bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between retinal vessel diameter with both retinal nerve fibre layer thickness and optic nerve head parameters in middle‐aged Caucasians: the Northern Finland Birth Cohort Eye study
Authors: Geneid Mohamed , Kettunen Joonas , Nuuttila Iida , Lintonen Timo , Uusitalo Janne‐Joonas , Saarela Ville , Liinamaa M. Johanna 
Published: December 2018

AbstractPurposeTo study the normal relationship between retinal vessel diameter (RVD) with retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) parameters in a cohort of middle‐aged Caucasians.MethodsWe investigated 3070 individuals (6140 eyes). Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured in the right eye using a semi‐automated computer‐assisted program. Retinal nerve fibre layer (RNFL) thickness and ONH parameters were assessed with Heidelberg retinal tomography (HRT).ResultsData from 2217 persons were analysed including RNFL, CRAE, CRVE, sex, body mass index, mean arterial pressure, diabetes status, smoking status, optic disc area, rim area, spherical refraction and intraocular pressure. A larger RVD was associated with a thicker mean global RNFL thickness especially in global and inferior segments of the retina and with larger optic discs. Each 10 μm increase in the retinal arteriolar calibre was associated with a 5.58 μm increase in mean global RNFL thickness; the corresponding value for a 10 μm increase in venular calibre was 3.79 μm (p < 0.001 for both). Retinal venular calibre displayed consistent associations with RNFL thickness in both genders (p < 0.001 for all), whereas the association of arteriolar calibre and RNFL was more prominent in men (p < 0.001).ConclusionWe found strong associations between larger RVD and thicker RNFL in all subjects. This study helps to clarify the association between RVD, RNFL thickness and ONH parameters and provides normal values for middle‐aged Caucasians that will help in future studies investigating the role of vascular aetiology in systemic and eye diseases.
Conjunctival melanoma and electrochemotherapy: preliminary results using 2D and 3D cell culture models in vitro
Authors: Fiorentzis Miltiadis , Katopodis Periklis , Kalirai Helen , Seitz Berthold , Viestenz Arne , Coupland Sarah E. 
Published: December 2018

AbstractPurposeTo investigate the cytotoxic effect of bleomycin, mitomycin C (MMC) and Fluorouracil (5‐FU) in combination with electroporation (EP) on human conjunctival melanoma (CM) and normal conjunctival cell lines using 2D and 3D cell culture systems in vitro.MethodsTwo CM (CRMM1, CRMM2) and one normal conjunctival epithelial cell line (HCjE‐Gi) were treated with various EP conditions and increasing concentrations of 5‐FU, MMC and bleomycin. Cell survival was assessed by MTT viability assay. All cell lines were seeded to create spheroids and were treated with bleomycin on day 3 and day 8 combined with EP. Spheroids were collected, fixed in buffered formalin and subsequently paraffin embedded for histological assessment of the effects of the treatment on cell viability.ResultsCM cell lines were resistant to electroporation alone and showed a reduction in cell number only when treated with 1000 Volts/cm and 8 pulses. HCjE‐Gi cells showed higher sensitivity to electric pulses over 750 Volts/cm. MMC and 5‐FU demonstrated a higher cytotoxicity for the HCjE‐Gi cell line. The CM cell lines were resistant to MMC and 5‐FU. Bleomycin (1 μg/ml) alone had no significant effect on the HCjE‐Gi even when combined with EP conditions ≥750 Volts/cm. In contrast, it significantly (p ‐, paired t‐test) reduced cell viability in the CM cell lines. Spheroids treated with bleomycin and EP showed a reduction in tumour mass and proliferation rates after treatment.ConclusionOur in vitro study using 2D and 3D models indicates that the application of EP may effectively enhance chemotherapy with bleomycin in CM. This may offer new viable perspectives for CM treatment.
Factors affecting non‐operative management of uncomplicated appendicitis in children: Should laparoscopic appendectomy be immediate, interval, or emergency?
Authors: Miyano Go , Ochi Takanori , Seo Shogo , Nakamura Hiroki , Okawada Manabu , Doi Takashi , Koga Hiroyuki , Lane Geoffrey J. , Yamataka Atsuyuki 
Published: December 2018

AbstractIntroductionWe conducted a prospective non‐randomized comparison of children with uncomplicated appendicitis treated either by primary laparoscopic appendectomy (PLA) or by non‐operative management (NOM) followed by interval laparoscopic appendectomy (ILA) if NOM was successful or emergency laparoscopic appendectomy (ELA) if NOM was unsuccessful.MethodsBefore 2015, all patients with uncomplicated appendicitis underwent PLA using a standard three‐port technique. Postoperatively, piperacillin/tazobactam was administered until the white blood cell count was less than 10 000/μL and patients were afebrile. Since 2015, in cases of uncomplicated appendicitis, intravenous analgesia has been administered once after assessment, and then NOM has been immediately employed, with repeat doses of piperacillin/tazobactam administered every 8 h after admission. We have also used standard management cut‐off criteria to determine when to perform laparoscopic appendectomy after NOM: if NOM fails, ELA is performed within 6 h, and if NOM is successful, ILA is planned.ResultsThere were 103 eligible subjects for this study. Eleven cases of suspected complicated appendicitis were excluded, leaving 34 PLA cases and 58 NOM cases. After NOM, 27 patients were treated with ILA and 31 with ELA. There was one recurrence after successful NOM, and in two cases, patients’ parents refused to consent to ILA after successful NOM. There were more perforations and significantly more residual abscesses in ELA than in PLA. Operative time and postoperative hospitalization were significantly longer among ELA patients than among PLA patients, and operative time was significantly shorter during ILA than in PLA.ConclusionFurther evaluation is required to confirm which patients will benefit most from NOM and what role PLA has in treating uncomplicated appendicitis.
Phylogeny and form in fishes: Genetic and morphometric characteristics of dragonets (Foetorepus sp.) do not align
Authors: Myun Park Joo , Powell Nicholas N. , Gillings Michael R. , Gaston Troy F. , Williamson Jane E. 
Published: December 2018

AbstractMeasures of biodiversity are often hindered by a lack of methodological practices that distinguish cryptic or morphologically similar cohabiting species. This is particularly difficult for marine fishes where direct observations of the ecology and demography of populations are difficult. Dragonets (Foetorepus c.f. calauropomus) were collected as bycatch from research trawls deployed in waters off north‐eastern Tasmania, Australia. Morphometric and genetic analyses were conducted on the 43 specimens recovered. Sequence analysis of two mitochondrial loci distinguished three genetic clusters, each having levels of dissimilarity consistent with species‐level distinctions between other members of the Callionymidae. While clear morphological distinctions were observed between male and female fish, limited morphometric analyses could not differentiate between members of the three genetic groups. This finding highlights questions about the ability of genetically distinct but morphologically similar groups to occupy the same ecological niche, and points to additional and undescribed hidden biodiversity amongst cryptic species of fish.
Novel therapeutic agents for relapsed classical Hodgkin lymphoma
Authors: von Keudell Gottfried , Younes Anas 
Published: December 2018

SummaryHodgkin Lymphoma (HL) is a B‐cell lymphoproliferative disorder with an excellent prognosis for the majority of patients who are treated with multi‐agent chemotherapy, with or without radiation. A subset of patient, however, does not respond to therapy or relapses after accomplishing an initial response. Their outcome is poor and new treatment strategies are urgently needed for this patient population. Recent advances in the understanding of the tumour biology of HL and its microenvironment have ushered a new era of targeted‐ and immuno‐therapies with remarkable activity. Most notably, the antibody‐drug conjugate brentuximab‐vedotin, and the immune checkpoint blockers pembrolizumab and nivolumab have recently been approved by the US Food and Drug Administration and have transformed the therapeutic landscape of this disease. Other novel drug compounds are being investigated either as single agents or in combination and hold promise to further the field.
Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations
Authors: Lin Richard J. , Ho Caleb , Hilden Patrick D. , Barker Juliet N. , Giralt Sergio A. , Hamlin Paul A. , Jakubowski Ann A. , Castro‐Malaspina Hugo R. , Robinson Kevin S. , Papadopoulos Esperanza B. , Perales Miguel‐Angel , Sauter Craig S. 
Published: December 2018

SummaryTP53 alterations portend extremely poor prognosis in patients with mantle cell lymphoma treated with standard treatment modalities. We reviewed outcomes of 42 patients with available TP53 status who had received a reduced‐intensity or non‐myeloablative allogeneic haematopoietic cell transplant at our institution. We demonstrated a 2‐year overall survival and progression‐free survival of 78% [95% confidence interval (CI) 60–88] and 61% (95% CI 43–75), respectively. The 2‐year cumulative incidences of relapse and non‐relapse mortality were 19% and 20%, respectively. Importantly, there is no significant difference among patients with and without TP53 alterations, suggesting for the first time a beneficial treatment modality for these high‐risk patients.
Bladder mapping of tumour recurrence after radical nephroureterectomy for upper tract urothelial carcinoma and its influence on oncological outcomes
Authors: Belhadj Yassine , Grande Pietro , Seisen Thomas , Gobert Aurelien , Gomez Florie D , Cussenot Olivier , Roupret Morgan 
Published: December 2018

ObjectivesTo assess the location of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), to determine the main predictive factors for IVR in the bladder‐cuff area (BCA), and to assess the effect of BCA recurrence (BCAR) on prognosis.Patients and methodsThis was a multicentre, retrospective study using the French collaborative database on UTUC, which includes data for all patients treated in 24 referral uro‐oncology centres across the country. All patients who underwent RNU with bladder‐cuff excision and who developed IVR between 1995 and 2010 were selected. Patients were divided into two groups: Group A: BCAR; and Group B: recurrence elsewhere in the bladder. The Kaplan–Meier method was used to estimate the probability of BCAR‐free survival. Groups were compared using the log‐rank test. Independent risk factors for BCAR were identified using a Cox proportional hazard regression model, with univariate and multivariate analyses.ResultsOverall, 163 patients were included in the final analysis: Group A, 87 patients (53.4%) and Group B, 76 (46.6%). The clinicopathological characteristics were similar in the groups. The median (interquartile range [IQR]) follow‐up was 36 (31.7–40.39) months. The median (IQR) time to IVR was 10.0 (8.6–13.39) months [Group A: 11.0 (8.8–13.2) months vs Group B: 10.0 (8.5–11.5) months; P = 0.35]. The probability of BCAR at 1, 2, and 3 years was 45.5% (95% confidence interval [CI] 40.1–50.9), 17.9% (95% CI 13.7–22.1), and 10.8% (95% CI 7.4–14.2) respectively, whereas the probability of recurrence elsewhere in the bladder was 42.1% (95% CI 36.4–47.8), 14.7% (95% CI 10.6–18.8), and 4.4% (95% CI 1.9–6.9), respectively (P = 0.35). Pathological tumour stage (≥pT3) was significantly related to the risk of BCAR (P = 0.03).ConclusionThere were more BCARs after RNU in advanced UTUC. However, no preferred site for recurrence was detected.
Sacral neuromodulation using the standardized tined lead implantation technique with a curved vs a straight stylet: 2‐year clinical outcomes and sensory responses to lead stimulation
Authors: Vaganée Donald , Kessler Thomas M. , Van de Borne Sigrid , De Win Gunter , De Wachter Stefan 
Published: December 2018

ObjectivesTo assess clinical follow‐up data over 24 months, comparing the use of a curved vs straight stylet in patients undergoing sacral neuromodulation using the standardized tined lead implantation technique.Patients and MethodsWe conducted a single tertiary‐centre, prospective study between August 2013 and June 2015 involving 40 patients with overactive bladder and 15 with non‐obstructive urinary retention refractory to first‐line treatment. The primary outcome was successful tined lead procedure according to intention‐to‐treat analyses at 12 and 24 months. The secondary outcome was number of optimal electrode configurations during programming. Statistical analysis was performed using plain non‐parametric tests for numerical and categorical data.ResultsSuccessful tined lead procedures were achieved in 33 of 35 patients (94%) implanted with the curved stylet compared with 13 of 20 patients (65%) implanted with the straight stylet (P = 0.005). Intention‐to‐treat analyses at 12 and 24 months showed success rates of 94% and 91%, respectively, in the curved stylet group vs 65% and 45%, respectively, in the straight stylet group (P = 0.002 and P < 0.001). In the curved stylet group, 60% and 25% of the electrode configurations were considered optimal and poor, respectively, vs 40% and 37%, respectively, in the straight stylet group (P < 0.001).ConclusionsThe use of the standardized implantation technique with the curved stylet led to more successful tined lead procedures, better success rates after 2 years of follow‐up and a greater number of optimal electrode configurations when compared to use of the straight stylet.
A National Cancer Database‐based nomogram to predict lymph node metastasis in penile cancer
Authors: Peak Taylor C. , Russell Gregory B. , Dutta Rahul , Rothberg Michael B. , Chapple Andrew G. , Hemal Ashok K. 
Published: December 2018

ObjectiveTo evaluate the predictive nature of several clinicopathological variables by developing a nomogram predictive for lymph node‐positive disease using the National Cancer Database cohort of patients with squamous cell carcinoma of the penis.MethodsStepwise logistic regression was used to find the best‐fit model; remaining clinical variables were used to create a nomogram to predict the probability of lymph node‐positive disease.ResultsOn multivariate analysis, high pathological grade (3–4 vs 1: odds ratio [OR] 3.27, 95% confidence interval [CI] 1.70–6.29; 2 vs 1: OR 2.58, 95% CI 1.39–4.79 [P = 0.002]), lymphovascular invasion (OR 2.49, 95% CI 1.61–3.84 [P < 0.001]), and positive clinical lymph node status (N1 vs N0: OR 20.0, 95% CI 11.4–35.7; N2 vs N0: OR 27.8, 95% CI 14.1–55.6; N3 vs N0: OR 49.2, 95% CI 14.8–162.8 [P < 0.001]) were predictors of lymph node metastasis in penile cancer. The bootstrap‐corrected concordance index of this nomogram was 0.880.ConclusionUsing tumour grade, tumour lymphovascular invasion and clinical lymph node status, we developed a nomogram highly predictive of pathologial lymph node metastasis that, after further external validation, could be helpful in the surgical decision‐making process.
Examining the geometry, age and genesis of buried Quaternary valley systems in the Midland Valley of Scotland, UK
Authors: Kearsey Timothy I. , Lee Jonathan R. , Finlayson Andrew , Garcia‐Bajo Marieta , Irving Anthony A. M. 
Published: December 2018

Buried palaeo‐valley systems have been identified widely beneath lowland parts of the UK including eastern England, central England, south Wales and the North Sea. In the Midland Valley of Scotland palaeo‐valleys have been identified yet the age and genesis of these enigmatic features remain poorly understood. This study utilizes a digital data set of over 100 000 boreholes that penetrate the full thickness of deposits in the Midland Valley of Scotland. It identified 18 buried palaeo‐valleys, which range from 4 to 36 km in length and 24 to 162 m in depth. Geometric analysis has revealed four distinct valley morphologies, which were formed by different subglacial and subaerial processes. Some palaeo‐valleys cross‐cut each other with the deepest features aligning east–west. These east–west features align with the reconstructed ice‐flow direction under maximum conditions of the Main Late Devensian glaciation. The shallower features appear more aligned to ice‐flow direction during ice‐sheet retreat, and were therefore probably incised under more restricted ice‐sheet configurations. The bedrock lithology influences and enhances the position and depth of palaeo‐valleys in this lowland glacial terrain. Faults have juxtaposed Palaeozoic sedimentary and igneous rocks and the deepest palaeo‐valleys occur immediately down‐ice of knick‐points in the more resistant igneous bedrock. The features are regularly reused and the fills are dominated by glacial fluvial and glacial marine deposits. This suggests that the majority of infilling of the features happened during deglaciation and may be unrelated to the processes that cut them.
MicroRNA‐143‐3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3
Authors: Guo Lingchuan , Fu Jianhong , Sun Shimei , Zhu Minsheng , Zhang Lifeng , Niu Hui , Chen Zhi , Zhang Yongsheng , Guo Lingling , Wang Shouli 
Published: December 2018

MicroRNAs, which regulate mRNAs, operate through a variety of signaling pathways to participate in the development of colorectal cancer (CRC). In this study, we found that microRNA (miR)‐143‐3p expression was significantly lower in both CRC and liver metastatic CRC tissues from liver compared with normal colonic tissues. Functional assays showed that miR‐143‐3p inhibited CRC cell invasion and migration in vitro. Using a bioinformatics approach, we identified miR‐143‐3p target mRNAs. Among the candidate targets, only the expression of integrin alpha 6 (ITGA6) and ArfGAP with the SH3 domain and ankyrin repeat and PH domain 3 (ASAP3) were significantly reduced by miR‐143‐3p mimics as examined by western blot, and the metastasis potential of CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown, determined by migration and invasion assays. Both ITGA6 and ASAP3 were upregulated in CRC tissues compared to normal tissues. Analysis of the relationship between clinicopathological features and ITGA6/ASAP3 protein expression in 200 patients with CRC showed a significant difference in positive ITGA6 expression between the early stage (I + II) and the advanced stage (III + IV), and ASAP3 expression levels positively correlated with metastasis in the lymph nodes. These results indicate that miR‐143‐3p acts as an anti‐oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.
Maternal Perinatal and Concurrent Anxiety and Mental Health Problems in Early Childhood: A Sibling‐Comparison Study
Authors: Gjerde Line C. , Eilertsen Espen M. , Eley Thalia C. , McAdams Tom A. , Reichborn‐Kjennerud Ted , Røysamb Espen , Ystrom Eivind 
Published: December 2018

Do associations between maternal anxiety symptoms and offspring mental health remain after comparing differentially exposed siblings? Participants were 17,724 offspring siblings and 11,553 mothers from the Norwegian Mother and Child Cohort study. Mothers reported anxiety and depressive symptoms at 30 weeks’ gestation, and 0.5, 1.5, 3, and 5 years postpartum. Child internalizing and externalizing problems were assessed at ages 1.5, 3, and 5, and modeled using multilevel analyses with repeated measures nested within siblings, nested within mothers. Maternal pre‐ and postnatal anxiety were no longer associated with child internalizing or externalizing problems after adjusting for maternal depression and familial confounding. Maternal anxiety when the children were in preschool age, however, remained significantly associated with child internalizing but not externalizing problems.
Rickettsioses: Cutaneous findings frequently lead to diagnosis – a review
Authors: Fischer Marcellus 
Published: December 2018

SummaryWhile epidemic typhus caused by Rickettsia prowazekii posed a significant threat in Europe before and throughout World War II due to its high mortality, the condition fortunately no longer plays a significant role. Nevertheless, rickettsioses, such as African tick bite fever, have been increasingly diagnosed in travelers returning from sub‐Saharan Africa.Caused by Rickettsia africae, African tick bite fever presents with characteristic cutaneous findings such as eschar (tache noir) and a rash. Similar findings are also observed in Mediterranean spotted fever caused by Rickettsia conorii. On the other hand, Rocky Mountain spotted fever – caused by Rickettsia rickettsii – is characterized by a rash without an eschar, in combination with distinctly more severe general symptoms.The objective of the present CME article is to familiarize dermatologists with the spectrum of the most common types of rickettsiosis in humans, including their epidemiology, clinical presentation, diagnostic workup, and treatment. Recognition of characteristic cutaneous manifestations and their correct interpretation facilitate early diagnosis. Prompt initiation of treatment usually results in recovery without sequelae.
Mesophotic ecosystems: Distribution, impacts and conservation in the South Atlantic
Authors: Soares Marcelo de Oliveira , Tavares Tallita Cruz Lopes , Carneiro Pedro Bastos de Macêdo 
Published: December 2018

AbstractAimThis study reviews recent research on the South Atlantic Mesophotic ecosystems (MEs) and the pressures threatening them, and offers suggestions for their management and conservation.LocationThe South Atlantic Ocean.MethodsA comprehensive compilation of the scientific literature was performed to examine the distribution, human impacts and conservation status of the South Atlantic MEs.ResultsOur review indicated that the South Atlantic Ocean (SAO) is one of the major MEs areas in the world's oceans. The South Atlantic MEs are composed of a mosaic of distinct seascapes, mainly rhodolith beds, mesophotic reefs (i.e., rocky and biogenic) and marine animal forests (e.g., sponge aggregations, octocoral and black coral forests) that occur along the East South American and West African coasts, seamounts and oceanic islands. Throughout the SAO, the distinct seascapes of MEs are usually formed on the middle and outer continental shelves, shelf‐edge, seamounts, submarine canyons, incised valleys and paleochannels, reef structures and insular shelves. We highlighted sea temperature anomalies, ocean acidification, extreme floods and droughts, fisheries, invasive species, marine debris, mining, and oil and gas exploitation as major threats to these ecosystems.Main conclusionsGiven the threats to the South Atlantic MEs, growing human pressures may degrade these ecosystems in the next years and undermine their unique biodiversity as well as their potential to provide connectivity between regions and depths. Our review revealed the existence of some extensive and unprotected formations, which urgently demand in‐depth investigations and conservation action.