bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leaf heteroblasty in Passiflora edulis as revealed by metabolic profiling and expression analyses of the microRNAs miR156 and miR172
Authors: Silva Priscila O , Batista Diego S , Cavalcanti João Henrique F , Koehler Andréa D , Vieira Lorena M , Fernandes Amanda M , Barrera-Rojas Carlos Hernan , Ribeiro Dimas M , Nogueira Fabio T S , Otoni Wagner C 
Published: February 2019

Abstract

Background and Aims
Juvenile-to-adult phase transition is marked by changes in leaf morphology, mostly due to the temporal development of the shoot apical meristem, a phenomenon known as heteroblasty. Sugars and microRNA-controlled modules are components of the heteroblastic process in Arabidopsis thaliana leaves. However, our understanding about their roles during phase-changing in other species, such as Passiflora edulis, remains limited. Unlike Arabidopsis, P. edulis (a semi-woody perennial climbing vine) undergoes remarkable changes in leaf morphology throughout juvenile-to-adult transition. Nonetheless, the underlying molecular mechanisms are unknown.

Methods
Here we evaluated the molecular mechanisms underlying the heteroblastic process by analysing the temporal expression of microRNAs and targets in leaves as well as the leaf metabolome during P. edulis development.

Key Results
Metabolic profiling revealed a unique composition of metabolites associated with leaf heteroblasty. Increasing levels of glucose and α-trehalose were observed during juvenile-to-adult phase transition. Accumulation of microRNA156 (miR156) correlated with juvenile leaf traits, whilst miR172 transcript accumulation was associated with leaf adult traits. Importantly, glucose may mediate adult leaf characteristics during de novo shoot organogenesis by modulating miR156-targeted PeSPL9 expression levels at early stages of shoot development.

Conclusions
Altogether, our results suggest that specific sugars may act as co-regulators, along with two microRNAs, leading to leaf morphological modifications throughout juvenile-to-adult phase transition in P. edulis.
Impact of Rotavirus Vaccine Introduction in Children Less Than 2 Years of Age Presenting for Medical Care With Diarrhea in Rural Matlab, Bangladesh
Authors: Schwartz Lauren M , Zaman K , Yunus Md , Basunia Ahasan-ul H , Faruque Abu Syed Golam , Ahmed Tahmeed , Rahman Mustafizur , Sugimoto Jonathan D , Halloran M Elizabeth , Rowhani-Rahbar Ali , Neuzil Kathleen M , Victor John C 
Published: February 2019

Abstract

Background
Following the conclusion of a human rotavirus vaccine (HRV) cluster-randomized, controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab’s routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age.

Methods
Interrupted time series were used to estimate the impact of HRV introduction. We used diarrheal surveillance collected between 2000 and 2014 within the 2 service delivery areas (International Centre for Diarrhoeal Disease Research, Bangladesh [icddr,b] service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System, administered by icddr,b. Age group–specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV–) diarrhea diagnoses of any severity presenting to the hospital. We used 2 models to assess the impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV– and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period, using outcomes from control-only villages.

Results
Both models demonstrated a downward trend in RV+ diarrheal incidences in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impacts of HRV on RV+ diarrhea incidences in GSA villages were not observed in either model. Differences in population-level impacts between the 2 delivery areas may be due to the varied rotavirus vaccine coverage and presentation rates to the hospital.

Conclusions
This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies are needed of the rotavirus vaccine impact after the nationwide introduction in Bangladesh.
Transmission-blocking Effects of Primaquine and Methylene Blue Suggest Plasmodium falciparum Gametocyte Sterilization Rather Than Effects on Sex Ratio
Authors: Bradley John , Soumaré Harouna M , Mahamar Almahamoudou , Diawara Halimatou , Roh Michelle , Delves Michael , Drakeley Chris , Churcher Thomas S , Dicko Alassane , Gosling Roly , Bousema Teun 
Published: February 2019

Abstract
Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
Trade and nationalism: market integration in interwar Yugoslavia*
Authors: Miladinović Luka 
Published: February 2019

AbstractThis article empirically analyses the relationship between nationalism and regional economic integration in the Kingdom of Yugoslavia between the First and the Second World War. It argues that prevailing nationalism had a negative impact on the economic integration of the regions within the Kingdom and further contributed to the political disintegration of the Kingdom. The analysis implies that the ideology of nationalism increased trade costs and thus retarded economic interconnectivity in the Kingdom of Yugoslavia, notwithstanding the favorable trade environment and the desire of the central elites to discourage ethnocentric sentiment.
Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice
Authors: Park Hahyun , Park Hee Seo , Lim Whasun , Song Gwonhwa 
Published: February 2019

Abstract
Ochratoxin A (OTA) is a mycotoxin originating from Penicillium and Aspergillus. In addition to toxic effects in various tissues and cells, including neurons, immune cells, hepatocytes, and nephrons, it also causes carcinogenesis and teratogenesis. Although the negative effects of OTA with respect to the pathogenesis of diseases and the malfunction of various organs have been studied widely, the biological signaling mechanisms in testicular cells are less well known. Therefore, we determined the hazardous effect of OTA in two types of testicular cells: TM3 (mouse Leydig cells) and TM4 (mouse Sertoli cells). Treatment with OTA led to a significant decrease in the proliferation of both cell lines, as revealed by an increased proportion of cells in the sub-G1 phase. In addition, the phosphorylation of signaling molecules belonging to the PI3K (Akt, P70S6K, and S6) and MAPK (ERK1/2 and JNK) pathways was regulated by OTA in a dose-dependent manner in TM3 and TM4 cells. Furthermore, the combination treatment of OTA and signaling inhibitors (LY294002, U0126, or SP600125) exerted synergistic antiproliferative effects in TM3 and TM4 cells. OTA also reduced the concentration of calcium ions in the cytosol and mitochondria, which disrupted the calcium homeostasis necessary for maintaining the normal physiological functions of testicular cells. In conclusion, the results of the present study demonstrate the mechanism underlying the antiproliferative effects of OTA in mouse testicular cells. Exposure to OTA may result in abnormal sperm maturation and the failure of spermatogenesis, which leads to male infertility.
The Price of Natural American Spirit Relative to Other Cigarette Brands
Authors: Epperson Anna E , Johnson Trent O , Schleicher Nina C , Henriksen Lisa 
Published: February 2019

Abstract

Introduction
American Spirit cigarettes feature American Indian/Alaska Native (AI/AN) imagery in the branding and are marketed as environmentally friendly, without additives, and four varieties contain organic tobacco. This study is the first to examine retail price of American Spirit relative to other cigarette brands and to assess how its price varies by neighborhood demography.

Methods
In a random sample of licensed tobacco retailers (n = 1277), trained data collectors recorded availability and price of American Spirit, Pall Mall, Newport, Marlboro, and the cheapest cigarettes regardless of brand. Data were collected in January–March 2017 in California, the state with the largest AI/AN population. Paired t tests assessed prices (before sales tax) of American Spirit relative to others. Ordinary least squares regressions modeled prices as a function of neighborhood demography, adjusting for store type.

Results
American Spirit was sold in 77% of stores at an average price of $7.03 (SD = 0.66), which was $0.75–$1.78 (12.0%–34.4%) higher than Pall Mall, Newport, and Marlboro in the same stores. American Spirit costs significantly less in neighborhoods with a higher proportion of school-age residents; however, this pattern was not unique to that brand. Contrary to expectation, American Spirit did not cost less in neighborhoods with a higher proportion of AI/ANs.

Conclusion
This study is the first to document lower prices for American Spirit in neighborhoods with a higher proportion of school-age youth. Future research should consider whether the ultra-premium price of American Spirit contributes to misperceptions that the brand is organic and less harmful than other cigarettes.

Implications
In a large random sample of licensed tobacco retailers in California, American Spirit costs significantly more than other brands, 12.0%–34.4% more than Pall Mall, Newport, and Marlboro in the same stores. After controlling for store type, American Spirit price was significantly lower in neighborhoods with a higher proportion of school-age residents. Research about how an ultra-premium price contributes to misperceptions that all American Spirit varieties are organic and the brand is less harmful and less addictive than other cigarette brands would be informative for ongoing litigation and product regulation.
Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease
Authors: Nakatsuka Yoshinari , Handa Tomohiro , Nakashima Ran , Tanizawa Kiminobu , Kubo Takeshi , Murase Yuko , Sokai Akihiko , Ikezoe Kohei , Hosono Yuji , Watanabe Kizuku , Tokuda Shinsaku , Uno Kazuko , Yoshizawa Akihiko , Tsuruyama Tatsuaki , Uozumi Ryuji , Nagai Sonoko , Hatta Kazuhiro , Taguchi Yoshio , Mishima Michiaki , Chin Kazuo , Mimori Tsuneyo , Hirai Toyohiro 
Published: February 2019

Abstract

Objective
We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD).

Methods
We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed.

Results
Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions.

Conclusion
Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.
Hypoalbuminemia Is an Independent Risk Factor for 30-Day Mortality, Postoperative Complications, Readmission, and Reoperation in the Operative Lower Extremity Orthopaedic Trauma Patient
Authors: Wilson Jacob M. , Lunati Matthew P. , Grabel Zachary J. , Staley Christopher A. , Schwartz Andrew M. , Schenker Mara L. 
Published: February 2019

Introduction:
Malnutrition, as indicated by hypoalbuminemia, is known to have detrimental effects on outcomes after arthroplasty, geriatric hip fractures, and multiple general surgeries. Hypoalbuminemia has been examined in the critically ill but has largely been ignored in the orthopaedic trauma literature. We hypothesized that admission albumin levels would correlate with postoperative course in the nongeriatric lower extremity trauma patient.

Methods:
Patients with lower extremity (including pelvis and acetabulum) fracture who underwent operative intervention were collected from the ACS-NSQIP database. Patients younger than 65 years were included. Patient demographic data, complications, length of stay, reoperation rate, and readmission rate were collected, and patient modified frailty index scores were calculated. Poisson regression with robust error variance was then conducted, controlling for potential confounders.

Results:
Five thousand six hundred seventy-three patients with albumin available were identified, and 29.6% had hypoalbuminemia. Hypoalbuminemic patients had higher rates of postoperative complications [9.3% vs. 2.6%; relative risk (RR) 1.63] including increased rates of: mortality (3.2% vs. 0.4%; RR 4.86, 95% confidence interval 2.66–8.87), sepsis (1.5% vs. 0.5%, RR 2.35), and reintubation (2.3% vs. 0.4%; RR 3.84). Reoperation (5.5% vs. 2.6%, RR 1.74) and readmission (11.4% vs. 4.1%; RR 2.53) rates were also higher in patients with low albumin.

Conclusion:
Hypoalbuminemia is a powerful predictor of acute postoperative course and mortality after surgical fixation in nongeriatric, lower extremity orthopaedic trauma patients. Admission albumin should be a routine part of the orthopaedic trauma workup. Further study into the utility of supplementation is warranted, as this may represent a modifiable risk factor.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Minimally Invasive Surgery for the Treatment of Traumatic Monosegmental Thoracolumbar Burst Fractures
Authors: Trungu Sokol , Forcato Stefano , Bruzzaniti Placido , Fraschetti Flavia , Miscusi Massimo , Cimatti Marco , Raco Antonino 
Published: February 2019

Study Design:This was a retrospective study of the clinical and radiologic outcomes of traumatic thoracolumbar (TL) burst fractures.Objectives:We aimed to evaluate the clinical and radiologic outcomes after 6 years of follow-up of 144 patients with monosegmental TL burst fractures treated with percutaneous short-segment pedicle screw fixation, comparing two groups with versus without placement of an intermediate screw at the fractured vertebra.Summary of Background Data:Traumatic TL fractures are the most common vertebral fractures, especially at the TL junction (T10–L2). Minimally invasive surgery (MIS) is a valuable treatment option for traumatic TL burst fractures.Materials and Methods:The clinical outcomes and radiologic parameters (Cobb angle, midsagittal index, and sagittal index) of 144 patients with traumatic monosegmental TL fractures treated with MIS were evaluated preoperatively, postoperatively, and after 3 and 6 years of follow-up. Patients were categorized into a nonintermediate screw group (nISG) and an intermediate screw group (ISG), and the groups were compared.Results:There were 71 patients (49.3%) in the nISG and 73 patients (50.7%) in the ISG. The radiologic parameters improved significantly more from the preoperative evaluation to the 6-year follow-up in the ISG than in the nISG (P<0.025). There were no significant differences in the mean Oswestry Disability Index (ODI) and Visual Analog Scale scores at the 6-year follow-up between the ISG and the nISG: 15.6% (ISG) versus 16.8% (nISG) for ODI (P<0.1) and 2.2 (ISG) versus 2.4 (nISG) for Visual Analog Scale score (P<0.85) (P<0.73).Conclusions:MIS showed good clinical outcomes 6 years after surgery in both the ISG and the nISG. The additional intermediate screw significantly improved radiologic parameters but not clinical outcomes.
α5GABAA receptors play a pronociceptive role and avoid the rate-dependent depression of the Hoffmann reflex in diabetic neuropathic pain and reduce primary afferent excitability
Authors: Hernández-Reyes José E. , Salinas-Abarca Ana B. , Vidal-Cantú Guadalupe C. , Raya-Tafolla Guadalupe , Elias-Viñas David , Granados-Soto Vinicio , Delgado-Lezama Rodolfo 
Published: February 2019

Abstract
Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. However, the role of extrasynaptic α5 subunit-containing GABAA (α5GABAA) receptors in this process is not known. The purpose of this study was to investigate the role of α5GABAA receptors in diabetes-induced tactile allodynia, loss of rate-dependent depression (RDD) of the Hoffmann reflex (HR), and modulation of primary afferent excitability. Intraperitoneal administration of streptozotocin induced tactile allodynia. Intrathecal injection of α5GABAA receptor inverse agonist, L-655,708, produced tactile allodynia in naive rats, whereas it reduced allodynia in diabetic rats. In healthy rats, electrical stimulation of the tibial nerve at 5 Hz induced RDD of the HR, although intrathecal treatment with L-655,708 (15 nmol) abolished RDD of the HR. Streptozotocin induced the loss of RDD of the HR, while intrathecal L-655,708 (15 nmol) restored RDD of the HR. L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4 to L6 dorsal root ganglion. Streptozotocin increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4 to L6 dorsal root ganglia in 10-week diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively, and are tonically active in primary afferents.
Nonadherence in Hemodialysis Patients and Related Factors: A Multicenter Study
Authors: Ozen Nurten , Cinar Fatma Ilknur , Askin Dilek , Mut Dilek , Turker Turker 
Published: February 2019

ABSTRACT

Background
Nonadherence to dietary and fluid restrictions, hemodialysis (HD), and medication treatment has been shown to increase the risks of hospitalization and mortality significantly. Sociodemographic and biochemical parameters as well as psychosocial conditions such as depression and anxiety are known to affect nonadherence in HD patients. However, evidence related to the relative importance and actual impact of these factors varies among studies.

Purpose
The aim of this study was to identify the factors that affect nonadherence to dietary and fluid restrictions, HD, and medication treatment.

Methods
This descriptive study was conducted on 274 patients who were being treated at four HD centers in Turkey. The parameters used to determine nonadherence to dialysis treatment were as follows: skipping multiple dialysis sessions during the most recent 1-month period, shortening a dialysis session by more than 10 minutes during the most recent 1-month period, and Kt/V < 1.4. The parameters used to determine nonadherence to dietary and fluid restriction were as follows: serum phosphorus level > 7.5 mg/dl, predialysis serum potassium level > 6.0 mEq/L, and interdialytic weight gain > 5.7% of body weight. The Morisky Green Levine Medication Adherence Scale was performed to determine nonadherence to medication treatment. A patient was classified as nonadherent if he or she did not adhere to one or more of these indices. The Hospital Anxiety and Depression Scale was used to identify patient risk in terms of anxiety and depression. Logistic regression was used to determine the predictors of nonadherence.

Results
The nonadherence rate was 39.1% for dietary and fluid restrictions, 33.6% for HD, and 20.1% for medication. The risk of nonadherence to dietary and fluid restriction was found to be 4.337 times higher in high school graduates (95% CI [1.502, 12.754], p = .007). The risk of nonadherence to HD treatment was 2.074 times higher in men (95% CI [1.213, 3.546], p = .008) and 2.591 times higher in patients with a central venous catheter (95% CI [1.171, 5.733], p = .019). Longer duration in HD resulted in 0.992 times decrease in risk of nonadherence to treatment (95% CI [0.986, 0.998], p = .005).

Conclusions/Implications for Practice
Educational status, being male, having a central venous catheter, and having a short HD duration were found to be risk factors for nonadherence. Nurses must consider the patient's adherence to the dietary and fluid restrictions, HD, and medication treatment at each visit.
Efficacy and toxicity of apatinib combined with or without chemotherapy for patients with advanced or metastatic chemotherapy-refractory gastric adenocarcinoma
Authors: Guo Yesong , Tang Jinhai , Huang Xin-En , Cao Jie 
Published: February 2019

Abstract
Apatinib (Jiangsu HengRui Medicine Co. Ltd), a vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, has been proven to be safe and to significantly prolong survival in advanced chemotherapy-refractory gastric cancer. This study aimed to assess and compare the efficacy and safety of apatinib combined with chemotherapy with that of chemotherapy alone as second- or higher-line treatment in patients with advanced and metastatic gastric or those with metastatic gastroesophageal junction adenocarcinoma (mGC).
Patients with chemotherapy-refractory mGC at Jiangsu Cancer Hospital & Research Institute were prospectively enrolled and assigned into 2 groups at a 2:1 ratio. The first group (combination group) comprised patients with combination treatment (apatinib + chemotherapy), while the second group comprised patients treated with chemotherapy alone (chemotherapy group). The dose of apatinib was 500 mg/d, and the chemotherapy regimens were based on fluoropyrimidine, platinum, and paclitaxel or irinotecan. The primary end points were progression-free survival (PFS).
Between November 2014 and December 2016, 175 patients were enrolled. PFS was significantly improved in the combination group compared with that in the chemotherapy group (8.5 months [95% confidence interval [CI], 6.45–10.54] vs 7.0 months [95% CI, 5.12–8.88] P = .021; hazard ratio (HR): 0.645 [95% CI: 0.429–0.969] P = .035). The disease control rate (DCR) was also higher in the combination group than that in the chemotherapy group (58.4% vs 41.9%, P = .041). Moreover, the incidence of Grade 3 to 4 hand-foot syndrome, proteinuria, and hypertension was significantly different between the 2 groups. Combined therapy (P = .040) and metastatic sites <2 (P = .008) were the independent prognostic factors for disease progression.
Compared with chemotherapy alone, the addition of apatinib to chemotherapy could better improve PFS and DCR with an acceptable safety profile for mGC refractory to 1 or more line of prior chemotherapy.