bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of Gender-Specific Authorship Disparities in the Pain Medicine Literature
Authors: Karri Jay , Navarro Sergio M , Duong Anne , Tang Tuan , Abd-Elsayed Alaa 
Published: November 2019

BackgroundGiven the readily increasing membership of the pain physician community, efforts toward correcting notable gender disparities are instrumental. The under-representation of women is particularly prevalent within leadership roles in academic medicine, thought to be driven largely by diminished research efforts. Consequently, we aimed to characterize gender differences among the highest impact pain literature.MethodsThe 20 highest cited articles per year from 2014 to 2018 were extracted from each of seven impactful journals affiliated to the largest pain medicine societies. Collected data from each article included genders of the first and last authors, the number of citations accumulated and the journal impact factor at the time of publication.ResultsAcross all considered literature, female authors were surprisingly not under-represented when considering the national prevalence of female pain physicians. However, more in-depth analysis found trends toward significance to suggest that female authorship was relatively diminished within more impactful and higher cited literature. When exploring gender–gender collaboration patterns, we found that male authors were favored over female counterparts with statistical significance; it must be noted that this likelihood analysis and preference toward male authors may be statistically obfuscated by the high prevalence of male authors. Nonetheless, these findings help to quantify overt, demonstrated disparity patterns. Of note, this inequity may also be fully secondary to the lower number of female pain physicians and/or those involved in research endeavors and decreased number of submissions from female physicians. Establishing gender discrimination patterns as causal factors in such disparities can be extremely challenging to determine.ConclusionIn our analysis of authorship between genders within the context of pain medicine literature, we found trends, although non-significant, toward women being lesser represented in the more impactful literature. We suggest that these inequities are possibly resultant of a markedly small and outnumbered female pain physician membership that has yet to achieve a critical mass and possible implicit gender biases that may restrict female authorship. However, further exploration and analysis of this issue are necessary to more clearly illuminate which systemic deficits exist and how they may, in turn, be corrected with cultural and macroscopic organizational-driven change.
Thoracic-paravertebral blocks: comparative anatomical study with different injection techniques and volumes
Authors: Seidel Ronald , Wree Andreas , Schulze Marko 
Published: November 2019

Background and objectivesWe hypothesized that different injection techniques and volumes in thoracic-paravertebral blocks (TPVB) lead to different patterns of dye spread. In particular, we investigated whether an alternating injection technique leads to complete staining of all adjacent intercostal nerves.MethodsThis comparative anatomical investigation was performed using 10 or 20 mL of dye (Alcian Blue) in 10 unfixed donor cadavers (54 injections) that were designated for education or research purposes.ResultsIn landmark-guided TPVB, the thoracic-paravertebral space (TPVS) was either not stained at all (spread of dye in the paraspinal muscles, n=3) or the dye was predominantly found in the epidural space (n=3). In ultrasound-guided TPVB, the TPVS was correctly identified in all cases (n=48). The sympathetic trunk was stained in 84.6% of injections (multi-injection technique: 100%), independent of injection technique and volume. The epidural space was stained more frequently (p≤0.001) if both the puncture site (sagittal transducer position) and guidance of the needle were more medial (77.8%). Finally, a higher injection volume (20 vs 10 mL) resulted in a higher number of stained intercostal nerves (p=0.04).ConclusionFor ultrasound-guided techniques, a higher injection volume resulted in a larger number of stained intercostal nerves. Staining of the sympathetic trunk was independent of the injection technique. Epidural spread was observed significantly less frequently if the injection was lateral (transducer transversal) or with a strictly cranial injection direction (transducer sagittal). Landmark-guided injections reliably achieved the TPVS (and the epidural space) only after a needle advance of 2.5 cm after initial contact with the transverse process.
BDNF augments rat internal anal sphincter smooth muscle tone via RhoA/ROCK signaling and nonadrenergic noncholinergic relaxation via increased NO release
Authors: Singh Arjun , Mohanty Ipsita , Singh Jagmohan , Rattan Satish 
Published: November 2019

Presently, there are no studies examining the neuromodulatory effects of brain-derived neurotropic factor (BDNF) on the basal internal anal sphincter (IAS) tone and nonadrenergic noncholinergic (NANC) relaxation. To examine this, we determined the neuromuscular effects of BDNF on basal IAS smooth muscle tone and the smooth muscle cells (SMCs) and the effects of NANC nerve stimulation before and after high-affinity receptor tyrosine kinase receptor B (TrkB) antagonist K252a. We also investigated the mechanisms underlying BDNF-augmented increase in the IAS tone and NANC relaxation. We found that BDNF-increased IAS tone and SMC contractility were TTX resistant and attenuated by K252a. TrkB-specific agonist 7,8-dihydroxyflavone, similar to BDNF, also produced a concentration-dependent increase in the basal tone, whereas TrkB inhibitors K252a and ANA-12 produced a decrease in the tone. In addition, BDNF produced leftward shifts in the concentration-response curves with U46619 and ANG II (but not with bethanechol and K+ depolarization), and these shifts were reversed by K252a. Effects of Y27632 and Western blot data indicated that the BDNF-induced increase in IAS tone was mediated via RhoA/ROCK. BDNF-augmented NANC relaxation by electrical field stimulation was found to be mediated via the nitric oxide (NO)/soluble guanylate cyclase (sGC) pathway rather than via increased sensitivity to NO. In conclusion, the net effect of BDNF was that it caused an increase in the basal IAS tone via RhoA/ROCK signaling. BDNF also augmented NANC relaxation via NO/sGC. These findings may have relevance to the role of BDNF in the pathophysiology and therapeutic targeting of the IAS-associated rectoanal motility disorders. NEW & NOTEWORTHY These studies for the first time to our knowledge demonstrate that increased levels of brain-derived neurotrophic factor (BDNF; conceivably released from smooth muscle cells and/or the enteric neurons) has two major effects. First, BDNF augments the internal anal sphincter (IAS) tone via tyrosine kinase receptor B/thromboxane A2-receptor, angiotensin II receptor type 1/RhoA/ROCK signaling; and second, it increases nonadrenergic noncholinergic relaxation via nitric oxide/soluble guanylate cyclase. These studies may have relevance in therapeutic targeting in the anorectal motility disorders associated with the IAS.
Development of the intrinsic innervation of the small bowel mucosa and villi
Authors: Hao Marlene M. , Fung Candice , Boesmans Werend , Lowette Katrien , Tack Jan , Vanden Berghe Pieter 
Published: November 2019

Detection of nutritional and noxious food components in the gut is a crucial component of gastrointestinal function. Contents in the gut lumen interact with enteroendocrine cells dispersed throughout the gut epithelium. Enteroendocrine cells release many different hormones, neuropeptides, and neurotransmitters that communicate either directly or indirectly with the central nervous system and the enteric nervous system, a network of neurons and glia located within the gut wall. Several populations of enteric neurons extend processes that innervate the gastrointestinal lamina propria; however, how these processes develop and begin to transmit information from the mucosa is not fully understood. In this study, we found that Tuj1-immunoreactive neurites begin to project out of the myenteric plexus at embryonic day (E)13.5 in the mouse small intestine, even before the formation of villi. Using live calcium imaging, we discovered that neurites were capable of transmitting electrical information from stimulated villi to the plexus by E15.5. In unpeeled gut preparations where all layers were left intact, we also mimicked the basolateral release of 5-HT from enteroendocrine cells, which triggered responses in myenteric cell bodies at postnatal day (P)0. Altogether, our results show that enteric neurons extend neurites out of the myenteric plexus early during mouse enteric nervous system development, innervating the gastrointestinal mucosa, even before villus formation in mice of either sex. Neurites are already able to conduct electrical information at E15.5, and responses to 5-HT develop postnatally. NEW & NOTEWORTHY How enteric neurons project into the gut mucosa and begin to communicate with the epithelium during development is not known. Our study shows that enteric neurites project into the lamina propria as early as E13.5 in the mouse, before development of the submucous plexus and before formation of intestinal villi. These neurites are capable of transmitting electrical signals back to their cell bodies by E15.5 and respond to serotonin applied to neurite terminals by birth.
Degradation of Praxis Brain Networks and Impaired Comprehension of Manipulable Nouns in Stroke
Authors: Riccardi Nicholas , Yourganov Grigori , Rorden Chris , Fridriksson Julius , Desai Rutvik 
Published: November 2019

Abstract
Distributed brain systems contribute to representation of semantic knowledge. Whether sensory and motor systems of the brain are causally involved in representing conceptual knowledge is an especially controversial question. Here, we tested 57 chronic left-hemisphere stroke patients using a semantic similarity judgment task consisting of manipulable and nonmanipulable nouns. Three complementary methods were used to assess the neuroanatomical correlates of semantic processing: voxel-based lesion–symptom mapping, resting-state functional connectivity, and gray matter fractional anisotropy. The three measures provided converging evidence that injury to the brain networks required for action observation, execution, planning, and visuomotor coordination are associated with specific deficits in manipulable noun comprehension relative to nonmanipulable items. Damage or disrupted connectivity of areas such as the middle posterior temporal gyrus, anterior inferior parietal lobe, and premotor cortex was related specifically to the impairment of manipulable noun comprehension. These results suggest that praxis brain networks contribute especially to the comprehension of manipulable object nouns.
Can Government Intervention Make Firms More Investment Ready? A Randomized Experiment in the Western Balkans
Authors: Cusolito Ana Paula , Dautovic Ernest , McKenzie David 
Published: November 2019

Abstract
Innovative firms with good ideas may still struggle to fine-tune them to the stage where they can attract outside funding. We conduct a five-country randomized experiment that tests the impact of an investment readiness program. Firms then pitched their ideas to independent judges. The program resulted in a 0.3 standard deviation increase in the investment readiness score. Two years later, the average impacts on firm investment outcomes are positive but small in magnitude and not statistically significant. Larger and statistically significant impacts on receiving outside funding occur for smaller firms and for firms with lower likelihoods of otherwise being funded.
Weight Loss Intervention Before Total Knee Replacement: A 12-Month Randomized Controlled Trial
Authors: Liljensøe A. , Laursen J. O. , Bliddal H. , Søballe K. , Mechlenburg I. 
Published: November 2019

Background and Aims: Obesity is an increasing problem in patients after total knee replacement. The aim of this study was to investigate whether a weight loss intervention before primary total knee replacement would improve quality of life, knee function, mobility, and body composition 1 year after surgery. Material and Methods: Patients scheduled for total knee replacement due to osteoarthritis of the knee and obesity were randomized to a control group receiving standard care or to an intervention group receiving 8-week low-energy diet before total knee replacement. Patient-reported quality of life, 6-Min Walk Test, and body composition by dual-energy X-ray absorptiometry were assessed before intervention for the diet group, and within 1 week preoperatively for both groups, and the changes in outcome from baseline to 1 year after total knee replacement were compared between groups. The number of participants was lower than planned, which might introduce a type-2 error and underestimate the trend for a better outcome after weight loss. Results: The analyses are based on a total of 76 patients, 38 in each group. This study showed major improvement in both study groups in quality of life and knee function, though no statistically significant differences between the groups were observed 1 year after total knee replacement. The average weight loss after 8-week preoperative intervention was 10.7 kg and consisted of a 6.7 kg reduction in fat mass. One year after total knee replacement, the participants in the diet group managed to maintain the weight reduction, whereas there was no change in the control group. Conclusion: The results suggest that it is feasible and safe to implement an intensive weight loss program shortly before total knee replacement. The preoperative intervention resulted in a 10% body weight loss, improved body composition, lower cardiovascular risk factors, and sustained s-leptin.
Annona atemoyaleaf extract ameliorates cognitive impairment in amyloid-β injected Alzheimer’s disease-like mouse model
Authors: Lim Hye-Sun , Kim Yu Jin , Sohn Eunjin , Yoon Jiyeon , Kim Bu-Yeo , Jeong Soo-Jin 
Published: November 2019

Annona atemoya is a hybrid of Annona squamosa and Annona cherimola that grow in several subtropical or tropical areas such as Florida in the US, Philippines, Cuba, Jamaica, Taiwan, and Jeju in South Korea. We report that the A. atemoya leaves (AAL) have inhibitory effects on the pathogenesis and regulatory mechanisms of Alzheimer’s disease (AD). Ethanol extract of AAL prevented amyloid-β (Aβ) aggregation and increased free radical scavenging activity. In addition, AAL extract exerted protective effects against neuronal cell death in HT22 hippocampal cells. Moreover, oral administration of AAL extract significantly improved memory loss in the passive avoidance task and Y-maze test, as well as downregulated the expression of neuronal markers neuronal nuclei and brain-derived neurotrophic factor in Aβ-injected AD mice. To verify the molecular mechanisms responsible for anti-AD actions of AAL, we conducted the antibody microarray analysis and found that epidermal growth factor receptor/G protein-coupled receptor kinase 2 signaling was activated in neuronal cells and AD-like mouse models. Additionally, quantitative analyses of the six standard compounds using high-performance liquid chromatography revealed that rutin is the most abundant compound of AAL. Furthermore, efficacy analyses of six standard compounds showed that rutin and isoquercitrin had significant inhibitory activity on Aβ aggregation. Taken together with biological activity and the content of compounds, rutin maybe a bioactive compound of AAL in the AD pathogenesis. Overall, our findings provide the first scientific support for the therapeutic effects of AAL in AD and AD-related disorders.Impact statementOur study was aimed to find a novel candidate drug for Alzheimer’s disease (AD) using natural products. We assessed the effects of Annona atemoya extracts on crucial events in the pathogenesis of AD. A. atemoya leaf (AAL) extract significantly inhibited amyloid-β aggregation, oxidative stress, neuronal cell death, and memory impairment through the epidermal growth factor receptor/G protein-coupled receptor kinase 2 pathway. Simultaneous analysis using HPLC determined six standard compounds of AAL extract, and rutin was identified as a bioactive compound. Of note, the anti-AD activity of AAL extract was more significant compared to other extracts from medicinal plants of which efficacy was previously reported. The potential of AAL extract as an anti-AD agent may provide insight into the new drug development for AD treatment.
Glucose and insulin levels are associated with arterial stiffness and concentric remodeling of the heart
Authors: Markus Marcello Ricardo Paulista , Rospleszcz Susanne , Ittermann Till , Baumeister Sebastian Edgar , Schipf Sabine , Siewert-Markus Ulrike , Lorbeer Roberto , Storz Corinna , Ptushkina Violetta , Peters Annette , Meisinger Christa , Bamberg Fabian , Nauck Matthias , Bahls Martin , Völzke Henry , Felix Stephan Burkhard , Bülow Robin , Rathmann Wolfgang , Dörr Marcus 
Published: November 2019

Abstract

Background
Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes.

Methods
Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models.

Results
In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m2.7 (1.80 to 0.57; p < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m2.7/ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity.

Conclusions
Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.
Iodine status of 8 to 10 years old children within 20 years following compulsory salt iodization policy in Shanghai, China
Authors: Wang Zhengyuan , Zang Jiajie , Shi Zhehuan , Zhu Zhenni , Song Jun , Zou Shurong , Jin Wei , Jia Xiaodong , Guo Changyi , Liu Shoujun 
Published: November 2019

Abstract

Background
In 1996, Shanghai implemented universal salt iodization and has became the last provincial unit in China to carry out this intervention. In this study, we summarized achievements in past 20 years, to provide suggestions and evidence for the next stage of iodine supplementation.

Methods
This study summarized and analyzed monitoring data of children from 1997, 1999, 2005, 2011, 2014, and 2017 in Shanghai. In each monitoring year, 30 streets or towns were selected using the probability-proportional-to-size sampling technique. One primary school was selected from each street or town by a simple random sampling technique. From each school, 40 children aged 8 to 10 years were randomly selected. The number of children was divided equally by sex and age.

Results
In 1997, 1999, 2005, 2011, 2014, and 2017, median urinary iodine (MUI) was 227.5 μg/L, 214.3 μg/L, 198.1 μg/L, 181.6 μg/L, 171.4 μg/L, and 183.0 μg/L, goiter rate was 3.07, 0.40, 0.08, 0.08, 0.86, and 1.90%, and median thyroid volume (MTvol) was 2.9 mL, 1.2 mL, 2.4 mL, 1.0 mL, 1.8 mL, and 2.8 mL, respectively. There was a linear correlation between goiter rate and median thyroid volume (MTvol) (r = 0.95, P = 0.014). Household salt iodine concentration (SIC) was dropping every monitoring (P < 0.05). There was a significant difference among different household SIC groups in MUI in 1999 and 2017, and in MTvol in 1999 (P < 0.05). No significant differences were detected in the other years.

Conclusions
In Shanghai, the iodine status of 8 to 10 years old children is adequate. Household SIC have little effect on iodine status of children. Future studies should analyze the dietary sources of iodine, especially from pre-packaged and prepared-away-from-home foods or meals. The regular monitoring of iodine status is important to human health.
STING: a master regulator in the cancer-immunity cycle
Authors: Zhu Yuanyuan , An Xiang , Zhang Xiao , Qiao Yu , Zheng Tongsen , Li Xiaobo 
Published: November 2019

AbstractThe aberrant appearance of DNA in the cytoplasm triggers the activation of cGAS-cGAMP-STING signaling and induces the production of type I interferons, which play critical roles in activating both innate and adaptive immune responses. Recently, numerous studies have shown that the activation of STING and the stimulation of type I IFN production are critical for the anticancer immune response. However, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For instance, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Moreover, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells. In this review, we focus on STING and the cancer immune response, with particular attention to the roles of STING activation in the cancer-immunity cycle. Additionally, the negative effects of STING activation on the cancer immune response and non-immune roles of STING in cancer have also been discussed.