bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the caudal hypothalamic arcuate nucleus with a focus on anorexic excitatory neurons
Authors: van den Pol Anthony N. , Acuna Claudio , Davis John N. , Huang Hao , Zhang Xiaobing 
Published: January 2019

Key points
Excitatory glutamate neurons are sparse in the rostral hypothalamic arcuate nucleus (ARC), the subregion that has received the most attention in the past. In striking contrast, excitatory neurons are far more common (by a factor of 10) in the caudal ARC, an area which has received relatively little attention.
These glutamate cells may play a negative role in energy balance and food intake. They can show an increase in phosphorylated Stat‐3 in the presence of leptin, are electrically excited by the anorectic neuromodulator cholecystokinin, and inhibited by orexigenic neuromodulators neuropeptide Y, met‐enkephalin, dynorphin and the catecholamine dopamine.
The neurons project local axonal connections that excite other ARC neurons including proopiomelanocortin neurons that can play an important role in obesity.
These data are consistent with models suggesting that the ARC glutamatergic neurons may play both a rapid and a slower role in acting as anorectic neurons in CNS control of food intake and energy homeostasis.
AbstractHere we interrogate a unique class of excitatory neurons in the hypothalamic arcuate nucleus (ARC) that utilizes glutamate as a fast neurotransmitter using mice expressing GFP under control of the vesicular glutamate transporter 2 (vGluT2) promoter. These neurons show a unique distribution, synaptic characterization, cellular physiology and response to neuropeptides involved in energy homeostasis. Although apparently not previously appreciated, the caudal ARC showed a far greater density of vGluT2 cells than the rostral ARC, as seen in transgenic vGluT2‐GFP mice and mRNA analysis. After food deprivation, leptin induced an increase in phosphorylated Stat‐3 in vGluT2‐positive neurons, indicating a response to hormonal cues of energy state. Based on whole‐cell recording electrophysiology in brain slices, vGluT2 neurons were spontaneously active with a spike frequency around 2 Hz. vGluT2 cells were responsive to a number of neuropeptides related to energy homeostasis; they were excited by the anorectic peptide cholecystokinin, but inhibited by orexigenic neuropeptide Y, dynorphin and met‐enkephalin, consistent with an anorexic role in energy homeostasis. Dopamine, associated with the hedonic aspect of enhancing food intake, inhibited vGluT2 neurons. Optogenetic excitation of vGluT2 cells evoked EPSCs in neighbouring neurons, indicating local synaptic excitation of other ARC neurons. Microdrop excitation of ARC glutamate cells in brain slices rapidly increased excitatory synaptic activity in anorexigenic proopiomelanocortin neurons. Together these data support the perspective that vGluT2 cells may be more prevalent in the ARC than previously appreciated, and play predominantly an anorectic role in energy metabolism.
Sepsis associated acute kidney injury
Authors: Poston Jason T , Koyner Jay L 
Published: January 2019

ABSTRACT
Sepsis is defined as organ dysfunction resulting from the host’s deleterious response to infection. One of the most common organs affected is the kidneys, resulting in sepsis associated acute kidney injury (SA-AKI) that contributes to the morbidity and mortality of sepsis. A growing body of knowledge has illuminated the clinical risk factors, pathobiology, response to treatment, and elements of renal recovery that have advanced our ability to prevent, detect, and treat SA-AKI. Despite these advances, SA-AKI remains an important concern and clinical burden, and further study is needed to reduce the acute and chronic consequences. This review summarizes the relevant evidence, with a focus on the risk factors, early recognition and diagnosis, treatment, and long term consequences of SA-AKI. In addition to literature pertaining to SA-AKI specifically, pertinent sepsis and acute kidney injury literature relevant to SA-AKI was included.
Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis
Authors: Carrer Alessandro , Trefely Sophie , Zhao Steven , Campbell Sydney L. , Norgard Robert J. , Schultz Kollin C. , Sidoli Simone , Parris Joshua L.D. , Affronti Hayley C. , Sivanand Sharanya , Egolf Shaun , Sela Yogev , Trizzino Marco , Gardini Alessandro , Garcia Benjamin A. , Snyder Nathaniel W. , Stanger Ben Z. , Wellen Kathryn E. 
Published: January 2019

Abstract

Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abundance regulates global histone acetylation, we hypothesized that altered acetyl-CoA metabolism might contribute to metabolic or epigenetic alterations that promote tumorigenesis. We found that acetyl-CoA abundance is elevated in KRAS-mutant acinar cells and that its use in the mevalonate pathway supports acinar-to-ductal metaplasia (ADM). Pancreas-specific loss of the acetyl-CoA–producing enzyme ATP-citrate lyase (ACLY) accordingly suppresses ADM and tumor formation. In PDA cells, growth factors promote AKT–ACLY signaling and histone acetylation, and both cell proliferation and tumor growth can be suppressed by concurrent BET inhibition and statin treatment. Thus, KRAS-driven metabolic alterations promote acinar cell plasticity and tumor development, and targeting acetyl-CoA–dependent processes exerts anticancer effects.

Significance:
Pancreatic cancer is among the deadliest of human malignancies. We identify a key role for the metabolic enzyme ACLY, which produces acetyl-CoA, in pancreatic carcinogenesis. The data suggest that acetyl-CoA use for histone acetylation and in the mevalonate pathway facilitates cell plasticity and proliferation, suggesting potential to target these pathways.
See related commentary by Halbrook et al., p. 326.
This article is highlighted in the In This Issue feature, p. 305
Circulating Tumor Cells: Come Together, Right Now, Over Metastasis
Authors: Rodrigues Paulo , Vanharanta Sakari 
Published: January 2019

Abstract

Summary:
Circulating tumor cells (CTC) are the source of metastases, but only an infinitesimal fraction of them eventually succeed in colonizing a distant organ. New results show that CD44-dependent aggregation in the circulation provides CTCs with cancer stem cell–like characteristics, suggesting an explanation for the low metastatic efficiency of CTCs, but also avenues for therapeutic intervention.
See related article by Liu et al., p. 96.
Evading the STING: LKB1 Loss Leads to STING Silencing and Immune Escape in KRAS-Mutant Lung Cancers
Authors: Della Corte Carminia Maria , Byers Lauren Averett 
Published: January 2019

Abstract

Summary:
Mutations in STK11 (LKB1) are a major cause of primary resistance to immunotherapy in non–small cell lung cancer. Kitajima and colleagues dissect the underlying mechanism of this immune-resistant phenotype, demonstrating that LKB1 loss leads directly to suppression of stimulator of interferon genes (STING) and insensitivity to cytoplasmic double-strand DNA detection. Therapies that reactivate LKB1 or theSTING pathway may boost anticancer immune response in cancers with resistance to immune-checkpoint blockade.
See related article by Kitajima et al., p. 34.
Something Old, Something New: The Tumor Microenvironment Comes of Age
Authors: Marie Kerrie L. , Merlino Glenn 
Published: January 2019

Abstract

Summary:
In this issue, Weeraratna and colleagues demonstrate that observed differences in melanoma aggressiveness in younger versus older patients can be explained not just by cell-intrinsic alterations over time, but by age-dependent changes in fibroblasts and the extracellular matrix they help create. Their findings identify novel cellular targets for melanoma therapy, as well as candidate prognostic biomarkers to better inform clinical decisions for patients with melanoma.
See related article by Kaur et al., p. 64.
See related article by Ecker et al., p. 82.
Cardiovascular Outcomes in African Americans with Sickle Cell Trait and Chronic Kidney Disease
Authors: Olaniran Kabir O. , Eneanya Nwamaka D. , Allegretti Andrew S. , Zhao Sophia H. , Achebe Maureen M. , Thadhani Ravi I. 
Published: January 2019

<b><i>Background:</i></b> Sickle cell trait (SCT) is common among African Americans and has been historically considered to be benign. Recently, SCT has been associated with an increased risk for chronic kidney disease (CKD) and cardiovascular disease in the general population. Our understanding of SCT has been extrapolated largely from data of patients with sickle cell disease (SCD). Notably, in SCD, the outcomes differ by sex. The effect of SCT on cardiovascular risk in the African American CKD population is unknown, and the interaction between SCT and sex on cardiovascular risk has not been investigated. <b><i>Methods:</i></b> We performed a 2-center retrospective cohort study of all African American patients with SCT using international classification of disease diagnosis codes and CKD (using the 2012 Kidney Disease Improving Global Outcomes criteria) with at least 1 year of follow-up between January 2005 and December 2017. A reference group of ­African American CKD patients without SCT was used as a comparator during the same period. SCT patients and the reference patients were matched at baseline for age, sex, comorbidities, and proteinuria. Primary outcomes were incident coronary artery disease (CAD), incident stroke, and all-cause mortality. Analysis of effect modification between sex and SCT on primary outcomes was performed. <b><i>Results:</i></b> We identified 621 African American CKD patients, 217 SCT patients, and 404 reference patients. The mean age was 56 ± 13 years and 66% were female. The mean estimated glomerular filtration rate was 69 ± 30 mL/min. The mean follow-up time was 8 ± 4 years. There were no significant differences in the primary outcomes comparing SCT patients to matched controls. The interaction term between SCT and sex, however, was significant in the CAD model (<i>p</i> &#x3c; 0.01). Stratification by sex showed no increased risk in females but a significantly increased risk for CAD in male SCT patients (hazard ratio [HR] 2.14; 95% CI 1.18–3.86), which persisted after multivariable analysis (HR 2.13; 95% CI 1.17–3.86). <b><i>Conclusion:</i></b> SCT is associated with an increased risk for CAD in African American males with CKD. The excess risk in males with SCT appears to follow the same pattern as risk in males with SCD. Larger studies are needed to confirm these findings.
Determinants of Case Fatality After Hospitalization for Stroke in France 2010 to 2015
Authors: Gabet Amélie , Grimaud Olivier , de Peretti Christine , Béjot Yannick , Olié Valérie 
Published: January 2019

Background and Purpose—
The aims of this study were to (1) describe early and late case fatality rates after stroke in France, (2) evaluate whether their determinants differed, and (3) analyze time trends between 2010 and 2015.

Methods—
Data were extracted from the Système National des données de santé database. Patients hospitalized for stroke each year from 2010 to 2015, aged ≥18 years, and affiliated to the general insurance scheme were selected. Cox regressions were used to separately analyze determinants of 30-day and 31- to 365-day case fatality rates for each stroke type (ischemic, intracerebral hemorrhage, and subarachnoid hemorrhage).

Results—
In 2015, of the 73 124 persons hospitalized for stroke, 26.8% died in the following year, with the majority of deaths occurring within the first 30 days (56.9%). Nonadmission to a stroke unit, older age, and having comorbidities were all associated with a poorer 30-day and 31- to 365-day prognosis. Female sex was associated with a lower 31- to 365-day case fatality rate for all patients with stroke. Living in an area with a high deprivation index was associated with both higher 30-day and 31- to 365-day case fatality rates for all stroke types. Between 2010 and 2015, significant decreases in both 30-day and 31- to 365-day case fatality rates for ischemic patients were observed.

Conclusions—
Case fatality rates after stroke remained high in 2015 in France, despite major improvements in stroke care and organization. Improvement in stroke awareness and preparedness, particularly in the most deprived areas, together with better follow-up after the acute phase are urgently needed.
Correction relating to the occurrence of Macrolophus pygmaeus (Hemiptera: Heteroptera: Miridae: Bryocorinae: Dicyphini) in New Zealand reported in 2008
Authors: FLYNN A. , EYLES A. C. , GEORGE S. 
Published: January 2019

Eyles et al. (2008) noted the first occurrence of Macrolophus pygmaeus (Rambur, 1839) in New Zealand in 2007, with a site locality reported as the Auckland Botanic Gardens.
A practical approach to active lateral suspension for railway vehicles
Authors: Park Joonhyuk , Shin Yujeong , Hur Hyunmoo , You Wonhee 
Published: January 2019

Background: Active lateral suspension (ALS) technologies have been well developed for several decades, but they have not been widely used in service operation due to relatively high costs for implementation and maintenance and concerns about fail-safe. Therefore, this paper suggests a more practical approach for the active suspension system, designed to achieve target performance with easy implementation and maintenance and high fail-safe. Methods: The control performance target and actuator type are determined from the vibration energy that the ALS has to absorb along the weight function for ride quality evaluation. The installation position of actuator and sensor is decided to decrease the time that it takes for field engineers to check the actuator for maintenance. In addition to fail-safe function of ALS system, conventional hydraulic lateral damper is installed in parallel with ALS to reduce the concern about fail-safe of the ALS. Results: Through the roller rig and filed tests, the performance of the proposed ALS was validated. Lateral ride quality was improved 7.1dB and 6.7dB in the roller rig test and field test, respectively. The fail-safe strategy was also verified during the filed test. Conclusion: Test results show that the suggested ALS is designed appropriately and can be used in practical implementation.
Living with schizophrenia: Perspectives of Turkish people with schizophrenia from two Patient Associations on how the illness affects their lives
Authors: Karanci Nuray A , Aras Aylin , Kumpasoğlu Guler Beril , Can Demet , Çakır Ekin , Karaaslan Cemrenur , Semerci Mine , Tüzün Duygu 
Published: January 2019

Background: Schizophrenia is a chronic mental illness affecting the social and occupational lives of the sufferers and posing a considerable burden on the patients and their families. Furthermore, negative societal reactions and the internalization of these attitudes exacerbate the difficulties encountered. This study examines the perspectives of Turkish people with schizophrenia on how they view the impact of the illness on their lives, the societal reactions and attitudes to schizophrenia and whether they agree with these reactions. Methods: Twenty-three adult participants, all members of two schizophrenia associations in Ankara, capital of Turkey, were recruited. Semistructured interviews were used to find out their perspectives on how the illness affected their lives, how the society reacts to them and their views on these reactions. Interviews were recorded, transcribed and thematic analysis was used to capture the general and the subthemes. Results: The findings suggest that causal attributions for the illness, the impact of illness on various life domains, challenges of living with the illness and finally stigmatization are general categories that capture the perspectives of the participants. Conclusion: People diagnosed with schizophrenia experience the impacts and burdens of their illness in various domains of their lives and negative societal reactions heighten these burdens. It seems important to consider the challenges faced by people with schizophrenia in living with their illness and the impacts of negative societal behaviors and attitudes in offering psychosocial interventions programs for supporting this group. Furthermore, combating negative societal attitudes also seems to be necessary.
Compassion and Caring: Missing Concepts in Social Studies Programs
Authors: Oliner Pearl 
Published: January 2019

Current social studies curricula in elementary and secondary schools reflect a generally humanistic perspective. They nonetheless suffer from a serious omission: they do not include the study of prosocial behaviors, that is, behaviors that evidence altruism, generosity, compassion, and caring. This omission has serious consequences, for it tends to legitimize the view that human behaviors are basically self-serving. It leaves little for youth to emulate in terms of their own prosocial behaviors. Since citizenship education is a primary concern of the social studies curriculum, it behooves curriculum developers to fashion programs that will help youth behave in caring and concerned ways toward others. Such programs need to include at least three elements: (1) opportunities for students to conceptualize prosocial behaviors, (2) opportunities for students to develop social cognition skills, and (3) the provision of prosocial models. Conceptualization focuses on the analysis of altruistic, generous, and caring behaviors in various periods and places in history. Social cognition includes those skills relating to understanding the feelings, intentions, and thoughts of others. Prosocial models include real figures of all ages and groups who have shown care and concern for others in ordinary and extraordinary ways.
A systematic review of the nutritional implications of military rations
Authors: Sotelo-Díaz Indira , Blanco-Lizarazo Carla María 
Published: January 2019

Background: The objective of this study was to assess military rations. Military rations must provide military personnel with suitable nutrition, as high-quality nutrition is crucial for promoting health. Aim: This systematic review provides information regarding the nutritional design of military rations according to energy and protein intake and supplements. Methods: A systematic search was conducted for articles published to date regarding the nutritional needs involved in a military diet for an active population of either gender, ranging from 18 to 60 years old, without excluding material by year, type of document, location, or author. The pertinent articles found were published from 1994 to 2017. Results: Physical activity and environmental factors directly affect calculating energy needs and carbohydrate intake when designing military rations. However, the results showed no influence on protein, fat and/or sodium intake. Furthermore, the search revealed that military populations have a high intake of dietary supplements; it is thus worth considering their incorporation into campaign rations. Conclusion: Military personnel macro- and micro-nutrient needs depend on physical activity and nutrient intake measurement methodologies. The data regarding military personnel dietary supplement consumption indicated that this is a niche worth considering when designing military rations. Research on nutritional needs for military rations could concentrate on optimizing the amount of macro- and micro-nutrients and their biological value, according to physical activity, as well as maintaining their sensory quality, safety and shelf life using different processing technologies.
Seeking consensus amongst UK-based interventional radiologists on the imaging diagnosis of pelvic vein incompetence in women with chronic pelvic pain: A modified Delphi study
Authors: Riding David M , Pond Emma J , McCollum Charles , Caress Ann L 
Published: January 2019

Objectives This modified Delphi study of vascular interventional radiologists sought to achieve consensus statements on the optimal imaging strategy and definitions of important imaging diagnostic features in women with pelvic vein incompetence. Method The UK-based interventional radiologists with the experience of investigating and treating pelvic vein incompetence responded to up to three rounds of online questionnaires. Results Three consensus statements emerged from 27 responders: (1) catheter venography is the ‘gold standard’ investigation for the diagnosis of pelvic vein incompetence; (2) pelvic vein incompetence should be defined as ‘retrograde flow along the ovarian or internal iliac veins’; (3) pelvic varices should be defined as ‘tortuous, often dilated, vulval, adnexal, para-uterine veins arising from incompetent internal iliac or ovarian veins.’ Conclusion This study achieved consensus statements on imaging diagnosis in women with suspected pelvic vein incompetence. These can be used to minimise heterogeneity of research protocols, and represent baseline positions which can, themselves, be tested.
The comparative efficacy of theta burst stimulation or functional electrical stimulation when combined with physical therapy after stroke: a randomized controlled trial
Authors: Khan Fayaz , Rathore Chaturbhuj , Kate Mahesh , Joy Josy , Zachariah George , Vincent P C , Varma Ravi Prasad , Radhakrishnan Kurupath 
Published: January 2019

Objective: To study the long-term effectiveness of Theta Burst Stimulation (TBS) or Functional Electrical Stimulation (FES) combined with Physical therapy (PT) as compared to PT alone for improving arm functions in patients with acute stroke. Design: Single blind randomized controlled trial. Setting: Outpatient clinics and inpatient wards at tertiary care neurology center. Subjects: Adult patients with acute middle cerebral artery territory ischemic stroke. Interventions: 60 patients were randomized into three groups of 20 each: TBS+PT; FES+PT; and PT alone. TBS group received intermittent TBS of ipsilesional hemisphere and continuous TBS of contralesional hemisphere while FES group received FES of paretic limb, both for four weeks. All groups received supervised physical therapy for four weeks followed by home physiotherapy for one year. Outcome measures: Fugl Meyer Assessment upper limb score (FMA-UL) was primary outcome measure. Patients were evaluated at baseline and subsequently at one, three and six months and one year. Results: Compared to PT group, mean FMA-UL scores were higher in TBS and FES groups at all follow-ups ( P < 0.001). From baseline to one year, mean (SD) FMA-UL scores increased from 14.9(2.1) to 55.55(2.46) in TBS group, 15.5(1.99) to 55.85(2.46) in FES group, and 14.3(2.2) to 43.3(4.22) in PT group indicating an increase of 273%, 260%, and 203% respectively. There was no difference between FES and TBS groups. Conclusion: A four-week intervention with TBS or FES combined with PT produces better long-term arm functions as compared to PT alone in patients with acute stroke.