bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel heterozygous variants in KMT2D associated with holoprosencephaly
Authors: Tekendo‐Ngongang Cedrik , Kruszka Paul , Martinez Ariel F. , Muenke Maximilian
Published: July 2019

Lysine methyltransferase 2D (KMT2D; OMIM 602113) encodes a histone methyltransferase involved in transcriptional regulation of the beta‐globin and estrogen receptor as part of a large protein complex known as activating signal cointegrator‐2‐containing complex (ASCOM). Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder. Neither holoprosencephaly nor other defects in human forebrain development have been previously associated with Kabuki syndrome. Here we report two patients diagnosed with alobar holoprosencephaly in their antenatal period with de novo monoallelic KMT2D variants identified by trio‐based exome sequencing. The first patient was found to have a stop‐gain variant c.12565G>T (p.Gly4189*), while the second patient had a missense variant c.5A>G (p.Asp2Gly). Phenotyping of each patient did not reveal any age‐related feature of Kabuki syndrome. These two cases represent the first report on association between KMT2D and holoprosencephaly.
Kernel Functional Maps
Authors: Wang L. , Gehre A. , Bronstein M. M. , Solomon J.
Published: July 2019

Functional maps provide a means of extracting correspondences between surfaces using linear‐algebraic machinery. While the functional framework suggests efficient algorithms for map computation, the basic technique does not incorporate the intuition that pointwise modifications of a descriptor function (e.g. composition of a descriptor and a nonlinearity) should be preserved under the mapping; the end result is that the basic functional maps problem can be underdetermined without regularization or additional assumptions on the map. In this paper, we show how this problem can be addressed through kernelization, in which descriptors are lifted to higher‐dimensional vectors or even infinite‐length sequences of values. The key observation is that optimization problems for functional maps only depend on inner products between descriptors rather than descriptor values themselves. These inner products can be evaluated efficiently through use of kernel functions. In addition to deriving a kernelized version of functional maps including a recent extension in terms of pointwise multiplication operators, we provide an efficient conjugate gradient algorithm for optimizing our generalized problem as well as a strategy for low‐rank estimation of kernel matrices through the Nyström approximation.
An explicit structure‐preserving numerical scheme for EPDiff
Authors: Azencot Omri , Vantzos Orestis , Ben‐Chen Mirela
Published: July 2019

We present a new structure‐preserving numerical scheme for solving the Euler‐Poincaré Differential (EPDiff) equation on arbitrary triangle meshes. Unlike existing techniques, our method solves the difficult non‐linear EPDiff equation by constructing energy preserving, yet fully explicit, update rules. Our approach uses standard differential operators on triangle meshes, allowing for a simple and efficient implementation. Key to the structure‐preserving features that our method exhibits is a novel numerical splitting scheme. Namely, we break the integration into three steps which rely on linear solves with a fixed sparse matrix that is independent of the simulation and thus can be pre‐factored. We test our method in the context of simulating concentrated reconnecting wavefronts on flat and curved domains. In particular, EPDiff is known to generate geometrical fronts which exhibit wave‐like behavior when they interact with each other. In addition, we also show that at a small additional cost, we can produce globally‐supported periodic waves by using our simulated fronts with wavefronts tracking techniques. We provide quantitative graphs showing that our method exactly preserves the energy in practice. In addition, we demonstrate various interesting results including annihilation and recreation of a circular front, a wave splitting and merging when hitting an obstacle and two separate fronts propagating and bending due to the curvature of the domain.
Möbius Registration
Authors: Baden Alex , Crane Keenan , Kazhdan Misha
Published: July 2019

Conformal parameterizations over the sphere provide high‐quality maps between genus zero surfaces, and are essential for applications such as data transfer and comparative shape analysis. However, such maps are not unique: to define correspondence between two surfaces, one must find the Möbius transformation that best aligns two parameterizations—akin to picking a translation and rotation in rigid registration problems. We describe a simple procedure that canonically centers and rotationally aligns two spherical maps. Centering is implemented via elementary operations on triangle meshes in ℝ3, and minimizes area distortion. Alignment is achieved using the FFT over the group of rotations. We examine this procedure in the context of spherical conformal parameterization, orbifold maps, non‐rigid symmetry detection, and dense point‐to‐point surface correspondence.
Costs are not necessarily correlated with threats in conservation landscapes
Authors: Sacre Edmond , Pressey Robert L. , Bode Michael
Published: July 2019

The priority of an area for conservation is determined by three primary factors: its biodiversity value, the level of threat it is facing, and its cost. Although much attention has been paid to the spatial relationship between biodiversity value and threats, and between biodiversity value and costs, little is known about how costs and threats are spatially correlated. The orthodox assumption in conservation science is that costs and threats are positively correlated. Here, we adapt a classic economic theory of land use to explain how conservation scientists came to expect a positive correlation between costs and threats. We then use high‐resolution, ground‐truthed datasets of land sales and habitat clearance to show that this assumption is false in the state of Queensland, Australia. Our results provide an empirical counterargument to a widespread assumption in conservation science, and illustrate why spatial prioritization needs to include independent measures of costs and threats.
Kidney donor outcomes ≥ 50 years after donation
Authors: Keys Daniel O. , Jackson Scott , Berglund Danielle , Matas Arthur J.
Published: July 2019

Many living kidney donors (LDs) are young at donation; yet there are little data on long‐term LD follow‐up. We report on 66 LDs who donated ≥50 years ago: 22 (33.3%) are still alive (current age, 78.5 ± 7.25 years); 39 (59%) died (mean age at death, 74.2 ± 12.3 years); and 5 are lost to follow‐up (mean age at last contact, 68.7 ± 4.6 years). Those who died were older at donation (P < .001). Causes of death included 12 (30.8% of deaths) cardiovascular diseases, 9 (23.0%) respiratory failures, 5 (12.8%) malignancies and 4 (10.3%) infections, and 9 (23%) were unknown or miscellaneous. Forty‐nine living donors (74%) developed hypertension at a mean age of 59.9 ± 14.0 years; 12 (18%) developed diabetes at a mean age of 62 ± 19.4 years; and 11 (16.7%) developed proteinuria at a mean age of 60.6 ± 18.2 years—each at a similar incidence as seen in the age‐matched general population. At last follow‐up, the eGFR by CKD‐EPI (mean ± SD) for donors currently alive was 60.2 ± 13.4 mL/min/1.73 m2; for those that died, 54.0 ± 21.5 mL/min/1.73 m2; for those lost to follow‐up, 55.6 ± 7.5 mL/min/1.73 m2. ESRD developed in 2 (3.3%). SF‐36 quality of life health survey scores (n = 21) were similar to the age‐matched general population.
Generalized congenital epithelioid blue nevi (pigmented epithelioid melanocytomas) in an infant: Report of case and review of the literature
Authors: Blebea Catherine , Li Dong , Castelo‐Soccio Leslie , Chu Emily Y.
Published: July 2019

The epithelioid blue nevus (EBN) is a variant of the blue nevus characterized by heavily pigmented epithelioid melanocytes and lightly or nonpigmented spindle cells. It may be associated with Carney complex, a multiple neoplasia syndrome. Congenital cases of EBN not associated with Carney complex are rarely reported. We herein describe an infant who presented with multiple blue‐gray nodules and papules involving the head, trunk, and extremities at birth, the corresponding histopathologic findings, and genetic testing results.
Cutaneous metastases of papillary renal cell carcinoma: A case report and review of the literature
Authors: Cardwell Leah A. , Bender Nicole R. , Sokumbi Olayemi
Published: July 2019

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that is typically encountered at early stages and has a high survival rate. Histopathology typically shows well‐defined papillary architecture with tumor cells lining fibrovascular cores and can be further subdivided into type 1 and type 2 tumors based on cytology and genetic basis. Type 1 tumors have a single layer of basophilic cells and low nuclear atypia, while type 2 tumors have a pseudostratified layer of eosinophilic cells and high nuclear atypia. Some tumors have overlapping features of both types. We present a unique case of cutaneous metastases of papillary RCC with typical papillary architecture in the dermis and review the literature on this rare entity.
Phytophthora species associated with dieback of sweet chestnut in Western Turkey
Authors: Akilli Şimşek Seçil , Katircioğlu Yakup Zekai , Ulubaş Serçe Çiğdem , Çakar Deniz , Rigling Daniel , Maden Salih
Published: July 2019

Sweet chestnut (Castanea sativa) is an important tree species in the Marmara and Aegean regions of Turkey as these two regions produce the great majority of edible nuts, especially those used for marron glacé production. Chestnut forests and orchards in these regions showing severe dieback symptoms not associated with chestnut blight were investigated to determine the role of Phytophthora spp. in the decline syndrome. Soil samples were collected from around 108 symptomatic chestnut trees at 29 sites and Phytophthora spp. isolated using soil baiting technique and selective medium. Species isolated were identified by cultural characteristics and ITS sequencing. Phytophthora x cambivora was the dominant species detected in 13 sites, followed by P. cinnamomi (5 sites), P. plurivora (3 sites) and P. cryptogea (1 site). Phytophthora x cambivora was present in both regions, while P. cinnamomi was found only in the Marmara region in coastal areas around Istanbul. When inoculated at the stem bases of 3‐year‐old chestnut saplings, P. cinnamomi produced significantly longer necrotic lesions (7.8–12.0 cm) than P. x cambivora (2.6–6.3 cm) by 12 days after inoculation. Phytophthora plurivora was the least aggressive species causing only small lesions. Phytophthora cryptogea, which represents the first record on chestnut in Turkey, produced intermediate sized lesions in between P. x cambivora and P. plurivora. These results indicate that P. x cambivora and in some areas P. cinnamomi play major roles in the observed dieback of sweet chestnut in western Turkey.
An integrative study of Sakia sisanganensis n. sp. (Rhabditida: Tylenchidae) from Sisangan forest, Iran, and new morphological observations for the genus
Authors: Panahandeh Yousef , Reza Atighi Mohammad , De Ley Irma Tandingan , Pourjam Ebrahim , Mundo‐Ocampo Manuel , Abolafia Joaquín , Koolivand Davoud , Jahanshahi Afshar Farahnaz , Pedram Majid
Published: July 2019

Further data on the morphology (the lip region characters) and phylogeny of the genus Sakia are presented. The new observations were based on scanning electron microscopy (SEM) and light microscopy (LM). A new species, Sakia sisanganensis n. sp., was recovered from rotten wood of a dead beech tree (Fagus orientalis) in northern Iran, herein described and illustrated based on an integrative approach, that is morphological, morphometric and molecular characters. The new species is characterized by a combination of the following features: fine transverse striae and vestigial single band in the lateral field in SEM. Labial area dorso‐ventrally flattened. Oral region with two concentric hexagonal plates, the inner one apparently elevated. Amphidial openings short, slit‐like. Stylet delicate. Median bulb fusiform to spindle‐shaped with weak valvular apparatus. Spermatheca functional. Tail filiform with faintly pointed tip and males common. The new species was morphologically compared with four known species of the genus, viz., S. alii, S. arboris, S. castori and S. indica, all having indistinct lateral fields. Molecular phylogenetic analyses were performed based on the small subunit ribosomal RNA gene (SSU rDNA). In the Bayesian inference (BI), S. sisanganensis n. sp. with two isolates was strongly supported as a sister taxon of a clade harbouring S. arboris + Lelenchus species. However, in the maximum likelihood (ML) analysis, the new species formed a clade with S. arboris, thus supporting the reciprocal monophyly of the genera Sakia and Lelenchus. Accordingly, the test of monophyly was performed (using Bayes factor) and the results did not reject the monophyly of sakia (i.e., S. sisanganensis n. sp. and S. arboris as sister taxa) based on the currently available data.
A novel, point‐of‐care, whole‐blood assay utilizing dielectric spectroscopy is sensitive to coagulation factor replacement therapy in haemophilia A patients
Authors: Maji Debnath , Nayak Lalitha , Martin Janet , Sekhon Ujjal D. S. , Sen Gupta Anirban , Mohseni Pedram , Suster Michael A. , Ahuja Sanjay P.
Published: July 2019

Background

Reliable monitoring of coagulation factor replacement therapy in patients with severe haemophilia, especially those with inhibitors, is an unmet clinical need. While useful, global assays, eg thromboelastography (TEG), rotational thromboelastometry (ROTEM) and thrombin generation assay (TGA), are cumbersome to use and not widely available.

Objective

To assess the utility of a novel, point‐of‐care, dielectric microsensor – ClotChip – to monitor coagulation factor replacement therapy in patients with haemophilia A, with and without inhibitors.

Methods

The ClotChip Tpeak parameter was assessed using whole‐blood samples from children with severe haemophilia A, with (n = 6) and without (n = 12) inhibitors, collected pre‐ and postcoagulation factor replacement therapy. ROTEM, TGA and chromogenic FVIII assays were also performed. Healthy children (n = 50) served as controls.

Results

ClotChip Tpeak values exhibited a significant decrease for samples collected postcoagulation factor replacement therapy as compared to baseline (pretherapy) samples in patients with and without inhibitors. A difference in Tpeak values was also noted at baseline among severe haemophilia A patients with inhibitors as compared to those without inhibitors. ClotChip Tpeak parameter exhibited a very strong correlation with clotting time (CT) of ROTEM, endogenous thrombin potential (ETP) and peak thrombin of TGA, and FVIII clotting activity.

Conclusions

ClotChip is sensitive to coagulation factor replacement therapy in patients with severe haemophilia A, with and without inhibitors. ClotChip Tpeak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.
Risk of osteoporotic fractures as a consequence of haemophilia: A nationwide population‐based cohort study
Authors: Tuan Sheng‐Hui , Hu Li‐Yu , Sun Shu‐Fen , Huang Wan‐Yun , Chen Guan‐Bo , Li Min‐Hui , Liou I‐Hsiu
Published: July 2019

Aim

Low bone mineral density occurs more commonly in patients with haemophilia (PWH) than the general population. However, the risk of haemophilia‐related osteoporotic fractures has not been well established. We aim to explore the relationship between haemophilia and the development of osteoporotic fractures following haemophilia.

Methods

This was a nationwide population‐based cohort study based on the data in the Taiwan National Health Insurance Research Database (TNHIRD). Patients who were diagnosed with haemophilia were selected. A comparison cohort was formed of patients without haemophilia who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of new‐onset osteoporotic fractures were calculated for both cohorts.

Results

The haemophilia cohort consisted of 75 patients, and the comparison cohort comprised 300 matched control patients without haemophilia. The risk of osteoporotic fractures was higher in the haemophilia cohort than in the comparison cohort (HR = 5.41, 95% confidence interval [CI] = 2.42‐12.1, P < 0.001). After adjustments for age, sex, comorbidities, urbanizations and socio‐economic status, PWH were 4.37 times more likely to develop osteoporotic fractures (95% CI = 1.88‐10.17, P = 0.001) as compared to matched cohort. In addition, the incidence of newly diagnosed osteoporotic fractures was significantly increased after 5‐year follow‐up durations.

Conclusion

Though our study by TNHIRD presented methodologic flaws by its design nature, we observed that haemophilia may increase the risk of osteoporotic fractures and the cumulative incidence was significantly higher for PWH diagnosed more than 5 years. Clinicians should pay particular attention to osteoporotic fractures following haemophilia in PWH as they age.
Intermittent pneumatic compression in patients with ESRD. A systematic review
Authors: Torres Christian , Fuentes Harry E. , Saadaldin Hassan , Salazar Juan P. , Paz Luis H. , Diaz Luis , Doukky Rami , Hart Peter D. , Tafur Alfonso J.
Published: July 2019

Introduction:Patients with end‐stage renal disease (ESRD) experience frequent hemodialysis (HD) complications. Intradialytic hypotension (IDH) is a common complication presenting in approximately between 20 and 50% of HD sessions. Available interventions such as volume replacement or vasoactive medications are associated with significant side effects.

Intermittent pneumatic compression (IPC) has been proposed as a feasible intervention for the prevention of IDH, treatment of peripheral arterial disease and venous ulcers. These devices apply intermittent pressure to the legs improving arterial blood flow, mobilization of pooled blood with an increase in venous return increasing the effective circulatory volume.

Our goal was to identify the published clinical evidence on whether IPC has a circulatory benefit and is it well‐tolerated among patients receiving HD.

Methods:We conducted a systematic review to identify studies assessing the efficacy and safety of IPC in patients with ESRD. Our primary outcome was IDH. Secondary outcomes such as HD comfort, ultrafiltration volume, and physical activity were collected. No restrictions where used and we included all observational and interventional studies. Two reviewers performed screening and study quality assessment.

Findings:We included seven studies. Out of the seven studies, five addressed IDH, and the rest were included for secondary outcomes such as physical capacity and HD comfort. In one randomized crossover trial comparing exercise against IPC, 21 patients were randomized to 3 different arms (no intervention, cycling, IPC) a decrease in the rates of IDH with IPC was described (43%, 38%, and 24% respectively P = 0.014). The smaller studies corroborated these results. All studies where at high risk of bias.

Discussion:IPC might offer significant benefits for patients undergoing HD not limited to prevention of IDH but also improvement of hemodialysis comfort and physical capacity. However, our results should be interpreted in the context of its limitations.
Evolution of Helicobacter pylori associated with gastroduodenal ulcers or erosions in children over the past 23 years: Decline or steady state?
Authors: Burgard Marie , Kotilea Kallirroi , Mekhael Joyce , Miendje‐Deyi Veronique Yvette , De Prez Carine , Vanderpas Jean , Cadranel Samy , Bontems Patrick
Published: July 2019

Background

Recent data suggest that in children, the proportion of gastroduodenal ulcers/erosions associated with Helicobacter pylori infection is currently lower than expected. In this study, we trace this proportion over two decades.

Methods

We reviewed the reports of all upper gastrointestinal endoscopies with biopsies for histology and culture over the past 23 years. H pylori status was assessed using several invasive methods. The infection rate during different time periods was compared between children with lesions and controls.

Results

A total of 7849 endoscopies were performed in 5983 children (2874 F/3109 M, median age 7.6 years, range 0.1‐17.9 years). The endoscopy report was missing in 316 patients. At the first upper gastrointestinal endoscopy, 12.1% of the children presented with gastric and/or duodenal ulcers or erosions with an H pylori infection rate of 35.4%, whereas no such lesions were observed in 87.9% of children in whom the H pylori infection rate was 21.3%. The risk factors associated with such lesions were older age (P < 0.001), male sex (P = 0.002), and H pylori infection (P < 0.0001). Gastric ulcers were not significantly associated with H pylori (24% infected), whereas 52% of duodenal ulcers, 33% of gastric erosions, and 38% of duodenal erosions were associated with H pylori. The proportion of gastroduodenal lesions associated with H pylori remained stable over time. Children with H pylori infection and ulcers were older than those with H pylori infection without ulcers (P < 0.001).

Conclusions

Our study indicates that in our pediatric population, the proportion of ulcers without H pylori infection is higher than previously suggested, and this prevalence has not changed over the past two decades.
Latin American Clinical Practice Guidelines on the Systemic Treatment of Psoriasis SOLAPSO – Sociedad Latinoamericana de Psoriasis (Latin American Psoriasis Society)
Authors: Kogan Nora , Raimondo Nélida , Gusis Simon E. , Izcovich Ariel , Abarca Duran Jorge A. , Barahona‐Torres Lilia , Blanco Orestes , Quintana Gerardo B. , Briones María C. , Castro Carla , Castro Vargas Evelyn G. , Criniti Juan , Diez de Medina Juan C. , Franco Manuel , Gómez Minerva , Levrero Patricia , Martínez López Jaime E. , Valenzuela Fernando
Published: July 2019

This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non‐biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque‐psoriasis, which was summarized in Tables ad‐hoc. The main end‐points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0‐1 and significant improvement of health‐related quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.
METS‐IR, a novel simple insulin resistance indexes, is associated with hypertension in normal‐weight Chinese adults
Authors: Liu Xing Zhen , Fan Jie , Pan Shu Jun
Published: July 2019

Insulin resistance (IR) plays a crucial role in the development of hypertension, so early recognition of IR is of substantial clinical importance for the management of hypertension. But traditional IR indexes are invasive, complex, and impractical. We aimed to evaluate the associations between three simple IR indexes and hypertension in different body mass index (BMI) categories. A total of 142 005 adults who did not take antihypertensive medication were included in this analysis. The ratio of triglycerides to high‐density lipoprotein cholesterol (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS‐IR) were calculated according to the corresponding formulas. The associations between them and hypertension were analyzed by logistic regression. Among the three indicators, only METS‐IR had positive correlations with blood pressure levels (all P < 0.001). After full adjustment, METS‐IR was significantly associated with hypertension in the normal BMI group but not in the elevated BMI group. The OR for hypertension in the normal BMI group in the highest quartile of METS‐IR was 2.884 (95% CI: 2.468‐3.369) in the total sample, 1.915 (95% CI: 1.614‐2.271) in females and 2.083 (95% CI: 1.717‐2.527) in males. Our findings indicate that METS‐IR, a simple and cost‐effective IR index, was strongly associated with hypertension in normal‐weight Chinese subjects. It could help monitor and manage hypertension in normal‐weight individuals.
NF‐κB/NKILA signaling modulates the anti‐cancerous effects of EZH2 inhibition
Authors: Duan Suzann , Chan Westin K. , Oman Andrew , Basile Dominic P. , Alvira Cristina M. , Buxton Iain L.O. , Iosef Cristiana
Published: July 2019

A wealth of evidence supports the broad therapeutic potential of NF‐κB and EZH2 inhibitors as adjuvants for breast cancer treatment. We contribute to this knowledge by elucidating, for the first time, unique regulatory crosstalk between EZH2, NF‐κB and the NF‐κB interacting long non‐coding RNA (NKILA). We define a novel signaling loop encompassing canonical and non‐canonical actions of EZH2 on the regulation of NF‐κB/NKILA homeostasis, with relevance to breast cancer treatment. We applied a respective silencing approach in non‐transformed breast epithelial cells, triple negative MDA‐MB‐231 cells and hormone responsive MCF‐7 cells, and measured changes in EZH2/NF‐κB/NKILA levels to confirm their interdependence. We demonstrate cell line‐specific fluctuations in these factors that functionally contribute to epithelial‐to‐mesenchymal transition (EMT) remodelling and cell fate response. EZH2 inhibition attenuates MDA‐MB‐231 cell motility and CDK4‐mediated MCF‐7 cell cycle regulation, while inducing global H3K27 methylation and an EMT phenotype in non‐transformed cells. Notably, these events are mediated by a cell‐context dependent gain or loss of NKILA and NF‐κB. Depletion of NF‐κB in non‐transformed cells enhances their sensitivity to growth factor signaling and suggests a role for the host microenvironment milieu in regulating EZH2/NF‐κB/NKILA homeostasis. Taken together, this knowledge critically informs the delivery and assessment of EZH2 inhibitors in breast cancer.
Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma
Authors: Gao Yixing , Zhang Erlong , Liu Bao , Zhou Kai , He Shu , Feng Lan , Wu Gang , Cao Mianfu , Wu Haibo , Cui Youhong , Zhang Xia , Liu Xindong , Wang Yan , Gao Yuqi , Bian Xiuwu
Published: July 2019

As a hallmark for glioblastoma (GBM), high heterogeneity causes a variety of phenotypes and therapeutic responses among GBM patients, and it contributes to treatment failure. Moreover, hypoxia is a predominant feature of GBM and contributes greatly to its phenotype. To analyse the landscape of gene expression and hypoxic characteristics of GBM cells and their clinical significance in GBM patients, we performed transcriptome analysis of the GBM cell line U87‐MG and the normal glial cell line HEB under normoxia and hypoxia conditions, with the results of which were analysed using established gene ontology databases as well as The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. We revealed core signal pathways, including inflammation, angiogenesis and migration, and for the first time mapped the components of the toll‐like receptor 6 pathway in GBM cells. Moreover, by investigating the signal pathways involved in homoeostasis, proliferation and adenosine triphosphate metabolism, the critical response of GBM to hypoxia was clarified. Experiments with cell lines, patient serum and tissue identified IL1B, CSF3 and TIMP1 as potential plasma markers and VIM, STC1, TGFB1 and HMOX1 as potential biopsy markers for GBM. In conclusion, our study provided a comprehensive understanding for signal pathways and hypoxic characteristics of GBM and identified new biomarkers for GBM patients.
A comparative dermoscopic and reflectance confocal microscopy study of naevi and melanoma with negative pigment network
Authors: Farnetani F. , Scope A. , Mazzoni L. , Mandel V.D. , Manfredini M. , Magi S. , Vaschieri C. , Kaleci S. , Longo C. , Ciardo S. , Stanganelli I. , Pellacani G.
Published: July 2019

Background

Negative pigment network (NPN) is a dermoscopic structure observed more frequently among melanomas than naevi. Precise tissue correlates of NPN are still elusive.

Objective

To describe the reflectance confocal microscopy (RCM) findings underlying NPN in melanocytic neoplasms.

Methods

We retrospectively identified all melanocytic neoplasms displaying dermoscopic NPN that were imaged with RCM and subsequently biopsied between 2011 and 2015. Images from study lesions (n = 50) were evaluated for dermoscopic and RCM Criteria. Histopathological correlational study was performed in a subset of cases (n = 15).

Results

The study data set consisted of 21 melanomas (42%) and 29 naevi (58%). Melanomas showed more frequently irregularly shaped globules than naevi (62% vs. 28%, P = 0.03); NPN also tended to be more asymmetrically located among melanomas (86%) than naevi (62%), albeit not significant (P = 0.06). Under RCM, we observed three patterns of dermal papillae (DP): (i) ‘Dark DP’ – whereby DP were devoid of nests and often surrounded by a junctional proliferation as thick‐Rings – this pattern was less common among melanomas (n = 10, 48%) than naevi (n = 23, 79%, P = 0.02); (ii) ‘Bulging DP’ – whereby junctional nests of melanocytes protrude into the DP, often in association with junctional proliferation as Meshwork – with comparable frequency among melanomas (n = 12, 57%) and naevi (n = 23, 79%, P = 0.09) and (iii) ‘Expanded DP’ – whereby junctional and/or dermal nests filled and expanded the DP, often in association with dermal–epidermal junction (DEJ) Clod pattern – seen more commonly among melanomas (n = 15, 71%) than naevi (n = 6, 21%, P < 0.001). Dermoscopy–RCM correlation and comparison to histopathological findings show that the hypo‐pigmented lines of NPN correlate with broadened epidermal retes, which often show overlying surface dells and wedge‐shaped hypergranulosis, while the pigmented globules of NPN correlate with a predominantly‐junctiona of melanocytes along and between the elongated retes.

Conclusions

Dermoscopic NPN correlates with three DEJ RCM patterns with differing frequency between naevi and melanomas.
No association between smoking and sentinel lymph node metastasis and survival in cutaneous melanoma
Authors: Tejera‐Vaquerizo A. , Descalzo‐Gallego M.A. , Traves V. , Requena C. , Bolumar I. , Pla A. , Nagore E.
Published: July 2019

Background

There is little evidence that smoking is associated with metastasis in patients with cutaneous melanoma.

Objective

Using a propensity score matching analysis, we assessed whether smoking was associated with a higher rate of sentinel lymph node (SLN) metastasis and worse survival in these patients.

Methods

Retrospective cohort study at a referral hospital for melanoma. We studied 762 patients with known smoking status from the melanoma database of the Instituto Valenciano de Oncología who underwent SLN biopsy between 1 January 2000 and 31 December 2016. The patients were matched by smoking status. The matching procedure was implemented using three logistic regression models featuring never vs. former smokers, never vs. current smokers and former vs. current smokers. The study outcomes were disease‐free survival (DFS), melanoma‐specific survival (MSS), overall survival (OS) and SLN status.

Results

The following groups were formed based on the propensity matching scores: 114 pairs of smokers vs. never smokers, 113 pairs of smokers vs. former smokers and 174 pairs of never smokers vs. former smokers. Smoking status was not associated with SLN metastasis or with DFS, MSS or OS in any of the three groups.

Conclusion

Smoking does not influence SLN metastasis or survival in patients with cutaneous melanoma.
Reassessment of venous thromboembolism and bleeding risk in medical patients receiving VTE prophylaxis
Authors: Tung Elaine C. , Yu Shi‐Yuan , Shah Kieran , Kinkade Angus , Tejani Aaron M.
Published: July 2019

Rationale, Aims, and Objectives

The majority of hospitalized nonsurgical medical patients receive pharmacological prophylaxis for venous thromboembolism (VTE), and reassessment of changes in thrombosis and bleeding risk factors during hospital admission may represent an opportunity to discontinue unnecessary or unsafe therapy. The use of validated, clinically derived risk assessment models (RAMs) represents a shift towards an individualized, patient‐centred approach to VTE prophylaxis. We are interested in using these tools to assess whether risk categories for VTE and bleeding change during admission and to assess whether such changes result in discontinuation of prophylaxis. Our primary objective was to determine whether VTE and bleed risk categories changed during the course of admission to warrant discontinuation of VTE prophylaxis, using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE and Bleed RAMs, respectively. Secondary objectives were to determine the number of patients whose risk categorizations for VTE and bleeding warranted discontinuation of VTE prophylaxis and to survey whether prophylaxis was continued or discontinued.

Methods

A retrospective review was undertaken for a cross‐sectional, randomly selected sample of patients who received VTE prophylaxis while admitted to medical wards in a collection of regional hospitals.

Results

Of the 351 medical records reviewed, only eight patients (2.3%) changed their VTE risk category and six (1.7%) changed their bleed risk category to warrant discontinuation of VTE prophylaxis. Ninety patients (26%) were at high risk of VTE and low risk of bleed throughout admission, warranting continued VTE prophylaxis. The majority of patients remained at low risk of VTE throughout admission but remained on VTE prophylaxis until discharge.

Conclusions

Risk categories for VTE and bleeding for medical patients did not appreciably change throughout hospital admission. Use of VTE RAMs at admission and prior to initiation of therapy should reduce unnecessary prophylaxis in the majority of medical patients who are at low risk of VTE.
Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1G93A mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS
Authors: Ravera Silvia , Torazza Carola , Bonifacino Tiziana , Provenzano Francesca , Rebosio Claudia , Milanese Marco , Usai Cesare , Panfoli Isabella , Bonanno Giambattista
Published: July 2019

Amyotrophic lateral sclerosis is an adult‐onset neurodegenerative disease that develops because of motor neuron death. Several mechanisms occur supporting neurodegeneration, including mitochondrial dysfunction. Recently, we demonstrated that the synaptosomes from the spinal cord of SOD1G93A mice, an in vitro model of presynapses, displayed impaired mitochondrial metabolism at early pre‐symptomatic stages of the disease, whereas perisynaptic astrocyte particles, or gliosomes, were characterized by mild energy impairment only at symptomatic stages. This work aimed to understand whether mitochondrial impairment is a consequence of upstream metabolic damage. We analyzed the critical pathways involved in glucose catabolism at presynaptic and perisynaptic compartments. Spinal cord and motor cortex synaptosomes from SOD1G93A mice displayed high activity of hexokinase and phosphofructokinase, key glycolysis enzymes, and of citrate synthase and malate dehydrogenase, key Krebs cycle enzymes, but did not display high lactate dehydrogenase activity, the key enzyme in lactate fermentation. This enhancement was evident in the spinal cord from the early stages of the disease and in the motor cortex at only symptomatic stages. Conversely, an increase in glycolysis and lactate fermentation activity, but not Krebs cycle activity, was observed in gliosomes from the spinal cord and motor cortex of SOD1G93A mice although only at the symptomatic stages of the disease. The cited enzymatic activities were enhanced in spinal cord and motor cortex homogenates, paralleling the time‐course of the effect observed in synaptosomes and gliosomes. The observed metabolic modifications might be considered an attempt to restore altered energetic balance and indicate that mitochondria represent the ultimate site of bioenergetic impairment.

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Influence of needle size and injection angle on the distribution pattern of facial soft tissue fillers
Authors: Pavicic Tatjana , Mohmand Humayun M. , Yankova Mariya , Schenck Thilo L. , Frank Konstantin , Freytag David L. , Green Jeremy B. , Hamade Hassan , Cassuto Daniel , Cotofana Sebastian
Published: July 2019

Background

Soft tissue filler injections are performed using either sharp‐tip needles or blunt‐tip cannulas. Product can change planes in an uncontrolled manner during needle injections, potentially leading to unintentional intra‐arterial placement. There is a paucity of data on the influence of injection angle on the dispersion patterns of soft tissue fillers.

Materials and Methods

A total of 126 injection procedures were conducted in seven Caucasian body donors (four males, three females) with a mean age of 75.29 ± 4.95 years and a mean body mass index of 23.53 ± 3.96 kg/m2. Injection procedures were performed in various facial regions (forehead, scalp, zygomatic arch, mandibular angle), utilizing different needle sizes (25G, 27G, 30G) and different angles (90°, 45°, 10°). Layer‐by‐layer dissections were performed to verify the location of the injected product. Dissections were facilitated by the colored material.

Results

Utilizing a 30G needle (compared to a 25G needle) reduces the superficial spread with OR 0.70 (95% CI, 0.48‐0.99) and P = 0.049, whereas injecting at 90° (vs 10° with the bevel down) increases the odds for superficial spread with OR 10.0 (95% CI, 7.11‐14.09) and P < 0.001.

Conclusion

Precision during soft tissue filler injections, defined as the product remaining in the plane of intended implantation, can be enhanced by changing the needle size and the injection angle. Utilizing a 30G needle and injecting at a 10° angle with bevel facing down reduces the uncontrolled product distribution into superficial fascial layers.
Disability: Missing from the Conversation of Violence
Authors: Mueller Carlyn O. , Forber‐Pratt Anjali J. , Sriken Julie
Published: July 2019

The data on violence against disabled people are scarce. The data on prevalence that does exist is staggering, however: disabled people make up one third to one half of all people killed by law enforcement and experience twice the rate of violence that others do. To study the relationships among ableism, violence, and disability as an intersectional identity, we use a DisCrit theoretical framework to conduct a selective review of three reports: a Bureau of Justice Statistics (2017) report on violence and disability, a Ruderman Foundation white paper on media coverage of police violence and disability (Perry and Carter‐Long), and a report from the Center for American Progress (CAP) investigating the mass incarceration of people with disabilities in the United States (Vallas). The authors examine ways the available data tell a particular story about disability and violence and identify crucial missing conversations. The findings from these analyses suggest that to combat ableism and the violence it causes, oppressive systems must be named, the voices of disabled individuals must be included, and data on disability must be more systematically gathered in all national efforts related to violence and violence prevention. We also present the implications of this work for social policy, psychologists, and larger contributions to the literature on victimization.
The Sequential Agglomerative Sorting task, a new methodology for the sensory characterization of large sets of products
Authors: Brard Margot , Lê Sébastien
Published: July 2019

The use of the free sorting task is compromised when the number of products to be assessed is too important. Some solutions have been put in place to manage these situations: (a) the use of incomplete presentation designs and (b) the use of predefined prototypes. These are unfortunately not optimal: the first brings out sensory dimensions of variability that are approximated at the level of the panel of participants; those revealed by the second may be conditioned by the predefined prototypes. The aim of this article is to present a new protocol of data collection that allows the characterization of large sets of products. It has been named the Sequential Agglomerative Sorting task (SAS task). It is partially based on a combination of the two previous solutions. All products are presented to the participant in the form of subsets. The latter are agglomerated by means of prototypes defined by the participant herself/himself. Thus, it reveals sensory dimensions that are neither approximated at the panel level nor conditioned by predefined prototypes. In this article, we present all the steps of implementation of the SAS task. A first study designed to test the performance of the SAS task is also presented.

Practical Applications

The Sequential Agglomerative Sorting task (SAS task) allows to obtain the sensory characterization of large sets of products. This new protocol of data collection was successfully applied to a set composed of 40 fragrances (study in this article). It can be applied to any kind of products: food, cosmetics, sport products, and so forth.
Exploring the reticulate evolution in the Asplenium pekinense complex and the A. varians complex (Aspleniaceae)
Authors: Liang Si‐Qi , Viane Ronald L. L. , Zhang Xian‐Chun , Wei Ran
Published: July 2019

The Asplenium pekinense complex mainly comprises one diploid, A. sarelii Hook. (rare), one autotetraploid, A. pekinense Hance (best known and very common), and shares two allotetraploids, A. anogrammoides Christ (common but often misidentified) and A. altajense (Komarov) Grubov (rare and endemic) with the A. varians complex. The latter is further constituted by two diploids, A. tenuicaule Hayata (widespread) and A. semivarians Viane & Reichstein (rare), as well as other three tetraploids, A. kansuense Ching (barely known), A. varians Wallich ex Hooker & Greville (well‐known, relatively common, and morphologically variable), and A. kukkonenii Viane & Reichstein (rare and often misidentified). These two species complexes are notorious for their taxonomic difficulty based on general morphology, which is mainly caused by their history of reticulate evolution. Here, we collected most species within the two complexes, and obtained ploidy information by spore size measurement and flow cytometry investigation. Phylogenetic analyses using DNA markers representing maternally inherited chloroplast and biparentally inherited nuclear genomes helped to reconstruct the reticulate evolution history. The present results support previous hypotheses that A. sarelii is the ancestor of both A. pekinense and A. anogrammoides, as well as that A. tenuicaule is the common progenitor of A. anogrammoides, A. varians, and A. kukkonenii. We also unraveled the autotetraploid origin of A. kansuense from A. tenuicaule for the first time, and found that A. altajense shares essentially identical genomes with A. anogrammoides.
Maternity or parental leave and breastfeeding duration: Results from the ELFE cohort
Authors: de Lauzon‐Guillain Blandine , Thierry Xavier , Bois Corinne , Bournez Marie , Davisse‐Paturet Camille , Dufourg Marie‐Noëlle , Kersuzan Claire , Ksiazek Eléa , Nicklaus Sophie , Vicaire Hélène , Wagner Sandra , Lioret Sandrine , Charles Marie Aline
Published: July 2019

Previous studies have shown a high level of noncompliance with recommendations on breastfeeding duration, especially in France. The objective was to describe the association between breastfeeding initiation and duration and the statutory duration of postnatal maternity leave, the gap between the end of legal maternity leave and the mother's return to work, and maternal working time during the first year post‐partum. Analyses were based on 8,009 infants from the French nationwide ELFE cohort. We assessed the association with breastfeeding initiation by using logistic regression and, among breastfeeding women, with categories of breastfeeding duration by using multinomial logistic regression. Among primiparous women, both postponing return to work for at least 3 weeks after statutory postnatal maternity leave (as compared with returning to work at the end of the statutory period) and working less than full‐time at 1 year post‐partum (as compared with full‐time) were related to higher prevalence of breastfeeding initiation. Among women giving birth to their first or second child, postponing the return to work until at least 15 weeks was related to a higher prevalence of long breastfeeding duration (at least 6 months) as compared with intermediate duration (3 to <6 months). Working part‐time was also positively related to breastfeeding duration. Among women giving birth to their third child or more, working characteristics were less strongly related to breastfeeding duration. These results support extending maternity leave or working time arrangements to encourage initiation and longer duration of breastfeeding.
Disentangling the complex microbial community of coral reefs using standardized Autonomous Reef Monitoring Structures (ARMS)
Authors: Pearman John K. , Aylagas Eva , Voolstra Christian R. , Anlauf Holger , Villalobos Rodrigo , Carvalho Susana
Published: July 2019

Autonomous Reef Monitoring Structures (ARMS) have been applied worldwide to describe eukaryotic cryptic reef fauna. Conversely, bacterial communities, which are critical components of coral reef ecosystem functioning, remain largely overlooked. Here we deployed 56 ARMS across the 2,000‐km spread of the Red Sea to assay biodiversity, composition and inferred underlying functions of coral reef‐associated bacterial communities via 16S rRNA gene sequencing. We found that bacterial community structure and diversity aligned with environmental differences. Indeed, sea surface temperature and macroalgae cover were key in explaining bacterial relative abundance. Importantly, taxonomic and functional alpha diversity decreased under more extreme environmental conditions (e.g., higher temperatures) in the southern Red Sea. This may imply a link between bacterial community diversity and functional capabilities, with implications for conservation management. Our study demonstrates the utility of ARMS to investigate the response of coral reef‐associated bacterial communities to environmental change.