bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and clinicopathologic significance of MicroRNA-125a-5p in cancers
Authors: Ye Haidong , Zhu Wei , Mei Lina , Lu Zhouxiang
Published: August 2019

The aim of the study was to estimate the prognostic and clinicopathologic significance of miR-125a-5p in human cancers. Eligible studies were obtained from PubMed, Embase, and the Cochrane Library. Combined hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the prognostic and clinicopathologic value of miR-125a-5p. In pan-cancer, high miR-125a-5p expression was associated with better overall survival (OS) (HR = 0.459, 95% confidence interval [CI]: 0.369–0.57, P < .001), and disease-free survival (HR = 0.343, 95% CI: 0.237–0.496, P < .001). Furthermore, favorable OS was also found in lung cancer (HR = 0.343, 95% CI: 0.228–0.517, P < .001) and gastric cancer (HR = 0.341, 95% CI: 0.160–0.725, P = .005) patients with high miR-125a-5p expression. Besides, high miR-125a-5p expression was correlated with early stage (OR = 0.413, 95% CI: 0.228–0.749, P = .004) and negative lymph node metastasis (OR = 0.262, 95% CI: 0.073–0.941, P = .04) in gastric cancer, and was linked with better tumor differentiation in pan-cancer (OR = 1.623, 95% CI: 1.064–2.476, P = .025) and lung cancer (OR = 2.371, 95% CI: 1.358–4.141, P = .002). In conclusion, miR-125a-5p is a tumor suppressor with prognostic and clinicopathologic values for human cancer, and miR-125a-5p overexpression predicted favorable prognosis, early stage, negative lymph node metastasis, and better tumor differentiation. More research should be conducted to test these results.
Clinicopathologic parameters associated with the FDG-avidity in staging of early gastric cancer using 18F-FDG PET
Authors: Yoon Joon-Kee , Byun Cheulsu , Jo Kyung Sook , Hur Hun , Lee Kee Myung , Lim Seon Kyo , Lee Dakeun , Lee Su Jin , An Young-Sil , Han Sang-Uk
Published: August 2019

This study investigated the clinicopathologic factors associated with 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.

Two hundred twenty-nine retrospectively enrolled patients underwent preoperative 18F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and 18F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.

18F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting 18F-FDG uptake (all P 
< .05). According to multivariate analysis, location (lower 3rd, P 
= .035), gross type (0–I, 0–IIa, P 
< .001), size (≥2.5 cm, P 
= .026), and depth of invasion (submucosa, P 
= .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.

18F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.
Validation of the Presence of Nursing Scale Using Data Triangulation
Authors: Hansbrough Wendy B. , Georges Jane M.
Published: August 2019

Background

Nursing presence has been developed as a distinct concept with identifiable behaviors but remains only partially defined as a quantifiable construct.

Objectives

This study asked if the Presence of Nursing Scale (PONS) is a reliable and valid instrument to measure nursing presence from the patient’s perspective.

Methods

A convenience sample of 75 adult acute care inpatients were verbally administered the 25-item PONS considering the registered nurse taking care of them on the day of data collection. Open-ended questions elicited the patients’ explanations of their ratings. They also rated their overall satisfaction with the nursing care provided by the subject nurse using a 5-point scale.

Results

The mean PONS score was 104.5 (SD = 17.26) on the 25–125 scale. Instrument reliability reported as a Cronbach’s alpha coefficient of .95 was .94 in this study. Instrument validity was tested correlating PONS scores to the satisfaction rating. The Spearman’s rho correlation was large and statistically significant, r (73) = .708. The higher the PONS score, the more satisfied the patient was with care from that nurse. Nineteen narratives selected from the lower quartile PONS scores (PONS < 99) and 11 from the upper quartile (PONS > 116) were thematically analyzed. Lower PONS scores corresponded with themes of patients being objectified as the work of the nurse without a respectful and caring nurse–patient relationship. Higher PONS scores coincided with patients’ perceptions of enhanced nurse–patient rapport, feelings of better coping, and decreased anxiety.

Discussion

These results demonstrate reliability and validity of the PONS and add to the body of evidence about nurse behaviors exhibited in the nurse–patient relationship, which influence patients’ feelings of being cared for and satisfied with nursing care. These findings may be useful in the development of educational materials aimed at the advancement of nursing presence competency.
Effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole, terbinafine) in current epidemic of altered dermatophytosis in India: A randomized pragmatic trial
Authors: Singh Sanjay , Chandra Usha , Verma Priyanka , Anchan Vinayak N , Tilak Ragini
Published: August 2019

Background

Dermatophyte infections have undergone unprecedented changes in India in recent past. Clinical trials comparing effectiveness of 4 main oral antifungal drugs are not available. We tested effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic-relapsing tinea corporis, tinea cruris and tinea faciei.

Methods

Two hundred microscopy confirmed patients were allocated to 4 groups, fluconazole (5mg/kg/day), griseofulvin (10 mg/kg/day), itraconazole (5mg/kg/day), and terbinafine (7.5mg/kg/day), by concealed block randomization and treated for 8 weeks or cure. Effectiveness was calculated based on intention to treat analysis.

Results

At 4 weeks, 4, 1, 2, and 4 patients were cured with fluconazole, griseofulvin, itraconazole and terbinafine, respectively (P=0.417). At 8 weeks, 21 (42%), 7 (14%), 33 (66%) and 14 (28%) patients were cured, respectively (P=0.000); itraconazole was superior to fluconazole, griseofulvin and terbinafine (P≤0.016). Relapse rates after 4 and 8 weeks of cure in different groups were similar. Numbers-needed-to-treat (NNT) (versus griseofulvin), calculated based on cure rates at 8 weeks, for itraconazole, fluconazole, and terbinafine were 2, 4 and 8, respectively.

Conclusion

In view of cure rates and NNT, itraconazole is the most effective drug, followed by fluconazole (daily), terbinafine and then griseofulvin, in chronic and chronic-relapsing dermatophytosis in India.

One Sentence Summary

Effectiveness of all four antifungals has declined, with itraconazole being the most effective currently in dermatophytosis in India.
Quantifying accuracy and heterogeneity in single-molecule super-resolution microscopy
Authors: Mazidi Hesam , Ding Tianben , Nehorai Arye , Lew Matthew D.
Published: August 2019

The resolution and accuracy of single-molecule localization micro-scopes (SMLMs) are routinely benchmarked using simulated data, calibration “rulers,” or comparisons to secondary imaging modalities. However, these methods cannot quantify the nanoscale accuracy of an arbitrary SMLM dataset. Here, we show that by computing localization stability under a well-chosen perturbation with accurate knowledge of the imaging system, we can robustly measure the confidence of individual localizations without ground-truth knowledge of the sample. We demonstrate that our method, termed Wasserstein-induced flux (WIF), measures the accuracy of various reconstruction algorithms directly on experimental 2D and 3D data of microtubules and amyloid fibrils. We further show that WIF confidences can be used to evaluate the mismatch between computational models and imaging data, enhance the accuracy and resolution of recon-structed structures, and discover hidden molecular heterogeneities. As a computational methodology, WIF is broadly applicable to any SMLM dataset, imaging system, and localization algorithm.
The computation of directional selectivity in the Drosophila OFF motion pathway
Authors: Gruntman Eyal , Romani Sandro , Reiser Michael B.
Published: August 2019

The direction of visual motion in Drosophila is computed by separate pathways for moving ON and OFF features. The 4th order neurons T4 (ON) and T5 (OFF) are the first neurons in their respective pathways to extract a directionally selective response from their non-selective inputs. Recent functional studies have found a major role for local inhibition in the generation of directionally selective responses. However, T5 lacks small-field inhibitory inputs. Here we use whole-cell recordings of T5 neurons and find an asymmetric receptive field structure, with fast excitation and persistent, spatially trailing inhibition. We assayed pairwise interactions of local stimulation across the receptive field, and find no active amplification, only passive suppression. We constructed a biophysical model of T5 based on the classic Receptive Field. This model, which lacks active conductances and was tuned only to match non-moving stimuli, accurately predicts responses to complex moving stimuli.
Irrelevant auditory and tactile signals, but not visual signals, interact with the target onset and modulate saccade latencies
Authors: Vidal Manuel , Desantis Andrea , Madelain Laurent
Published: August 2019

Saccadic eye movements bring events of interest to the center of the retina, enabling detailed visual analysis. This study explored whether irrelevant auditory (experiments A, B & F), visual (C & D) or tactile signals (E & F) delivered around the onset of a visual target modulates saccade latency. Participants were instructed to execute a quick saccade toward a target stepping left or right from a fixation position. We observed an interaction between auditory beeps or tactile vibrations and the oculomotor reaction that included two components: a warning effect resulting in faster saccades when the signal and the target were presented simultaneously; and a modulation effect with shorter – or longer – latencies when auditory and tactile signals were delivered before – or after – the target onset. Combining both modalities only increased the modulation effect to a limited extent, pointing to a saturation of the multisensory interaction with the motor control. Interestingly, irrelevant visual stimuli (black background or isoluminant noise stripes in peripheral vision, flashed for 10 ms) increased saccade latency whether they were presented just before or after target onset. The lack of latency reduction with visual signals suggests that the modulation observed in the auditory and tactile experiments was not related to priming effects but rather to low-level audio- and tactile-visual integration. The increase in saccade latency observed with irrelevant visual stimuli is discussed in relation to saccadic inhibition. Our results demonstrate that signals conveying no information regarding where and when a visual target would appear modulate saccadic reactivity, much like in multisensory temporal binding, but only when these signals come from a different modality.
Lymphocyte subpopulations and mast cells intestinal changes as indicators of inflammatory bowel disease in dogs
Authors: Espinoza-Zambrano Andrés , González Carlos Manuel
Published: August 2019

Inflammatory bowel disease (IBD) is a disease with recurring gastrointestinal symptoms. Lymphocytes and mast cells are proposed as important components in the immunopathology of IBD in dogs. Mast cells depend on degranulation, a process that compromises mucosal permeability and normal intestinal barrier function, which alters the normal inflammatory process by allowing recruitment of lymphocytes in dogs with IBD. In this study, T and B lymphocyte populations and mast cells were examined in situ in 39 intestinal samples of dogs affected by IBD, by immunohistochemistry. Both T lymphocytes and mast cells numbers were significantly higher in the lamina propria of the intestinal wall of dogs with IBD compared with control dogs. Out of the total number of mast cells detected by CD117 expression significantly less cells appear to be granulated according to granule staining with Toluidine Blue, suggesting that an important degranulation process takes place in IBD. Single and double immune staining for tryptase and chymase showed that mast cells can express only one or both enzymes. Tryptase positive cells were significantly higher in number that chymase positive and tryptase/chymase positive cells. T lymphocytes were concentrated mostly at the upper portion of the intestinal villi lamina propria while mast cells were distributed mainly among crypts. These results suggest that populations of T lymphocytes and mast cells play a role in the immunopathology and development of IBD in dogs, also these changes could be helpful as complementary indicators of canine IBD.
Dopamine neuron ensembles signal the content of sensory prediction errors
Authors: Stalnaker Thomas A. , Howard James D. , Takahashi Yuji K. , Gershman Samuel J. , Kahnt Thorsten , Schoenbaum Geoffrey
Published: August 2019

Dopamine neurons respond to errors in predicting value-neutral sensory information. These data, combined with causal evidence that dopamine transients support sensory-based associative learning, suggest that the dopamine system signals a multidimensional prediction error. Yet such complexity is not evident in individual neuron or average neural activity. How then do downstream areas know what to learn in response to these signals? One possibility is that information about content is contained in the pattern of firing across many dopamine neurons. Consistent with this, here we show that the pattern of firing across a small group of dopamine neurons recorded in rats signals the identity of a mis-predicted sensory event. Further, this same information is reflected in the BOLD response elicited by sensory prediction errors in human midbrain. These data provide evidence that ensembles of dopamine neurons provide highly specific teaching signals, opening new possibilities for how this system might contribute to learning.
Spin resolved electron density study of YTiO3in its ferromagnetic phase: signature of orbital ordering
Authors: Voufack Ariste Bolivard , Kibalin Iurii , Yan Zeyin , Claiser Nicolas , Gueddida Saber , Gillon Béatrice , Porcher Florence , Gukasov Arsen , Sugimoto Kunishisa , Lecomte Claude , Dahaoui Slimane , Gillet Jean-Michel , Souhassou Mohamed
Published: August 2019

The present work reports on the charge and spin density modelling of YTiO3in its ferromagnetic state (TC= 27 K). Accurate polarized neutron diffraction and high-resolution X-ray diffraction (XRD) experiments were carried out on a single crystal at the ORPHÉE reactor (LLB) and SPRING8 synchrotron source. The experimental data are modelled by the spin resolved pseudo-atomic multipolar model (Deutschet al., 2012). The refinement strategy is discussed and the result of this electron density modelling is compared with that from XRD measured at 100 K and with density functional theory calculations. The results show that the spin and charge densities around the Ti atom have lobes directed away from the O atoms, confirming the filling of thet2gorbitals of the Ti atom. Thedxyorbital is less populated thandxzanddyz, which is a sign of a partial lift of degeneracy of thet2gorbitals. This study confirms the orbital ordering at low temperature (20 K), which is already present in the paramagnetic state above the ferromagnetic transition (100 K).
Crystal structure of the Schizosaccharomyces pombe U7BR E2-binding region in complex with Ubc7
Authors: Hann Zachary S. , Metzger Meredith B. , Weissman Allan M. , Lima Christopher D.
Published: August 2019

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. cerevisiae, and structures of E2–E2BR complexes from both species have been determined. In addition to sequence and structural differences between the human and S. cerevisiae E2BRs, the binding of E2BRs also elicits different biochemical outcomes with respect to E2 charging by E1 and E2 discharge. Here, the Schizosaccharomyces pombe E2BR was identified and purified with Ubc7 to resolve a 1.7 Å resolution co-crystal structure of the E2BR in complex with Ubc7. The S. pombe E2BR binds to the back side of the E2 as an α-helix and, while differences exist, it exhibits greater similarity to the human E2BR. Structure-based sequence alignments reveal differences and conserved elements among these species. Structural comparisons and biochemistry reveal that the S. pombe E2BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.
A constraint programming approach to type-2 assembly line balancing problem with assignment restrictions
Authors: Pinarbasi Mehmet , Alakas Hacı Mehmet , Yuzukirmizi Mustafa
Published: August 2019

Purpose

Main constraints for an assembly line balancing problem (ALBP) are cycle time/number of stations and task precedence relations. However, due to the technological and organizational limitations, several other restrictions can be encountered in real production systems. These restrictions are called as assignment restrictions and can be task assignment, station, resource and distance limitations. The purpose of the study is to evaluate the effects of these restrictions on ALBP using constraint programming (CP) model.

Design/methodology/approach

A novel CP model is proposed and compared to mixed-integer programming (MIP) as a benchmark. The objective is to minimize the cycle time for a given number of stations. The authors also provide explicit anthology of the assignment restriction effects on line efficiency, the solution quality and the computation time.

Findings

The proposed approach is verified with the literature test instances and a real-life problem from a furniture manufacturing company. Computational experiments show that, despite the fact that additional assignment restrictions are problematic in mathematical solutions, CP is a versatile exact solution alternative in modelling and the solution quality.

Practical implications

Assembly line is a popular manufacturing system in the making of standardized high volume products. The problem of assembly line balancing is a crucial challenge in these settings and consists of assigning tasks to the stations by optimizing one or more objectives. Type-2 AR-ALBP is a specific case with the objective function of minimizing the cycle time for a given number of stations. It further assumes assignment restrictions that can be confronted due to the technological limitations or the strategic decisions of the company management. This is especially encountered in rebalancing lines.

Originality/value

Several solution approaches such as mathematical modelling, heuristic and meta-heuristic are proposed to solve the ALBP in the literature. In this study, a new approach has been presented using CP. Efficient models are developed for Type-2 ALBP with several assignment restrictions. Previous studies have not considered the problem to the presented extent. Furthermore, to the best of the authors’ knowledge, the paper is the first study that solves ALBP with assignment restrictions using CP.
Refined bond-based peridynamics for thermal diffusion
Authors: Gu Xin , Zhang Qing , Madenci Erdogan
Published: August 2019

Purpose

This paper aims to review the existing bond-based peridynamic (PD) and state-based PD heat conduction models, and further propose a refined bond-based PD thermal conduction model by using the PD differential operator.

Design/methodology/approach

The general refined bond-based PD is established by replacing the local spatial derivatives in the classical heat conduction equations with their corresponding nonlocal integral forms obtained by the PD differential operator. This modeling approach is representative of the state-based PD models, whereas the resulting governing equations appear as the bond-based PD models.

Findings

The refined model can be reduced to the existing bond-based PD heat conduction models by specifying particular influence functions. Also, the refined model does not require any calibration procedure unlike the bond-based PD. A systematic explicit dynamic solver is introduced to validate 1 D, 2 D and 3 D heat conduction in domains with and without a crack subjected to a combination of Dirichlet, Neumann and convection boundary conditions. All of the PD predictions are in excellent agreement with the classical solutions and demonstrate the nonlocal feature and advantage of PD in dealing with heat conduction in discontinuous domains.

Originality/value

The existing PD heat conduction models are reviewed. A refined bond-based PD thermal conduction model by using PD differential operator is proposed and 3 D thermal conduction in intact or cracked structures is simulated.
Bioinspired designs impart robots with unique capabilities
Authors: Bogue Robert
Published: August 2019

Purpose

This paper aims to provide an insight into robot developments that use bioinspired design concepts.

Design/methodology/approach

Following a short introduction to biomimetics, this paper first provides examples of bioinspired terrestrial, aerial and underwater robot navigation techniques. It then discusses bioinspired locomotion and considers a selection of robotic products and developments inspired by snakes, bats, diving birds, fish and dragonflies. Finally, brief concluding comments are drawn.

Findings

The application of design concepts that mimic the capabilities and processes found in living creatures can impart robots with unique abilities. Bioinspired techniques used by insects and other organisms, notably optic flow and sunlight polarisation sensing, allow robots to navigate without the need for methods such as simultaneous localisation and mapping, GPS or inertial measurement units. Bioinspired locomotion techniques have yielded robots capable of operating in water, air and on land and in some cases, making the transition between different media.

Originality/value

This shows how bioinspired design concepts can impart robots with innovative and enhanced navigation and locomotion capabilities.
Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection
Authors: Basharkhah Samira , Sabet Faezeh , Ghezeldasht Sanaz Ahmadi , Mosavat Arman , Jahantigh Hamid Reza , Barati Elham , Shamsian Khosrow , Saleh‐Moghaddam Masoud , Sharebyani Hiva , Hassannia Tahereh , Shamsian Seyed Ali Akbar
Published: August 2019

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross‐sectional study, blood samples were taken from 249 recently diagnosed HCV‐infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV‐RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut‐off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV‐RNA load. Regression model: log viral load = 7.69 − 1.01 × G3 − 0.7 × G1 + 0.002 × ALT − 0.86 × fatigue.
Do networks or performance impact the promotion of Chinese officials? Evidence from prefecture‐level cities
Authors: Lu Chin‐Hwa , Shen Chung‐Hua
Published: August 2019

This study examines the effects of connections and economic performance on the promotion of Chinese city mayors. Our study differs from the published literature in four respects. First, this study covers a comprehensive data set, including 1,422 mayors from 284 prefecture‐level cities. The use of a large data set helps resolve mixed results of past studies. Second, we use a broader range of top leaders. Third, we apply a more comprehensive definition of connections than earlier studies. Finally, we examine the effects of the policy shift of the 11th 5‐year plan on promotion of mayors. Our results reveal that the performance of a city mayor assisted his/her promotion to party secretary before 2006 but not afterwards. However, a mayor's connection with five types of top leaders is helpful. Among the four types of connection, colleagueship is the most effective in expediting the promotion of mayors. Graduating from the same university and department is also helpful but to a lesser extent. Township connection is not useful.
Hypothalamic mTORC2 is essential for metabolic health and longevity
Authors: Chellappa Karthikeyani , Brinkman Jacqueline A. , Mukherjee Sarmistha , Morrison Mark , Alotaibi Mohammed I. , Carbajal Kathryn A. , Alhadeff Amber L. , Perron Isaac J. , Yao Rebecca , Purdy Cole S. , DeFelice Denise M. , Wakai Matthew H. , Tomasiewicz Jay , Lin Amy , Meyer Emma , Peng Yajing , Arriola Apelo Sebastian I. , Puglielli Luigi , Betley J. Nicholas , Paschos Georgios K. , Baur Joseph A. , Lamming Dudley W.
Published: August 2019

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Although the beneficial effect of rapamycin on longevity is generally attributed to reduced mTORC1 signaling, disruption of mTORC2 signaling can also influence the longevity of worms, either positively or negatively depending on the temperature and food source. Here, we show that loss of hypothalamic mTORC2 signaling in mice decreases activity level, increases the set point for adiposity, and renders the animals susceptible to diet‐induced obesity. Hypothalamic mTORC2 signaling normally increases with age, and mice lacking this pathway display higher fat mass and impaired glucose homeostasis throughout life, become more frail with age, and have decreased overall survival. We conclude that hypothalamic mTORC2 is essential for the normal metabolic health, fitness, and lifespan of mice. Our results have implications for the use of mTORC2‐inhibiting pharmaceuticals in the treatment of brain cancer and diseases of aging.
Intraindividual changes in brain GABA, glutamate, and glutamine during monitored abstinence from alcohol in treatment‐naive individuals with alcohol use disorder
Authors: Prisciandaro James J. , Schacht Joseph P. , Prescot Andrew P. , Brenner Helena M. , Renshaw Perry F. , Brown Truman R. , Anton Raymond F.
Published: August 2019

Proton magnetic resonance spectroscopy (1H‐MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in treatment‐seeking individuals with moderate‐severe alcohol use disorder (AUD) following acute withdrawal. In contrast, few studies have investigated neurochemical changes across early abstinence in less severe, treatment‐naïve AUD. The present study, which represents the primary report of a research grant from ABMRF/The Alcohol Research Fund, measured dorsal anterior cingulate cortex (dACC) GABA, glutamate, and glutamine levels in treatment‐naïve AUD (n = 23) via three 1H‐MRS scans spaced across a planned week of abstinence from alcohol. In addition to AUD participants, 12 light drinkers completed two scans, separated by 48 hours, to ensure that results in AUD were not produced by between‐scan differences other than abstinence from alcohol. 1H‐MRS spectra were acquired in dACC at each scan using 2D J‐resolved point‐resolved spectroscopy. Linear mixed modeling results demonstrated a significant increase in GABA, but not glutamate or glutamine (Ps = .237‐.626), levels between scans 1 and 2 (+8.88%, .041), with no difference between scans 2 and 3 (+1.00%, .836), in AUD but not LD (F = 1.24, .290) participants. Exploratory regression analyses tentatively revealed a number of significant prospective associations between changes in glutamine levels and heavy drinking, craving, and withdrawal symptoms. Most notably, the present study demonstrated return from abnormally low to normal GABA levels in treatment‐naïve AUD within 3 days of their last drink; the pattern of results was consistent with glutamate and glutamine disturbances being exclusive to relatively more severe AUD.
Can women's self‐help groups improve access to information, decision‐making, and agricultural practices? The Indian case
Authors: Raghunathan Kalyani , Kannan Samyuktha , Quisumbing Agnes R.
Published: August 2019

Effective agricultural extension is key to improving productivity, increasing farmers’ access to information, and promoting more diverse sets of crops and improved methods of cultivation. In India, however, the coverage of agricultural extension workers and the relevance of extension advice is poor. We investigate whether a women's self‐help group (SHG) platform could be an effective way of improving access to information, women's empowerment in agriculture, agricultural practices, and production diversity. We use cross‐sectional data on close to 1,000 women from five states in India and employ nearest‐neighbor matching models to match SHG and non‐SHG women along a range of observed characteristics. We find that participation in an SHG increases women's access to information and their participation in some agricultural decisions, but has limited impact on agricultural practices or outcomes, possibly due to financial constraints, social norms, and women's domestic responsibilities. SHGs need to go beyond provision of information to changing the dynamics around women's participation in agriculture to effectively translate knowledge into practice.
The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target
Authors: Hokland Peter , Woll Petter S. , Hansen Marcus C. , Bill Marie
Published: August 2019

The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real‐time benefit for AML patients.
Outcome of CARE: a 6‐year national registry of acquired haemophilia A in China
Authors: Sun Boyang , Xue Feng , Feng Ying , Sun Jing , Yu Ziqiang , Hou Ming , Zhang Jingyu , Zeng Xiaojing , Zhao Yongqiang , Lian Shimei , Huang Meijuan , Niu Ting , Cui Zhongguang , Wu Jingsheng , Yang Renchi
Published: August 2019

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty‐seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow‐up. The mean age for the survivors [51 years (IQR, 35–65 years)] was significantly lower than that of the non‐survivors [79 years (IQR, 67–86 years)] (P < 0·001). Overall survival was higher in non‐malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913–1·889, P = 0·015).
Radiographic changes of trabecular bone density after loading of implant‐supported complete dentures: A 3‐year prospective study
Authors: Gerhardt Maurício N. , Villarinho Eduardo A. , Rockenbach Maria Ivete B. , Vigo Álvaro , dos Reis Rodrigo C. P. , Shinkai Rosemary S. A.
Published: August 2019

Background

Bone tissues may undergo remodeling under functional mechanical stimuli.

Purpose

This prospective study on implant‐supported fixed complete dentures (IFCDs) evaluated the radiographic trabecular bone changes in density by means of gray levels and texture analysis variables after up to 3‐year loading.

Materials and Methods

The sample consisted of digital periapical radiographs of 63 distal implants of hybrid IFCDs installed in 30 patients (22 women, mean age of 62 ± 7.8 years). Digital periapical radiographs were taken after prosthesis installation, and 1 and 3 years after IFCD loading. Longitudinal images of each implant were superimposed, and the same regions of interest were selected for measurement of gray levels statistics (mean gray levels, SD, and coefficient of variation [CV]) and texture parameters (correlation, contrast, entropy, and angular second moment). Data were analyzed by mixed regression models.

Results

Mean gray levels increased for 1 year (P < .05), for 3 years (P < .01) and for maximum bite force (P < .01). The interaction between bruxism and time in 1 year was significant (P < .01) for a decrease in CV. No significant effect of texture analysis variables was found (P > .05).

Conclusions

The results suggest an increase of radiographic bone density as measured by an increase in mean gray levels and a decrease in CV in IFCD distal implants up to 3 years of loading.
Patch test reactions through the lens of dermoscopy: Further insights, particularly on weak allergic reactions
Authors: Corazza Monica , Toni Giulia , Scuderi Valeria , Forconi Riccardo , Borghi Alessandro
Published: August 2019

Background

Distinguishing weak allergic reactions from irritant patch test reactions may be difficult.

Objectives

To describe the dermoscopic features of allergic reactions (especially weak allergic ones) and irritant patch test reactions, and to assess the suitability of dermoscopy in supporting differential diagnosis.

Methods

Eligible participants for this observational, cross‐sectional study included consecutive adult outpatients patch tested during a 12‐month period, who developed any skin reaction. Healthy volunteers were patch tested with sodium lauryl sulfate as irritant controls. At the 72‐hour reading, patch test reactions were recorded both with a digital camera and a digital dermoscopic system. For each reaction, clinical and dermoscopic variables were separately assessed, scored, and then compared.

Results

Erythema, vessels, and vesiculation were constant dermoscopic features of allergic reactions (n = 173). In 46 weak (+) allergic reactions, dermoscopy showed (a) erythema (100%), (b) dense polymorphic vessels (100%), and (c) whitish vesicles (78.3%). Scores for vesicles and dotted vessels were significantly higher in weak allergic than in irritant reactions. Vesicles were identified as the chief dermoscopic parameter for correctly distinguishing weak allergic from irritant reactions.

Conclusions

Dermoscopy can improve accuracy in the differential diagnosis between weak allergic and irritant patch test reactions.
An extravascular fluid transport system based on structural framework of fibrous connective tissues in human body
Authors: Li Hongyi , Yang Chongqing , Yin Yajun , Wang Fang , Chen Min , Xu Liang , Wang Naili , Zhang Di , Wang Xiaoxia , Kong Yiya , Li Qing , Su Si , Cao Yupeng , Liu Wentao , Ao Zhuo , Dai Luru , Ma Chao , Shang Lijun , Han Dong , Ji Fusui , Li Hua
Published: August 2019

Objective

Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long‐distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long‐distance interstitial fluid transport network beyond vascular circulations.

Materials and methods

We first used 20 volunteers to determine hypodermic entrant points to visualize long‐distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long‐distance pathways from extremity ending to associated visceral structures were identified.

Results

Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro‐CT data showed these pathways were neither blood nor lymphatic vessels but long‐distance oriented fibrous matrices, which contained the longitudinally assembled micro‐scale fibres consistently from thumb to superficial tissues on right atrium.

Conclusions

These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long‐distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving‐transfer mechanisms beyond vascular circulations.
Phenotypic variability promotes diversity and stability in competitive communities
Authors: Maynard Daniel S. , Serván Carlos A. , Capitán José A. , Allesina Stefano
Published: August 2019

Intraspecific variation is at the core of evolutionary theory, and yet, from an ecological perspective, we have few robust expectations for how this variation should affect the dynamics of large communities. Here, by adapting an approach from evolutionary game theory, we show that the incorporation of phenotypic variability into competitive networks dramatically alters the dynamics across ecological timescales, stabilising the systems and buffering the communities against demographic perturbations. The beneficial effects of phenotypic variability are strongest when there are substantial differences among phenotypes and when phenotypes are inherited with moderately high fidelity; yet even low levels of variation lead to significant increases in diversity, stability, and robustness. By identifying a simple and ubiquitous stabilising force in competitive communities, this work contributes to our core understanding of how biological diversity is maintained in natural systems.
Endogenous business cycles in a perpetual youth model with financial market imperfections**
Authors: Kunieda Takuma , Nishimura Kazuo
Published: August 2019

An economy in which entrepreneurs and financiers interact with each other through an imperfect financial market is investigated by applying a dynamic general equilibrium theory. In each period, there is a certain probability of each entrepreneur's life ending, and a certain number of entrepreneurs are newly born. Although entrepreneurs are potential capital producers, they receive an idiosyncratic productivity shock in each period. Therefore, entrepreneurs who draw higher productivity become capital producers and those who draw lower productivity become lenders. Financiers do not have an entrepreneurial talent for capital production, and thus they lend their assets in the financial market to acquire an interest income. In equilibrium, deterministic endogenous business cycles can occur at the intermediate level of financial constraints.
Application of Cudrania tricuspidata leaf extract as a washing agent to inactivate Listeria monocytogenes on fresh‐cut romaine lettuce and kale
Authors: Woo Hyuk‐Je , Kang Ji‐Hoon , Lee Chae‐Hun , Song Kyung Bin
Published: August 2019

The present study aimed to examine the antimicrobial activity of silkworm thorn (Cudrania tricuspidata) leaf extract (CTLE) and its application as a washing agent for fresh‐cut romaine lettuce and kale. The antimicrobial activities of CTLE at various concentrations against Listeria monocytogenes were determined using disc diffusion and viable cell count assays, and CTLE exhibited strong inactivation of L. monocytogenes. In particular, after the treatment with 0.4% CTLE, the protein content of L. monocytogenes cells was significantly (P < 0.05) decreased from 507.21 to 254.58 μg mL−1, and damaged cells were observed by scanning electron microscopy. CTLE washing resulted in approximately 2‐log reduction of microbial growth, similar to that of 0.01% NaOCl. In addition, CTLE washing did not affect the quality of romaine lettuce and kale. Therefore, these results suggest that CTLE is applicable as a new washing agent for inactivating L. monocytogenes on fresh‐cut romaine lettuce and kale.
Sex, puberty, and ethnicity have a strong influence on growth and metabolic comorbidities in children and adolescents with obesity: Report on 1300 patients (the Madrid Cohort)
Authors: Martos‐Moreno Gabriel Á. , Martínez‐Villanueva Julián , González‐Leal Rocío , Chowen Julie A. , Argente Jesús
Published: August 2019

Background

The capacity to correctly assess insulin resistance and its role in further obesity‐associated metabolic derangement in children is under debate, and its determinants remain largely unknown.

Objective

We investigated the association of the insulin secretion profile with other metabolic derangements and anthropometric features in children and adolescents with obesity, exploring the role of ethnicity.

Patients and Methods

Growth and metabolic features, including fasting insulin levels and insulin secretory profile in an oral glucose tolerance test (OGTT), were analyzed according to ethnicity in 1300 patients with obesity (75.8% Caucasians/19.0% Latinos).

Results

Height and bone age were influenced by sex, ethnicity, and insulinemia. Latino patients had higher insulin (P < .001), but similar glycemia both prepubertally and postpubertally, compared with Caucasians. Type 2 diabetes was uncommon (0.1%). Impaired glucose tolerance was associated to higher age, BMI, uric acid, and triglyceride levels (all P < .05), as was fasting hyperinsulinism. Impaired fasting glucose or HbA1c 5.7% to 6.4% showed no association with further metabolic derangement. A delayed insulin peak in the OGTT was associated to more severe metabolic disturbances.

Conclusions

Obesity‐associated hyperglycemia is unusual in our environment whereas fasting and late postprandial hyperinsulinemia are highly prevalent, with this being influenced by race and closely related with lipid metabolism impairment.