bluuebunny/crossref_metadata_2025 huggingface dataset:
A low MW inhibitor of CD44 dimerization for the treatment of glioblastoma
Authors: Wang Chongwu , Wang Zhaotao , Chen Chen , Fu Xiaojun , Wang Ji , Fei Xiaowei , Yan Xiaojing , Xu Ruxiang
Published: February 2020

Background and Purpose

As a hallmark of glioblastoma multiforme (GBM), CD44 plays a crucial role in promoting glioblastoma stem cell (GSC) stemness phenotypes and multiple drug resistance. The therapeutic potential of CD44 has been validated by the clinical successes of several CD44 inhibitors, including antibodies and hyaluronan‐related drugs.

Experimental Approach

We used systemsDock software to predict verbascoside as a candidate CD44 inhibitor. Microscale thermophoresis was used to confirm the interaction between CD44 and verbascoside. Four glioblastoma cell lines and a patient‐derived glioblastoma cell line were used to test the influences of verbascoside on glioblastoma. CD44‐overexpressing and CD44‐knockout cell lines were also used. Real‐time quantitative PCR and western blot analyses were performed. A xenograft mouse model was used to test verbascoside.

Key Results

Verbascoside bound to CD44 and suppressed its dimerization. By inhibiting CD44 dimerization, verbascoside decreased the release of the CD44 intracellular domain (CD44ICD) and suppressed the expression of CD44 downstream genes. Verbascoside treatment suppressed the stemness phenotypes of cells with high CD44 expression. In a mouse model of glioma, verbascoside treatment highly reduced the growth of intracranial tumours and inhibited CD44ICD release. Both stem cell marker and mesenchymal GBM subtype marker genes were down‐regulated in verbascoside‐treated mice.

Conclusion and Implications

Verbascoside suppressed growth of glioblastoma cells by inhibiting CD44 dimerization. Stem cell‐like cell properties and tumour cell growth were also suppressed by verbascoside, both in vitro and in vivo. Verbascoside significantly prolonged survival of xenografted mice.
To what extent are digital influencers creative?
Authors: Sette Guilherme , Brito Pedro Quelhas
Published: February 2020

Our research goal is to assess creativity and innovation in the profiles of digital influencers (DIs) and examine how they participate in the shared process of content creation with their partner brands. Based on in‐depth interviews with 30 Brazilian DI who had at least one partnership with a brand, we showed that they expressed four out of the nine dimensions of creativity, in addition to a new attribute that we designated as ‘Originality’. We also found that DIs regard as strategic sharing creative, innovative, quality content and also being involved in content production with the brands during the different stages of message development. The current literature tends to stress DIs’ reactive role in the co‐creation experience. We analysed how they manifest (process) their creative task as well as their strategies for generating innovative content. Our results help brand managers to cooperate more efficiently and respectfully with their DIs.
The evolution of the human capital of women
Authors: Bowlus Audra , Robinson Chris
Published: February 2020

The labour market attachment of females has increased dramatically over the last half century, converging to a pattern similar to that of males. Human capital theory predicts an associated increase in human capital investment by females and a convergence in the life‐cycle human capital investment profiles of males and females. This paper explores wage‐based and job skills‐based approaches to measuring the increased supply of efficiency units of human capital by females over the last four decades. Results suggest that the magnitude of the contribution of the increased human capital of women to post‐war economic growth is substantially underestimated by conventional methods of measuring human capital and labour inputs. A complete picture of the evolution of the human capital of women requires new approaches to measuring their human capital.
Computational‐based discovery of FAK FERM domain chemical probes that inhibit HER2‐FAK cancer signaling
Authors: Stahl Erik , Nott Rohini , Koessel Karissa , Cance William , Marlowe Timothy
Published: February 2020

The N‐terminal FERM domain of focal adhesion kinase (FAK) contributes to FAK scaffolding and interacts with HER2, an oncogene and receptor tyrosine kinase. The interaction between HER2 and FAK drives resistance to FAK‐kinase domain inhibitors through FAK Y397 transphosphorylation and FAK re‐activation upon inhibition. As such, FAK FERM remains an attractive drug discovery target. In this report, we detail an alternative approach to targeting FAK through virtual screening‐based discovery of chemical probes that target FAK FERM. We validated the binding interface between HER2 and FAK using site‐directed mutagenesis and GST pull‐down experiments. We assessed the ligandability of key‐binding residues of HER2 and FAK utilizing computational tools. We developed a virtual screening method to screen ~200,000 compounds against the FAK FERM domain, identifying 20 virtual chemical probes. We performed GST pull‐down screening on these compounds, discovering two hits, VS4 and VS14, with nanomolar IC50s in disrupting HER2‐FAK. We performed further testing, including molecular docking, immunofluorescence, phosphorylation, and cellular invasion assays to evaluate the compounds’ biological effects. One probe, VS14, was identified with the ability to block both auto‐ and transphosphorylation of Y397. In all, these studies identify two new probes that target FAK FERM, enabling future investigation of this domain.
The potential of marginal coastal nursery habitats for the conservation of a culturally important Caribbean marine species
Authors: Stieglitz Thomas C. , Dujon Antoine M. , Peel Joanne R. , Amice Erwan
Published: February 2020

Aim

Identifying the potential of marginal habitats for species conservation is of key importance when their core high‐quality habitats are under substantial disturbances and threats. However, there is currently a knowledge gap on how useful marine marginal habitats may be for conserving endangered marine species. Here, we investigate the potential of groundwater‐fed coastal areas for the conservation of the queen conch, an economically and culturally important marine gastropod.

Location

The inlet of Xel‐Há, typical of groundwater‐fed coastal areas widely distributed along the Yucatan Peninsula coast in Mexico and partially protected by a network of marine protected areas.

Methods

We tracked 66 queen conchs (Lobatus gigas) using acoustic telemetry over a period of 3.5 years. We investigated for ontogenetic niche shift using a network analysis and by modelling their growth.

Results

The queen conchs exhibited the same ontogenetic niche shift required to complete their life cycle in this marginal habitat as they do in offshore core habitats. A total of 33 individuals departed the inlet and migrated from shallow groundwater‐affected nursery grounds to deeper marine habitats more suitable for breeding aggregation.

Main conclusions

As the broad‐scale movement behaviour of queen conch in this inlet is similar to that observed on the overfished core habitats, our findings suggest that groundwater‐fed coastal areas should be included in conservation planning for an effective management of this species within a network of marine protected areas.
Edge effects on insect–plant food webs: assessing the influence of geographical orientation and microclimatic conditions
Authors: Bernaschini María Laura , Valladares Graciela , Salvo Adriana
Published: February 2020

1. Geographical orientation affects the magnitude of microclimatic edge effects, mainly by altering the exposure to solar radiation. There is considerable evidence available concerning the influence of microclimatic edge effects on organisms at the population level, although little is known about effects at the community level, and variations with edge geographical orientation have barely been addressed. The present study investigated the influence of microclimatic conditions at the forest interior and edges with different geographical orientation on plant–leafminer–parasitoid food webs in the fragmented Chaco Serrano forest located in Central Argentina.

2. Microclimatic variables were measured in three locations: interior, north, and south‐facing edges of six forest fragments. In each location, plant resource availability was assessed and mined leaves were collected to investigate plant–leafminer–parasitoid communities by rearing leafminer and parasitoid adults.

3. The results obtained revealed changes in the specific composition of plant, leafminer and parasitoid communities among locations, although they failed to detect location influences on most variables linked to abundance (except for leafminers), richness or food web structure. Leafminer abundance was negatively related to temperature, whereas their richness was related, also negatively, to moisture. Instead, parasitoids were favoured by higher temperatures and light levels, stronger winds, and lower humidity.

4. The results of the present study indicate that the effects of microclimatic conditions may depend on the trophic level considered. Moreover, the findings suggest that possible trade‐offs between direct and indirect effects (such as plant quality, floral resources, etc.) of microclimatic conditions could influence plant and insect responses to location.
Modulation change detection in human auditory cortex: Evidence for asymmetric, non‐linear edge detection
Authors: Kim Seung‐Goo , Poeppel David , Overath Tobias
Published: February 2020

Changes in modulation rate are important cues for parsing acoustic signals, such as speech. We parametrically controlled modulation rate via the correlation coefficient (r) of amplitude spectra across fixed frequency channels between adjacent time frames: broadband modulation spectra are biased toward slow modulate rates with increasing r, and vice versa. By concatenating segments with different r, acoustic changes of various directions (e.g., changes from low to high correlation coefficients, that is, random‐to‐correlated or vice versa) and sizes (e.g., changes from low to high or from medium to high correlation coefficients) can be obtained. Participants listened to sound blocks and detected changes in correlation while MEG was recorded. Evoked responses to changes in correlation demonstrated (a) an asymmetric representation of change direction: random‐to‐correlated changes produced a prominent evoked field around 180 ms, while correlated‐to‐random changes evoked an earlier response with peaks at around 70 and 120 ms, whose topographies resemble those of the canonical P50m and N100m responses, respectively, and (b) a highly non‐linear representation of correlation structure, whereby even small changes involving segments with a high correlation coefficient were much more salient than relatively large changes that did not involve segments with high correlation coefficients. Induced responses revealed phase tracking in the delta and theta frequency bands for the high correlation stimuli. The results confirm a high sensitivity for low modulation rates in human auditory cortex, both in terms of their representation and their segregation from other modulation rates.
Predicting soil test phosphorus decrease in non‐P‐fertilized conditions
Authors: Appelhans Stefania C. , Carciochi Walter D. , Correndo Adrian , Gutierrez Boem Flavio H. , Salvagiotti Fernando , Garcia Fernando O. , Melchiori Ricardo J.M. , Barbagelata Pedro A. , Ventimiglia Luis A. , Ferraris Gustavo N. , Vivas Hugo S. , Caviglia Octavio P. , Ciampitti Ignacio A.
Published: February 2020

Monitoring the availability of phosphorus (P) in soil under continuous cropping facilitates finding deficiency in crops and contributes to improving crop growth and nutrient management models. Soil P availability for crops is usually estimated by soil test P (STP), such as Bray‐1. This is widely used in the Americas. The relationship between the decrease of STP Bray‐1 and cumulative removal of P was evaluated in non‐P‐fertilized areas in long‐term studies. This removal was the sum of annual P removal over the study period as P exported in grains/crop outside the soil. The objectives were to: (a) quantify changes in STP as a function of cumulative P removal, (b) assess the relationship between relative decrease rate of STP and soil variables as well as annual removal of P by crops, and (c) develop a model to predict decrease of STP Bray‐1. Exponential decay functions were used to describe annual cumulative removal of P and STP from soil over time for 12 long‐term studies where no addition of P fertilizer was carried out. Changes in the relative rate of decrease of STP, relative to the initial STP Bray‐1 value at the onset of the experiment, were predicted by the ratio of soil organic matter to clay and silt and the average annual P removal by exponential decay (R2adj = 0.64; RMSE = 3.2 mg kg−1). We propose this predictive model as suitable to provide estimates of the relative decrease rate of STP by Bray‐1 and thereby improve management of P for optimizing crop yield.

Highlights

STP Bray‐1 decrease and cumulative P removal were related by exponential decay functions.

Relative decrease rate of STP Bray‐1 was related to SOM/(clay+silt) ratio and annual P removal.

A predictive model of the relative decrease rate of STP Bray‐1 was fitted and validate.

Our model is a useful tool to help predict soil P availability and nutrient management.
Same same but different: A Web‐based deep learning application revealed classifying features for the histopathologic distinction of cortical malformations
Authors: Kubach Joshua , Muhlebner‐Fahrngruber Angelika , Soylemezoglu Figen , Miyata Hajime , Niehusmann Pitt , Honavar Mrinalini , Rogerio Fabio , Kim Se‐Hoon , Aronica Eleonora , Garbelli Rita , Vilz Samuel , Popp Alexander , Walcher Stefan , Neuner Christoph , Scholz Michael , Kuerten Stefanie , Schropp Verena , Roeder Sebastian , Eichhorn Philip , Eckstein Markus , Brehmer Axel , Kobow Katja , Coras Roland , Blumcke Ingmar , Jabari Samir
Published: February 2020

Objective

The microscopic review of hematoxylin‐eosin–stained images of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex remains challenging. Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. We trained a convolutional neural network (CNN) to classify both entities and visualize the results. Additionally, we propose a new Web‐based deep learning application as proof of concept of how deep learning could enter the pathologic routine.

Methods

A digital processing pipeline was developed for a series of 56 cases of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex to obtain 4000 regions of interest and 200 000 subsamples with different zoom and rotation angles to train a neural network. Guided gradient‐weighted class activation maps (Guided Grad‐CAMs) were generated to visualize morphological features used by the CNN to distinguish both entities.

Results

Our best‐performing network achieved 91% accuracy and 0.88 area under the receiver operating characteristic curve at the tile level for an unseen test set. Novel histopathologic patterns were found through the visualized Guided Grad‐CAMs. These patterns were assembled into a classification score to augment decision‐making in routine histopathology workup. This score was successfully validated by 11 expert neuropathologists and 12 nonexperts, boosting nonexperts to expert level performance.

Significance

Our newly developed Web application combines the visualization of whole slide images with the possibility of deep learning–aided classification between focal cortical dysplasia IIb and tuberous sclerosis complex. This approach will help to introduce deep learning applications and visualization for the histopathologic diagnosis of rare and difficult‐to‐classify brain lesions.
Activation of RAW264.7 macrophage by Exopolysaccharide from Aphanothece halaphytica (EPSAH) and the underlying mechanisms
Authors: Ou Yu , Zhu Lei , Xu Shuya , Wei Qingfang
Published: February 2020

Exopolysaccharide from Aphanothece halophytica (EPSAH), a potent antitumor agent and immunological adjuvant, was investigated for the activation effect on RAW264.7 macrophages and the underlying mechanisms. EPSAH could significantly enhance macrophage phagocytosis and the secretion of nitric oxide, increase the mRNA expression levels of the pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐12, and TNF‐α), anti‐inflammatory cytokine IL‐10, and chemokines (MCP‐1 and MIP‐1α). When RAW264.7 cells were treated with EPSAH, the mRNA expression of TLR4 and its downstream molecules TRAF6 and MyD88 were upregulated. When TLR4 was blocked using a TLR4‐specific neutralizing antibody, nitric oxide secretion from the macrophages was significantly inhibited. EPSAH was further shown to induce phosphorylation of the mitogen‐activated protein kinases (MAPKs) ERK, JNK, and p38, and promote cytoplasmic IκB phosphorylation and increase nuclear NF‐κB p65 levels remarkably in RAW264.7 cells. These data demonstrate the capacity of EPSAH to induce macrophage activation possibly via TLR4/MyD88 pathway, which leads to the activation of its main signaling downstream molecules MAPKs and NF‐κB.
Immunoglobulin superfamily beat‐Ib mediates intestinal regeneration induced by reactive oxygen species in Drosophila
Authors: Nagai Hiroki , Kurata Shoichiro , Yano Tamaki
Published: February 2020

Reactive oxygen species (ROS) often injure intestinal epithelia that cause loss of damaged cells, which is mainly repaired by proliferation of intestinal stem cells (ISCs). To maintain the homeostatic state, coordination of sensing of the ROS injury and the subsequent epithelial cell loss with the replenishment by cell renewal is crucial. However, little is known about how gut epithelial cells initiate regenerative responses against ROS to maintain the tissue integrity. Here, we carried out a genome‐wide screen, by which we identify immunoglobulin superfamily beaten path Ib (beat‐Ib) as an essential gene for provoking ISC proliferation against ROS in Drosophila intestine. Interestingly, the beat‐Ib function is required in differentiated enterocytes, the main targeted cells by ROS in the intestinal tract, but is dispensable in the stem cells. Moreover, beat‐Ib is not involved in enterocyte apoptosis at ROS injury. These findings indicate the essential role of beat‐Ib in Drosophila midgut enterocytes for initiating the non‐cell‐autonomous induction of ISC division in response to environmental ROS stresses.
A single centre retrospective study of low dose prophylaxis with extended half‐life factor IX for severe haemophilia B
Authors: Rampotas Alexandros , Desborough Michael J. R. , Raza‐Burton Sayma , Taylor Stephanie , Wilkinson Alice , Hall Georgina W , Shapiro Susan , Curry Nicola
Published: February 2020

Introduction

Extended half‐life factor IX concentrates (EHL‐FIX) can be administered weekly to prevent bleeding for persons with severe haemophilia B. We report the experience of a large UK haemophilia comprehensive care centre using low dose EHL‐FIX for persons with severe haemophilia B.

Aim

The low doses used in real world are approximately half of the doses used in clinical trials. We aim to assess the efficacy and safety of low dose EHL‐FIX.

Methods

Data from a cohort of 13 patients who were switched from standard half‐life factor IX (SHL‐FIX) to Alprolix® (mean dose 31.5 IU/kg) and seven patients who switched from standard half‐life factor IX to Idelvion® (mean dose 20.2 IU/kg) were included.

Results

The median annualized bleeding rate was similar for SHL‐FIX (median 3, interquartile range [IQR] 1‐5) and EHL‐FIX (median 3, IQR 1‐5.25). Quality of life scores, measured using the European Quality of Life 5 Dimensions assessment were similar for SHL‐FIX (median 0.76, IQR: 0.63‐0.84) and EHL‐FIX (median 0.79, IQR: 0.58‐0.88).

Conclusion

This study shows that EHL‐FIX given at low doses can be effective for prevention of bleeding for persons with severe haemophilia B.
Deregulation and institutional conversion in the Greek hotel industry: an employment relations model in transition
Authors: Papadopoulos Orestis , Lyddon Dave
Published: February 2020

Before the debt crisis of 2010 forced Greece into almost permanent austerity, its hotel workers enjoyed wages and conditions (through a sector collective agreement) similar to those in other economic sectors. This was against the international trend where low wages and poor conditions were standard. Sweeping deregulation by Greek governments has brought much of the hotel industry into line with other countries. The sector agreement, now covering a much smaller proportion of the workforce, survived but has experienced ‘institutional conversion’, delivering a much poorer outcome. Despite buoyant tourism, institutional deregulation and derogation have delivered the employers' major objective of matching the workforce to the fluctuating demand for labour.
Nutritional and bone health status in young men with mild‐to‐moderate intellectual disability and without intellectual disability residing in community setting in Malaysia
Authors: Jamil Nor Aini , Jia Ling Chang , Md Ibrahim Hawa Izzati , Hamzaid Nur Hana , Chin Kok Yong
Published: February 2020

Background

This study aimed to compare the nutritional and bone health status between young men with mild‐to‐moderate intellectual disability and those without intellectual disability and to determine predictors for their bone health status.

Method

A total of 95 men (47 men with intellectual disability; 48 men without intellectual disability), aged 20–39 years, participated in this study. Anthropometric profile, dietary intake, physical activity level and calcaneal speed of sound (SOS) were collected.

Results

The men with intellectual disability had moderate diet quality whilst the men without intellectual disability had poor diet quality. More participants with intellectual disability (97.9%) were inactive compared with their counterparts (10.4%). The SOS value was similar between groups and was lower than the reference. Increasing age and low physical activity level were negative predictors for bone health status.

Conclusion

Both young men with and without intellectual disability have suboptimal nutritional and bone health status. Strategies to improve their nutritional and bone health status are warranted.
Predictive model for growth of Salmonella Newport on Romaine lettuce
Authors: Oscar Thomas P.
Published: February 2020

Cross‐contamination of ready‐to‐eat (RTE) salad vegetables with Salmonella from raw chicken followed by growth during meal preparation are important risk factors for human salmonellosis. To better predict and manage this risk, a model (general regression neural network) for growth of a chicken isolate of Salmonella Newport (0.91 log) on Romaine lettuce (0.18 g) at times (0–8 hr) and temperatures (16–40°C) observed during meal preparation was developed with Excel, NeuralTools, and @Risk. Model performance was evaluated using the acceptable prediction zones (APZ) method. The proportion of residuals in the APZ (pAPZ) was 0.93 for dependent data (n = 210) and 0.93 for independent data (n = 72) for interpolation. A pAPZ ≥0.70 indicates acceptable model performance. Thus, the model was successfully validated for interpolation and can be used with confidence to predict and manage this important risk to public health.
Refining Trauma‐Informed Perinatal Care for Urban Prenatal Care Patients with Multiple Lifetime Traumatic Exposures: A Qualitative Study
Authors: Gokhale Priyanka , Young Maria R. , Williams Makayla N. , Reid Shayla N. , Tom Laura S. , O'Brian Catherine A. , Simon Melissa A.
Published: February 2020

Introduction

Because lifetime trauma exposure has been linked to multiple adverse pregnancy outcomes, there is a need for all perinatal care providers to be versed in trauma‐informed care practices. However, there are few data to guide trauma‐informed practice during the perinatal period. The objective of this study was to refine ongoing development of a trauma‐informed care framework for perinatal care by conducting a qualitative study of all trauma experiences and preferred screening practices of pregnant patients at an urban prenatal clinic.

Methods

In this qualitative study, we conducted semistructured interviews with 30 women receiving prenatal care at an urban clinic. Participants also completed a trauma history questionnaire. Inductive coding was used to generate themes and subthemes.

Results

Participants described multiple lifetime traumatic exposures as well as background exposure to community violence. Not all participants desired routine trauma screening; factors limiting disclosure included fear of retraumatization and belief that prior trauma is unrelated to the current pregnancy. Strong therapeutic relationships were identified as critical to any trauma history discussion.

Discussion

This study supports a trauma‐informed care approach to caring for pregnant women with prior traumatic exposures, including trauma screening without retraumatization and trusting patient‐provider relationships.
Anosognosia for limb and bucco‐facial apraxia as inferred from the recognition of gestural errors
Authors: Scandola Michele , Canzano Loredana , Avesani Renato , Leder Mara , Bertagnoli Sara , Gobbetto Valeria , Aglioti Salvatore M. , Moro Valentina
Published: February 2020

Anosognosia is a multifaceted syndrome characterized by a lack of awareness of motor, cognitive, or emotional deficits. While most studies have focused on basic motor disorders such as hemiplegia, only recently, the issue of whether anosognosia also concerns higher‐order motor disorders like apraxia has been addressed. Here, we explore the existence of a specific form of anosognosia for apraxia in forty patients with uni‐hemispheric vascular lesions. The patients were requested to imitate actions involving upper limb or bucco‐facial body parts and then judge their performance. Successively, they were also asked to observe video recordings of the same actions performed by themselves or by other patients and judge the accuracy of the displayed actions. The comparison of participants versus examiner judgement and between error recognition of others’ versus self’s actions was considered as an index of awareness deficit for the online and offline conditions, respectively. Evidence was found that awareness deficits occurred both immediately after action execution (online anosognosia) and in the video recording task (offline anosognosia). Moreover, bucco‐facial and limb apraxic patients were specifically unaware of their errors in bucco‐facial and limb actions, respectively, indicating for the first time a topographical organization of the syndrome. Our approach allowed us to distinguish awareness deficits from more general disorders in error recognition; indeed, anosognosic patients were able to identify errors when the same action was executed by another patient but not when the video showed their own actions. Finally, we provide evidence that anosognosia for apraxia might be associated with frontal cortical and subcortical networks.
Prognostic role of maspin expression in patients with cervical dysplasia and cervical cancer
Authors: Isci Bostanci Esra , Guler Ismail , Dikmen Asiye U. , Erdem Ozlem , Guner Haldun , Onan Mehmet Anil , Taskiran Cagatay
Published: February 2020

Aim

Mammary serine protease inhibitor (maspin) acts as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are increased in some types of malignant cells. The aim of this study was to investigate the maspin expression in cervical dysplasia and cervical cancer, and to analyze its' relation with survival.

Methods

Maspin expression was detected by immunohistochemistry using labeled streptavidin biotin method to determine cytoplasmic and nuclear maspin expressions in cervical intraepithelial neoplasia grade 1 (CIN1), cervical intraepithelial neoplasia grade 2 (CIN2), cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer.

Results

A total of 89 patients with CIN (29 cases of CIN1, 30 cases of CIN2 and 30 cases of CIN3), and 27 patients with cervical cancer were included to the study. 7.8% of the patients with CIN had maspin staining positivity. On the other hand maspin staining was positive in 20 of 27 patients (74.1%) with cervical carcinoma (P = 0.001). Of these patients 20 (100%) had cytoplasmic, and 8 (40%) had nuclear maspin staining positivity. Cytoplasmic maspin immunoreactive scores were found to be significantly higher in carcinoma group when compared to the patients with CIN1/3 (respectively; P = 0.01, P = 0.02). No difference was noted for nuclear maspin expression. Significant overall survival advantage was detected for patients with nuclear maspin staining (P = 0.03).

Conclusion

The current study shows that nuclear maspin expression is related with better overall survival in cervical cancer. Maspin staining can be a useful diagnostic marker to discriminate cervical intraepithelial neoplasia from cervical carcinoma.
The influence of tongue strength on children's performance in computer games reliant on lingual force generation
Authors: Furlan Renata Maria Moreira Moraes , Santana Guilherme André , Amaral Mariana Souza , Motta Andréa Rodrigues , de Las Casas Estevam Barbosa
Published: February 2020

Oral motor exercises, for recovering tongue strength, can be integrated with computer games to increase motivation, especially for treatments in children. The aim of this study was to investigate the influence of tongue strength on motor performance in computer games reliant on lingual force generation. An observational study was carried out at a speech‐language pathology outpatient university clinic. Twenty participants (10 with normal tongue strength and 10 with reduced tongue strength) aged 8‐13 years used an intra‐oral joystick controlled by the tongue to play six computer games during which they had to reach targets that appeared on the screen. Motor performance was measured by the number of attempts to score and the time during which the target force was maintained. Tongue motor performance was compared between groups and across directions of tongue movement, resistance force levels, order of target appearance, continuous force application time on the target, age and sex. Children with normal tongue strength had a lower number of attempts to score (P = .014) and maintained the target force for longer periods (P = .002) than those with reduced tongue strength. The performance was better for both groups (a) in the downward direction compared with the performance in other directions, (b) in games with the lowest resistive force level (0.5 N) compared to those with other levels of resistive force and (c) in the second and third rounds compared with the first round. There were no gender‐related differences in performance. Older participants performed better than younger participants. Tongue strength, direction of movement, force to reach the target, time of continuous force application, order of target appearance and age influenced tongue motor performance.
Three‐spined stickleback armour predicted by body size, minimum winter temperature and pH
Authors: Smith C. , Zięba G. , Spence R. , Klepaker T. , Przybylski M.
Published: February 2020

Similar phenotypes evolve under equivalent environmental conditions through parallel evolution. Because they have repeatedly invaded and adapted to new freshwater environments, the three‐spined stickleback (Gasterosteus aculeatus) offers a powerful system for understanding the agents of selection in nature that drive parallel evolution. Here, we examine the ecological and environmental variables responsible for morphological variation in three‐spined stickleback populations across its European range. We collected fish from 85 populations, encompassing much of the European latitudinal range of the species and including lowland rivers and lakes, coastal lagoons and moorland ponds. We measured biotic and environmental variables at all sites along with morphological traits for 2,358 individuals. Using an information theory approach, we identified body size, minimum average winter temperature and pH as primary predictors of stickleback armour evolution, challenging current hypotheses for stickleback morphological diversification and demonstrating the fundamental role played by body size and scaling in mediating responses to selection. Stickleback lateral plate phenotype represents a potentially powerful tool for monitoring change in climate variables across the northern temperate region.
Parallel adaptation to climate above the 35th parallel
Authors: Burns Robin , Novikova Polina Yu.
Published: February 2020

Independent or parallel evolution of similar traits is key to understanding the genetics and limitations of adaptation. Adaptation from the same genetic changes in different populations defines parallel evolution. Such genetic changes can derive from standing ancestral variation or de novo mutations and excludes instances of adaptive introgression. In this issue of Molecular Ecology, Walden et al.(2020) investigate the scale of parallel climate adaptation from standing genetic variation between two North American Arabidopsis lyrata lineages, each formed by a distinct evolutionary history during the last glacial cycle. By identifying adaptive variants correlated with three ecologically significant climatic gradients, they show that instead of the same genetic variants or even genes, parallel evolution is only observed at the level of biological processes. The evolution of independent adaptive variants to climate in two genetically close lineages is explained by their different post‐glacial demographic histories. Separate glacial refugia and strong population bottlenecks were probably sufficient to change the landscape of shared allele frequencies, hindering the possibility of parallel evolution.
New landscapes: Thinking beyond community in the conceptualisation of online medical education
Authors: Rashid Ahmed , Alexander Kirsty , Griffin Ann
Published: February 2020

When are Communities of Practice not enough? Rashid argues that this influential model ignores important complexity in medical education and highlights the concept of Landscapes of Practice as a way to better conceptualize modern training environments.
Lessons from the implementation of developmental progress assessment: A scoping review
Authors: St‐Onge Christina , Vachon Lachiver Élise , Langevin Serge , Boileau Elisabeth , Bernier Frédéric , Thomas Aliki
Published: February 2020

Objectives

Educators and researchers recently implemented developmental progress assessment (DPA) in the context of competency‐based education. To reap its anticipated benefits, much still remains to be understood about its implementation. In this study, we aimed to determine the nature and extent of the current evidence on DPA, in an effort to broaden our understanding of the major goals and intended outcomes of DPA as well as the lessons learned from how it has been executed in, or applied across, educational contexts.

Methods

We conducted a scoping study based on the methodology of Arksey and O’Malley. Our search strategy yielded 2494 articles. These articles were screened for inclusion and exclusion (90% agreement), and numerical and qualitative data were extracted from 56 articles based on a pre‐defined set of charting categories. The thematic analysis of the qualitative data was completed with iterative consultations and discussions until consensus was achieved for the interpretation of the results.

Results

Tools used to document DPA include scales, milestones and portfolios. Performances were observed in clinical or standardised contexts. We identified seven major themes in our qualitative thematic analysis: (a) underlying aims of DPA; (b) sources of information; (c) barriers; (d) contextual factors that can act as barriers or facilitators to the implementation of DPA; (e) facilitators; (f) observed outcomes, and (g) documented validity evidences.

Conclusions

Developmental progress assessment seems to fill a need in the training of future competent health professionals. However, moving forward with a widespread implementation of DPA, factors such as lack of access to user‐friendly technology and time to observe performance may render its operationalisation burdensome in the context of competency‐based medical education.
How do local differences in saltmarsh ecology influence disease vector mosquito populations?
Authors: Rowbottom R. , Carver S. , Barmuta L. A. , Weinstein P. , Allen G. R.
Published: February 2020

Saltmarsh breeding mosquitoes are an important source of vectors for arboviral transmission. In southern Australia, the most prominent vector borne disease, Ross River virus (Togaviridae: Alphavirus) (RRV), is transmitted by the saltmarsh mosquito (Diptera: Culicidae) Aedes camptorhynchus (Thomson). However, the factors driving the abundance of this mosquito within and among saltmarshes are poorly understood. To predict the abundance of this mosquito within saltmarshes, the environmental conditions and aquatic invertebrate ecology of three temperate saltmarshes habitats were monitored over two seasons. Up to 44% of first‐instar mosquito numbers and 21% of pupal numbers were accounted for by environmental variables. Samphire vegetation cover was a common predictor of first‐instar numbers across sites although, between saltmarshes, aquatic factors such as high salinity, temperatures less than 22 °C and water body volume were important predictors. The identified predictors of pupal numbers were more variable and included high tides, waterbody volume and alkalinity. The composition of invertebrate functional feeding groups differed between saltmarshes and showed that an increased diversity led to fewer mosquitoes. It was evident that apparently similar saltmarshes can vary markedly in invertebrate assemblages, water availability and conditions through tidal inundations, rainfall or waterbody permanency. The present study advances insight into predictors of vector mosquito numbers that drive the risk of RRV outbreaks.
Laser therapy versus topical desensitising agents in the management of dentine hypersensitivity: A meta‐analysis
Authors: Zhou Kaiyan , Liu Qiulin , Yu Xueting , Zeng Xiaojuan
Published: February 2020

Objectives

To compare the effectiveness of lasers and topical desensitising agent treatments for dentine hypersensitivity.

Methods

PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and ISI Web of Knowledge were electronically searched without restrictions. Study search, selection, data extraction and assessment of risk of bias were conducted independently by two reviewer authors. All analyses were performed using Review Manager 5.3 (Cochrane Collaboration).

Results

This meta‐analysis included 13 eligible studies that compared topical desensitising agents and Nd:YAG or diode laser. Four, six and three studies were considered to have low, moderate and high risks of bias, respectively. The follow‐up period varied from immediate to 9 months. All comparisons except the 3‐month Nd:YAG laser parallel group and 6‐month diode laser group showed that the clinical efficacy of lasers for dentine hypersensitivity was not significantly different with topical desensitising agents.

Conclusion

We found low‐quality evidence that was insufficient to draw any conclusions regarding the superiority of lasers or conventional topical desensitising agents in the treatment of DH. Further well‐designed RCTs on this topic are needed to draw definitive conclusions.
Anionic Conjugated Polyelectrolytes for FRET‐based Imaging of Cellular Membrane Potential
Authors: Nag Okhil K. , Jeong Ji‐Eun , Le Van Sang , Oh Eunkeu , Woo Han Young , Delehanty James B.
Published: February 2020

We report a Förster resonance energy transfer (FRET)‐based imaging ensemble for the visualization of membrane potential in living cells. A water‐soluble poly(fluorene‐cophenylene) conjugated polyelectrolyte (FsPFc10) serves as a FRET donor to a voltage‐sensitive dye acceptor (FluoVolt™). We observe FRET between FsPFc10 and FluoVolt™, where the enhancement in FRET‐sensitized emission from FluoVolt™ is measured at various donor/acceptor ratios. At a donor/acceptor ratio of 1, the excitation of FluoVolt™ in a FRET configuration results in a three‐fold enhancement in its fluorescence emission (compared to when it is excited directly). FsPFc10 efficiently labels the plasma membrane of HEK 293T/17 cells and remains resident with minimal cellular internalization for ~ 1.5 h. The successful plasma membrane‐associated colabeling of the cells with the FsPFc10‐FluoVolt™ donor‐acceptor pair is confirmed by dual‐channel confocal imaging. Importantly, cells labeled with FsPFc10 show excellent cellular viability with no adverse effect on cell membrane depolarization. During depolarization of membrane potential, HEK 293T/17 cells labeled with the donor‐acceptor FRET pair exhibit a greater fluorescence response in FluoVolt™ emission relative to when FluoVolt™ is used as the sole imaging probe. These results demonstrate the conjugated polyelectrolyte to be a new class of membrane labeling fluorophore for use in voltage sensing schemes.
Do red cell alloantibodies continue to challenge breast fed babies?
Authors: Rasalam Jess E. , Kumar Snehil , Amalraj Pushpanathan , Bal Harshjeet S. , Mathai John , Kumar Manish , Sridhar Santhanam , Daniel Dolly
Published: February 2020

Background

Newborns have limited specific immune capability at birth, owing to delayed and constrained development of adaptive immunity. To supplement this period the mother passively transfers antibodies to the child either transplacentally or through breast milk. When maternal alloimmunisation occurs through foreign or fetal red cell surface antigens, stimulating the production of immunoglobulin G (IgG) antibodies, these IgG antibodies can cross the placenta and cause haemolytic disease of the fetus and the newborn.

Objective

We present two case reports of a neonate and an infant in whom IgG red cell alloantibodies were transferred through maternal breast milk.

Methods

Maternal serum, baby's serum and expressed breast milk samples were tested for the presence of red cell alloantibodies using gel card. Antibody screening, antibody identifications and titres alongside monospecific direct antiglobulin test, IgG subtypes were performed using the standard methods.

Results

In the first case, a 6‐month‐old child was incidentally found to have positive antibody screen. Anti‐KELL1 was identified, which was also present in maternal serum and breast milk. The second neonate was evaluated for haemolysis and was found to have anti‐D. Anti‐D was also detected in the maternal serum and breast milk. Both babies did not have any sensitising events. The first baby was asymptomatic, but the second baby had ongoing haemolysis until 1 month.

Conclusion

We report that maternal anti‐KELL1 and anti‐D antibodies were present in breast milk and were capable of being transferred to a feeding child. Our case report also raises interesting and unanswered immunologic fundamentals that should be considered in neonates with unexplained anaemia or delayed and persistent haemolysis.
Deaths and complications associated with the management of acute immune thrombotic thrombocytopenic purpura
Authors: Colling Meaghan , Sun Lova , Upadhyay Vivek , Ryu Justine , Li Ang , Uhl Lynne , Kaufman Richard M. , Stowell Christopher P. , Dzik Walter H. , Makar Robert S. , Bendapudi Pavan K.
Published: February 2020

BACKGROUND

The introduction of therapeutic plasma exchange (TPE) dramatically decreased mortality in patients with immune thrombotic thrombocytopenic purpura (iTTP). However, there are few modern descriptions of residual causes of death from iTTP and complications associated with TPE.

STUDY DESIGN AND METHODS

This was a retrospective study in a multi‐institutional cohort of 109 patients with iTTP between 2004 and 2017. Complications of TPE were analyzed in a subset of this cohort (74 patients representing 101 treatment courses).

RESULTS

Death occurred in 8 of 109 patients (7.3%) and in 8 of 219 captured episodes of acute iTTP (mortality rate per episode: 3.7%). Neither the number of TPE treatments nor length of hospitalization predicted mortality. The majority of deaths (5/8) were associated with delay in the diagnosis of iTTP or initiation of TPE or presentation to the hospital in a moribund state. A subset of patients (N = 74) was analyzed for TPE‐related complications. Most patients (56/74; 76%) had at least one minor or major complication of TPE. Seven of 101 (6.9%) discrete treatment courses were associated with one or more severe complications, including anaphylaxis and line‐associated infections and thrombosis. Overall, the most frequent adverse events were mild allergic (urticarial) transfusion reactions, which affected 34 of 101 (34%) treatment courses. One patient died from a TPE‐related complication, line‐associated bacteremia.

CONCLUSION

Early identification of patients with iTTP and the rapid initiation of TPE are paramount in preventing mortality. While TPE was associated with a high rate of adverse events, the vast majority were treatable and TPE‐related mortality is low.
Evaluation of partial tarsal plate excision using a transconjunctival approach for the treatment of distichiasis in dogs
Authors: Palella Gómez Alberto , Mazzucchelli Samuela , Scurrell Emma , Smith Kinley , Pinheiro de Lacerda Rodrigo
Published: February 2020

Purpose

To evaluate the clinical outcome, possible complications, and recurrence rate of distichiasis in dogs treated with partial tarsal plate excision (PTPE) technique using a transconjunctival approach.

Methods

Retrospective study including 17 client‐owned canine patients affected with distichiasis and presenting with associated clinical signs (ie, blepharospasm, epiphora, chronic keratoconjunctivitis, or corneal ulceration) that underwent surgical removal of the aberrant lashes using a PTPE technique between January 2018 and February 2019. Data collected included breed, age, sex, affected eyelid(s), number of distichia, and tear film breakup time (TBUT). Resected cilia‐bearing tarsoconjunctival strips were submitted for histopathological analysis.

Results

Thirty eyes (52 eyelids) from 17 dogs were included in the study. The median age was 688 days (range 118‐4243 days). A successful outcome, defined as complete resolution of clinical signs attributable to the distichia, occurred in all eyes after a single procedure, with a mean follow‐up time of 239 days (range 69‐480 days). Appearance of new distichia occurred in 14/30 eyes (46.3%), and of these, three eyes needed a new PTPE procedure. Recurrence of the distichia only occurred in one eye (3.3%) which was asymptomatic. Following surgery, TBUT decreased below the normal value in 7/24 eyes (29.1%) although none developed clinical signs of qualitative tear film deficiency. Post‐operative complications included trichiasis and cicatricial entropion, which developed in two eyes (6.6%), and these were successfully managed with corrective eyelid surgery.

Conclusions

Partial tarsal plate excision, using a transconjunctival approach, had an excellent clinical outcome with a low incidence of complications.