bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the prognostic value of surgery and postoperative radiotherapy for patients with thymic neuroendocrine tumors: A propensity‐matched study based on the SEER database
Authors: Wen Junmiao , Chen Jiayan , Chen Donglai , Liu Di , Xu Xinyan , Huang Lv , Cao Jianzhao , Zhang Junhua , Gu Yu , Fan Min , Chen Yongbing
Published: October 2018

Background

The prognostic value of surgery and postoperative radiotherapy (PORT) for primary thymic neuroendocrine tumors (TNETs) was estimated using the SEER database.

Methods

This retrospective study used SEER data of TNET patients between 1998 and 2015. Propensity score matching (PSM) was performed according to whether surgery was performed. The prognostic effects on overall survival (OS) and cancer‐specific survival (CSS) were evaluated using multivariate Cox regression.

Results

A total of 3947 patients were included: 293 (7.4%) TNET, 2788 (70.6%) thymoma, and 866 (21.9%) thymic carcinoma. Compared to other subtypes, TNET patients were younger, included a larger proportion of men, had a well or moderately differentiated histological grade, higher disease stage at diagnosis, and were more likely to have regional lymph node metastasis. The median OS and CSS for TNET were 82.9 (95% confidence interval 74.3–91.4) and 101.9 (95% confidence interval 91.9–111.8) months, respectively, significantly shorter than for thymomas. In the matched cohort of TNET patients, multivariate analysis of OS and CSS revealed a significantly poorer prognosis in the non‐surgery group (P < 0.001). Compared to total/radical resection, TNET patients who underwent debulking resection had significantly inferior outcomes (P < 0.05). Postoperative radiotherapy favorably impacted OS and CSS in Masaoka–Koga stage III–IV TNET patients; this OS impact was also observed in stage IIB patients.

Conclusion

TNETs are extremely rare with relatively dismal outcomes. This analysis revealed the role of complete surgical resection and the favorable effect of postoperative radiotherapy in specific TNET subgroups.
Clinical complete response after chemoradiotherapy for carcinoma of thoracic esophagus: Is esophagectomy always necessary? A systematic review and meta‐analysis
Authors: Wang Jun , Qin Jianjun , Jing Shaowu , Liu Qing , Cheng Yunjie , Wang Yi , Cao Feng
Published: October 2018

Background

Although a clinical complete response (cCR) after chemoradiotherapy (CRT) could lead to a better prognosis, the choice of a following strategy, such as surgical or non‐surgical approach, remains controversial.

Methods

All articles relevant to a comparison of surgical and non‐surgical treatment (including further definitive chemoradiotherapy or active surveillance) for esophageal carcinoma patients with a cCR after CRT were retrieved for meta‐analysis. The final date for data retrieval was 30 June 2018.

Results

Four retrospective studies including 648 patients met the inclusion criteria: 620 with squamous cell carcinoma and 28 with adenocarcinoma. The CRT + surgery group had an advantage over the non‐surgery group in regard to two‐year disease‐free survival (DFS); however, the two groups showed similar results in five‐year DFS. The CRT + surgery group had an advantage over the non‐surgery group in two‐year overall survival (OS); nevertheless, the two groups showed similar results in five‐year OS.

Conclusions

Based on the available evidence, the addition of surgery to thoracic locally advanced esophageal carcinoma patients with a cCR after neoadjuvant CRT provided no advantage to long‐term survival. As an exception, the two‐year DFS and OS could be improved. This research conclusion might be more suitable to patients with squamous cell carcinoma.
Adjuvant radiotherapy, chemotherapy or surgery alone for high‐risk histological node negative esophageal squamous cell carcinoma: Protocol for a multicenter prospective randomized controlled trial
Authors: Guo Xufeng , Fang Wentao , Li Zhigang , Yu Zhengtao , Rong Tiehua , Fu Jianhua , Han Yongtao , Tan Lijie , Chen Chun , Liu Shuoyan , Liao Yongde , Xiao Gaoming , Wei Yucheng , Zhu Chengchu , Li Hecheng , Luo Jinhua , Xing Wenqun
Published: October 2018

Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after radical resection still carries a significant risk of recurrence, especially in high‐risk patients. Our previous study showed that the risk of recurrence was associated with tumor location and cell differentiation, as well as the presence of lymphovascular invasion. Most recurrence occurs within two years after surgery. There is still a lack of knowledge on the risks or potential benefits of postoperative adjuvant therapies for high‐risk pN0 ESCC patients. This study was designed to evaluate the efficacy and toxicity of adjuvant therapies after radical surgery in high‐risk patients with pN0 ESCC. This study is a multicenter, prospective, controlled randomized trial, which will compare the differences between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone for high‐risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant chemotherapy with paclitaxel and cisplatin, patients in group B will receive adjuvant radiotherapy with intensity‐modulated radiation of 50 Gy, and patients in group C (the control) will receive surgery alone. The primary endpoint is three‐year disease‐free survival. Secondary endpoints include toxicity of adjuvant therapies and five‐year overall survival. One hundred and sixty‐two patients in each group are required and a total of 486 patients will finally be enrolled into the study. This will be the first randomized trial to investigate the necessity or potential benefit of postoperative adjuvant therapies for high‐risk pN0 ESCC patients.
Honey bee‐assisted surveillance for early plant virus detection
Authors: Roberts John M. K. , Ireland Kylie B. , Tay Wee T. , Paini Dean
Published: October 2018

Incursions of plant viral pathogens are a primary concern for horticulture as they can significantly impact crop yields and require expensive management. Early detection of plant viruses is critical for effective plant biosecurity because it enables growers to respond quickly and limit their spread. However, current surveillance methods relying on enzyme‐linked immunosorbent assay and PCR testing of plant material can only operate at a limited scale. It quickly becomes unfeasible to test a large number of samples for area‐wide surveillance of multiple viruses and ineffective in novel virus discovery. Advances in high‐throughput sequencing (HTS) platforms have greatly improved our surveillance capability and its value demonstrated for screening plant material for viral pathogens. However, while HTS can improve detection, it does not necessarily address the issue of sampling effort needed to achieve early detection. The solution is to couple HTS with a method of constant surveillance and sampling from potentially infected plants. We propose that when managed honey bee (Apis mellifera) hives are brought to flowering crops to deliver essential pollination services, they can also provide valuable surveillance by effectively “sampling” entire crops as they collect pollen and nectar. Combining the ability of honey bees to create a representative sample from a large number of plants with the sensitivity of HTS offers a powerful system for early detection of plant viruses. We describe a novel approach to plant biosecurity where HTS virus detection in honey bees was found to provide earlier detection of plant virus incursions in Australia than current surveillance programmes. In 2013–2014, a national virus survey of honey bees was conducted, which used HTS screening of pooled honey bee samples across Australia. This HTS data simultaneously identified multiple plant viruses in these samples and showed the presence of cucumber green mottle mosaic virus in several states of Australia before its subsequent detection from diseased plant material.
Meta‐Analysis of Genetic Influences on Initial Alcohol Sensitivity
Authors: Edwards Alexis C. , Deak Joseph D. , Gizer Ian R. , Lai Dongbing , Chatzinakos Chris , Wilhelmsen Kirk P. , Lindsay Jonathan , Heron Jon , Hickman Matthew , Webb Bradley T. , Bacanu Silviu‐Alin , Foroud Tatiana M. , Kendler Kenneth S. , Dick Danielle M. , Schuckit Marc A.
Published: October 2018

Background

Previous studies indicate that low initial sensitivity to alcohol may be a risk factor for later alcohol misuse. Evidence suggests that initial sensitivity is influenced by genetic factors, but few molecular genetic studies have been reported.

Methods

We conducted a meta‐analysis of 2 population‐based genome‐wide association studies of the Self‐Rating of the Effects of Alcohol scale. Our final sample consisted of 7,339 individuals (82.3% of European descent; 59.2% female) who reported having used alcohol at least 5 times. In addition, we estimated single nucleotide polymorphism (SNP)‐based heritability and conducted a series of secondary aggregate genetic analyses.

Results

No individual locus reached genome‐wide significance. Gene and set based analyses, both overall and using tissue‐specific expression data, yielded largely null results, and genes previously implicated in alcohol problems and consumption were overall not associated with initial sensitivity. Only 1 gene set, related to hormone signaling and including core clock genes, survived correction for multiple testing. A meta‐analysis of SNP‐based heritability resulted in a modest estimate of  = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683,  = 0.36, SE = 0.14, p = 0.04). No significant genetic correlations with other relevant outcomes were observed.

Conclusions

Findings yielded only modest support for a genetic component underlying initial alcohol sensitivity. Results suggest that its biological underpinnings may diverge somewhat from that of other alcohol outcomes and may be related to core clock genes or other aspects of hormone signaling. Larger samples, ideally of prospectively assessed samples, are likely necessary to improve gene identification efforts and confirm the current findings.
A novel heterozygous variant p.(Trp538Arg) of SYNM is identified by whole‐exome sequencing in a Chinese family with dilated cardiomyopathy
Authors: Zhang Shu‐Bing , Liu Yu‐Xing , Fan Liang‐Liang , Huang Hao , Li Jing‐Jing , Jin Jie‐Yuan , Xiang Rong
Published: October 2018

Dilated cardiomyopathy (DCM) is a relatively frequent myocardial disease that may lead to heart failure, syncope, and sudden cardiac death. Genetic factors play important roles in the etiology of the disease. To date, at least 50 genes have been identified in patients with DCM, among them, only three mutations have been reported in Synemin (SYNM) gene. In this study, we investigate a Chinese family of three generations with four patients with DCM. Employing whole‐exome sequencing (WES) and bioinformatics strategies, a novel heterozygous missense mutation p.(Trp538Arg) of SYNM was identified and cosegregated with the affected family members. The missense mutation locates in the C‐terminal domain of SYNM and leads to a substitution of tryptophan by arginine and may cause the structure change of synemin protein. In conclusion, we employed WES to detect the mutations of DCM patients and identified a novel likely pathogenic mutation in SYNM gene. Our study not only expands the spectrum of SYNM mutations, it further confirms that mutations in SYMN may underlie nonfamilial DCM, and offers genetic testing information to additional DCM patients.
Public‐Sector Unions and the Size of Government
Authors: Paglayan Agustina S.
Published: October 2018

Public‐sector unions are generally thought to increase the size of government through collective bargaining. This article challenges this idea for the case of teacher unions in the United States and argues that while collective bargaining institutions sometimes lead to increased education spending, this is not the norm. Using a new longitudinal data set spanning all states before and after they granted collective bargaining rights to teachers, the article shows that although states that mandate districts to bargain with teachers have higher education expenditures than states that do not, the differences precede collective bargaining. Difference‐in‐differences analyses find no evidence that introducing collective bargaining rights led to average increases in the level of resources devoted to education. Although existing theories cannot explain these null findings, the article shows one reason behind them is that most laws granting collective bargaining rights to teachers were not unambiguously prolabor, but included both pro‐ and anti‐union provisions.
Impact of change in head and neck position on ultrasound localisation of the cricothyroid membrane: an observational study
Authors: Dixit A. , Ramaswamy K. K. , Perera S. , Sukumar V. , Frerk C.
Published: October 2018

The ideal position for performing surgical cricothyroidotomy is with full neck extension. Some authors have recommended marking the cricothyroid membrane before general anaesthesia, typically with the patient's head and neck in a neutral position. The primary aim of this observational study was to determine whether skin marks made over the centre of the cricothyroid membrane with the head and neck in the neutral position moved outside the boundaries of the membrane when the neck was subsequently extended. The secondary aim was to assess changes in the height of the cricothyroid membrane between the neutral and extended positions. Twenty‐two volunteers completed the study. With the head and neck in the neutral position, the distance between the upper and lower borders (‘height’) of the cricothyroid membrane was measured by a radiologist using ultrasound. The skin was marked over the mid‐point of the membrane. The subject then maximally extended the neck, and the measurements and marking were repeated. The skin marking over the centre point of the cricothyroid membrane moved by median (IQR [range]) 5 (4–6 [0–10]) mm when the head and neck were moved from a neutral to a fully extended position. The initial skin mark moved to lie outside the boundary of the cricothyroid membrane in 12 of 22 subjects after extending the neck. The height of the cricothyroid membrane increased by 30% with the neck extended. We recommend that marking the skin in preparation for cricothyroidotomy should be performed with the neck extended, not with the head and neck in the neutral position as previously suggested.
Holocene climate vs. catchment forcing on a shallow, eutrophic lake in eastern Poland
Authors: Zawiska Izabela , Apolinarska Karina , Woszczyk Michał
Published: October 2018

This paper presents a sedimentary record from Lake Łukie located in the southeastern part of the Central European Plain, beyond the reach of the maximum extent of the last glaciation. The lake has thermokarstic origin and developed during the last glacial termination due to subsidence of the sub‐Quaternary carbonate basement triggered by permafrost thawing. A sediment core was investigated to reconstruct water trophic state and lake depth changes during the Holocene. We aimed at showing the relationship between ecological and geochemical changes in the lake and regional/supraregional climatic and hydrological trends throughout the Holocene. Results of subfossil Cladocera analysis were combined with data on the geochemistry and stable C and O isotopes in sedimentary carbonates. Isotopic and geochemical proxies helped to detect sources of sedimentary particles in the lake and thus to reconstruct changes in the intensity of atmospheric and catchment processes (e.g. precipitation and surface runoff). The Cladocera analysis results indicated endogenic processes in the lake such as trophic changes. Our data revealed that Lake Łukie has always been a rather eutrophic water body and the periods of particularly high productivity were in the lower Preboreal and upper Subatlantic. Periods of increased water depth were recorded in the lower Preboreal, lower Boreal and upper Subboreal, whereas low water stands were obtained during the late Preboreal, late Boreal, late Atlantic and Atlantic/Subboreal transition as well as during the lower Subboreal. The sediment succession from Lake Łukie provides the first full Holocene record of carbon and oxygen stable isotopes in lacustrine carbonates from the eastern part of the Central European Lowland. The record is characterized by uncommonly high δ13C and δ18O values of the carbonates resulting from a combination of within‐lake processes and dissolution of the carbonate bedrock of Cretaceous age. The impact of the old carbonates on isotope values was helpful in the reconstruction of the catchment forcing on the lake.
Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594: a novel fluorescent probe for the N/OFQ (NOP) receptor
Authors: Bird M F , Guerrini R , Willets J M , Thompson J P , Caló G , Lambert D G
Published: October 2018

Background and Purpose

The nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is a member of the opioid receptor family and is involved in a number of physiological responses, pain and immune regulation as examples. In this study, we conjugated a red fluorophore‐ATTO594 to the peptide ligand N/OFQ (N/OFQATTO594) for the NOP receptor and explored NOP receptor function at high (in recombinant systems) and low (on immune cells) expression.

Experimental Approach

We assessed N/OFQATTO594 receptor binding, selectivity and functional activity in recombinant (CHO) cell lines. Live cell N/OFQATTO594 binding was measured in (i) HEK cells expressing NOP and NOPGFP receptors, (ii) CHO cells expressing the hNOPGαqi5 chimera (to force coupling to measurable Ca2+ responses) and (iii) freshly isolated human polymorphonuclear cells (PMN).

Key Results

N/OFQATTO594 bound to NOP receptor with nM affinity and high selectivity. N/OFQATTO594 activated NOP receptor by reducing cAMP formation and increasing Ca2+ levels in CHOhNOPGαqi5 cells. N/OFQATTO594 was also able to visualize NOP receptors at low expression levels on PMN cells. In NOP‐GFP‐tagged receptors, N/OFQATTO594 was used in a FRET protocol where GFP emission activated ATTO, visualizing ligand–receptor interaction. When the NOPGFP receptor is activated by N/OFQATTO594, movement of ligand and receptor from the cell surface to the cytosol can be measured.

Conclusions and Implications

In the absence of validated NOP receptor antibodies and issues surrounding the use of radiolabels (especially in low expression systems), these data indicate the utility of N/OFQATTO594 to study a wide range of N/OFQ‐driven cellular responses.
Identification and pharmacological profile of SPP1, a potent, functionally selective and brain penetrant agonist at muscarinic M1 receptors
Authors: Broad Lisa M , Sanger Helen E , Mogg Adrian J , Colvin Ellen M , Zwart Ruud , Evans David A , Pasqui Francesca , Sher Emanuele , Wishart Graham N , Barth Vanessa N , Felder Christian C , Goldsmith Paul J
Published: October 2018

Background and Purpose

We aimed to identify and develop novel, selective muscarinic M1 receptor agonists as potential therapeutic agents for the symptomatic treatment of Alzheimer's disease.

Experimental Approach

We developed and utilized a novel M1 receptor occupancy assay to drive a structure activity relationship in a relevant brain region while simultaneously tracking drug levels in plasma and brain to optimize for central penetration. Functional activity was tracked in relevant native in vitro assays allowing translational (rat–human) benchmarking of structure–activity relationship molecules to clinical comparators.

Key Results

Using this paradigm, we identified a series of M1 receptor selective molecules displaying desirable in vitro and in vivo properties and optimized key features, such as central penetration while maintaining selectivity and a partial agonist profile. From these compounds, we selected spiropiperidine 1 (SPP1). In vitro, SPP1 is a potent, partial agonist of cortical and hippocampal M1 receptors with activity conserved across species. SPP1 displays high functional selectivity for M1 receptors over native M2 and M3 receptor anti‐targets and over a panel of other targets. Assessment of central target engagement by receptor occupancy reveals SPP1 significantly and dose‐dependently occupies rodent cortical M1 receptors.

Conclusions and Implications

We report the discovery of SPP1, a novel, functionally selective, brain penetrant partial orthosteric agonist at M1 receptors, identified by a novel receptor occupancy assay. SPP1 is amenable to in vitro and in vivo study and provides a valuable research tool to further probe the role of M1 receptors in physiology and disease.
On publication, refereeing and working hard
Authors: Baghestanian Sascha , Popov Sergey V.
Published: October 2018

We present a model for academia with heterogeneous author types and endogenous effort to evaluate recent changes in the publication process in economics. We analyze the implications of these developments on research output. Lowering the precision of refereeing signals lowers the effort choices of intermediate ability authors, but invites more submissions from less able authors. Increasing the number of journals stimulates less able authors to submit their papers. The editor can improve the journal's quality pool of submitted manuscripts by improving the precision of refereeing, but not by lowering acceptance standards. The submission strategy of an author is informative of his ability.
Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics study
Authors: Yang Jing‐Wen , Wang Xue‐Rui , Zhang Meng , Xiao Ling‐Yong , Zhu Wen , Ji Cai‐Shuo , Liu Cun‐Zhi
Published: October 2018

Aims

Acupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high‐resolution liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ‐LC‐MS/MS strategy to unravel the underlying mechanism of acupuncture.

Methods

Wistar rats were subjected to vascular dementia with bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3 days after surgery. The Morris water maze was used to assess the cognitive function. Proteins were screened by quantitative proteomics and analyzed by bioinformatic analysis. Four differentially expressed proteins (DEPs) were validated by western blot. The reactive oxygen species (ROS) production, neuron cell loss, and long‐term potentiation (LTP) were determined after western blot.

Results

Acupuncture at proper acupoints significantly improved cognitive function. A total of 31 proteins were considered DEPs. Gene ontology (GO) analysis showed that most of the DEPs were related to oxidative stress, apoptosis, and synaptic function, which were regarded as the major cellular processes related to acupuncture effect. Western blot results confirm the credibility of iTRAQ results. Acupuncture could decrease ROS production, increase neural cell survival, and improve LTP, which verified the three major cellular processes.

Conclusion

Acupuncture may serve as a promising clinical candidate for the treatment of vascular dementia via regulating oxidative stress, apoptosis, or synaptic functions.
Use of beta‐blocker is associated with lower mortality in patients with coronary artery disease with or without COPD
Authors: Rezaei Safoura Sheikh , Rinner Christoph , Ratajczak Paulina , Grossmann Wilfried , Gall Walter , Wolzt Michael
Published: October 2018

Introduction

Beta‐blockers are indicated for secondary prevention of coronary artery disease (CAD). However, in patients with co‐morbidity of chronic obstructive pulmonary disease (COPD) an underuse of beta‐blocker has been reported.

Materials and Methods

Prescription and demographic data and information on hospital discharge diagnoses from 13 Austrian health insurance funds for the years 2006‐2007 were analyzed. The primary end point was all‐cause mortality of patients with CAD with or without COPD and its association with use of beta‐blockers.

Results

In 2006 and 2007, 65717 patients (37% female, 63% male) were discharged with a diagnosis of CAD. Among these patients, 46% had a co‐diagnosis of COPD, 24% had diabetes, and 75% received beta‐blockers. Use of beta‐blockers was comparable in CAD patients with COPD and without COPD with 77% and 74%, respectively.

Thousand eight hundred seventy‐two (8.1%) and 1473 (5.6%) patients with and without COPD, who used beta‐blockers died within months in 2006 and 2007. Thousand five hundred fifty‐three (22.0%) and 1862 (22.2%) of patients with and without COPD and without beta‐blockers died during the corresponding time period.

Discussion

Use of beta‐blockers was similar in patients with CAD with or without co‐diagnosis of COPD. However, mortality of beta‐blocker users was markedly lower than that of nonusers in patients with CAD with or without COPD.
Inducing Downstream Information Sharing via Manufacturer Information Acquisition and Retailer Subsidy
Authors: Li Guo , Zheng Hong , Sethi Suresh P. , Guan Xu
Published: October 2018

We investigate a manufacturer's information acquisition and subsidization strategies in a supply chain featuring two competing retailers who sell substitutable products and have private demand information. The manufacturer can decide whether to acquire demand information at a cost and further decide whether to offer subsidies simultaneously to retailers to induce their sharing of private demand information. We demonstrate that subsidizing retailers is always in the manufacturer's interest, but direct information acquisition is profitable only if its cost is low. Information acquisition helps the manufacturer gain superior demand information and leverages the retailer's information advantage, thereby reducing the expenditure of subsidization. Compared with the simultaneous subsidy provision scheme, we further investigate the sequential and partial subsidy schemes and find that the simultaneous and sequential subsidy schemes result in an identical equilibrium outcome that dominates the equilibrium outcome in the partial subsidy scheme when three subsidy provision schemes are all feasible. Although the outcomes are the same, we show that the simultaneous subsidy scheme can be applied in a broader range than the sequential subsidy scheme can. Otherwise, if complete information sharing cannot be achieved, the partial subsidy scheme may be the optimal choice for the manufacturer.
The ontogeny of intent‐based normative judgments
Authors: Proft Marina , Rakoczy Hannes
Published: October 2018

When evaluating norm transgressions, children begin to show some sensitivity to the agent's intentionality around preschool age. However, the specific developmental trajectories of different forms of such intent‐based judgments and their cognitive underpinnings are still largely unclear. The current studies, therefore, systematically investigated the development of intent‐based normative judgments as a function of two crucial factors: (a) the type of the agent's mental state underlying a normative transgression, and (b) the type of norm transgressed (moral versus conventional). In Study 1, 5‐ and 7‐year‐old children as well as adults were presented with vignettes in which an agent transgressed either a moral or a conventional norm. Crucially, she did so either intentionally, accidentally (not intentionally at all) or unknowingly (intentionally, yet based on a false belief regarding the outcome). The results revealed two asymmetries in children's intent‐based judgments. First, all age groups showed greater sensitivity to mental state information for moral compared to conventional transgressions. Second, children's (but not adults') normative judgments were more sensitive to the agent's intention than to her belief. Two subsequent studies investigated this asymmetry in children more closely and found evidence that it is based on performance factors: children are able in principle to take into account an agent's false belief in much the same way as her intentions, yet do not make belief‐based judgments in many existing tasks (like that of Study 1) due to their inferential complexity. Taken together, these findings contribute to a more systematic understanding of the development of intent‐based normative judgment.
Structural and functional neuroimaging in attention‐deficit/hyperactivity disorder
Authors: Albajara Sáenz Ariadna , Villemonteix Thomas , Massat Isabelle
Published: October 2018

Over the last decade, there has been a dramatic increase in the number of neuroimaging studies in attention‐deficit/hyperactivity disorder (ADHD). In terms of brain structure, magnetic resonance imaging (MRI), and diffusion tensor imaging studies have evidenced differences in volume, surface‐based measures (cortical thickness, surface area, and gyrification), and white matter integrity in different cerebral regions, in children and adults with ADHD compared to population norms. Abnormalities in the basal ganglia, prefrontal structures, and the corpus callosum have been the most consistently reported findings across studies. Hemodynamic (functional MRI, functional near‐infrared spectroscopy, positron emission tomography, single‐photon emission computed tomography) and magnetoencephalography measurements have also shown differences in neural activity during the execution of neuropsychological tasks and during rest, in widespread regions of the brain. Importantly, multimodal studies combining structural and functional methods have shown an intercorrelation between structural and functional abnormalities in ADHD. Further longitudinal studies are needed to clarify the effects of age and medication on brain structure and function in individuals with ADHD.

What this paper adds

In attention‐deficit/hyperactivity disorder (ADHD), the brain is characterized by abnormal neural network interplay.

Structural and functional cerebral abnormalities in ADHD are intercorrelated.

Currently there is no neural biomarker that can be used in diagnosis.

Longitudinal studies have shed light on the brain correlates of ADHD over the lifespan.

The effects of stimulant intake on the brain correlates of ADHD remain unclear.
Cognitive activity in a sitting position is protectively associated with cognitive impairment among older adults
Authors: Kurita Satoshi , Doi Takehiko , Tsutsumimoto Kota , Hotta Ryo , Nakakubo Sho , Kim Minji , Shimada Hiroyuki
Published: October 2018

Aim

Previous studies have obtained inconsistent results regarding the association between sedentary behavior and cognitive impairment. The present study aimed to examine the association between cognitive activity in a sitting position (CAS) and cognitive impairment among older adults.

Methods

Community‐dwelling older adults, from Obu or Nagoya in Japan, participated in a survey in 2013. A total of 5300 participants (mean age 75.0 ± 5.1 years; women 52.9%) met the criteria for the present study. We assessed the frequency and variety of CAS composed of six activities, including reading books or newspapers, writing a diary or letters, solving crossword puzzles, playing board games, using a computer and maintaining housekeeping records. The frequency of engagement in CAS was one or more time(s)/week. The variety of CAS was assessed by the number of engagements in CAS. Cognitive impairment was defined by two or more tests at least 1.5 standard deviations below the reference threshold in four neuropsychological tests. Logistic regression analysis was carried out to examine the associations between the frequency and variety of CAS and cognitive impairment, adjusted for covariates.

Results

The proportion of participants engaging in each CAS varied from 12.3% (playing board games) to 93.6% (reading books or newspaper). After adjustment, five CAS were significantly associated with cognitive impairment (OR 0.33–0.65, all P < 0.001). The variety of CAS was significantly associated with the reduced OR of cognitive impairment (OR 0.61, 95% confidence interval 0.55–0.68).

Conclusions

Almost every CAS and a greater variety of CAS are associated with cognitive impairment among older people. Geriatr Gerontol Int 2019; 19: 98–102.
IDIOSYNCRATIC RISK, AGGREGATE RISK, AND THE WELFARE EFFECTS OF SOCIAL SECURITY
Authors: Harenberg Daniel , Ludwig Alexander
Published: October 2018

We ask whether a pay‐as‐you‐go financed social security system is welfare improving in an economy with idiosyncratic and aggregate risk. We show that the whole welfare benefit from insurance against both risks is greater than the sum of benefits from insurance against the isolated risks. One reason is the convexity of the welfare gain. The other reason is a direct risk interaction amplifying the utility losses from risk. Our quantitative evaluation shows that introducing a minimum pension leads to sizeable welfare gains, despite substantial crowding out. About 60% of these gains would be missing from summing up the isolated benefits.
Predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy: Analysis of 359 cases with a median follow‐up period of 26 months
Authors: Abdel Raheem Ali , Chang Ki Don , Alenzi Mohammed Jayed , Ham Won Sik , Han Woong Kyu , Choi Young Deuk , Rha Koon Ho
Published: October 2018

Objectives

Our aim was to evaluate the predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy.

Methods

The study cohort consisted of 359 consecutive non‐metastatic prostate cancer patients who underwent Retzius‐sparing robot‐assisted radical prostatectomy between November 2012 and January 2016. According to the National Comprehensive Cancer Network prostate cancer risk classification, 164 patients (45.7%) had high‐ or very high‐risk prostate cancer. No patient received adjuvant therapy until documented biochemical recurrence. Biochemical recurrence‐free survival was estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression models were used to determine variables predictive of biochemical recurrence.

Results

The median follow‐up period was 26 months (interquartile range 19–38 months). The overall biochemical recurrence rate was 14.8%, and the median time to biochemical recurrence was 11 months (interquartile range 6–22 months). The 3‐year biochemical recurrence‐free survival probability was 71.2%, 72.1%, 88.7%, 82.3% and 95.7% in very high‐, high‐, intermediate‐, low‐ and very low‐risk prostate cancer, respectively (log–rank, P < 0.001). On multivariable analysis, preoperative prostate‐specific antigen (hazard ratio 1.03, 95% confidence interval 1.02–1.04; P < 0.0001), percentage of maximum core involvement on biopsy (hazard ratio 1.02, 95% confidence interval 1.01–1.03; P = 0.029) and clinical stage ≥T3a (hazard ratio 2.12, 95% confidence interval 1.02–4.39; P = 0.043) were predictors of biochemical recurrence, whereas pathological Gleason score ≥8 (hazard ratio 5.63, 95% confidence interval 1.62–19.61; P = 0.007) and pathological tumor volume (hazard ratio 1.08, 95% confidence interval 1.04–1.20; P < 0.001) were the main pathological predictors of biochemical recurrence.

Conclusions

Retzius‐sparing robot‐assisted radical prostatectomy confers effective biochemical recurrence control at the mid‐term follow‐up period. Preoperative prostate‐specific antigen, advanced clinical stage and higher Gleason score were important predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy. Long‐term oncological safety still needs to be established.
L‐carnitine prevents ammonia‐induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes
Authors: Wang Ting , Suzuki Kazuyuki , Kakisaka Keisuke , Onodera Mio , Sawara Kei , Takikawa Yasuhiro
Published: October 2018

Background and Aim

L‐carnitine (L‐CA) has been used therapeutically to treat hepatic encephalopathy with hyperammonemia, but the mechanism by which L‐CA contributes to ammonia detoxification in the brain is still unclear. Thus, the cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with hyperammonemia following L‐CA administration were studied.

Methods

Human astrocytes were treated with ammonium chloride (NH4Cl), L‐CA or a mixture of NH4Cl, and L‐CA under defined conditions. Total intracellular reactive oxygen species and lactate dehydrogenase leakage were measured following different treatment periods. The intracellular levels of AAs in astrocytes were determined using metabolomic analysis.

Results

Intracellular total reactive oxygen species and lactate dehydrogenase leakage were significantly increased after treatment with NH4Cl. In contrast, co‐treatment with L‐CA significantly inhibited the cytotoxic effects of NH4Cl. The intracellular levels of almost all AAs involving glutamine and branched‐chain AAs (BCAAs) were significantly increased in the NH4Cl‐treated cells compared with in the control cells; these changes in BCAA levels were reduced with L‐CA co‐treatment. Additionally, the level of 3‐methyl‐2‐oxovaleric acid, which is a metabolite from isoleucine and plays a critical role in neurological damage, was significantly increased in the NH4Cl‐treated cells, but this metabolite was significantly decreased with L‐CA co‐treatment.

Conclusion

L‐CA protects human astrocytes from ammonia‐induced acute cytotoxic effects and the increased intracellular levels of glutamine and BCAAs.
Favorable outcomes of prepackaged low‐residue diet on bowel preparation for colonoscopy: Endoscopist‐blinded randomized controlled trial
Authors: Lee Jung Won , Choi Joon Young , Yoon Hyuk , Shin Cheol Min , Park Young Soo , Kim Nayoung , Lee Dong Ho
Published: October 2018

Background and Aim

2 L polyethylene glycol plus an ascorbic acid (PEGA) is known to be as effective. However, 2 L polyethylene glycol‐based regimens are often still difficult for patients to tolerate. Therefore, we conducted this study to evaluate the potential of 1 L PEGA with prepackaged low‐residue diet (PLD) as an alternative to 2 L PEGA before colonoscopy.

Methods

The subjects were randomly assigned to either of the two groups. The 2 L PEGA group received 2 L PEGA split regimen. The 1 L PEGA with PLD group received PLD on the day preceding colonoscopy and 1 L PEGA. All endoscopic procedures were performed by one physician who did not know patients allocation. Bowel preparation status were graded using Boston Bowel Preparation Score (BBPS). A questionnaire regarding tolerability and safety was administered. This trial is registered at ClinicalTrials.gov (NCT03329339).

Results

A total of 173 patients completed the study (86 in the 2 L PEGA group and 87 in the 1 L PEGA with PLD group). Bowel preparation was adequate in 88.4% (76/86) of patients in the 2 L PEGA group and 93.1% of patients in the 1 L PEGA with PLD group (81/87, P = 0.28). The patients in the 1 L PEGA with PLD group had higher whole Boston Bowel Preparation Scale score (P = 0.02) and expressed more satisfaction and willingness to repeat the procedure (P < 0.01). There was no significant difference with respect to compliance or safety.

Conclusion

1 L PEGA with PLD showed equivalent efficacy, greater satisfaction, and more willingness to repeat compared with 2 L PEGA for bowel preparation.
The Case for Mobility Assessment in Hospitalized Older Adults: American Geriatrics Society White Paper Executive Summary
Authors: Wald Heidi L. , Ramaswamy Ravishankar , Perskin Michael H. , Roberts Lloyd , Bogaisky Michael , Suen Winnie , Mikhailovich Anna ,   for the Quality and Performance Measurement Committee of the American Geriatrics Society
Published: October 2018

Mobility can be defined as the ability to move or be moved freely and easily. In older adults, mobility impairments are common and associated with risk for additional loss of function. Mobility loss is particularly common in these individuals during acute illness and hospitalization, and it is associated with poor outcomes, including loss of muscle mass and strength, long hospital stays, falls, declines in activities of daily living, decline in community mobility and social participation, and nursing home placement. Thus, mobility loss can have a large effect on an older adult's health, independence, and quality of life. Nevertheless, despite its importance, loss of mobility is not a widely recognized outcome of hospital care, and few hospitals routinely assess mobility and intervene to improve mobility during hospital stays. The Quality and Performance Measurement Committee of the American Geriatrics Society has developed a white paper supporting greater focus on mobility as an outcome for hospitalized older adults. The executive summary presented here focuses on assessing and preventing mobility loss in older adults in the hospital and summarizes the recommendations from that white paper. The full version of the white paper is available as Text S1. J Am Geriatr Soc 67:11–16, 2019.
Interenterprise Credit and Adjustment during Financial Crises: The Role of Firm Size
Authors: CORICELLI FABRIZIO , FRIGERIO MARCO
Published: October 2018

Small and medium‐sized enterprises (SMEs) suffered a sharp contraction in their borrowing from banks during the Great Recession. Analyzing a large firm‐level database for European countries, the paper shows that trade credit amplified the liquidity squeeze on SMEs, with adverse effects on their real activity. SMEs sharply increased their net trade credit and thus transferred financial resources to larger firms. Given the large weight of SMEs in the economy of European countries, the liquidity squeeze of SMEs likely contributed to the depth of the output fall and the slow recovery in Europe during the Great Recession.
Epigenetic cues modulating the generation of cell‐type diversity in the cerebral cortex
Authors: Amberg Nicole , Laukoter Susanne , Hippenmeyer Simon
Published: October 2018

The cerebral cortex is composed of a large variety of distinct cell‐types including projection neurons, interneurons, and glial cells which emerge from distinct neural stem cell lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that neural stem cell and radial glial progenitor lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell‐type diversity during cortical development.
Six‐week pretreatment with growth hormone improves clinical outcomes of poor ovarian responders undergoing in vitro fertilization treatment: A self‐controlled clinical study
Authors: Cai Mei‐Hong , Liang Xiao‐Yan , Wu Yao‐Qiu , Huang Rui , Yang Xing
Published: October 2018

Aim

The purpose was to explore whether the 6 weeks of growth hormone (GH) pretreatment could increase the live birth rate of poor ovarian responders (POR).

Methods

This self‐controlled, retrospective study was performed among 380 POR who had GH adjuvant (GH+) at a university‐affiliated hospital in Guangzhou, China, from October 2010 to April 2016. Growth hormone was injected daily beginning with the previous menstruation and maintained until ovum pickup, for approximately 6 weeks. Clinical variables between the GH+ cycle and the other GH‐free (GH‐) cycle of each patient were compared. Both cycles were conducted with a similar conventional control ovarian hyperstimulation protocol for in vitro fertilization treatment. One to one case–control matching was performed to adjust essential confounding factors between GH+ cycles and GH‐ cycles.

Results

GH pretreatment improved embryo quality (1.14 ± 1.50 vs 0.11 ± 0.48, P < 0.05) and decreased miscarriage (18.8% vs 80.0%, P < 0.05) significantly, resulting in an increase in the live birth rate (23.5% vs 3.9%, P < 0.05). The oocyte utilization rate in GH+ cycles was remarkably improved, even with older patients and more failed previous attempts. Significant improvement in embryo quality was shown by an increased number of good‐quality embryos and improved oocyte utilization rate after matching.

Conclusions

The longer term use of low‐dose GH administration for 6 weeks could be beneficial for the utilization of oocytes and for finally increasing the live birth rates of POR.
The new neuroendocrinology—a perspective
Authors: Hökfelt T.
Published: October 2018

Content List ‐ Read more articles from the symposium: Neuroendocrine Interfaces in Physiology and Disease
Is Two Too Many? Parity and Mothers' Labor Force Exit
Authors: Doren Catherine
Published: October 2018

Objective: How do women's chances of labor force exit vary by the number of children they have?

Background: Conventional wisdom suggests that there may be a tipping point at the second child when women are particularly likely to leave. Women who only have one child, by contrast, are thought to be uniquely unlikely to exit.

Method: Using data from the nationally representative 1979 to 2012 waves of the National Longitudinal Survey of Youth 1979 (
https://www.nlsinfo.org/content/cohorts/nlsy79), event history methods estimate the likelihood of labor force exit as women progress across parity transitions.

Results: The results show no evidence for a tipping point around the birth of second children. Women are instead most likely to leave the labor force when they are pregnant with their first child, and each subsequent child is associated with a smaller increase in the probability of exit. In addition, women who only ever have one child are less likely to leave the labor force than those who have more children, and these differences arise as early as their pregnancies with their first children. College‐educated women who only have one child are especially unlikely to exit.

Conclusion: The findings thus do not support the second child tipping point hypothesis, but they emphasize the importance of completed parity and the transition to motherhood for mothers' labor force behavior.
Magnetic resonance imaging findings in dogs with orbital inflammation
Authors: Fischer M. C. , Busse C. , Adrian A. M.
Published: October 2018

Objectives

To describe MRI features of canine retrobulbar inflammation, their association with clinical findings and outcome and to assess the value of MRI in detecting orbital foreign bodies.

Materials and Methods

Clinical records of dogs with confirmed (23 of 31) and suspected (eight of 31) retrobulbar inflammation that underwent low field MRI studies were analysed retrospectively.

Results

Of the 31 dogs included in the study there was abscessation in 19. Extraocular myositis (27 of 31) was concurrent with strabismus in three cases. Of 25 patients with exophthalmos, 14 had concurrent optic nerve swelling and, of these, five had permanent loss of vision. There was no vision loss in patients without nerve swelling. One case of suspected retinal detachment on MRI was confirmed clinically. Extensive abnormal contrast enhancement in the temporalis, masseter and pterygoideus muscles was associated with facial (n=3) and trigeminal nerve deficits (n=1). Three patients with inflammation extending into the nasal cavity and frontal sinus (one of 31) or meningeal contrast enhancement (two of 31), showed optic and oculomotor nerve deficits. On MRI a foreign body was not visible in 20 of 31 case or “appeared likely” in 11 of 31 dogs. A foreign body was found at surgery in one case.

Clinical Significance

MRI outlines the extent of retrobulbar inflammation. Clinical findings were associated with imaging findings. MRI overestimated the presence of foreign bodies.