bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obese children aged 4–6 displayed decreased fasting and postprandial ghrelin levels in response to a test meal
Authors: Önnerfält Jenny , Erlanson‐Albertsson Charlotte , Montelius Caroline , Thorngren‐Jerneck Kristina 
Published: November 2017

AbstractAimGhrelin is a hunger hormone that plays a role in glucose homoeostasis and its levels increase before a meal and decrease during and after eating. This study compared the fasting ghrelin and insulin levels of obese children aged 4–6 with those of normal weight children and tested postprandial ghrelin levels in the obese children after a standard breakfast.MethodsWe recruited 67 children at Lund University Hospital from 2008 to 2011. They comprised 30 obese children from a weight study and 37 normal weight children receiving minor elective surgery. Their mean ages were 4.7 ± 0.6 and 4.3 ± 0.8 years, respectively. The obese children ate a standard breakfast, and postprandial ghrelin was measured after 60 minutes.ResultsThe obese children had lower ghrelin levels than the controls (p < 0.01). A significant inverse relation was found between body mass index and fasting ghrelin levels. Obese children had significantly lower fasting ghrelin levels after a standard breakfast (p < 0.01), but there were no gender‐related differences.ConclusionObese children aged 4–6 years had reduced ghrelin and increased insulin levels in the fasting state and postprandial ghrelin was suppressed, suggesting that their energy metabolism was already dysregulated at this young age. Early obesity interventions are essential.
Effects of female sex hormones on folic acid–induced anti‐angiogenesis
Authors: Lee W.‐S. , Lu Y.‐C. , Kuo C.‐T. , Chen C.‐T. , Tang P.‐H. 
Published: November 2017

AbstractAimPregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti‐angiogenic activity. As angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the foetus to escape from the FA‐induced anti‐angiogenesis. This study was designed to investigate the effect of female sex hormones on the FA‐induced anti‐angiogenic activity.MethodsThe protein levels and protein‐protein interaction were examined by Western blot analysis and immunoprecipitation assay respectively. The cell proliferation and migration were examined by MTT assay and wound healing assay respectively. The in vivo angiogenesis was evaluated by Matrigel angiogenesis assay.ResultsIn human umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy levels of progesterone (P4) or oestradiol (E2) prevented FA‐induced inhibitions of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA‐induced anti‐angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited the signalling pathways involved in FA‐induced inhibitions of proliferation and migration in HUVEC.ConclusionFemale sex hormones interrupt the FA‐induced anti‐angiogenic action through receptor‐receptor interaction.
Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies
Authors: Vinjamur Divya S. , Bauer Daniel E. , Orkin Stuart H. 
Published: November 2017

SummaryThe major β‐haemoglobinopathies, sickle cell disease and β‐thalassaemia, represent the most common monogenic disorders worldwide and a steadily increasing global disease burden. Allogeneic haematopoietic stem cell transplantation, the only curative therapy, is only applied to a small minority of patients. Common clinical management strategies act mainly downstream of the root causes of disease. The observation that elevated fetal haemoglobin expression ameliorates these disorders has motivated longstanding investigations into the mechanisms of haemoglobin switching. Landmark studies over the last decade have led to the identification of two potent transcriptional repressors of γ‐globin, BCL11A and ZBTB7A. These regulators act with additional trans‐acting epigenetic repressive complexes, lineage‐defining factors and developmental programs to silence fetal haemoglobin by working on cis‐acting sequences at the globin gene loci. Rapidly advancing genetic technology is enabling researchers to probe deeply the interplay between the molecular players required for γ‐globin (HBG1/HBG2) silencing. Gene therapies may enable permanent cures with autologous modified haematopoietic stem cells that generate persistent fetal haemoglobin expression. Ultimately rational small molecule pharmacotherapies to reactivate HbF could extend benefits widely to patients.
Growth‐faults from delta collapse – structural and sedimentological investigation of the Last Chance delta, Ferron Sandstone, Utah
Authors: Braathen Alvar , Midtkandal Ivar , Mulrooney Mark J. , Appleyard Tyler R. , Haile Beyene Girma , van Yperen Anna E. 
Published: November 2017

AbstractInvestigations of syn‐sedimentary growth faults in the Last Chance delta (Ferron Sandstone, Utah, USA) show that fault‐bounded half‐grabens arrested high amounts of sand in the mouth bar and/or distributary channel areas. Fault‐controlled morphology causes changes in routing of the delta top to delta front drainage towards the long axis of half‐grabens. Faulting was spatially and temporally non‐systematic, and polyphase, with 3D cusp/listric fault geometries instigated by linkage of variously oriented segments. Hanging wall rollover folds consisting of wedge‐shaped syn‐kinematic sand attest to rapid <1‐m slip increments on faults followed by mild erosion along crests of fault blocks and sedimentary infill of adjacent accommodation. Triangle‐zones in prodelta to delta front muds are located underneath steeper faults and interconnected rotated fault‐flats. Their geometry is that of antiformal stack duplexes, in an arrangement of low‐angle‐to‐bedding normal faults at the base, replaced by folded thrusts upwards. These faults show a brittle, frictional flow deformation mechanism ascribed to early compaction of mud. For syn‐kinematic sand, there is a change from general granular/hydroplastic flow in shear zones to later brittle failure and cataclasis, a transition instigated by precipitation of calcite cement. Extensional faulting in the Last Chance delta was likely controlled by gravity driven collapse towards the delta slope and prodelta, as is commonly observed in collapsing deltas. The trigger and driving mechanism is envisioned as localized loads from sand deposited within distributary channels/mouth bars and fault‐controlled basins along the delta top. A regional tilt and especially displacement of compacted mud below sand bodies towards less compacted muds also contributed to the faulting.
PRDM14 directly interacts with heat shock proteins HSP90α and glucose‐regulated protein 78
Authors: Moriya Chiharu , Taniguchi Hiroaki , Nagatoishi Satoru , Igarashi Hisayoshi , Tsumoto Kouhei , Imai Kohzoh 
Published: November 2017

PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem‐like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 need to be clarified. Here, we identified the proteins interacting with PRDM14 in triple‐negative breast cancer (TNBC) cells, which do not express the three most common types of receptor (estrogen receptors, progesterone receptors, and HER2). We obtained 13 candidates that were pulled down with PRDM14 in TNBC HCC1937 cells and identified them by mass spectrometry. Two candidates—glucose‐regulated protein 78 (GRP78) and heat shock protein 90‐α (HSP90α)—were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA‐MB231). Surface plasmon resonance analysis using GST‐PRDM14 showed that these two proteins directly interacted with PRDM14 and that the interactions required the C‐terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase‐based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem‐like CD24− CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggest that HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
Downregulation of dual‐specificity tyrosine‐regulated kinase 2 promotes tumor cell proliferation and invasion by enhancing cyclin‐dependent kinase 14 expression in breast cancer
Authors: Imawari Yoshimi , Mimoto Rei , Hirooka Shinichi , Morikawa Toshiaki , Takeyama Hiroshi , Yoshida Kiyotsugu 
Published: November 2017

Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual‐specificity tyrosine‐regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion. Here, using a comprehensive expression profiling approach, we show that cyclin‐dependent kinase 14 (CDK14) is a target of DYRK2. We found that reduced DYRK2 expression increases CDK14 expression, which promotes cancer cell proliferation and invasion in vitro, in addition to tumorigenicity in vivo. CDK14 and DYRK2 expression inversely correlated in human breast cancer tissues. We further identified androgen receptor (AR) as a candidate of DYRK2‐dependent transcription factors regulating CDK14. Taken together, our findings suggest a mechanism by which DYRK2 controls CDK14 expression to regulate tumor cell proliferation and invasion in breast cancer. Targeting of this pathway may be a promising therapeutic strategy for treating breast cancer.
Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of ‘expanded spectra’ – a review
Authors: Dansingani Kunal K , Gal‐Or Orly , Sadda Srinivas R , Yannuzzi Lawrence A , Freund K Bailey 
Published: November 2017

AbstractThe term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.
Early impairment of the full‐field photopic negative response in patients with Stargardt disease and pathogenic variants of the ABCA4 gene
Authors: Abed Edoardo , Placidi Giorgio , Campagna Francesca , Federici Matteo , Minnella Angelo , Guerri Giulia , Bertelli Matteo , Piccardi Marco , Galli‐Resta Lucia , Falsini Benedetto 
Published: November 2017

AbstractBackgroundTo study the photopic negative response of the full‐field photopic electroretinography (ERG) in Stargardt patients with pathogenic variants in the ABCA4 gene.MethodsA retrospective analysis of 35 Stargardt patients with ABCA4 gene pathogenic variants, compared to normal age‐matched controls. Patients were clinically followed at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli/Università Cattolica del Sacro Cuore, Rome, Italy.ResultsThe photopic negative response of the full‐field photopic ERG was compromised in most Stargardt patients. In the presence of a normal B‐wave, the amplitude ratio between the photopic negative response and the B‐wave displayed a 97% accuracy in detecting diseased eyes (receiver operating characteristic curves).ConclusionsIn Stargardt patients with ABCA4 pathogenic mutations, the photopic negative response of the full‐field photopic ERG is a very sensitive disease read‐out. Its inclusion in standard ERG analysis would be a no‐cost addition of practical consequence in the follow‐up of Stargardt disease. The early impairment of the photopic negative response suggests that inner retinal function might be affected in Stargardt disease earlier than previously acknowledged.
Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve measured with a diffusion magnetic resonance imaging sequence in patients with normal tension glaucoma
Authors: Boye Dirk , Montali Margherita , Miller Neil R , Pircher Achmed , Gruber Philipp , Killer Hanspeter E , Remonda Luca , Berberat Jatta 
Published: November 2017

AbstractImportanceThis study offers a new approach for the quantification of CSF dynamics.BackgroundNon‐invasive method to quantify the CSF dynamics in the subarachnoid space of the optic nerve is highly desirable. The aim of the study was to measure slow‐flow CSF velocities in healthy controls and normal tension glaucoma patients between the intracranial cavity and the subarachnoid space of the optic nerve.DesignProspective observational study.ParticipantsEleven age‐matched healthy volunteers and 15 normal tension glaucoma patients.MethodsUsing phase contrast images, the phase shift in MRI diffusion images can be used to determine the flow velocity. Flow‐range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated.Main Outcome MeasureFlow‐range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated.ResultsFirst, phantom measurements were provided to validate the slow‐flow velocity calculations. Second, flow‐range ratio was validated for the healthy controls (0.63 ± 0.05), with the range being similar for the right and left optic nerve (P = 0.1). Statistically significant results were obtained (P < 0.05) when comparing the flow‐range ratio in the optic nerve of healthy controls (n = 22 eyes, 0.63 ± 0.05) with the flow‐range ratio in pathological optic nerves (n = 23, 0.55 ± 0.08) of normal tension glaucoma patients. MANOVA revealed no dependency between flow‐range ratio and patient dependent variables.Conclusion and RelevanceDiffusion‐weighted imaging provides a method to evaluate CSF flow within the subarachnoid space of the optic nerve in a non‐invasive manner. Compared to healthy controls, patients with normal tension glaucoma measure a significantly lower flow‐range ratio. This finding suggests a possible role of impaired CSF dynamics in the pathophysiology in normal tension glaucoma.
Risk of recurrence of sigmoid volvulus: a single‐centre cohort study
Authors: Johansson N. , Rosemar A. , Angenete E. 
Published: November 2017

AbstractAimSigmoid volvulus is a condition with a tendency to recur if treated conservatively. Little is known about the best type of treatment or when to perform definitive surgery. The aim of this study was to review treatment, and assess the outcome, of sigmoid volvulus in adult patients treated at a Swedish university hospital.MethodThe medical records of patients treated for sigmoid volvulus at Sahlgrenska University Hospital, Sweden from January 2000 to September 2016 were reviewed retrospectively. Median follow‐up time was 8.3 years.ResultsOne hundred and sixty‐eight patients were included with a total of 453 admissions for sigmoid volvulus. Nonoperative decompression was attempted as the initial treatment in 438/453 (97%), with a success rate of 92% (403/438), which was not influenced by whether it was the first episode or a recurrence. Without planned surgery, recurrence occurred after 84% of successful nonoperative decompressions with a median of two recurrences (1–16). Recurrence was less common after the first episode compared with subsequent episodes. Median time until recurrence was 58 days. Mortality after planned surgery following successful decompression was 3.3% (2/61) compared with 13% (6/46) following emergency surgery.ConclusionIn our cohort, the recurrence rate of sigmoid volvulus following successful nonoperative decompression was high. Still, more than 20% of patients did not experience a recurrence after their first episode. Nonoperative decompression could thus be suggested as the sole treatment for the first episode of volvulus. However, after the second episode it is probable that early planned surgery would improve outcome and reduce health‐care consumption.
The relationship between 18F‐FDG‐PETCT‐derived markers of tumour metabolism and systemic inflammation in patients with recurrent disease following surgery for colorectal cancer
Authors: McSorley S. T. , Khor B. Y. , Tsang K. , Colville D. , Han S. , Horgan P. G. , McMillan D. C. 
Published: November 2017

AbstractAim18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG‐PETCT)‐derived markers of tumour metabolism have been reported to have prognostic significance in a variety of tumours. Host inflammation is also recognized to have prognostic significance. The aim of the present study was to investigate the relationship between these markers and host systemic inflammation in patients undergoing elective surgery for colorectal cancer.MethodPatients with histologically confirmed colorectal cancer who underwent elective surgery between 2008 and 2015 and also underwent 18F‐FDG‐PETCT at a single centre were included (n = 103). The neutrophil–lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) were derived from routine blood tests. The maximum standardized uptake (SUVmax), peak standardized uptake (SUVpeak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured.ResultsThere was no association between 18F‐FDG‐PETCT measures of tumour metabolism and systemic inflammation in the 33 patients who underwent preoperative imaging. Of the 70 patients with recurrent disease who underwent 18F‐FDG‐PETCT during follow‐up, patients with NLR ≥ 5 had a significantly higher SUVmax (20 vs 7, P = 0.002), SUVpeak (14 vs 5, P < 0.001), MTV (29 g vs 2 g, P = 0.001) and TLG (338 g vs 9 g, P < 0.001). Similarly, patients with a mGPS of 1–2 at the time of 18F‐FDG‐PETCT had a significantly higher median SUVmax (11 vs 6, P = 0.048), SUVpeak (8 vs 4, P = 0.046), MTV (13 ml vs 2 ml, P = 0.005) and TLG (146 g vs 10 g, P = 0.004).ConclusionThe present study reports a direct association between 18F‐FDG‐PETCT‐derived measures of tumour metabolism and systemic inflammation in patients with recurrent colorectal cancer.
Ileus Management International (IMAGINE): protocol for a multicentre, observational study of ileus after colorectal surgery
Authors:   EuroSurg Collaborative
Published: November 2017

AbstractAimThe management of postoperative ileus following colorectal surgery remains controversial. It is the commonest complication after elective colorectal resection and is associated with an increased incidence of postoperative adverse events. The prevention and management of postoperative ileus remains unstandardized. This study aims to describe an international profile of gastrointestinal recovery after colorectal surgery and will assess the role of non‐steroidal anti‐inflammatory drugs, when used as postoperative analgesia, in expediting the return of gastrointestinal function.MethodsA multicentre, student‐ and trainee‐led, prospective cohort study will be conducted across both Europe and Australasia. Adult patients undergoing elective colorectal resection during 2‐week data collection periods between January and April 2018 will be included. A site‐specific questionnaire will capture compliance to Enhanced Recovery after Surgery components at participating centres. The primary outcome is time to gastrointestinal recovery, measured using a composite outcome of bowel function and oral tolerance. The impact of non‐steroidal anti‐inflammatory drugs on gastrointestinal recovery will be evaluated along with safety data with respect to anastomotic leak, acute kidney injury and complications within 30 days of surgery.DiscussionThis protocol describes the methodology of an international, observational assessment of gastrointestinal recovery after colorectal surgery. It discusses key challenges and describes how the results will impact on future investigation. The study will be conducted across a large student‐ and trainee‐led collaborative network, with prospective quality assurance and data validation strategies.
Presence of stratum corneum serum in non‐palmoplantar psoriasis
Authors: Chahal Sunisha , Tallon Ben 
Published: November 2017

BackgroundPsoriasis is a common, chronic skin eruption characterized by abnormal hyperproliferation of the epidermis. When assessing psoriasis histologically, it is historically considered a “dry” disease, with significant amounts of serum not expected within lesional stratum corneum. However, this specific feature is not often mentioned within the literature. A retrospective study was undertaken to assess prevalence of serum within stratum corneum in cases of non‐palmoplantar psoriasis.MethodsWe evaluated 27 specimens diagnosed histologically as psoriasis between January 2015 and June 2016. In addition to serum, we assessed for psoriasiform hyperplasia, hypogranulosis, suprapapillary thinning and parakeratosis with neutrophils. The cases were then categorized as either diagnostic for, or consistent with, psoriasis and were followed up with clinicians to assess whether the clinical course was consistent with psoriasis.ResultsA total of 27 hematoxylin and eosin (H&E)‐stained biopsies were examined from 21 patients, with periodic acid‐Schiff (PAS) performed on 20 of the biopsies. Of these, 12 biopsies had serum present (44.4%). Of the 12 lesions considered to clinically and histologically represent psoriasis, 5 (41.7%) had serum.ConclusionOur results suggest serum within stratum corneum is possibly an acceptable feature within the spectrum of psoriasis histopathology and should not necessarily detract from the diagnosis.