3 weeks. The rats of the control group did not receive treatment (n = 11). At the end of the experiment (21 ± 3 days after laparoscopy), re-evaluation and determination of size of heterotopies as well as histological study were carried out in two groups. In all the rats of the main group, treated with letrozole, the decrease in the size of heterotopies was revealed; the percentage of reduction was 79.92% ± 7.89% (p < 0.0001). Growth of all endometriotic foci was observed in the control group. Thus, the use of the aromatase inhibitor letrozole in the treatment of endometriosis is effective.
Comparison of Bond Strength of Monolithic CAD-CAM Materials to Resin Cement Using Different Surface Treatment Methods
Authors: Cinar Sevki , Altan Bike , Akgungor Gokhan
Published: August 2019

Objective:

To compare the bond strength of monolithic CAD-CAM materials to resin cement using different surface treatment methods.

Materials and Methods:

Lithium disilicate glass ceramic (IPS e-max CAD), zirconia-reinforced lithium silicate ceramic (Vita Suprinity), resin nanoceramic (Lava Ultimate), and hybrid ceramic (Vita Enamic) were used. Five groups of CAD-CAM blocks were treated as follows: control (C), HF etching (HF), HF etching + silanization (HF + S), sandblasting (SB), and sandblasting + silanization (SB + S). After surface treatments, SEM analyses were conducted. Specimens were cemented with self-adhesive resin cement (Theracem) and stored in distilled water at 37°C for 24 h. Shear bond strength (SBS) was measured, and failure types were categorized. Results were analyzed using two-way ANOVA and the post-hoc Tukey test.

Results:

Statistical analysis revealed significant differences between SBS values obtained for different surface treatments and CAD-CAM block types ( P < .001). Among the CAD-CAM materials, the highest SBS was reported in the HF + S group for Vita Enamic. Although IPS e.max CAD, Vita Suprinity, and Vita Enamic showed higher bond strength when treated with HF + S, Lava Ultimate has the highest bond strength value when treated with SB + S.

Conclusions:

The bond strength of CAD-CAM materials was influenced by surface treatment. Additionally, silanization significantly improved the bond strength of all materials except Lava Ultimate.
A Definition of Significant Instability and a Scoring System for Predicting Meniscal Tears in ACL-Deficient Knees
Authors: Joshi Amit , Singh Nagmani , Pradhan Ishor , Basukala Bibek , Banskota Ashok Kumar
Published: August 2019

Background:

Patients with anterior cruciate ligament (ACL)–deficient knees risk recurrent instability of the affected knee, which may predispose to meniscal injuries. Various studies have correlated the incidence of meniscal tear with elapsed time from ACL tear and number of instability events. However, it is not clear how significant an instability event needs to be to contribute to a meniscal tear.

Purpose/Hypothesis:

The purpose of this study was to (1) define a significant instability episode and (2) develop a checklist and scoring system for predicting meniscal tears based on significant instability episode. We hypothesized that patients with ACL-deficient knees who met the scoring threshold for a significant instability episode would have a higher incidence of meniscal tears compared with those who did not meet the threshold.

Study Design:

Cohort study (prognosis); Level of evidence, 2.

Methods:

This retrospective study included patients with magnetic resonance imaging (MRI)–confirmed isolated ACL tear for longer than 3 months. We determined parameters for assessing instability episodes and defined any instability events between the MRI and ACL reconstruction as significant or insignificant. Patients were then grouped into a significant instability group (≥1 significant episode) and an insignificant instability group, and the incidence and types of meniscal tears found during surgery were compared between groups.

Results:

There were 108 study patients: 62 in the significant instability group and 46 in the insignificant instability group. During surgery, 58 meniscal tears (46 medial, 12 lateral) were recorded, for an overall meniscal injury rate of 53.70%. In the significant instability group, 47 patients (75.81%) had a meniscal tear and 15 (24.19%) had intact menisci ( P < .001). In the insignificant instability group, 11 patients (23.91%) had a meniscal tear and 35 (76.08%) had intact menisci ( P < .001). Regarding the 58 patients with a meniscal tear, 47 (81.03%) had ≥1 significant episode of instability before surgery, as compared with 11 (18.97%) who had insignificant or no instability. The odds of having a medial meniscal tear at ACL reconstruction was 10 times higher in the significant instability group versus the insignificant instability group.

Conclusion:

The incidence of a medial meniscal tear was 10 times greater in patients with a significant episode of instability versus those with insignificant instability, as defined using a predictive scoring system. The incidence of lateral meniscal tear did not change with instability episodes.
“We Want to Build a Network”: Professional Experiences of Case Managers Working With Military Families
Authors: Englert Robyn , Dell’Acqua Renee , Fitzmaurice Shannon , Yablonsky Abigail Marter
Published: August 2019

Optimizing case management (CM) services increases service member readiness at home and abroad. However, little research has been conducted on the experiences of case managers providing services to military families within the Military Health System. Semistructured qualitative interviews were conducted to explore the professional experiences of case managers to identify factors that may affect care to military families. A total of 53 case managers from military medical treatment facilities (MTFs) varying in size, location, and branch of service were interviewed by telephone to explore their perspectives. Qualitative content analysis was performed. Case managers serve a variety of functions, but specific roles vary between MTFs. Factors that affect CM services for military families were identified: (1) need for pediatric specialization, (2) heavy workload, (3) appropriate staff, (4) patient handoffs, and (5) the role of CM. Recommendations for improving CM services to facilitate the well-being of military families are discussed.
Experiences With Stress Among African American Men Living With Type 2 Diabetes: A Qualitative Inquiry
Authors: Sherman Ledric D. , Comer-Hagans DeLawnia , Pattin Anthony J.
Published: August 2019

Self-managing type 2 diabetes (T2D) is critical but often presents a challenge among African American men. Stress may exacerbate both mental and physical problems, which can lead to poor self-management; however, the evidence is sparse. The purpose of this manuscript is to examine the relationship the role of stress in type 2 diabetes management among a prospective group of African American men living in the southern United States. Nineteen African American men with T2D were recruited from barbershops and churches. Interviews were conducted using a semi structured interview guide. Transcripts were analyzed using a phenomenological approach and focused on identifying common themes describing the responses regarding any stress that the participants have pertaining to living with and managing T2D. The themes that emerged from the participant responses are: (a) experiencing less stress, (b) stress not attributed from diabetes, (c) avoid thinking about stress, and (d) some stress is prevalent. Overall, participants expressed either that diabetes was not attributing to the stress that they have or that they have less stress than they did prior to being diagnosed with T2D. In this sample of African American men, stress became a factor for some participants when considering the complications that can occur from diabetes. These findings suggest the need for key considerations to only incorporate general information about diabetes and stress management, but should be gender and culturally relevant to African American men.
Comparison of Simulated Surgical Skills Using Different Camera Aperture Settings for Digitally Assisted Vitreoretinal Surgery
Authors: González-Saldivar Gerardo , Chow David R.
Published: August 2019

Purpose:

This cross-sectional, randomized, single-blinded study evaluates simulated surgical skills during digitally assisted vitreoretinal surgery (DAVS) with different camera aperture settings to determine maximal surgical performance and preference.

Methods:

Fifteen retina fellows performed 3 different surgical simulator tests with a DAVS visualization system. To evaluate maximal surgical performance and preference, DAVS was evaluated at different camera apertures (30% and 75%) with a fixed magnification (12×) and television (TV) viewing distance (1.2 m [4 ft]). Comparisons were made of the time needed to complete each test as well as the number of errors. At the end of the 3 tests, participants were asked for their camera aperture preference.

Results:

The time it took to perform each simulated surgical test was significantly less with the 30% aperture than with the 75% aperture ( P = .036). Furthermore, the number of errors made with the 30% aperture was always less than with the 75% aperture ( P = .009). After completing all tests, evaluation of surgeon preference for camera aperture settings showed that 83% of the participants preferred the 30% aperture over the 75% aperture.

Conclusions:

Optimization of DAVS parameters directly influences surgical performance. A 30% camera aperture in DAVS outperforms larger camera apertures, not only in depth of field and lateral resolution values, but also in simulated surgical skills. A smaller number of errors, as well as less time needed to complete tests, was achieved with these settings. We suggest that the optimal settings for DAVS enhancement are a 30% camera aperture and a TV viewing distance of 1.2 m.
Paramedian Midbrain Infarction Presenting as Bilateral Asymmetric Ptosis: A Case Report and Review of Literature
Authors: Gupta Dhananjay , R. Pradeep , Mehta Anish , Javali Mahendra , Acharya Purshottam T. , Srinivasa Rangasetty
Published: August 2019

Brainstem strokes can have protean ophthalmological manifestations including pupillary and extraocular muscle pareses. Incomplete paresis of oculomotor function is more common than complete paresis owing to the selective involvement of subnuclei or fascicles for various extraocular muscles. Here, we report a case of right paramedian midbrain stroke presented with asymmetric bilateral ptosis. We discuss the anatomical correlation of this presentation with the structure of oculomotor nerve nuclei and its fascicles.
Cognitive-Behavioral Interventions for Improving Activity Outcomes After Stroke: A Narrative Review of the Literature
Authors: Camillieri Susan
Published: August 2019

The use of cognitive-behavioral interventions for the remediation of motor impairments is receiving increasing scientific attention. Previous investigators have established that interventions that incorporate an individual’s motivation and foster self-efficacy can potentiate the benefits of traditional neurological rehabilitation. The hemiparetic upper extremity may be particularly susceptible to these non-motor interventions as there is often a discrepancy between objective motor function and real-world arm use in the postacute phase after stroke. One possible explanation for this discrepancy lies within the learned nonuse phenomenon, which theorizes that decreased upper extremity use is learned and which has the potential to be reversed via behavioral techniques. Several interventions have been developed that aim to influence these behavioral contributors. However, despite having similar components and theoretical constructs, they use a distinct nomenclature and employ various methods of administration making comparison challenging. The purpose of this literature review is to examine several cognitive-behavioral interventions which have been described in the literature (motivational interviewing, individualized coaching, self-management training, and cognitive strategy training), and to investigate the current evidence supporting their use for the remediation of motor and functional impairments after stroke.
A Paradigm Shift for Acute Rehabilitation of Stroke
Authors: Camillieri Susan
Published: August 2019

Current best practice standards for rehabilitation after stroke call for increasing the dose and intensity of interventions for optimal therapeutic benefit. Despite this, those within inpatient rehabilitation during the acute phase are often sedentary, and they receive a lower dose and intensity of therapy than recommended. This may be due to the lack of therapeutic opportunities outside of therapies, program structure characteristics, or a lack of efficiency in therapeutic encounters, all of which have the potential to reduce therapeutic outcomes. Circuit class therapies and group therapies provide a method of increasing the dose and intensity of therapy provided, and may reduce redundancy and inefficiency within programs, but do not satisfy the 3-hour rule under the current Prospective Payment System in the United States. The Centers for Medicare and Medicaid Services require that individual therapy be the primary mode of intervention provision, which limits programs from providing these evidence-based interventions, at a higher volume in a group or circuit format. Providing an enriched environment outside of structured therapies should be mandated to maximize benefits experienced by patients and reduce sedentary time. Empirical study is required to determine which interventions may be effectively delivered when provided via a nonindividual basis, and to explore the feasibility and fiscal implication of alternative models of care. Reform of regulatory standards may be required to align with best practice standards.
Quantifying Poststroke Gait Deviations: A Meta-analysis of Observational and Cross-sectional Experimental Trials
Authors: Sharififar Sharareh , Vincent Heather K. , Shuster Jonathan , Bishop and Mark
Published: August 2019

The hemiparetic walking pattern is a common feature of an upper motor neuron impairment caused by stroke. Previous studies have recorded deviations in hemiparetic walking patterns. We aimed to quantify gait alterations poststroke relative to healthy gait across a range of walking speeds by a systematic review and meta-analysis. We searched databases including MEDLINE via PubMed, Web of Science, SPORTDiscus, Cumulative Literature Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from 1927 to the end of July 2015 for all instrumented measured gait variables in (a) observational studies with stroke patients only and (b) interventional studies in healthy, age-matched (elderly) participants, and those with stroke published in English. We analyzed data using a patient-weighted random-effects method. The heterogeneity of methods and measures employed across studies limited the intended analyses. The search pooled 2,223 articles, of which we included 49 observational and 124 interventional studies involving 960 healthy elders and 4,691 participants with stroke. As expected, those with stroke have gait-speed-related statistical differences from those without stroke. Specifically, this meta-analysis determined that (a) only 2 spatial parameters consistently changed according to gait speed – step length and stride length – and (b) irrespective of speed, 9 spatiotemporal measures, 5 sagittal kinematic, and 3 kinetic measures from the analysis were statistically different from the healthy counterparts ( P < .05). These findings suggest the importance of using instrumented measurement techniques for evaluating stroke gait rehabilitation.
Does Minocycline Improve Recovery After Acute Ischemic Stroke?
Authors: Singh Rajinder , Augustin Sherwin Joy , Jane Marlie , Cheong Jocelyn M. Y. , Haur Lee Sze , Choo Tai Bee
Published: August 2019

Objective: We assessed the efficacy of minocycline in improving outcomes in acute ischemic stroke patients.

Method: This was a multicenter, randomized, double-blind, placebo-controlled clinical trial, where acute ischemic stroke patients were randomized to either oral minocycline or placebo within 3 to 48 hours of symptom onset. The primary endpoint was the modified Rankin (mRS) score at day 90. Secondary outcomes included the National Institutes of Health Stroke Scale (NIHSS) scores, the Barthel index, and vascular outcomes at day 90.

Results: A total of 139 subjects (73.4% male; mean age 62 [range 19-88] years) were randomized to receive minocycline (n = 69) or placebo (n = 70). At day 90, no significant difference was noted in the proportion of subjects given minocycline with mRS score ≤1 compared to placebo (56% versus 51%). The odds ratio of favorable outcome in the minocycline group compared to placebo was 1.20 (95% CI [0.58, 2.47], P = 0.60). No difference was recorded between the 2 groups in secondary outcomes of the NIHSS score (OR 1.11: 95% CI [0.98, 2.54]), the Barthel index (OR 0.78: 95% CI [0.33, 1.86]), or vascular events (OR 2.09 95% CI [0.29, 23.77]). A planned interim analysis was performed after approximately half the subjects reached the primary endpoint. The data and safety monitoring board recommended ending the trial for futility after determining that it was highly unlikely for minocycline to show significant efficacy over placebo in improving functional outcomes at day 90 if all subjects were randomized. No safety concerns were identified.

Interpretation: Oral minocycline administered for acute ischemic stroke was ineffective in improving functional outcomes.
Dysregulation of the TET family of epigenetic regulators in lymphoid and myeloid malignancies
Authors: Lio Chan-Wang J. , Yuita Hiroshi , Rao Anjana
Published: August 2019

TET2 is frequently mutated in lymphoid and myeloid malignancy. Lio et al review the current understanding of the role of TET enzymes in lymphoid and myeloid malignancy, highlighting that loss of TET protein function can occur either by mutation or as a result of metabolic alteration.
Airway morphometry in COPD with bronchiectasis: a view on all airway generations
Authors: Everaerts Stephanie , McDonough John E. , Verleden Stijn E. , Josipovic Iván , Boone Matthieu , Dubbeldam Adriana , Mathyssen Carolien , Serré Jef , Dupont Lieven J. , Gayan-Ramirez Ghislaine , Verschakelen Johny , Hogg James C. , Verleden Geert M. , Vanaudenaerde Bart M. , Janssens Wim
Published: August 2019

The pathophysiological processes underlying bronchiectasis in chronic obstructive pulmonary disease (COPD) are not understood. In COPD, both small and large airways are progressively lost. It is currently not known to what extent the different airway generations of patients with COPD and bronchiectasis are involved.

COPD explant lungs with bronchiectasis were compared to COPD explant lungs without bronchiectasis and unused donor lungs as controls. In order to investigate all airway generations, a multimodal imaging approach using different resolutions was conducted. Per group, five lungs were frozen (n=15) and underwent computed tomography (CT) imaging for large airway evaluation, with four tissue cores per lung imaged for measurements of the terminal bronchioles. Two additional lungs per group (n=6) were air-dried for lobar microCT images that allow airway segmentation and three-dimensional quantification of the complete airway tree.

COPD lungs with bronchiectasis had significantly more airways compared to COPD lungs without bronchiectasis (p<0.001), with large airway numbers similar to control lungs. This difference was present in both upper and lower lobes. Lack of tapering was present (p=0.010) and larger diameters were demonstrated in lower lobes with bronchiectasis (p=0.010). MicroCT analysis of tissue cores showed similar reductions of tissue percentage, surface density and number of terminal bronchioles in both COPD groups compared to control lungs.

Although terminal bronchioles were equally reduced in COPD lungs with and without bronchiectasis, significantly more large and small airways were found in COPD lungs with bronchiectasis.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study
Authors: Huhn Gregory D. , Eron Joseph J. , Girard Pierre-Marie , Orkin Chloe , Molina Jean-Michel , DeJesus Edwin , Petrovic Romana , Luo Donghan , Van Landuyt Erika , Lathouwers Erkki , Nettles Richard E. , Brown Kimberley , Wong Eric Y.
Published: August 2019

Background

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a once-daily, single-tablet regimen for treatment of HIV-1 infection. The efficacy/safety of switching to D/C/F/TAF versus continuing boosted protease inhibitor (bPI) + emtricitabine/tenofovir disoproxil fumarate (control) were demonstrated in a phase 3, randomized study (EMERALD) of treatment-experienced, virologically suppressed adults through week 48. The objective of this analysis was to evaluate EMERALD outcomes across subgroups of patients based on demographic characteristics, prior treatment experience, and baseline antiretroviral regimen.

Methods

EMERALD patients were virologically suppressed (viral load [VL] < 50 copies/mL for ≥ 2 months at screening). Prior non-darunavir virologic failure (VF) was allowed. Primary endpoint was proportion of patients with virologic rebound (confirmed VL ≥ 50 copies/mL) cumulative through week 48. Virologic response was VL < 50 copies/mL (FDA snapshot). Safety was assessed by adverse events, renal proteinuria markers, and bone mineral density. Outcomes were examined for prespecified subgroups by age (≤/> 50 years), gender, race (black/non-black), prior number of antiretrovirals used (4/5/6/7/> 7), prior VF (0/≥ 1), baseline bPI (darunavir/atazanavir or lopinavir), and baseline boosting agent (ritonavir/cobicistat).

Results

Among 1141 patients in the D/C/F/TAF (n = 763) and control (n = 378) arms, virologic rebound rates (2.5% and 2.1%, respectively) were similar, and this was consistent across all subgroups. Virologic response rates ranged from 91 to 97% (D/C/F/TAF) and 89 to 99% (control) across all subgroups, with differences between treatment arms of 0 and 6%. Adverse event rates were low in both arms and across subgroups. Improvements in renal and bone parameters were observed with D/C/F/TAF across demographic subgroups.

Conclusions

For treatment-experienced, virologically suppressed patients, switching to D/C/F/TAF was highly effective and safe, regardless of demographic characteristics, prior treatment experience, or pre-switch bPI.

Trial registration ClinicalTrials.gov Identifier: NCT02269917. Registered 21 October 2014. https://clinicaltrials.gov/ct2/show/NCT02269917
Utility of clinical features with fine needle aspiration biopsy for diagnosis of Warthin tumor
Authors: So Thomas , Sahovaler Axel , Nichols Anthony , Fung Kevin , Yoo John , Weir Michele M. , MacNeil S. Danielle
Published: August 2019

Background

Conservative management of Warthin tumor (WT) may be a viable alternative to surgery, but there are concerns of missed malignancies on fine needle aspiration biopsy (FNAB). The purpose of this study is to measure the sensitivity and positive predictive value of FNAB for WT, and to identify clinical features associated with WT that can aid in this diagnosis.

Methods

Retrospective analysis of patients from January 1, 2006 to April 30, 2017 at a tertiary care center in London, Ontario, Canada. All patients with a diagnosis of WT on FNAB or resection were included. Electronic medical records were identified for 177 patients that fit the criteria. Study outcomes included the sensitivity and positive predictive value of FNAB alone for WT, and, when including clinical features associated with WT.

Results

The mean age of patients in this study was 63.2 years (SD 10.4); 115 (65%) were male, and 157 (89%) were past or present smokers. The measured sensitivity and positive predictive value of FNAB for WT were 95.8 and 97.2% respectively. Two cases were classified as WT on FNAB but confirmed at resection as mucoepidermoid carcinoma and acinic cell carcinoma. When only patients with multifocal, bilateral or incidental tumors were assessed, sensitivities and positive predictive values for each were 100%. Isolating for inferior pole location also resulted in a positive predictive value of 100%.

Conclusions

The sensitivity and positive predictive value of FNAB for WT in this study are high, with two false negatives on FNAB. Multifocal, bilateral, incidentaloma and inferior pole location were identified as potential clinical features that may increase the diagnostic confidence for WT, strengthening the argument for conservative management in these patients. Overall, this study serves as an initial exploration into whether clinical features may be included with FNAB results to improve the sensitivity and positive predictive value of diagnosing WT. Further research is necessary before these findings can be translated into clinical practice.
Cancer cell reprogramming: a promising therapy converting malignancy to benignity
Authors: Gong Lanqi , Yan Qian , Zhang Yu , Fang Xiaona , Liu Beilei , Guan Xinyuan
Published: August 2019

In the past decade, remarkable progress has been made in reprogramming terminally differentiated somatic cells and cancer cells into induced pluripotent cells and cancer cells with benign phenotypes. Recent studies have explored various approaches to induce reprogramming from one cell type to another, including lineage‐specific transcription factors‐, combinatorial small molecules‐, microRNAs‐ and embryonic microenvironment‐derived exosome‐mediated reprogramming. These reprogramming approaches have been proven to be technically feasible and versatile to enable re‐activation of sequestered epigenetic regions, thus driving fate decisions of differentiated cells. One of the significant utilities of cancer cell reprogramming is the therapeutic potential of retrieving normal cell functions from various malignancies. However, there are several major obstacles to overcome in cancer cell reprogramming before clinical translation, including characterization of reprogramming mechanisms, improvement of reprogramming efficiency and safety, and development of delivery methods. Recently, several insights in reprogramming mechanism have been proposed, and determining progress has been achieved to promote reprogramming efficiency and feasibility, allowing it to emerge as a promising therapy against cancer in the near future. This review aims to discuss recent applications in cancer cell reprogramming, with a focus on the clinical significance and limitations of different reprogramming approaches, while summarizing vital roles played by transcription factors, small molecules, microRNAs and exosomes during the reprogramming process.
Decoupling induced polarization effect from time domain electromagnetic data in a Bayesian framework
Authors: Li Hai , Xue Guoqiang , He Yiming
Published: August 2019

We have developed a scheme for decoupling the induced polarization (IP) effect from time-domain electromagnetic (TDEM) data. This scheme is achieved by simultaneously sampling the resistivity and pseudochargeability in a Bayesian framework. The TDEM and IP responses are simulated separately with the sampled model parameters and then are stacked to fit the IP-affected TDEM data. Thus, the influence of the IP phenomenon is eliminated in the process of recovering the resistivity. To reduce the computational cost brought by the Bayesian sampling, we use a 2D parametrization instead of sampling the full 3D space and we use a linear perturbation approximation for calculating the IP response. The linearized inversion results are used as the initial model, and a multiple proposed points algorithm is used to accelerate the sampling. We validate the proposed method with synthetic and field examples showing that it restores accurate estimates of electrical structures from the TDEM data that are significantly affected by the IP phenomenon. Our method could advance the application of the TDEM method to the scenario in which the IP may affect the TDEM data and mask the underlying geologic targets.
Estimated Cost and Savings in a Patient Management Program for Oral Oncology Medications: Impact of a Split-Fill Component
Authors: Staskon Francis C. , Kirkham Heather S. , Pfeifer Amy , Miller Richard T.
Published: August 2019

PURPOSE:

A national specialty pharmacy implemented a split-fill option within an oral oncology patient management program to reduce pharmacy costs and medication wastage resulting from early discontinuations. Payers covered dispensed medications at half-quantity intervals for each dispense up to 3 months. Proactive outreach to patients before they had used up the initial dispensed medication quantity helped assess the patient’s tolerance to the new medication and adverse effects. This study compared costs for patients with a split-fill option to similar costs for patients without this option taking into account patient discontinuation rates, patient-reported adverse effects rates, estimated pharmacy costs, and potential wastage.

METHODS:

This retrospective cohort study included patients who were new to therapy on a split-fill medication between September 2015 and August 2017. A 1:1 greedy match algorithm was conducted using propensity variables to match patients from each cohort. Per-month discontinuation rates were determined for both split-fill and non–split-fill groups. The non–split-fill potential wastage was calculated as monthly costs for discontinuations in the following month and weighted by split-fill discontinuation rates.

RESULTS:

Of the 2,363 program patients who met selection criteria for the 11 medications, 671 patients from each group were matched. Payers with a split-fill program had significant medication savings per covered month ($2,147.60 at 1 month) and at a cumulative 6 months. Modeled wastage indicated that payers without a split-fill program could expect to save $2,646.74 monthly by using this option. Both cohorts had similar rates of adverse effects and time until first reported adverse effect.

CONCLUSION:

In the first 6 months, the split-fill patient managed program had lower discontinuation rates, significantly reduced pharmacy costs, and reduced potential wastage.
The osmorespiratory compromise in the euryhaline killifish: water regulation during hypoxia
Authors: Wood Chris M. , Ruhr Ilan M. , Schauer Kevin L. , Wang Yadong , Mager Edward M. , McDonald Danielle , Stanton Bruce , Grosell Martin
Published: August 2019

Freshwater- and seawater-acclimated Fundulus heteroclitus were exposed to acute hypoxia (10% air saturation, 3h), followed by normoxic recovery (3h). In both salinities, ventilation increased and heart rate fell in the classic manner, while MO2 initially declined by ∼50%, with partial restoration by 3h of hypoxia, and no O2 debt repayment during recovery. Gill paracellular permeability (measured with [14C] PEG-4000) was 1.4-fold higher in seawater, and declined by 50% during hypoxia with post-exposure overshoot to 188%. A similar pattern with smaller changes occurred in freshwater. Drinking rate (also measured with [14C] PEG-4000) was 8-fold higher in seawater fish, but declined by ∼90% during hypoxia in both groups, with post-exposure overshoots to ∼270%. Gill diffusive water flux (measured with 3H2O) was 1.9-fold higher in freshwater fish, and exhibited a ∼35% decrease during hypoxia, which persisted throughout recovery, but was unchanged during hypoxia in seawater fish. Nevertheless, freshwater killifish gained weight while seawater fish lost weight during hypoxia and these changes were not corrected during normoxic recovery. We conclude that this hypoxia-tolerant teleost beneficially reduces gill water permeability in a salinity-dependent fashion during hypoxia, despite attempting to simultaneously improve MO2, but nevertheless incurs a net water balance penalty in both freshwater and seawater.
Bank Networks and Systemic Risk: Evidence from the National Banking Acts
Authors: Anderson Haelim , Paddrik Mark , Wang Jessie Jiaxu
Published: August 2019

The National Banking Acts (NBAs) of 1863–1864 established rules governing the amounts and locations of interbank deposits, thereby reshaping the bank networks. Using unique data on bank balance sheets and detailed interbank deposits in 1862 and 1867 in Pennsylvania, we study how the NBAs changed the network structure and quantify the effect on financial stability in an interbank network model. We find that the NBAs induced a concentration of interbank deposits at both the city and bank levels, creating systemically important banks. Although the concentration facilitated diversification, contagion would have become more likely when financial center banks faced large shocks. (JEL E44, G01, G21, G28, L14, N21)
Family Health Behaviors
Authors: Fadlon Itzik , Nielsen Torben Heien
Published: August 2019

We study how health behaviors are shaped through family spillovers. We leverage administrative data to identify the effects of health shocks on family members’ consumption of preventive care and health-related behaviors, constructing counterfactuals for affected households using households that experience the same shock but a few years in the future. Spouses and adult children immediately improve their health behaviors and their responses are both significant and persistent. These spillovers are far-reaching as they cascade even to coworkers. While some responses are consistent with learning information about one’s own health, the evidence points to salience as a major operative explanation. (JEL D15, D83, I12, J12)
The Effects of Rent Control Expansion on Tenants, Landlords, and Inequality: Evidence from San Francisco
Authors: Diamond Rebecca , McQuade Tim , Qian Franklin
Published: August 2019

Using a 1994 law change, we exploit quasi-experimental variation in the assignment of rent control in San Francisco to study its impacts on tenants and landlords. Leveraging new data tracking individuals’ migration, we find rent control limits renters’ mobility by 20 percent and lowers displacement from San Francisco. Landlords treated by rent control reduce rental housing supplies by 15 percent by selling to owner-occupants and redeveloping buildings. Thus, while rent control prevents displacement of incumbent renters in the short run, the lost rental housing supply likely drove up market rents in the long run, ultimately undermining the goals of the law. (JEL R23, R31, R38)
Pharmacological treatment and current controversies in COPD
Authors: Cazzola Mario , Rogliani Paola , Stolz Daiana , Matera Maria Gabriella
Published: August 2019

Bronchodilators, corticosteroids, and antibiotics are still key elements for treating chronic obstructive pulmonary disease in the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations and this is due in part to our current inability to discover new drugs capable of decisively influencing the course of the disease. However, in recent years, information has been produced that, if used correctly, can allow us to improve the use of the available therapies.
What Does M. Montessori Offer for Modern Education?
Authors: Сумнительный К. , Sumnitel'nyy K.
Published: August 2019

The article discusses the features of the pedagogical system of M. Montessori. The importance of its system for the development of modern education is revealed. Attention is paid to the bias of the concept of M. Montessori that has developed in Russian pedagogy and the risks of its development within the framework of the national pedagogical and sociocultural context. The main problems associated with the use of the Montessori method in the domestic pedagogical space are analyzed. The features of the methodological and didactic support of the pedagogical process in the Montessori classes for diff erent age groups are considered. The pedagogical and psychological sense of the teacher’s activity in the Montessori classroom is revealed. The problem of training teachers for M. Montessori classes and the possible reactions of students to the shock of the proposed change in professional stereotypes are discussed.
Beauty Is in the Eye of the Beholder: Toward a Contextual Understanding of Compensation of Information Technology Professionals Within and Across Geographies
Authors: Whitaker Jonathan , Mithas Sunil , Liu Che-Wei
Published: August 2019

This study provides new insights on compensation and human resources practices of multinational corporations (MNCs) and how they differ from those of domestic companies. The authors focus on cross-geography differences in compensation for IT professionals and take a closer look at returns on master of business administration (MBA) education and information technology (IT) experience. They analyze data on more than 20,000 IT professionals across the United States and India and compare practices of United States–based MNCs and India-based firms for IT professionals in India and of United States–based MNCs for IT professionals in the United States and India. The study finds that MNCs source IT talent from emerging markets because of the lower cost of IT professionals in these markets, coupled with the availability of a large pool of technically qualified professionals. For IT professionals in India, results indicate that United States–based MNCs pay a premium (compared with India firms) for each year of IT experience. By contrast, India firms pay a premium (compared with United States–based MNCs) for IT professionals in India with an MBA. Interestingly, whereas United States–based MNCs do not pay a premium for MBA education in India, they do pay a premium for MBA education in the United States. The findings are informative for IT professionals to decide whether to pursue an MBA or invest in gaining firm-specific experience. The results also provide indirect evidence that MNCs apply a portfolio approach to optimize their profits by using knowledge workers in various locations based on their skills and costs.
From Bricks to an Edifice: Cultivating Strong Inference in Information Systems Research
Authors: Tiwana Amrit , Kim Stephen K.
Published: August 2019

MIS research studies often account for prior empirical research findings (i.e., they empirically cumulate) but do not conceptually build atop their ideas and those in adjacent research streams (i.e., they are theoretically less cumulative than they can be). An analogy for disciplines such as ours is that we end up making high-quality, standalone bricks when the intent all along was to build an edifice. We develop two philosophy-of-science ideas—nomological rubberbanding and retroduction—to help cultivate greater theoretical cumulation by shifting the MIS research community’s thinking from “weak” to “strong” inference. This shift characterizes faster-progressing disciplines such as molecular biology and nuclear physics. We use the IT-outsourcing literature to illustrate the application of the two ideas developed here. The two-pronged approach advocated here leverages the cross-disciplinary nature of the MIS discipline, the diversity of research traditions that it encompasses, and its strong culture of empirical cumulation.
Mobile App Introduction and Online and Offline Purchases and Product Returns
Authors: Narang Unnati , Shankar Venkatesh
Published: August 2019

This paper models the relationship between a retailer’s mobile app launch and product purchases and returns in its online and offline channels.