bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractProton 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

AbstractEffective 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

SummaryThe 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

SummaryAcquired 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

AbstractBackgroundBone tissues may undergo remodeling under functional mechanical stimuli.PurposeThis 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 MethodsThe 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.ResultsMean 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).ConclusionsThe 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

AbstractBackgroundDistinguishing weak allergic reactions from irritant patch test reactions may be difficult.ObjectivesTo 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.MethodsEligible 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.ResultsErythema, 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.ConclusionsDermoscopy 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

AbstractObjectiveInterstitial 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 methodsWe 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.ResultsUsing 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.ConclusionsThese 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

AbstractIntraspecific 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

AbstractAn 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

SummaryThe 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

SummaryBackgroundThe 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.ObjectiveWe 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 MethodsGrowth 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).ResultsHeight 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.ConclusionsObesity‐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.
A population-based study of prescribing trends in a potentially vulnerable paediatric population from 1999 to 2012
Authors: Sears Kim , Elms Sherri , Whitehead Marlo , Tranmer Joan E , Edge Dana S , VanDenKerkhof Elizabeth G 
Published: August 2019

Abstract

Objectives
There is a limited understanding of paediatric medication prescribing trends and patterns, thus poorly positioning decision-makers to identify quality and safety concerns related to medication use. The objective of this study was to determine overall medication prescribing trends and patterns among children receiving Ontario Drug Benefits over a thirteen-year period in the province of Ontario, Canada.

Methods
Administrative health databases housed within the Institute for Clinical Evaluative Sciences (ICES), Ontario, Canada, were used to identify outpatient prescriptions dispensed from 1999 to 2012 through a publicly funded programme to children ≤18 years of age. Medications were classified according to the American Hospital Formulary Service Pharmacologic-Therapeutic Classification system. Descriptive statistics were used to summarize prescribing patterns.

Key findings
This study identified 457 037 children who were dispensed a new prescription between 1999 and 2012. About 56% received their first prescription before 6.5 years of age, and 85% of the children in this study were from families who received social assistance. The most commonly prescribed drugs were antiinfectives (56.1%). Prescriptions for several central nervous system agents, including antipsychotics and agents for attention-deficit/hyperactivity disorder, increased across the study period. Changes in prescribing patterns within opioids, hormones and autonomic agents were noted. The results suggest that historically, prescribing trends have shifted with public policy, pharmaceutical marketing and diagnostic patterns, thus identifying them as a possible tool to measure the impact of policydriven practice changes. Anti-infective prescribing increased markedly with the global H1N1 pandemic. Pharmaceutical marketing, formulary decisions and diagnostic trends may affect the prescribing of ADHD medications globally. The prescribing of codeine-containing products and medroxyprogesterone appeared to fluctuate in response to important publications in the medical literature, and the use of epinephrine syringes increased after public policy changes in the province of Ontario. The steady rise in the use of medications whose long-term effects in children are unknown, such as antipsychotics and proton pump inhibitors, identifies areas in need of future research.

Conclusions
This study presents the first overview of Canadian prescribing trends for children, the majority of which are of low socioeconomic status and represent a potentially vulnerable population. Our analysis suggests that future research is required to determine whether prescribing trends could be used as indicators of policy effectiveness, pharmacovigilance and diagnostic trends.