bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Tobacco Advertising Appeal With Intentions to Use Alternative Tobacco Products Among Young Tobacco Users Experiencing Homelessness
Authors: Shadel William G. , Tucker Joan S. , Seelam Rachana , Golinelli Daniela , Siconolfi Daniel
Published: October 2019

Purpose:

Virtually nothing is known about the potential effects of tobacco advertising on tobacco use among youth experiencing homelessness, a vulnerable population with high tobacco use rates. This study examines associations between the appeal of advertising for 5 classes of tobacco product (electronic cigarettes, hookah, cigars, cigarillos, and smokeless tobacco) and future intentions to use those products again among homeless youth who had indicated any level of lifetime use.

Design:

A cross-sectional design was used.

Setting:

Settings were 25 service and street sites in Los Angeles County.

Participants:

A probability sample of 469 young tobacco users experiencing homelessness (mean age = 22; 71% male; 29% non-Hispanic White) was recruited.

Measures:

Assessments included product-specific tobacco advertising appeal and future intentions to use the product again, as well as a range of covariate controls (eg, demographics, homelessness severity, current tobacco use, general advertising exposure).

Analysis:

Linear regression tested for associations between the appeal of advertising for a specific tobacco product and intentions to use that product again in the future, controlling for myriad covariates.

Results:

Advertising appeal was positively associated with future intentions to use again for electronic cigarettes ( P = .006) and hookah ( P = .001), but not cigars ( P = .486), cigarillos ( P = .126), or smokeless tobacco ( P = .109).

Conclusion:

Results suggest that advertising appeal may increase use of certain tobacco products among youth experiencing homelessness. However, differences in themes emphasized by advertising for specific tobacco products could differentially influence use in this population.
Development and Implementation of a Pharmacy Technician Medication History Program
Authors: Davidson Tamara R. , Hobbins Melissa A. , Blubaugh Charlene M.
Published: October 2019

Purpose:

The development and implementation of a pharmacy technician medication history program, current experience with the program, and control elements are described.

A pharmacy technician medication history program was developed and implemented at a large community teaching hospital at the recommendation of a system-wide interdisciplinary medication reconciliation core team to improve the current process. Important initial steps included creation of a high-level plan for program rollout, determination of program scope and design, evaluation of staffing and workspace needs, and identification of training requirements. Development of a data collection plan for the analysis of process and outcomes measures was established to support program continuation and expansion. At the pharmacy level, regularly scheduled meetings were held to gather feedback and implement changes as the program expanded in services and scope. Educational materials were revised and additional resources created to maintain consistency with technician education. Incorporation of control elements such as monthly review of process measure data, biannual accuracy validation, and annual competency assessment helped affirm program sustainability. Throughout program implementation, the importance of using an interdisciplinary approach and establishing strong interprofessional relationships were identified as key elements for continued success.

Conclusion:

A successful medication history program utilizing pharmacy technicians to gather medication information can be implemented and maintained through the use of standardized training documents, regularly scheduled meetings for feedback and education, and continued interdisciplinary collaboration.
The Looming Geriatrician Shortage: Ramifications and Solutions
Authors: Lester Paula E. , Dharmarajan T. S. , Weinstein Eleanor
Published: October 2019

Objective: Geriatricians are skilled in the recognition of asymptomatic and atypical presentations that occur in the elderly and provide comprehensive medication management including recognizing adverse drug events, reducing polypharmacy, and de-prescribing. However, despite the increasing average age of the U.S. population, with the number of individuals above 65 years old predicted to increase 55% by 2030, the geriatric workforce capacity in the United States has actually decreased from 10,270 in 2000 to 8,502 in 2010. Method: We describe physiologic changes in older adults, historical trends in geriatric training, and propose solutions for this looming crisis. Results: Many factors are responsible for the shortage of skilled geriatric providers. Discussion: We discuss the historical context of the lack of geriatricians including changes to the training system, describe the impact of expert geriatric care on patient care and health system outcomes, and propose methods to improve recruitment and retention for geriatric medicine.
‘As syllable from sound’: the sonic dimensions of confinement at the State Hospital for the Insane at Worcester, Massachusetts
Authors: Bourque Kearin Madeline
Published: October 2019

As the first state hospital in the USA, the Worcester State Hospital for the Insane at Worcester, Massachusetts (est. 1833), set a precedent for asylum design and administration that would be replicated across the country. Because the senses were believed to provide a direct conduit into a person’s mental state, the intended therapeutic force of the Worcester State Hospital resided in its particular command over sensory experience. In this paper, I examine how aurality was used as an instrument in the moral architecture of the asylum; how the sonic design of the asylum collided with the day-to-day logistics of institutional management; and the way that patients experienced and engaged with the resultant patterns of sound and silence.
Impact of stringent response in proteinuria on long-term renal outcomes in proliferative lupus nephritis
Authors: Won J , Lee J S , Oh J S , Kim Y-G , Lee C-K , Yoo B , Hong S
Published: October 2019

Objectives

Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN.

Methods

We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD).

Results

The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% ( p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063–0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047–0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894–59.089, p = 0.064).

Conclusion

Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.
Pauli Murray: The US firebrand’s unique opportunity to influence a continent
Authors: Dabscheck Braham
Published: October 2019

This review article discusses Rosalind Rosenberg’s study of Pauli Murray’s pivotal role in enhancing the civil rights of African Americans and American women. Pauli Murray should be properly regarded as one of the leading legal thinkers of Twentieth-Century America. She played a role in the development of the jurisprudential thinking, which brought about an end to race discrimination as enshrined in the ‘separate but equal’ doctrine in the Supreme Court’s 1896 decision in Plessy v. Ferguson and ending sex discrimination beginning with the Supreme Court’s 1971 decision in Reed v. Reed. The objective of this review article is to provide an account of her approach to attacking both legally based race and sex discrimination. Drawing on Rosenberg and referencing key legal texts, it begins with a brief account of Murray’s life and times. This is followed by an examination of her thinking on both race and sex discrimination. The review concludes by commending Rosenberg for her analysis of the intersections between the private and public personas of Pauli Murray in a century which witnessed fundamental changes in America.
Understanding the Minority Voice in a Pluralistic Society: The Case of Islamic Schools
Authors: Shatara Leila H. , Barakat Maysaa , Bourkiza Mounir
Published: October 2019

With a growing number of faith-based private schools, charter schools, and public schools divided along ethnic and racial lines, the school system in the United States is becoming more segregated. This study aims to examine the reasons some Muslim parents choose Islamic schools over other school options and aspires to inform district and school-based administrators of what could be done to make public schools more responsive to the needs of Muslim students.
Application of Artificial Intelligence in the Health Care Safety Context: Opportunities and Challenges
Authors: Ellahham Samer , Ellahham Nour , Simsekler Mecit Can Emre
Published: October 2019

There is a growing awareness that artificial intelligence (AI) has been used in the analysis of complicated and big data to provide outputs without human input in various health care contexts, such as bioinformatics, genomics, and image analysis. Although this technology can provide opportunities in diagnosis and treatment processes, there still may be challenges and pitfalls related to various safety concerns. To shed light on such opportunities and challenges, this article reviews AI in health care along with its implication for safety. To provide safer technology through AI, this study shows that safe design, safety reserves, safe fail, and procedural safeguards are key strategies, whereas cost, risk, and uncertainty should be identified for all potential technical systems. It is also suggested that clear guidance and protocols should be identified and shared with all stakeholders to develop and adopt safer AI applications in the health care context.
Integrating Lean Thinking and Implementation Science Determinants Checklists for Quality Improvement: A Scoping Review
Authors: Standiford Taylor , Conte Marisa L. , Billi John E. , Sales Anne , Barnes Geoffrey D.
Published: October 2019

It is not known how often lean tools and implementation determinants frameworks or checklists are used concurrently in health care quality improvement activities. The authors systematically reviewed the literature for studies that used a lean tool along with an implementation science determinants framework (January 1999 through August 2018). Seven studies (8 publications) were identified, inclusive of 2 protocols and 6 research articles across multiple continents. All included studies used the consolidated framework for implementation research as their implementation science determinants framework. Lean tools included in more than 1 publication were process mapping (4 publications), process redesign (3 publications), and 5S standardization (2 publications). Only 1 study proposed using a lean tool concurrently with an implementation science determinants framework in the design and execution of the QI project. Few published studies utilize both an implementation science determinants framework or checklist and 1 or more lean tool in their study design.
Violent Life in an Inclusive Classroom: Come on, Read, Peter! Moving From Moral Judgment to an Onto-Epistemological Ethics
Authors: Van de Putte Inge , De Schauwer Elisabeth , Van Hove Geert , Davies Bronwyn
Published: October 2019

In this article, we begin with a story in which a teacher is perceived as cruel, a boy experiences exclusion, and a support worker feels guilty for not responding. Working together with students, we have written a play script that explores the entangled intra-active perceptions of the various players. The script was used in the professional development of educators as a means of exploring the diffractive movements through which differences are made in inclusive classrooms. It opens the possibility of moving away from thinking in terms of individual accountability toward an intra-active exploration of the ethics of such encounters.
Effect of isometric handgrip exercise on the size of cephalic veins in patients with stage 3 and 4 chronic kidney disease: A randomized controlled trial
Authors: Kumar A/L S Katheraveloo Krishna , Suryani Safri Lenny , Guo Hou Loo , Hafiz Maliki Aminnur , Md Idris Mohamad Azim , Harunarashid Hanafiah
Published: October 2019

Background:

Proper vascular access is essential for the long-term survival of chronic haemodialysis patients. The preferred vascular access in terms of long-term function is the native arteriovenous fistula. The success of native arteriovenous fistula depends mainly on a sufficient vein diameter. Thus, any intervention that could increase vein diameter before arteriovenous fistula creation could improve its patency. We conduct a study to investigate the effect of local physical training, namely handgrip exercise, on the distal forearm cephalic vein diameter in patients with chronic renal disease.

Material and methods:

A total of 34 chronic renal disease patients (stage 3 and 4) were recruited in a randomized controlled trial. Handgrip exercise was performed for 8 weeks in the intervention group. Handgrip-strength measurement and distal forearm cephalic vein diameter of a non-dominant hand with and without tourniquet was recorded (measurement is taken 1 cm proximal to the radial styloid).

Results:

After 8 weeks, the mean cephalic vein diameter in the intervention group increased from 1.77 and 1.97 mm to 2.15 and 2.43 mm, without and with a tourniquet, respectively ( p < 0.05). There is also a significant change in the mean diameter of distal forearm cephalic vein ( p < 0.05) in the intervention group when measured in both the absence (mean change 0.39 ± 0.06 mm vs 0.01 ± 0.02 mm) and the presence of tourniquet (mean change 0.47 ± 0.07 mm vs 0.01 ± 0.01 mm).

Conclusion:

These findings suggest that non-invasive handgrip exercise can increase in the diameter of the distal forearm cephalic vein, thereby increasing the rate of successful arteriovenous fistula creation.
The effect of auricular therapy on blood pressure: A systematic review and meta-analysis
Authors: Gao JiaLiang , Chen Guang , He HaoQiang , Liu Chao , He QingYong , Li Jun , Wang Jie
Published: October 2019

Background:

Although a number of clinical studies have investigated the effectiveness and safety of auricular therapy for treating hypertension, the overall evidence remains uncertain.

Aims:

We aimed to evaluate the evidence for the effect of auricular therapy on blood pressure using meta-analysis methodology.

Methods:

We searched PubMed, Embase, Cochrane Library databases, Clinicalkey, China National Knowledge Infrastructure, China Scientific Journal Database and Wanfang Database and Chinese Biomedicine for trials that compared the effects of auricular therapy to that of sham auricular therapy, antihypertensive drugs, or no intervention on blood pressure. Blood pressure values before and after treatment, magnitude of blood pressure change between baseline and post-intervention, and the efficacy rate, as outcomes, were synthesized by RevMan 5.3. Continuous outcomes were expressed as weighted mean differences, and dichotomous data were expressed as relative risks with 95% confidence intervals.

Results:

We systematically reviewed 44 randomized controlled trials (involving 5022 patients through June 2018). Auricular acupressure plus antihypertensive drugs might be more effective than antihypertensive drugs alone in both reducing systolic blood pressure value after treatment ( n=464 patients; mean difference, −5.06 mm Hg; 95% confidence interval, –6.76– −3.36, p<0.00001; I2=32%), decreasing diastolic blood pressure after treatment ( n=464 patients; mean difference, −5.30 mm Hg; 95% confidence interval, –6.27– −4.33, p<0.00001; I2=0%) and the efficacy rate (relative risk, 1.22; 95% confidence interval, 1.17–1.26; p<0.00001; I2=0%).

Conclusion:

Auricular therapy could be provided to patients with hypertension as an adjunct to antihypertensive drugs for lowering blood pressure value and achieving blood pressure targets.
Overview of endovascular thrombectomy accessibility gap for acute ischemic stroke in Asia: A multi-national survey
Authors: Tsang Anderson Chun On , Yang I-Hsiao , Orru Emanuele , Nguyen Quang-Anh , Pamatmat Roselyn V , Medhi Gorky , Wan Yue , Huang Song
Published: October 2019

Endovascular thrombectomy revolutionized the treatment of acute ischemic stroke. Nevertheless, access to endovascular thrombectomy is limited in many parts of the world. Asia holds 60% of the world’s population and its countries carry some of the highest stroke disease burden. To understand the availability of endovascular thrombectomy and intravenous thrombolysis in this region, we interviewed stroke neurologists and neuro-interventionists of 19 Asian countries, and found a large disparity in access to endovascular thrombectomy and intravenous thrombolysis between high- and low-income countries. Lack of neuro-interventionists, comprehensive stroke units, stroke triage systems and high treatment cost are the major obstacles to wider accessibility of endovascular thrombectomy, especially among developing countries. The potential solutions to provide equitable access to stroke revascularization therapy are discussed.
Reliability assessment in dynamic field environment incorporating multiple environmental effects
Authors: Cai Yikun , Zhao Yu , Ma Xiaobing , Zhou Kun
Published: October 2019

The product’s reliability is influenced by multiple environmental factors in the dynamic field environment. In this article, a field reliability assessment method is proposed. This method links the effects of multiple environmental factors in the dynamic field environment to the product’s reliability with the acceleration models. Three environmental modeling methods are developed taking into full consideration the variability, dependency, and randomness of the field environment. Then the three methods are applied to calculate the acceleration factor for the material exposed to the corrosive atmosphere and the time-to-whisker-nucleation for semiconductor devices, incorporating the nonlinear acceleration effects of multiple environmental factors. The results are more accurate and significantly better than conventional reliability assessment methods. The method can help to study the influence of environmental factors on the failure process and predict the product’s life and reliability in a dynamic field environment.
Systematic review of cardiac rehabilitation guidelines: Quality and scope
Authors: Mehra Vrati M , Gaalema Diann E , Pakosh Maureen , Grace Sherry L
Published: October 2019

Cardiac rehabilitation is a comprehensive model of secondary prevention proven to reduce mortality and morbidity. The World Health Organization is developing a Package of Rehabilitation Interventions for implementation by ministries of health as part of universal healthcare across the continuum. Through a systematic review, we sought to identify the best-quality cardiac rehabilitation guidelines, and extract their recommendations for implementation by member states. A systematic search was undertaken of academic databases and guideline repositories, among other sources, through to April 2019, for English-language cardiac rehabilitation guidelines from the last 10 years, free from conflicts, and with strength of recommendations. Two authors independently considered all citations. Potentially eligible guidelines were rated for quality using the Appraisal of Guidelines for Research and Evaluation tool, and for other characteristics such as being multi-professional, comprehensive and international in perspective; the latter criteria were used to inform selection of 3–5 guidelines meeting inclusion criteria. Equity considerations were also extracted. Altogether, 2076 unique citations were identified. Thirteen passed title and abstract screening, with six guidelines potentially eligible for inclusion in the Package of Rehabilitation Interventions and rated for quality; for two guidelines the Appraisal of Guidelines for Research and Evaluation tool ratings did not meet World Health Organization minimums. Of the four eligible guidelines, three were selected: the International Council of Cardiovascular Prevention and Rehabilitation (2016), National Institute for Health and Care Excellence (#172; 2013) and Scottish Intercollegiate Guideline Network (#150; 2017). Extracted recommendations were comprehensive, but psychosocial recommendations were contradictory and diet recommendations were inconsistent. A development group of the World Health Organization will review and refine the recommendations which will then undergo peer review, before open source dissemination for implementation.
Occurrence and characteristics of faecal immunochemical screen‐detected cancers vs non–screen‐detected cancers: Results from a Flemish colorectal cancer screening programme
Authors: van de Veerdonk Wessel , Hoeck Sarah , Peeters Marc , Van Hal Guido , Francart Julie , De Brabander Isabel
Published: October 2019

Background

Colorectal cancer (CRC) and its precursor lesions are detected at an early stage by CRC screening programmes, which reduce CRC‐related mortality. An important quality indicator for CRC screening is the occurrence of interval CRC (IC) between screening rounds. Currently there is no guideline regarding acceptable levels of ICs in CRC screening programmes, and ICs reported in prior work vary considerably.

Methods

This study describes the occurrence of screen‐detected (SD) CRC and non–screen‐detected CRC within the population‐based CRC screening programme of Flanders, stratified by multiple variables such as sex, age, tumour location and tumour stage between October 2013 and July 2017. In addition, faecal immunochemical test (FIT) IC proportions over the sum of SD‐CRCs and FIT‐ICs are calculated, together with FIT sensitivity and programme sensitivity to display the effectiveness of detecting CRC by the screening programme.

Results

Of 1,212,354 FIT participants, 4094 were diagnosed with SD‐CRC, whereas 772 participants were diagnosed with CRC between FIT‐screening rounds. Significant associations were shown between people not being SD for CRC and women, older individuals, right‐sided tumour location and more advanced tumour stage. Furthermore, a clear distinction was shown between the right‐sided and the left‐sided colorectum concerning all above‐mentioned variables and distributions of tumour stages.

Conclusion

The Flemish FIT‐interval CRC proportion of 15.9% was within the limits of previously published results. In addition, calculations show that the effectiveness of the screening programme is dependent on tumour location, suggesting that future research should report results stratified by location.
Messages From Former Students and Families: Analysis of Statements From One State’s Post-School Outcomes Survey
Authors: Alverson Charlotte Y. , Yamamoto Scott H.
Published: October 2019

We conducted an exploratory descriptive qualitative study on extant data of responses to the state’s open-ended question from their annual post-school outcomes survey: “ If you could tell your school one thing, what would you tell them (make a suggestion to help better prepare current students for life after high school)?” Respondents from one northwest state consisted of former students with disabilities who had been out of school for 1 year or their designee. We analyzed 1,493 statements using consensual qualitative research–modified (CQR-M) method: a modification of CQR in which large quantities of simple qualitative data are analyzed inductively. Findings clustered in four domains: advice, help, satisfaction, and awareness. Implications for stakeholders and recommendations for further research are provided.
Knee Loading After ACL-R Is Related to Quadriceps Strength and Knee Extension Differences Across the Continuum of Care
Authors: Garrison J. Craig , Hannon Joseph , Goto Shiho , Kosmopoulos Victor , Aryal Subhash , Bush Curtis , Bothwell James M. , Singleton Steven B.
Published: October 2019

Background:

Quadriceps strength and knee extension are believed to be important in the ability to effectively load the knee after anterior cruciate ligament (ACL) reconstruction (ACL-R).

Purpose:

To compare quadriceps strength (QUADS), side-to-side knee extension difference (ExtDiff), and knee energy absorption contribution (EAC) in patients preoperatively, 12 weeks postoperatively, and at return to sport (RTS). A secondary aim was to determine how the factors of QUADS and ExtDiff contributed to the ability to load the knee (knee EAC) at each of the 3 time points.

Study Design:

Case series; Level of evidence, 4.

Methods:

Overall, 41 individuals (mean ± SD age, 15.95 ± 1.63 years) were enrolled in this study. QUADS, ExtDiff, and knee EAC during a double-limb squat were collected preoperatively, 12 weeks postoperatively, and at RTS. Isokinetic QUADS was collected at 60 deg/s, normalized to body mass, and averaged across 5 trials. Knee extension was measured with a goniometer, and ExtDiff was calculated for analyses. Knee EAC was measured during double-limb squat descent and was calculated as a percentage of total energy absorption for the limb. Observations were obtained from both the surgical and nonsurgical limbs at the 3 time points. A mixed regression model with random intercept to compare change over the 3 time points was used, and a model selection was conducted with Akaike information criteria. Significance was set at P < .05.

Results:

Surgical limb QUADS was significantly lower preoperatively (mean ± SD, 1.37 ± 0.49 N·m/kg; P = .0023) and at 12 weeks (1.11 ± 0.38 N·m/kg; P < .0001) than at RTS (1.58 ± 0.47 N·m/kg). Nonsurgical limb QUADS was also significantly lower preoperatively (2.01 ± 0.54 N·m/kg; P < .0256) and at 12 weeks (2.03 ± 0.48 N·m/kg; P < .0233) than at RTS (2.18 ± 0.54 N·m/kg). Knee EAC for the surgical limb was significantly lower at 12 weeks than at RTS (40.98% ± 13.73% vs 47.50% ± 12.04%; P < .0032), and ExtDiff was significantly greater preoperatively than at RTS (–2.68° ± 3.19° vs –0.63° ± 1.43°; P < .0001). Preoperatively, QUADS for both the surgical ( P < .0003) and nonsurgical ( P = .0023) limbs was a significant predictor of surgical limb knee EAC, explaining 33.99% of the variance. At 12 weeks, surgical limb QUADS was a significant predictor ( P < .0051) of surgical limb knee EAC, explaining 18.83% of the variance. At RTS, ExtDiff was a significant predictor ( P = .0201) of surgical limb knee EAC, explaining 12.92% of the variance.

Conclusion:

The ability to load the knee after ACL injury changes across the continuum of care and is related to QUADS and ExtDiff. These results provide clinicians with insight into potential contributing factors that may limit knee loading during the rehabilitation process.
The politics of disaster vulnerability: Flooding, post-disaster interventions and water governance in Baltistan, Pakistan
Authors: Arifeen Awais , Eriksen Siri
Published: October 2019

This paper uses governance of water infrastructure in two settlements of Baltistan as an entry point to examine the co-production of power and vulnerability. Access to water and irrigated land is a critical factor in determining how the effects of disasters, such as flooding, are socially distributed within a community. At the same time, the governance of water is intimately linked to the longer-term politics of disaster vulnerability. We examine three different forms of disputes over water infrastructure where struggles over authority and social ordering materialise: (i) between and within settlements over access to a water resource; (ii) within settlements over post-disaster water infrastructure development and (iii) between a settlement and the district government over land, water rights and flood protection. The findings illustrate that the governance of water infrastructure involves continuous negotiations, contestations and disputes over access rights. Access to water resources as an expression of rights plays a key role in the recognition of authority relations. In particular, influential individuals seek to legitimise their leadership role in a settlement by representing the rights and interests of groups in the negotiation of these disputes. However, environmental variability and change, including disasters and post-disaster development interventions, alter perceptions of what constitute legitimate rights, and provide spaces for popular contestation of authority relations through silent non-compliance with decisions. The close interlinkages between material and non-material effects of a disaster are a key feature of the co-production of power and vulnerability. By adding authority relations to studies of village-level practices around disasters, we enrich our understanding of the co-production of power and vulnerability and how these dynamics unfold over time. It is only by investigating this co-production that a deeper understanding can be developed of the mechanisms through which vulnerability is either exacerbated or reduced for particular groups.
A homology-guided, genome-based proteome for improved proteomics in the alloploid Nicotiana benthamiana
Authors: Kourelis Jiorgos , Kaschani Farnusch , Grosse-Holz Friederike M. , Homma Felix , Kaiser Markus , van der Hoorn Renier A. L.
Published: October 2019

Background

Nicotiana benthamiana is an important model organism of the Solanaceae (Nightshade) family. Several draft assemblies of the N. benthamiana genome have been generated, but many of the gene-models in these draft assemblies appear incorrect.

Results

Here we present an improved proteome based on the Niben1.0.1 draft genome assembly guided by gene models from other Nicotiana species. Due to the fragmented nature of the Niben1.0.1 draft genome, many protein-encoding genes are missing or partial. We complement these missing proteins by similarly annotating other draft genome assemblies. This approach overcomes problems caused by mis-annotated exon-intron boundaries and mis-assigned short read transcripts to homeologs in polyploid genomes. With an estimated 98.1% completeness; only 53,411 protein-encoding genes; and improved protein lengths and functional annotations, this new predicted proteome is better in assigning spectra than the preceding proteome annotations. This dataset is more sensitive and accurate in proteomics applications, clarifying the detection by activity-based proteomics of proteins that were previously predicted to be inactive. Phylogenetic analysis of the subtilase family of hydrolases reveal inactivation of likely homeologs, associated with a contraction of the functional genome in this alloploid plant species. Finally, we use this new proteome annotation to characterize the extracellular proteome as compared to a total leaf proteome, which highlights the enrichment of hydrolases in the apoplast.

Conclusions

This proteome annotation provides the community working with Nicotiana benthamiana with an important new resource for functional proteomics.
Towards a patient journey perspective on causes of unplanned readmissions using a classification framework: results of a systematic review with narrative synthesis
Authors: Singotani R. G. , Karapinar F. , Brouwers C. , Wagner C. , de Bruijne M. C.
Published: October 2019

Background

Several literature reviews have been published focusing on the prevalence and/or preventability of hospital readmissions. To our knowledge, none focused on the different causes which have been used to evaluate the preventability of readmissions. Insight into the range of causes is crucial to understand the complex nature of readmissions.

With this review we aim to: 1) evaluate the range of causes of unplanned readmissions in a patient journey, and 2) present a cause classification framework that can support future readmission studies.

Methods

A literature search was conducted in PUBMED and EMBASE using “readmission” and “avoidability” or “preventability” as key terms. Studies that specified causes of unplanned readmissions were included. The causes were classified into eight preliminary root causes: Technical, Organization (integrated care), Organization (hospital department level), Human (care provider), Human (informal caregiver), Patient (self-management), Patient (disease), and Other. The root causes were based on expert opinions and the root cause analysis tool of PRISMA (Prevention and Recovery Information System for Monitoring and Analysis). The range of different causes were analyzed using Microsoft Excel.

Results

Forty-five studies that reported 381 causes of readmissions were included. All studies reported causes related to organization of care at the hospital department level. These causes were often reported as preventable. Twenty-two studies included causes related to patient’s self-management and 19 studies reported causes related to patient’s disease. Studies differed in which causes were seen as preventable or unpreventable. None reported causes related to technical failures and causes due to integrated care issues were reported in 18 studies.

Conclusions

This review showed that causes for readmissions were mainly evaluated from a hospital perspective. However, causes beyond the scope of the hospital can also play a major role in unplanned readmissions. Opinions regarding preventability seem to depend on contextual factors of the readmission. This study presents a cause classification framework that could help future readmission studies to gain insight into a broad range of causes for readmissions in a patient journey.

In conclusion, we aimed to: 1) evaluate the range of causes for unplanned readmissions, and 2) present a cause classification framework for causes related to readmissions.
Opportunities and challenges for the inclusion of patient preferences in the medical product life cycle: a systematic review
Authors: Janssens Rosanne , Huys Isabelle , van Overbeeke Eline , Whichello Chiara , Harding Sarah , Kübler Jürgen , Juhaeri Juhaeri , Ciaglia Antonio , Simoens Steven , Stevens Hilde , Smith Meredith , Levitan Bennett , Cleemput Irina , de Bekker-Grob Esther , Veldwijk Jorien
Published: October 2019

Background

The inclusion of patient preferences (PP) in the medical product life cycle is a topic of growing interest to stakeholders such as academics, Health Technology Assessment (HTA) bodies, reimbursement agencies, industry, patients, physicians and regulators. This review aimed to understand the potential roles, reasons for using PP and the expectations, concerns and requirements associated with PP in industry processes, regulatory benefit-risk assessment (BRA) and marketing authorization (MA), and HTA and reimbursement decision-making.

Methods

A systematic review of peer-reviewed and grey literature published between January 2011 and March 2018 was performed. Consulted databases were EconLit, Embase, Guidelines International Network, PsycINFO and PubMed. A two-step strategy was used to select literature. Literature was analyzed using NVivo (QSR international).

Results

From 1015 initially identified documents, 72 were included. Most were written from an academic perspective (61%) and focused on PP in BRA/MA and/or HTA/reimbursement (73%). Using PP to improve understanding of patients’ valuations of treatment outcomes, patients’ benefit-risk trade-offs and preference heterogeneity were roles identified in all three decision-making contexts. Reasons for using PP relate to the unique insights and position of patients and the positive effect of including PP on the quality of the decision-making process. Concerns shared across decision-making contexts included methodological questions concerning the validity, reliability and cognitive burden of preference methods. In order to use PP, general, operational and quality requirements were identified, including recognition of the importance of PP and ensuring patient understanding in PP studies.

Conclusions

Despite the array of opportunities and added value of using PP throughout the different steps of the MPLC identified in this review, their inclusion in decision-making is hampered by methodological challenges and lack of specific guidance on how to tackle these challenges when undertaking PP studies. To support the development of such guidance, more best practice PP studies and PP studies investigating the methodological issues identified in this review are critically needed.
Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion
Authors: Packer Milton
Published: October 2019

Four large-scale trials in type 2 diabetes have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the occurrence of serious heart failure events. Additionally, the DAPA-HF trial demonstrated a benefit of dapagliflozin to reduce major adverse outcomes in patients with established heart failure with a reduced ejection fraction. The trial sheds light on potential mechanisms. In DAPA-HF, the benefits of dapagliflozin on heart failure were seen to a similar extent in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related cardiotoxicity. The action of SGLT2 inhibitors to promote ketogenesis is also primarily a feature of the action of these drugs in patients with diabetes, raising doubts that enhanced ketogenesis contributes to the benefit on heart failure. Also, dapagliflozin does not have a meaningful effect to decrease circulating natriuretic peptides, and it did not potentiate the actions of diuretics in DAPA-HF; moreover, intensification of diuretics therapy does not reduce cardiovascular death, questioning a benefit of SGLT2 inhibitors that is mediated by an action on renal sodium excretion. Finally, although hematocrit increases with SGLT2 inhibitors might favorably affect patients with coronary artery disease, in DAPA-HF, the benefit of dapagliflozin was similar in patients with or without an ischemic cardiomyopathy; furthermore, increases in hematocrit do not favorably affect the clinical course of patients with heart failure. Therefore, the results of DAPA-HF do not support many currently-held hypotheses about the mechanism of action of SGLT2 inhibitors in heart failure. Ongoing trials are likely to provide further insights.
KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RARα
Authors: Wang Xinrui , Fan Huiyong , Xu Congling , Jiang Guojuan , Wang Haiwei , Zhang Ji
Published: October 2019

Background

A hallmark of acute promyelocytic leukemia (APL) is the expression of PML/RARα fusion protein. Treatment with all-trans retinoic acid (ATRA) results in the terminal differentiation of neutrophil granulocytes. However, the underlying mechanisms remain largely unknown. Here, we identify and elucidate a novel differentiation-suppressive model of APL involving the histone demethylase KDM3B, which has been identified as a suppressor of the tumor genes involved in hematopoietic malignancies.

Methods

First, we established a KDM3B knockdown NB4 cell model to determine the functional characteristics of KDM3B by cell proliferation assay and flow cytometry. Then, we performed ChIP-seq and ATAC-seq to search for potential relationships among KDM3B, histone modification (H3K9me1/me2) and the chromatin state. Finally, molecular biological techniques and a multi-omics analysis were used to explore the role of KDM3B in differentiation of the leukemia cells after ATRA treatment.

Results

We found that knocking down KDM3B contributed to the growth of NB4 APL cells via the promotion of cell-cycle progression and blocked granulocytic differentiation. Through global and molecular approaches, we provided futher evidence that knocking down KDM3B altered the global distribution of H3K9me1/me2 and increased the chromatin accessibility. Moreover, knocking down KDM3B inhibited the ATRA-induced degradation of the PML/RARα oncoprotein.

Conclusion

Our study suggested that KDM3B was able to inhibit APL progression by maintaining chromatin in a compact state and facilitating the ATRA-mediated degradation of PML/RARα. Taken together, the results show that KDM3B may be an alternative target for the treatment regimens and the targeted therapy for APL by sustaining the function of PML/RARα fusion protein.
The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway
Authors: He Feng , Xiao Zonghui , Yao Hailan , Li Sen , Feng Miao , Wang Wei , Liu Zhewei , Liu Zhuo , Wu Jianxin
Published: October 2019

Background

The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear.

Methods

We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus.

Results

We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time.

Conclusions

miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.
Natural Language Processing Approaches to Detect the Timeline of Metastatic Recurrence of Breast Cancer
Authors: Banerjee Imon , Bozkurt Selen , Caswell-Jin Jennifer Lee , Kurian Allison W. , Rubin Daniel L.
Published: October 2019

PURPOSE

Electronic medical records (EMRs) and population-based cancer registries contain information on cancer outcomes and treatment, yet rarely capture information on the timing of metastatic cancer recurrence, which is essential to understand cancer survival outcomes. We developed a natural language processing (NLP) system to identify patient-specific timelines of metastatic breast cancer recurrence.

PATIENTS AND METHODS

We used the OncoSHARE database, which includes merged data from the California Cancer Registry and EMRs of 8,956 women diagnosed with breast cancer in 2000 to 2018. We curated a comprehensive vocabulary by interviewing expert clinicians and processing radiology and pathology reports and progress notes. We developed and evaluated the following two distinct NLP approaches to analyze free-text notes: a traditional rule-based model, using rules for metastatic detection from the literature and curated by domain experts; and a contemporary neural network model. For each 3-month period (quarter) from 2000 to 2018, we applied both models to infer recurrence status for that quarter. We trained the NLP models using 894 randomly selected patient records that were manually reviewed by clinical experts and evaluated model performance using 179 hold-out patients (20%) as a test set.

RESULTS

The median follow-up time was 19 quarters (5 years) for the training set and 15 quarters (4 years) for the test set. The neural network model predicted the timing of distant metastatic recurrence with a sensitivity of 0.83 and specificity of 0.73, outperforming the rule-based model, which had a specificity of 0.35 and sensitivity of 0.88 ( P < .001).

CONCLUSION

We developed an NLP method that enables identification of the occurrence and timing of metastatic breast cancer recurrence from EMRs. This approach may be adaptable to other cancer sites and could help to unlock the potential of EMRs for research on real-world cancer outcomes.