bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsidering the concept of difference: A proposal to connect education and neuroscience in new ways
Authors: Aronsson Lena
Published: May 2019

Connecting neuroscience and education is a desire in contemporary society, related to the recurring calls for education to become more evidence-based. Research in educational neuroscience strives towards such interdisciplinary knowledge production and to an enhanced interaction between neuroscience research and educational practice. However, various problems and difficulties in achieving these collaborations are often reported. Discrepancies, hierarchies, misconceptions and communication problems can be described as creating a ‘discourse of difficulty’. The aim of this paper is to trace the specific difficulties that have created this discourse, and to problematize these difficulties in ways that enable new conceptions of what might be entailed by interaction and mutual knowledge development between the fields of neuroscience and education, and between academic theory and educational practice. The most significant difficulty is caused by a binary understanding of the concept of difference in relation to understanding the fields. Instead of understanding the fields in opposition to each other, I will suggest an understanding that implies difference emerging in each of the collaborating fields as the self-differing effects of the encounter. In the concluding discussion, I will argue that an understanding of the concept of difference as a process of mutual transformation can be essential for reciprocity and bi-directionality in collaborations. Instead of producing contradictions and hierarchies between scientific fields and between theory and practice, such an understanding of difference might facilitate an investigation of the polarizations that always position something as of lesser value, and ultimately, creates the gaps that collaborations want to bridge.
Evaluating the Scope of Malignant Bone Tumor Using ADC Measurement on ADC Map
Authors: Chen Haisong , Wu Zengjie , Xu Wenjian , Pang Jing , Jia Meng , Dong Cheng , Li Xiaoli
Published: May 2019

Background:

It is very important for surgeons to know the accurate borders of malignant bone tumors before they can precisely resect the tumors. The objective of the study is to investigate the usefulness of apparent diffusion coefficient value for estimating the extent of malignant bone tumor.

Methods:

VX2 tumor fragments were implanted into the tibiae of 30 rabbits. After 4 weeks, magnetic resonance plain scans were performed and then tumor specimens were cut into sagittal sections and partitioned into histology slices for dot-to-dot comparisons with microscopic findings. The sizes of the tumors measured separately on specimen, conventional magnetic resonance imaging sequences, and diffusion-weighted imaging (by measuring apparent diffusion coefficient value on apparent diffusion coefficient mapping) were compared statistically with each other.

Results:

The mean tumor sizes measured on specimen and apparent diffusion coefficient mapping (by calculating apparent diffusion coefficient value) were 5.20 ± 0.89 cm and 5.31 ± 0.87 cm, respectively; there was no significant difference between the 2 ( P > .05). The tumor sizes measured on T1WI, T2WI, T2WI with fat suppression were 4.82 ± 0.87 cm, 5.58 ± 0.87 cm, 5.63 ± 0.85 cm, respectively, and these values were significantly different from that measured on specimen (5.20 ± 0.89 cm, P < .05).

Conclusion:

The extent of the VX2 malignant bone tumor can be estimated accurately by measurement of apparent diffusion coefficient value.
It’s All About the Networks
Authors: Shih Jerry J.
Published: May 2019

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Good Outcome in Cardiac Arrest Patients in Refractory Status Epilepticus: A Result of Aggressive Treatment or EEG Reclassification
Authors: Lee Jong Woo
Published: May 2019

[Box: see text]
Inflammatory Effects of Subacute Exposure of Roundup in Rat Liver and Adipose Tissue
Authors: Pandey Aparamita , Dabhade Prachi , Kumarasamy Anand
Published: May 2019

Roundup is a popular herbicide containing glyphosate as an active ingredient. The formulation of Roundup is speculated to have critical toxic effects, one among which is chronic inflammation. The present study analyzed adverse inflammatory effects in the liver and adipose tissue of rats after a subacute exposure of Roundup. Adult male rats were exposed to various doses of Roundup (0, 5, 10, 25, 50, 100 and 250 mg/kg bodyweight [bw] glyphosate) orally, everyday for 14 days. On day 15, liver and adipose tissues from dosed rats were analyzed for inflammation markers. C-reactive protein in liver, cytokines IL-1β, TNF-α, IL-6, and inflammatory response marker, and prostaglandin–endoperoxide synthase were upregulated in liver and adipose of rats exposed to higher (100 and 250 mg/kg bw/d) doses of Roundup. Cumulatively, our data suggest development of inflammation in lipid and hepatic organs upon exposure to Roundup. Furthermore, liver histological studies showed formation of vacuoles, fibroid tissue, and glycogen depletion in the groups treated with doses of higher Roundup. These observations suggest progression of fatty liver disease in Roundup-treated adult rats. In summary, our data suggest progression of multiorgan inflammation, liver scarring, and dysfunction post short-term exposure of Roundup in adult male rats.
Tool wear monitoring using generalized regression neural network
Authors: Kang Ling , Wang Sibao , Wang Shilong , Ma Chi , Yi Lili , Zou Haixu
Published: May 2019

To improve the modeling accuracy and efficiency of the tool wear monitoring system, a generalized regression neural network is adopted to build the tool wear prediction model because its excellent performance on learning speed and fast convergence to the optimal results whether the sample data are small or large. The low predictive accuracy and efficiency are caused by traditionally manual adjustment of the spread parameters in generalized regression neural network and then the improved fruit fly optimization algorithm is proposed to optimize the spread parameters of regression neural network automatically. Combining the improved fruit fly optimization and generalized regression neural network, the tool wear prediction method is proposed in the paper. Various experiments are carried out to validate the proposed method and the comparison results show a good agreement. In addition, the proposed method is compared to the tool wear prediction method in the literature, and the comparison results also show that the proposed method can achieve better performance.
Analysis and multi-objective optimization design of wheel based on aerodynamic performance
Authors: Wang Dengfeng , Zhang Shuai , Zhang Sutie , Wang Yong
Published: May 2019

In the past studies, the influence of wheel structure design and optimization on the aerodynamic drag of car and heat transfer performance of brake disc was less studied. To study the influence mechanism, the finite element model for wheel aerodynamic analysis was established using computational fluid dynamic method and the correctness of the model was verified by the wind tunnel test data. The influence mechanism of the flow field on aerodynamic drag of car and wheel and heat transfer performance of brake disc was studied. The influence of wheel disc structure on aerodynamic drag coefficient of the car and average convective heat transfer coefficient of the brake discs was studied. The parametric model of the wheel under the computational fluid dynamic analysis was established using mesh morphing technology. A total of 100 and 10 sample points were extracted using the Hammersley Design and Optimal Latin Hypercube Design, respectively, to fit the radial basis function surrogate model and test the accuracy of the surrogate model. Based on the established surrogate model, taking the minimum of the wheel mass, the minimum of the aerodynamic drag coefficient of the car and the maximum of the average surface convective heat transfer coefficient of brake discs as objectives and design variables of wheel as constraints to ensure the wheel structural strength, the non-dominated sorting genetic algorithm was adopted to carry out multi-objective optimization design for the wheel. Pareto frontier was obtained and a compromise solution was selected as the optimization design result. After the optimization design, the wheel mass is reduced by 8.28%, the aerodynamic drag coefficient of the car is reduced by 3.17% and the average surface convective heat transfer coefficient of brake discs is increased by 9.31%.
A national economic and clinical model for ischemic stroke care development in Saudi Arabia: A call for change
Authors: Al-Senani Fahmi , Al-Johani Mohammed , Salawati Mohammad , ElSheikh Souda , AlQahtani Maha , Muthana Jamal , AlZahrani Saeed , Shore Judith , Taylor Matthew , Ravest Valeska S , Eggington Simon , Cuche Matthieu , Davies Heather , Lobotesis Kyriakos , Saver Jeffrey L
Published: May 2019

Background

Stroke is a significant burden in Saudi Arabia and the Saudi Ministry of Health's stroke committee has identified an urgent need to improve care.

Aim

The purpose of this study was to undertake a health-economic analysis to quantify the impact of developing stroke care in the country.

Methods

An economic model was developed to assess the costs and clinical outcomes associated with an ischemic stroke care development program compared with current stroke care. Based on Saudi epidemiological data, cohorts of ischemic stroke patients enter the model each year for the first 10 years based on increasing incidence. Four treatment options were modeled including reperfusion and non-reperfusion treatments. The development scenario estimates the impact of gradually increasing uptake of more effective treatments over 10 years. Changes in the stroke care organization are considered along with resources required to increase capacity, allowing more patients to be admitted to stroke hospitals and access effective treatments.

Results

The stroke care development program is associated with an increase in functionally independent patients and a decrease in disabling strokes compared with current stroke care. Additionally, the development program is associated with estimated cost savings of $602 million over 15 years ($255 million direct costs, $348 million indirect costs).

Conclusions

The model predicts that the stroke care development program is associated with improved patient outcomes and lower overall costs compared with the current stroke care program.
Remote Temperature Monitoring in Patients With Visual Impairment Due to Diabetes Mellitus: A Proposed Improvement to Current Standard of Care for Prevention of Diabetic Foot Ulcers
Authors: Killeen Amanda L. , Brock Kara M. , Dancho James F. , Walters Jodi L.
Published: May 2019

Background:

Two debilitating sequelae of diabetes are foot ulcerations and vision impairing conditions including retinopathy, open-angle glaucoma, and cataracts. Current standard of care recommends daily visual screening of feet. Despite willingness, many patients are impeded by visual impairment. We investigate whether once-daily remote temperature monitoring can improve self-screening for patients at risk for diabetic foot complications.

Methods:

We followed four male veterans with diabetes mellitus, peripheral neuropathy, impaired visual acuity, and at least one other diabetes-related visual impairment in a high-risk podiatry clinic. Patients received a telemedicine remote temperature monitoring mat and instructed on proper daily use. Each patient developed a “hotspot,” defined as a 1.75°C localized temperature difference between matched pedal locations, which resulted in telephone triage outreach.

Results:

In three cases, outreach resulted in a sooner appointment where patients were found to have a relevant outcome at the hotspot. Patients in cases 1-3 had University of Texas (UT) 1A ulcerations. The patient in case 4 had inflammation from trauma. All patients had refractive errors plus another vision impairing condition that potentially delayed identification of lesions. Patients in cases 1 and 2 have cataracts, patients in cases 2 and 3 have retinopathy, and patient in case 4 has glaucoma.

Conclusions:

As an adjunct to daily preventative diabetic self-care, once-daily remote temperature monitoring technology can augment self-screening to prompt necessary outreach and treatment and potentially prevent costly and debilitating diabetic foot complications. This case series serves as a pilot study for real-world application of thermometry, where further large-scale research is needed.
The Perceptions of Nurses About the Behavioral Needs for Daylighting and View to the Outside in Inpatient Facilities
Authors: Gharaveis Arsalan , Yekita Hamed , Shamloo Gholamreza
Published: May 2019

Objectives:

This research aims to explore the perceptions of nursing staff regarding the effects of daylighting on behavioral factors including mood, stress, satisfaction, medical error, and efficiency.

Background:

In spite of an extensive body of literature seeking to investigate the impact of daylighting on patients, a limited number of studies have been done for the sake of nurses’ perceptions and behavioral responses.

Method:

A mixed-methods approach, comprised of qualitative explorations (structured interviews) and a validated survey, was applied and the results were compared and triangulated. Five nurses were interviewed and 156 nurses volunteered for a lighting survey from six departments of three inpatient facilities in Iran.

Results:

The findings of this study are consistent with the existing evidence that daylighting and view to the outside enhance nurses’ perceptions regarding satisfaction, mood, stress, medical error, and alertness, while reducing fatigue and stress.

Conclusion:

Patient rooms and work stations are the most crucial areas to provide daylighting from nurses’ perspectives.
Adverse effects of BMPR2 suppression in macrophages in animal models of pulmonary hypertension
Authors: West James , Chen Xinping , Yan Ling , Gladson Santhi , Loyd James , Rizwan Hamid , Talati Megha
Published: May 2019

Inflammatory cells contribute to irreversible damage in pulmonary arterial hypertension (PAH). We hypothesized that in PAH, dysfunctional BMPR2 signaling in macrophages contributes to pulmonary vascular injury and phenotypic changes via proinflammatory cytokine production. Studies were conducted in: (1) Rosa26‐rtTA2 3 X TetO7‐Bmpr2delx4 FVB/N mice (mutant Bmpr2 is universally expressed, BMPR2delx4 mice) given a weekly intra‐tracheal liposomal clodronate injections for four weeks; and (2) LysM‐Cre X floxed BMPR2 X floxed eGFP monocyte lineage‐specific BMPR2 knockout (KO) mouse model (Bmpr2 gene expression knockdown in monocytic lineage cells) (BMPR2KO) following three weeks of sugen/hypoxia treatment. In the BMPR2delx4 mice, increased right ventricular systolic pressure (RVSP; P < 0.05) was normalized by clodronate, and in monocyte lineage‐specific BMPR2KO mice sugen hypoxia treatment increased (P < 0.05) RVSP compared to control littermates, suggesting that suppressed BMPR2 in macrophages modulate RVSP in animal models of PH. In addition, in these mouse models, muscularized pulmonary vessels were increased (P < 0.05) and surrounded by an increased number of macrophages. Elimination of macrophages in BMPR2delx4 mice reduced the number of muscularized pulmonary vessels and macrophages surrounding these vessels. Further, in monocyte lineage‐specific BMPR2KO mice, there was significant increase in proinflammatory cytokines, including C‐X‐C Motif Chemokine Ligand 12 (CXCL12), complement component 5 a (C5a), Interleukin‐16 (IL‐16), and secretory ICAM. C5a positive inflammatory cells present in and around the pulmonary vessels in the PAH lung could potentially be involved in pulmonary vessel remodeling. In summary, our data indicate that, in BMPR2‐related PAH, macrophages with dysfunctional BMPR2 influence pulmonary vascular remodeling and phenotypic outcomes via proinflammatory cytokine production.
Five-year results of endovascular aortic repair used according to instructions for use give a good general outcome for abdominal aortic aneurysm
Authors: Unsgård Runa G , Altreuther Martin , Lange Conrad , Hammer Tommy , Mattsson Erney
Published: May 2019

Objectives:

The primary aim of this study was to investigate the rate of sac enlargement and secondary procedures after 5 years when instructions for use are strictly applied with endovascular aortic repair. The secondary aim was to investigate if strict indications with endovascular aortic repair, rendering more open operations, would change the general outcome of patients with abdominal aortic aneurysm.

Materials and methods:

Patients having their abdominal aortic aneurysm procedure in a single institution between 01 January 2002 and 31 December 2006 were included. Indications for endovascular aortic repair were as follows: aortic neck: length 15 mm or more, diameter 32 mm or less and straight configuration; iliac arteries: length > 10 mm, 7.5–20 mm in diameter. Sac enlargement was defined as an increase in diameter of 5 mm or more.

Results:

A total of 123 patients were intended to be treated electively with endovascular aortic repair from 2002 to 2007 using Cook Zenith stent grafts. In the same period, 147 patients were treated with elective open repair. At 5 years, 7.3% (N = 9) of the elective intended-to-treat patients with endovascular aortic repair had a sac enlargement. Thirty-five percent of the patients were registered with endoleaks, 13% of the patients had secondary procedures, 12.2% of the patients had early and 6.5% late complications during the follow-up period. Aneurysm rupture was seen in 1.6% of the patients. During the 5-year follow-up period, 34 (27.6%) of the endovascular aortic repair patients died. Five-year mortality for open repair was 23.8%, and 12.2% of the open repair patients had secondary procedures.

Conclusion:

Endovascular aortic repair for abdominal aortic aneurysm in accordance with instructions for use gives a low long-term risk for increased diameter and low rate of secondary procedures. There was similar mortality after elective endovascular aortic repair and open repair for abdominal aortic aneurysm. Applying endovascular aortic repair according to instructions for use does not seem to change the general outcome of patients with abdominal aortic aneurysm but improves the outcome with the method.
Enhanced Screening and Research Data Collection via Automated EHR Data Capture and Early Identification of Sepsis
Authors: Umberger Reba , Indranoi Chayawat “Yo” , Simpson Melanie , Jensen Rose , Shamiyeh James , Yende Sachin
Published: May 2019

Clinical research in sepsis patients often requires gathering large amounts of longitudinal information. The electronic health record can be used to identify patients with sepsis, improve participant study recruitment, and extract data. The process of extracting data in a reliable and usable format is challenging, despite standard programming language. The aims of this project were to explore infrastructures for capturing electronic health record data and to apply criteria for identifying patients with sepsis. We conducted a prospective feasibility study to locate and capture/abstract electronic health record data for future sepsis studies. We located parameters as displayed to providers within the system and then captured data transmitted in Health Level Seven® interfaces between electronic health record systems into a prototype database. We evaluated our ability to successfully identify patients admitted with sepsis in the target intensive care unit (ICU) at two cross-sectional time points and then over a 2-month period. A majority of the selected parameters were accessible using an iterative process to locate and abstract them to the prototype database. We successfully identified patients admitted to a 20-bed ICU with sepsis using four data interfaces. Retrospectively applying similar criteria to data captured for 319 patients admitted to ICU over a 2-month period was less sensitive in identifying patients admitted directly to the ICU with sepsis. Classification into three admission categories (sepsis, no-sepsis, and other) was fair (Kappa .39) when compared with manual chart review. This project confirms reported barriers in data extraction. Data can be abstracted for future research, although more work is needed to refine and create customizable reports. We recommend that researchers engage their information technology department to electronically apply research criteria for improved research screening at the point of ICU admission. Using clinical electronic health records data to classify patients with sepsis over time is complex and challenging.
Accidental Laser-Induced Macular Holes: A Case Series
Authors: Alnuaimi Rawdha , Issa Sharif
Published: May 2019

Purpose:

The purpose of this article is to report various types of maculopathy caused by momentary exposure to a high-power handheld blue laser.

Methods:

The design included a consecutive case series of 4 patients. Evaluation included a full ophthalmic examination and macular spectral-domain optical coherence tomography. Main outcome measures included an analysis of the types of maculopathy and vitreoretinal pathological features.

Results:

All patients were young men. The most common setting for injury was accidental at play. The types of maculopathies encountered were a full-thickness macular hole (FTMH) in 4 eyes, a premacular subhyaloid hemorrhage in 5 eyes, premacular sub–internal limiting membrane hemorrhage in 2 eyes, an outer retinal disruption at the fovea in 1 eye, an epimacular membrane in 1 eye, and a schisis-like cavity in 1 eye. Snellen best-corrected visual acuity (BCVA) at presentation ranged from 20/40 to 4/200 (mean, 20/290). Only 4 eyes (29%) improved spontaneously with increase in vision, whereas 10 eyes (71%) required intervention. All 4 FTMHs were closed successfully after pars plana vitrectomy. Final mean BCVA in all cases was 20/35.

Conclusions:

Exposure to high-power handheld laser devices can cause a variety of maculopathies that can reduce central vision permanently. Although vision may improve spontaneously, most cases require intervention. Unrestricted access to commercially available high-power handheld laser devices is dangerous, and public awareness should be encouraged.
Premenstrual Dysphoric Disorder: Ranking the Symptoms and Severity in Indian College Students
Authors: Bansal Deepali , Raman Rajesh , Rao T. S. Sathyanarayana
Published: May 2019

Background: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common conditions causing significant impairment in various domains of life. Both the conditions are associated with physical, emotional, and behavioral symptoms. There is dearth of studies regarding symptomatology and severity of the condition in Indian college students.

Aim: Aim of this study is to categorize and rank the symptoms and severity of PMDD in college students in India.

Materials and methods: A cross-sectional survey was conducted in various colleges of Mysuru. A total of 600 girls were approached over a period of 1 year. Confidentiality was assured and written informed consent was taken. Girls with irregular periods and those who had an absence of menstruation since last 3 consecutive menstrual cycles were excluded. A total of 571 filled up forms were taken for analysis. Data was analyzed using SPSS 22 version software. Chi-square test was used as the test of significance for qualitative data.

Results: The mean age of participants was 21.12 ± 2.6 years. Majority of the subjects were unmarried and were from urban background. The prevalence of PMS/PMDD was 46.1%, out of which 10.2% met the criteria for PMDD. Physical symptoms (91.4%) were the most commonly reported symptom domain in the PMDD category, followed by anger or irritability (84.5%). Almost half of the subjects with no or mild PMS had reported physical symptoms. The least reported symptom was insomnia. PMDD group had reported maximum impairment in the domain of relationship with family members (77.6%), followed by home responsibilities and relationship with coworkers.

Conclusion: This study suggests that the prevalence of clinically relevant PMS/PMDD is higher than widely cited estimates and is a cause of concern for health care authorities in India. Physical complaints are the most commonly reported among all the symptoms in all groups. There is a need to actively assess for premenstrual symptoms in young women for comprehensive treatment and good outcome.
Tranexamic acid modulates the immune response and reduces postsurgical infection rates
Authors: Draxler Dominik F. , Yep Kah , Hanafi Gryselda , Winton Anoushka , Daglas Maria , Ho Heidi , Sashindranath Maithili , Wutzlhofer Lisa M. , Forbes Andrew , Goncalves Isaac , Tran Huyen A. , Wallace Sophia , Plebanski Magdalena , Myles Paul S. , Medcalf Robert L.
Published: May 2019

Tranexamic acid (TXA) is an antifibrinolytic agent that blocks plasmin formation. Because plasmin is known to promote inflammatory and immunosuppressive responses, we explored the possibility that plasmin-mediated immunosuppression in patients undergoing cardiac surgery can be directly reversed by TXA and decrease postoperative infection rates. The modulatory effect of TXA on inflammatory cytokine levels and on innate immune cell activation were evaluated with multiplex enzyme-linked immunosorbent assay and flow cytometry, respectively. Postoperative infection rates were determined in patients undergoing cardiac surgery and randomized to TXA (ACTRN12605000557639; http://www.anzca.edu.au). We demonstrate that TXA-mediated plasmin blockade modulates the immune system and reduces surgery-induced immunosuppression in patients following cardiac surgery. TXA enhanced the expression of immune-activating markers while reducing the expression of immunosuppressive markers on multiple myeloid and lymphoid cell populations in peripheral blood. TXA administration significantly reduced postoperative infection rates, despite the fact that patients were being administered prophylactic antibiotics. This effect was independent of the effect of TXA at reducing blood loss. TXA was also shown to exert an immune-modulatory effect in healthy volunteers, further supporting the fibrin-independent effect of TXA on immune function and indicating that baseline plasmin levels contribute to the regulation of the immune system in the absence of any comorbidity or surgical trauma. Finally, the capacity of TXA to reduce infection rates, modulate the innate immune cell profile, and generate an antifibrinolytic effect overall was markedly reduced in patients with diabetes, demonstrating for the first time that the diabetic condition renders patients partially refractory to TXA.
Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
Authors: Im Seock-Ah , Mukai Hirofumi , Park In Hae , Masuda Norikazu , Shimizu Chikako , Kim Sung-Bae , Im Young-Hyuck , Ohtani Shoichiro , Huang Bartlett Cynthia , Lu Dongrui R. , Iyer Shrividya , Mori Yuko , Mori Ave , Gauthier Eric , Finn Richard S. , Toi Masakazu
Published: May 2019

PURPOSE

In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians.

PATIENTS AND METHODS

Of 666 enrolled postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety.

RESULTS

Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.48; 95% CI, 0.27 to 0.87; P = .007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer–specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v –0.069; P = .0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL).

CONCLUSION

Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL.
Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics
Authors: Fest Jesse , Vijfhuizen Lisanne S , Goeman Jelle J , Veth Olga , Joensuu Anni , Perola Markus , Männistö Satu , Ness-Jensen Eivind , Hveem Kristian , Haller Toomas , Tonisson Neeme , Mikkel Kairit , Metspalu Andres , van Duijn Cornelia M , Ikram Arfan , Stricker Bruno H , Ruiter Rikje , van Eijck Casper H J , van Ommen Gert-Jan B , ʼt Hoen Peter A C
Published: May 2019

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance–based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall–Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (<2 years). Our data did not support the branched-chain amino acids identified earlier in several US cohorts as potential biomarkers for pancreatic cancer. Thus, although we identified glutamine and histidine as potential biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.
Longitudinal Metabolic Impacts of Perinatal Exposure to Phthalates and Phthalate Mixtures in Mice
Authors: Neier Kari , Cheatham Drew , Bedrosian Leah D , Gregg Brigid E , Song Peter X K , Dolinoy Dana C
Published: May 2019

Developmental exposures to phthalates are suspected to contribute to risk of metabolic syndrome. However, findings from human studies are inconsistent, and long-term metabolic impacts of early-life phthalate and phthalate mixture exposures are not fully understood. Furthermore, most animal studies investigating metabolic impacts of developmental phthalate exposures have focused on diethylhexyl phthalate (DEHP), whereas newer phthalates, such as diisononyl phthalate (DINP), are understudied. We used a longitudinal mouse model to evaluate long-term metabolic impacts of perinatal exposures to three individual phthalates, DEHP, DINP, and dibutyl phthalate (DBP), as well as two mixtures (DEHP+DINP and DEHP+DINP+DBP). Phthalates were administered to pregnant and lactating females through phytoestrogen-free chow at the following exposure levels: 25 mg of DEHP/kg of chow, 25 mg of DBP/kg of chow, and 75 mg of DINP/kg of chow. One male and female per litter (n = 9 to 13 per sex per group) were weaned onto control chow and followed until 10 months of age. They underwent metabolic phenotyping at 2 and 8 months, and adipokines were measured in plasma collected at 10 months. Longitudinally, females perinatally exposed to DEHP only had increased body fat percentage and decreased lean mass percentage, whereas females perinatally exposed to DINP only had impaired glucose tolerance. Perinatal phthalate exposures also modified the relationship between body fat percentage and plasma adipokine levels at 10 months in females. Phthalate-exposed males did not exhibit statistically significant differences in the measured longitudinal metabolic outcomes. Surprisingly, perinatal phthalate mixture exposures were statistically significantly associated with few metabolic effects and were not associated with larger effects than single exposures, revealing complexities in metabolic effects of developmental phthalate mixture exposures.
Umbilical Cord miRNAs in Small-for-Gestational-Age Children and Association With Catch-Up Growth: A Pilot Study
Authors: Mas-Parés Berta , Xargay-Torrent Sílvia , Bonmatí Alexandra , Lizarraga-Mollinedo Esther , Martínez-Calcerrada José Maria , Carreras-Badosa Gemma , Prats-Puig Anna , de Zegher Francis , Ibáñez Lourdes , López-Bermejo Abel , Bassols Judit
Published: May 2019

Context

Catch-up growth in infants who are small for gestational age (SGA) is a risk factor for the development of cardiometabolic diseases in adulthood. The basis and mechanisms underpinning catch-up growth in newborns who are SGA are unknown.

Objective

To identify umbilical cord miRNAs associated with catch-up growth in infants who are SGA and study their relationship with offspring’s cardiometabolic parameters.

Design

miRNA PCR panels were used to study the miRNA profile in umbilical cord tissue of five infants who were SGA with catch-up (SGA-CU), five without catch-up (SGA-nonCU), and five control infants [appropriate for gestational age (AGA)]. The miRNAs with the smallest nominal P values were validated in 64 infants (22 AGA, 18 SGA-nonCU, and 24 SGA-CU) and correlated with anthropometric parameters at 1 (n = 64) and 6 years of age (n = 30).

Results

miR-501-3p, miR-576-5p, miR-770-5p, and miR-876-3p had nominally significant associations with increased weight, height, weight catch-up, and height catch-up at 1 year, and miR-374b-3p, miR-548c-5p, and miR-576-5p had nominally significant associations with increased weight, height, waist, hip, and renal fat at 6 years. Multivariate analysis suggested miR-576-5p as a predictor of weight catch-up and height catch-up at 1 year, as well as weight, waist, and renal fat at 6 years. In silico studies suggested that miR-576-5p participates in the regulation of inflammatory, growth, and proliferation signaling pathways.

Conclusions

Umbilical cord miRNAs could be novel biomarkers for the early identification of catch-up growth in infants who are SGA. miR-576-5p may contribute to the regulation of postnatal growth and influence the risk for cardiometabolic diseases associated with a mismatch between prenatal and postnatal weight gain.
Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes
Authors: Hjort Rebecka , Löfvenborg Josefin E , Ahlqvist Emma , Alfredsson Lars , Andersson Tomas , Grill Valdemar , Groop Leif , Sørgjerd Elin P , Tuomi Tiinamaija , Åsvold Bjørn Olav , Carlsson Sofia
Published: May 2019

Objective

We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

Methods

We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP).

Results

The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO.

Conclusions

Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.
Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child
Authors: Dutta Pinaki , Reddy Kavita S , Rai Ashutosh , Madugundu Anil K , Solanki Hitendra S , Bhansali Anil , Radotra Bishan D , Kumar Narendra , Collier David , Iacovazzo Donato , Gupta Prakamya , Raja Remya , Gowda Harsha , Pandey Akhilesh , Devgun Jagtar Singh , Korbonits Márta
Published: May 2019

Context

Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma.

Case Description

The patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35‒mm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated.

Conclusion

Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.
Reflecting in the Vernacular
Authors: Williams Richard David
Published: May 2019

In early modern North India, knowledge systems developed simultaneously in multiple “classical” and “vernacular” languages. This article examines the processes of multilingual knowledge transmission through an analysis of a Brajbhasha (classical Hindi) music treatise, the Sangitadarpana (“Mirror of Music”) of Harivallabha (ca. 1653). Harivallabha was translating a recent Sanskrit work of the same name: an old-fashioned treatise that nonetheless proved extremely influential in Persian and other Sanskrit works, as well as in miniature painting. This article examines the implications of the vernacular rendering of the Sangitadarpana and Harivallabha's seminal influence on the musicological intellectual culture that followed in his wake. Drawing on other translations and treatises in other forms of Hindi and Bengali, the article also considers the limits of Brajbhasha's circulation, and the wider implications of using a vernacular language for reading, listening, visual, and performance practices.
Within-individual behavioural variability and division of labour in social insects
Authors: Jeanson Raphaël
Published: May 2019

Division of labour, whereby individuals divide the workload in a group, is a recurrent property of social living. The current conceptual framework for division of labour in social insects is provided by the response-threshold model. This model posits that the differences between individuals (i.e. between-individual variability) in responsiveness to task-associated stimuli is a key feature for task specialisation. The consistency of individual behaviours (i.e. within-individual variability) in task performance represents an additional but little-considered component driving robust patterns of division of labour. On the one hand, the presence of workers with a high level of within-individual variability presumably allows colonies to rapidly adapt to external fluctuations. On the other hand, a reduced degree of within-individual variability promotes a stricter specialisation in task performance, thereby limiting the costs of task switching. The ideal balance between flexibility and canalisation probably varies depending on the developmental stage of the colony to satisfy its changing needs. Here, I introduce the main sources of within-individual variability in behaviours in social insects and I review neural correlates accompanying the changes in behavioural flexibility. I propose the hypothesis that the positive scaling between group size and the intensity of task specialisation, a relationship consistently reported both within and between taxa, may rely on reduced within-individual variability via self-organised processes linked to the quality of brood care. Overall, I emphasise the need for a more comprehensive characterisation of the response dynamics of individuals to better understand the mechanisms shaping division of labour in social insects.
Renal cystic lesions characterization using spectral detector CT (SDCT): Added value of spectral results
Authors: Kessner Rivka , Große Hokamp Nils , Ciancibello Les , Ramaiya Nikhil , Herrmann Karin A.
Published: May 2019

Objectives:

To evaluate the added value of spectral results derived from Spectral Detector CT (SDCT) to the characterization of renal cystic lesions (RCL).

Methods:

This retrospective study was approved by the local Institutional review board. 70 consecutive patients who underwent abdominopelvic SDCT and had at least one RCL were included. 84 RCL were categorized as simple, complex or neoplastic based on attenuation values on single-phase post-contrast images. Attenuation values were measured in each lesion on standard conventional CT images (stCI) and virtual monoenergetic images of 40keV and 100keV. A spectral curve slope was calculated and intra lesional iodine concentration (IC) was measured using iodine-density maps. Reference standard was established using histopathologic correlation, prior and follow-up imaging. Analysis of variance (ANOVA) was used to compare between the groups.

Results:

Mean attenuation values for benign simple and complex RCL differed significantly (42 ± 16 vs 8 ± 3 HU; p < 0.001). IC was almost identical in benign simple and complex RCL (0.23 ± 0.04 mg ml−1  vs 0.24 ± 0.04 mg ml−1), while IC in neoplastic RCL was significantly higher (2.10 ± 0.08 mg ml−1 ; p < 0.001). The mean spectral curve slope did not differ significantly between simple and complex RCL (0.30 ± 0.03 vs 0.33 ± 0.05) but was significantly higher in neoplastic RCL (2.60 ± 0.10; p < 0.001).

Conclusions:

Spectral results of SDCT are highly promising in distinguishing benign complex RCL from enhancing neoplastic RCL based on single-phase post-contrast imaging only.

Advances in knowledge:

SDCT can assist in differentiating between benign complex and neoplastic renal cystic lesions.
Revisiting the excitation/inhibition imbalance hypothesis of ASD through a clinical lens
Authors: Port Russell G , Oberman Lindsay M , Roberts Timothy PL
Published: May 2019

Autism spectrum disorder (ASD) currently affects 1 in 59 children, although the aetiology of this disorder remains unknown. Faced with multiple seemingly disparate and noncontiguous neurobiological alterations, Rubenstein and Merzenich hypothesized that imbalances between excitatory and inhibitory neurosignaling (E/I imbalance) underlie ASD. Since this initial statement, there has been a major focus examining this exact topic spanning both clinical and preclinical realms.

The purpose of this article is to review the clinical neuroimaging literature surrounding E/I imbalance as an aetiology of ASD. Evidence for E/I imbalance is presented from several complementary clinical techniques including magnetic resonance spectroscopy, magnetoencephalography and transcranial magnetic stimulation. Additionally, two GABAergic potential interventions for ASD, which explicitly attempt to remediate E/I imbalance, are reviewed.

The current literature suggests E/I imbalance as a useful framework for discussing the neurobiological etiology of ASD in at least a subset of affected individuals. While not constituting a completely unifying aetiology, E/I imbalance may be relevant as one of several underlying neuropathophysiologies that differentially affect individuals with ASD. Such statements do not diminish the value of the E/I imbalance concept—instead they suggest a possible role for the characterization of E/I imbalance, as well as other underlying neuropathophysiologies, in the biologically-based subtyping of individuals with ASD for potential applications including clinical trial enrichment as well as treatment triage.
Immunology of membranous nephropathy
Authors: Akiyama Shin'ichi , Imai Enyu , Maruyama Shoichi
Published: May 2019

Accounting for about 20 to 50% of cases of primary nephrotic syndrome, membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. A rat model created nearly 60 years ago to research the primary MN disorder, Heymann nephritis, has provided us with a plethora of important information. Recently, our knowledge about MN has dramatically progressed. Heymann nephritis and human MN are now known to share a high degree of similarity in pathogenesis. This review summarizes our current understanding of MN pathogenesis while focusing particularly on the immunological aspects.