bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining gene network, metabolic and leaf-level models shows means to future-proof soybean photosynthesis under rising CO2
Authors: Kannan Kavya , Wang Yu , Lang Meagan , Challa Ghana S , Long Stephen P , Marshall-Colon Amy 
Published: June 2019

AbstractGlobal population increase coupled with rising urbanization underlies the predicted need for 60% more food by 2050, but produced on the same amount of land as today. Improving photosynthetic efficiency is a largely untapped approach to addressing this problem. Here, we scale modelling processes from gene expression through photosynthetic metabolism to predict leaf physiology in evaluating acclimation of photosynthesis to rising atmospheric concentrations of CO2 ([CO2]). Model integration with the yggdrasil interface enabled asynchronous message passing between models. The multiscale model of soybean (Glycine max) photosynthesis calibrated to physiological measures at ambient [CO2] successfully predicted the acclimatory changes in the photosynthetic apparatus that were observed at 550 ppm [CO2] in the field. We hypothesized that genetic alteration is necessary to achieve optimal photosynthetic efficiency under global change. Flux control analysis in the metabolic system under elevated [CO2] identified enzymes requiring the greatest change to adapt optimally to the new conditions. This predicted that Rubisco was less limiting under elevated [CO2] and should be down-regulated allowing re-allocation of resource to enzymes controlling the rate of regeneration of ribulose-1,5-bisphosphate (RuBP). By linking the Gene Regulatory Network through protein concentration to the metabolic model, it was possible to identify transcription factors (TFs) that matched the up- and down-regulation of genes needed to improve photosynthesis. Most striking was TF Gm-GATA2, which down-regulated genes for Rubisco synthesis while up-regulating key genes controlling RuBP regeneration and starch synthesis. The changes predicted for this TF most closely matched the physiological ideotype that the modelling predicted as optimal for the future elevated [CO2] world.
p53 modifications: exquisite decorations of the powerful guardian
Authors: Liu Yanqing , Tavana Omid , Gu Wei 
Published: June 2019

AbstractThe last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression. The exquisite regulation of p53 functions is of vital importance for cell fate decisions. Among the multiple layers of mechanisms controlling p53 function, posttranslational modifications (PTMs) represent an efficient and precise way. Major p53 PTMs include phosphorylation, ubiquitination, acetylation, and methylation. Meanwhile, other PTMs like sumoylation, neddylation, O-GlcNAcylation, adenosine diphosphate (ADP)-ribosylation, hydroxylation, and β-hydroxybutyrylation are also shown to play various roles in p53 regulation. By independent action or interaction, PTMs affect p53 stability, conformation, localization, and binding partners. Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases, especially in cancers. This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.
Increasing Number and Volume of Cavitary Lesions on Chest Computed Tomography Are Associated With Prolonged Time to Culture Conversion in Pulmonary Tuberculosis
Authors: Hernandez-Romieu Alfonso C , Little Brent P , Bernheim Adam , Schechter Marcos C , Ray Susan M , Bizune Destani , Kempker Russell 
Published: June 2019

Abstract

Background
Cavitary lesions (CLs) primarily identified by chest x-ray (CXR) have been associated with worse clinical outcomes among patients with pulmonary tuberculosis (PTB). Chest computed tomography (CT), which has better resolution and increased sensitivity to detect lung abnormalities, has been understudied in PTB patients. We compared detection of CLs by CT and CXR and assessed their association with time to sputum culture conversion (tSCC).

Methods
This was a retrospective cohort study of 141 PTB patients who underwent CT. We used multivariate Cox proportional hazards models to evaluate the association between CLs on CXR and the number and single largest volume of CLs on CT with tSCC.

Results
Thirty (21%) and 75 (53%) patients had CLs on CXR and CT, respectively. CT detected cavities in an additional 44 patients (31%) compared with CXR. After multivariable adjustment, we observed a negative association between CLs and tSCC, with an adjusted hazard ratio (aHR) of 0.56 (95% confidence interval [CI], 0.32 to 0.97) for single CLs and 0.31 (95% CI, 0.16 to 0.60) for multiple CLs present on CT. Patients with a CL volume ≥25 mL had a prolonged tSCC (aHR, 0.39; 95% CI, 0.21 to 0.72). CLs on CXR were not associated with increased tSCC after multivariable adjustment.

Conclusions
CT detected a larger number of cavities in patients with PTB relative to CXR. We observed an association between increasing number and volume of CLs on CT and delayed tSCC independent of sputum microscopy result. Our findings highlight a potential role for CT in the clinical and research setting as a tool to risk-stratify patients with PTB.
Impact of an Antiretroviral Stewardship Team on the Care of Patients With Human Immunodeficiency Virus Infection Admitted to an Academic Medical Center
Authors: DePuy Ashley M , Samuel Rafik , Mohrien Kerry M , Clayton Elijah B , Koren David E 
Published: June 2019

Abstract

Background
Interdisciplinary antiretroviral stewardship teams, comprising a human immunodeficiency virus pharmacist specialist, an infectious diseases physician, and associated learners, have the ability to assist in identification and correction of inpatient antiretroviral-related errors.

Methods
Electronic medical records of patients with antiretroviral orders admitted to our hospital were evaluated for the number of interventions made by the stewardship team, number of admissions with errors identified, risk factors for occurrence of errors, and cost savings. Risk factors were analyzed by means of multivariable logistic regression. Cost savings were estimated by the documentation system Clinical Measures.

Results
A total of 567 admissions were included for analysis in a 1-year study period. Forty-three percent of admissions (245 of 567) had ≥1 intervention, with 336 interventions in total. The following were identified as risk factors for error: multitablet inpatient regimen (odds ratio, 1.834; 95% confidence interval, 1.160–2.899; P = .009), admission to the intensive care unit (2.803; 1.280–6.136; P = .01), care provided by a surgery service (1.762; 1.082–2.868; P = .02), increased number of days reviewed (1.061; 1.008–1.117; P = .02), and noninstitutional outpatient provider (1.375; .972–1.946; P = .07). The 1-year cost savings were estimated to be $263 428.

Conclusions
Antiretroviral stewardship teams optimize patient care through identification and correction of antiretroviral-related errors. Errors may be more common in patients with multitablet inpatient regimens, admission to the intensive care unit, care provided by a surgery service, and increased number of hospital days reviewed. Once antiretroviral-related errors are identified, the ability to correct them provides cost savings.
Helicobacter pylori infection and the risk of colorectal cancer: a nationwide population-based cohort study
Authors: Liu I-L , Tsai C -H , Hsu C -H , Hu J -M , Chen Y -C , Tian Y -F , You S -L , Chen C -Y , Hsiao C -W , Lin C -Y , Chou Y -C , Sun C -A 
Published: June 2019

Abstract

Background
The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings.

Aims
This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study.

Methods
A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan’s National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC.

Results
The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37–2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection.

Conclusions
Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.
Crowden v Aldridge—the correct approach to variations?
Authors: Saunders James 
Published: June 2019

Abstract
Deeds of variation are often utilised in practice but the manner in which they operate remains obscure. Jonathan Sumption QC’s 1993 decision in Crowden v Aldridge attempted to shed light on the topic but has remained largely untouched ever since. This article reanalyses testamentary variations in order to clarify their mode of operation, essential requirements and broad utility.
Society of Behavioral Medicine position statement: Support the updated hypertension guidelines and modify Medicare Part B to improve hypertension management
Authors: Kang Augustine W , Freedland Kenneth E , Janke Amy , Sumner Jennifer A , Hayman Laura L , Fitzgibbon Marian , Buscemi Joanna , Dulin Akilah 
Published: June 2019

Abstract
Hypertension contributes to significant global health and economic burdens. The American College of Cardiology/American Heart Association’s latest guideline lowers the blood pressure threshold for hypertension, and as a result, the number of adults with hypertension has increased. Hypertension is a major risk factor for cardiovascular morbidity, especially among older adults. Many individuals who are diagnosed with hypertension at the new, lower threshold may benefit from lifestyle counseling, but changes to existing Medicare policies are required to increase utilization of evidence-based lifestyle counseling approaches to hypertension management. We recommend appropriate funding for the reimbursement of evidence-based lifestyle counseling for hypertension management, the expansion of medical nutrition therapy counseling coverage as an option for Medicare beneficiaries with hypertension, the inclusion of home-based blood pressure monitoring devices in the list of Durable Medical Equipment Coverage, and modifications to the Medicare Benefit Policy Manual to prioritize evidence-based programs such as Dietary Approaches to Stop Hypertension, American Heart Association, and plant-predominant dietary programs.
Medication Safety of Patients With Parkinson’s Disease During Care Transitions: Educating Nursing Students
Authors: Ellis Diane M. , Hickey Shelley , Prieto Patricia , Doyle Adeline , Galvin Meghan , Vernon Gwyn , O'Connor Melissa 
Published: June 2019

Abstract
The purpose of this study was to increase awareness and educate undergraduate nursing students and clinical faculty regarding the importance of missed or omitted Parkinson’s disease medications during care transitions. To improve quality and safety among this vulnerable population, an innovative, simulated unfolding case study focusing on incomplete medication reconciliation and omission of time-sensitive medications was conducted. Second-degree BSN students (n = 94) and clinical faculty (n = 7) participated in the study. Pretest/posttest results were compared. Findings indicated increased understanding among students and faculty regarding the impact of medication reconciliation and the timely administration of Parkinson’s disease medication.
Current market trends in anterior ocular inflammatory disease landscape
Authors: Khan Rubba Shoukat , Rizvi Salman , Syed Basharut A. , Bielory Leonard 
Published: June 2019

Purpose of review
In the US anterior ocular inflammatory disease (AOID) composed of the spectrum of ocular allergies, different forms of infectious conjunctivitis, and dry eye diseases, affects over 40% of the population. This review evaluates the current economic costs for AOID associated pharmacotherapies.

Recent findings
In recent years, with improved understanding in pathophysiology of the AOID, providing novel targets for pharmacotherapy, have led to considerable improvements in outcomes for patients. Despite these advances, there continues to be a need for interventions that inhibit key inflammatory mediators or pathways in the ophthalmic space. In 2018, AOID drugs market represents ∼40% of the costs for the total ophthalmic drugs: dry eye (43%), antiinfectives (15%), antiallergics (13%), and antiinflammatory agents (29%). With increasing treatment costs, the need for improved, cost-effective modalities persists along with treatment algorithms to derive optimal benefits for patients.

Summary
There has been a dramatic increase in the economic burden of AOID with the annual expenditure for the prescription drugs approaching close to $11 billion in 2018. With increasing prevalence of ocular disease, further investment is required to provide more effective treatment options and deliver improved public health and economic outcomes.
Are 15-Year Trajectories of Low Back Pain and Sciatica Associated With Cardiovascular Autonomic Function in the General Population?
Authors: Oura Petteri , Hautala Arto , Kiviniemi Antti , Auvinen Juha , Puukka Katri , Tulppo Mikko , Huikuri Heikki , Seppänen Tapio , Karppinen Jaro 
Published: June 2019

Study Design.
A population-based cohort study.

Objective.
The aim of this study was to examine whether 15-year trajectories of low back pain (LBP) and sciatica are associated with cardiovascular autonomic function in a large general population sample.

Summary of Background Data.
Previous studies using mainly small patient samples have suggested that LBP and sciatica are associated with abnormal cardiovascular autonomic function, namely altered heart rate variability (HRV) and baroreflex sensitivity (BRS). We examined this association in a large general population sample.

Methods.
The data collections of the Northern Finland Birth Cohort 1966 consisted of pain questionnaires at 31 and 46 years (history of LBP, sciatica, and other musculoskeletal pains during the previous year; yes/no for each) and measurements of HRV and BRS at 46 years (heart rate, HR; root mean square of successive differences in beat-to-beat intervals, rMSSD; low-frequency systolic blood pressure variability, SBPV; cross-spectral BRS, BRS; each while seated and standing). The data collections also comprised several confounders. Trajectories for LBP, sciatica, and both together (“no pain,” “decreasing,” “increasing,” “long-term pain”) were constructed and general linear models were used to perform comparisons between trajectories (for HR/rMSSD, n = 3398; for SBPV/BRS, n = 1667).

Results.
In the crude models, LBP and sciatica were associated with higher HR, lower rMSSD, higher SBPV, and lower BRS, but these associations were mostly attenuated by adjustments. Regarding both LBP and sciatica, only the “increasing” trajectory was associated with two of the eight outcomes (standing SBPV, seated BRS) after adjustments. Regarding LBP, the “increasing” trajectory was associated with three (standing SBPV, seated BRS, standing BRS), the “long-term pain” trajectory with one (standing BRS), and the “decreasing” trajectory with one outcome (seated SBPV) after adjustments. Sciatica showed no association with the outcomes after adjustments.

Conclusion.
We conclude that the 15-year trajectories of LBP and sciatica do not have a consistent independent association with cardiovascular autonomic function among the general population.

Level of Evidence: 3
Postoperative Resolution of MR T2 Increased Signal Intensity in Cervical Spondylotic Myelopathy
Authors: Machino Masaaki , Ando Kei , Kobayashi Kazuyoshi , Ota Kyotaro , Morozumi Masayoshi , Tanaka Satoshi , Ito Keigo , Kato Fumihiko , Ishiguro Naoki , Imagama Shiro 
Published: June 2019

Study Design.
A prospective comparative imaging study.

Objective.
This study investigated whether postoperative resolution of spinal cord increased signal intensity (ISI) reflected symptom improvement and surgical outcomes in cervical spondylotic myelopathy (CSM) patients.

Summary of Background Data.
Although some CSM patients exhibit magnetic resonance imaging (MRI) ISI, its alteration and resolution have not been investigated. The association between postoperative ISI resolution and surgical outcomes in CSM patients remains controversial.

Methods.
A total of 505 consecutive CSM patients (311 males; 194 females) aged a mean of 66.6 years (range, 41–91) were enrolled. All were treated with laminoplasty and underwent MRI scans preoperatively and after an average of 26.5 months postoperatively (range 12–66 months). ISI was classified pre- and postoperatively based on sagittal T2-weighted magnetic resonance images into Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The patients’ pre- and postoperative neurological statuses were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy [Japanese Orthopedic Association (JOA) score] and other quantifiable tests, including the 10-s grip and release (10-s G&R) test and 10-s step test.

Results.
A total of 337 patients showed preoperative ISI. Among these, 42 (12.5%) showed postoperative ISI resolution, associated with better postoperative JOA score and recovery rate, 10-s G&R and 10-s step test scores than those who retained it. Patients with preoperative Grade 2 ISI had no postoperative ISI resolution. Patients with ISI improvement from Grade 1 to Grade 0 had better outcomes than those with ISI worsening from Grade 1 to Grade 2.

Conclusion.
Postoperative ISI resolution in CSM patients reflects postoperative symptoms and surgical outcomes. Patients who exhibit ISI resolution have better clinical outcomes.

Level of Evidence: 3
Follicular lymphomas in vulnerable/older patients
Authors: Tucci Alessandra , Rossi Giuseppe 
Published: June 2019

Purpose of review
Unlike for diffuse large-cell lymphoma, both the management of elderly patients with follicular lymphoma and the role of comprehensive geriatric evaluation to optimize treatment choices have been rarely addressed. This review analyses available evidence on follicular lymphoma occurring in aged persons.

Recent findings
Most retrospective studies and expert recommendations agree that the diagnostic approach and the treatment algorithm in elderly follicular lymphoma should not differ from younger patients up to the age of 80. However, slowly progressing follicular lymphoma low-tumor burden should start treatment even though asymptomatic. Prospective identification of those unfit patients is needed where a treatment deintensification may not be detrimental. Octogenarians have more aggressive disease and do not benefit from chemoimmunotherapy more than from single-agent rituximab. An activity of daily living loss significantly impact on their outcome and specific prognostic scores may help in the better manage these oldest patients.

Summary
Given the lack of prospective studies there is an urgent need to investigate if geriatric assessment including comorbidities, geriatric parameters, patient's reported outcomes and quality of life issues, may help selecting those frail elderly follicular lymphoma patients less suitable for full-dose treatments. In addition, the potential usefulness of the new noncytotoxic agents of proven efficacy in follicular lymphoma warrants specific investigations in older patients.
miR-222 expression is correlated with the ATA risk stratifications in papillary thyroid carcinomas∗
Authors: Xiang Dapeng , Tian Bin , Yang Tianyao , Li Zhiyu 
Published: June 2019

Abstract

Background:
miR-222 is one of the most consistently overexpressed miRNAs in papillary thyroid carcinoma (PTC). Previous studies demonstrated that miR-222 overexpression conferred high-risk features in PTC patients, suggesting its value in risk-stratification. However, studies in term of miR-222's utility on stratifying PTCs are lacking.

Methods:
One hundred patients including 10 with multinodular goiter and 90 with PTC were enrolled. Formalin-fixed paraffin-embedded samples were exploited for miR-222 quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Correlations between miR-222 expression and different clinicopathological features, Tumor-node-metastasis (TNM) staging and ATA risk level were analyzed.

Results:
miR-222 expression of the PTC group was significantly higher than that of the goiter group (P < .001). Furthermore, miR-222 expression was significantly higher in PTCs with advanced features like larger tumor, capsular invasion, vascular invasion and lymph nodes metastasis. The majority of patients (61%) were in stage I group (similar to ATA low-risk) by TNM staging system. As to the ATA system, the majority (73%) were in intermediate-risk group (similar to TNM stage II and III roughly). Contrary to previous report, here we found that miR-222 expression was correlated with the ATA risk level (P < .001), but not with the TNM staging (P = .122).

Conclusion:
In the present study, we demonstrated that miR-222 overexpression was correlated with advanced features like capsular invasion, vascular invasion, larger tumor size and lymph node metastasis in PTCs. Most importantly, miR-222 expression was correlated with ATA risk levels, suggesting its potential value in PTC risk-stratification.