bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic balloon dilation for gastrojejunal anastomotic stricture after Roux‐en‐Y gastric bypass: A case series
Authors: Chen Wen‐Hsu , Chen I‐Sung , Chen Tzu‐Haw , Hsu Ming‐Hung , Tsai Ying‐Nan , Tai Chi‐Ming
Published: April 2021

Roux‐en‐Y gastric bypass (RYGB) is an effective bariatric procedure but is encountered with gastrojejunal (GJ) anastomotic stricture as a major complication. We aimed to evaluate the efficacy and complications of endoscopic balloon dilation in the management of GJ anastomotic stricture after RYGB. Patients who underwent balloon dilation for GJ anastomotic stricture secondary to RYGB between March 2009 and April 2013 in E‐Da hospital were reviewed retrospectively. A smaller balloon size (8 mm) was routinely chosen initially and the balloon size was increased gradually. Dilation was stopped if the patients felt abdominal pain or up to 15 mm in size. Thirteen patients (nine men and four women) with a median age of 26 years (range 20‐42 years) and a median body mass index of 41.5 kg/m2 (range 35.3‐65.4 kg/m2) were enrolled. Anastomotic size ranged from 1 to 4 mm. The median interval between surgery and the first dilation was 43 days (range 20‐112 days). Nine patients (69.2%) required only one dilation, three (23.1%) required two dilations, and one (7.7%) required three dilations. Seven patients (53.8%) had anastomotic ulcers. Two patients had perforation and were treated conservatively. Twelve patients (92.3%) were successfully treated by balloon dilation. One patient was found to have a total obstruction 4 months after the first dilation and underwent operation. This study suggests that endoscopic balloon dilation is effective in the management of GJ anastomotic stricture after RYGB and most of the patients responded to one dilation session. Although perforation occurred, it can be treated conservatively in our case series.
Surface engineering of biomaterials in orthopedic and dental implants: Strategies to improve osteointegration, bacteriostatic and bactericidal activities
Authors: Liu Ziqian , Liu Xiaoling , Ramakrishna Seeram
Published: April 2021

Background

The success of biomedical implants in orthopedic and dental applications is usually limited due to insufficient bone‐implant integration, and implant‐related infections. Biointerfaces are critical in regulating their interactions and the desirable performance of biomaterials in biological environment. Surface engineering has been widely studied to realize better control of the interface interaction to further enhance the desired behavior of biomaterials.

Purpose and Scope

This review aims to investigate surface coating strategies in hard tissue applications to address insufficient osteointegration and implant‐related infection problems.

We first focused on surface coatings to enhance the osteointegration and biocompatibility of implants by emphasizing calcium phosphate‐related, nanoscale TiO2‐related, bioactive tantalum‐based and biomolecules incorporated coatings. Different coating strategies such as plasma spraying, biomimetic deposition, electrochemical anodization and LENS are discussed. We then discussed techniques to construct anti‐adhesive and bactericidal surface while emphasizing multifunctional surface coating techniques that combine potential osteointegration and antibacterial activities. The effects of nanotopography via TiO2 coatings on antibacterial performance are interesting and included. A smart bacteria‐responsive titanium dioxide nanotubes coating is also attractive and elaborated.

Conclusion

Developing multifunctional surface coatings combining osteogenesis and antimicrobial activity is the current trend. Surface engineering methods are usually combined to obtain hierarchical multiscale surface structures with better biofunctionalization outcomes.
Synthetic logic circuits using RNA aptamer against T7 RNA polymerase
Authors: Kim Jongmin , Quijano Juan F. , Kim Jeongwon , Yeung Enoch , Murray Richard M.
Published: April 2021

Recent advances in nucleic acids engineering introduced several RNA‐based regulatory components for synthetic gene circuits, expanding the toolsets to engineer organisms. In this work, we designed genetic circuits implementing an RNA aptamer previously described to have the capability of binding to the T7 RNA polymerase and inhibiting its activity in vitro. We first demonstrated the utility of the RNA aptamer in combination with programmable synthetic transcription networks in vitro. As a step to quickly assess the feasibility of aptamer functions in vivo, we tested the aptamer and its sequence variants in the cell‐free expression system, verifying the aptamer functionality in the cell‐free testbed. The expression of aptamer in E. coli demonstrated control over GFP expression driven by T7 RNA polymerase, indicating its ability to serve as building blocks for logic circuits and transcriptional cascades. This work elucidates the potential of T7 RNA polymerase aptamer as regulators for synthetic biological circuits and metabolic engineering.
Social Worker and Midwife Decision Making Regarding Child Protection Risk and the Unborn Baby: A Qualitative Study
Authors: Mc Elhinney Helena , Sinclair Marlene , Taylor Brian
Published: April 2021

A newborn baby is vulnerable to abuse and neglect, and the professional role may involve assessment before the baby is born. The aim of this paper is to explore the perspectives and experiences of midwives and child protection social workers regarding the protection of unborn babies within Northern Ireland. Data were gathered using four focus groups (14 midwives and 16 child protection social workers) within one Health and Social Care Trust. The data were analysed in terms of understanding risk factors and forming a professional judgement. The mental wellbeing of the pregnant woman, drug use, alcohol use, domestic violence, the pregnant woman's childhood experiences, gestation period and antenatal care attendance were the main risks identified. Observations, engaging with the pregnant woman and using ‘soft intelligence’ were key aspects in forming a professional judgement. The appraisal of the ability of the pregnant woman to recognise danger was an important moderating factor, and perhaps formed part of a professional judgement heuristic to assist in making sense of wide‐ranging information about diverse risks.

‘Explore[s] the perspectives and experiences of midwives and child protection social workers regarding the protection of unborn babies within Northern Ireland’

Key Practitioner Messages

Identified risk factors included mental wellbeing, age, feelings about the pregnancy, drug and alcohol use, domestic violence, the pregnant woman's childhood experiences, gestation period and antenatal care attendance.

Pregnant women were unable to recognise the dangers in misusing illegal or prescription drugs, excessive alcohol consumption and initiating/maintaining relationships with sex offenders.

Key skills in forming a professional judgement involved engagement with the pregnant woman, professionals' experience and observations, and the use of ‘soft intelligence’.
Dermatofibrosarcoma protuberans in a child, that’s why soft tissue lesions are not always innocent in children
Authors: Kambouri Katerina , Chatzipantelis Paschalis , Foutzitzi Soultana , Dimitriadou Chrysavgi , Aggelidou Maria , Giatromanolaki Alexandra , Deftereos Savas
Published: April 2021

Pediatric soft tissue tumors should be always operated and sent for a biopsy.
Many‐objective evolutionary computation based on adaptive hypersphere dynamic angle vector dominance
Authors: Yu Weiwei , Zhang Li
Published: April 2021

In real‐world, more and more MaOP (MaOPs) have emerged, which pose great challenge for traditional multi‐objective evolutionary algorithms (MOEAs). In this paper, a many‐objective evolutionary computation based on adaptive hypersphere dynamic angle vector dominance (AHDAVD‐MOEA) is proposed. The AHDAVD‐MOEA has three remarkable characteristics: (1) Based on the angle domination, a dynamic angle vector dominance relationship is proposed. In the evolution process, DAVD can dynamically adjust the population target space coordinate system according to the distribution of each generation of population in the target space, and at the same time calculate the angle vector of individuals to compare the dominance relations. Therefore, DAVD can dynamically describe the convergence and diversity of population, so as to achieve the goal of balancing the convergence and diversity of many target population. (2) Based on DAVD, an adaptive hypersphere dynamic angle vector dominance (AHDAVD) is proposed. After the DAVD process, AHDAVD adds an adaptive radiusRto all dimensions of each non‐dominated solution to form a hypersphere to expand the dominance range of individuals. The dominance relationship among individuals is judged by the dominance range of the extended solution individuals, which further enhances the convergence of the population. (3) Based on the simplified harmonic normalized distance method, a simplified harmonic normalized distance method (SHNDM‐Lp) based onLp‐norm (Wherepis set to 1/M, andMis the target number) is proposed. SHNDM‐Lpuses Euclidean distance to measure the distance between individuals in many space, and uses fractional normal form to evaluate the proximity distance of solution individuals in many target space more effectively. The validity of the adaptive hypersphere dynamic angle vector dominance and the AHDAVD‐MOEA are tested by DTLZ and WFG series of 5‐, 8‐ and 10‐targets. The experimental results show that: (1) Compared with AD and other representative improved dominance relations, the adaptive hypersphere dynamic angle vector dominance relationship has significantly better performance; (2) Compared with other five classical many‐objective evolutionary algorithms, AHDAVD‐MOEA has obvious advantages in population convergence and diversity. Overall, the proposed AHDAVD‐MOEA is a promising optimizer in many‐objective optimization.
Hybrid grass bee optimization‐multikernal extreme learning classifier: Multimodular fusion strategy and optimal feature selection for multimodal sentiment analysis in social media videos
Authors: Alqahtani Abdullah Saleh , Pandiaraj Saravanan , Murali Maheswari , Alshmrany Sami , Alsarrayrih Haytham
Published: April 2021

Presently, large recordings like audio and video are uploaded each day on the public networks particularly Facebook, YouTube, etc. Such postings generate unlimited data via the Internet. Over the next few decades adapting and dealing with data mining to obtain relevant details from social media is considered as a difficult task. To tackle these challenges, a novel text‐audio‐video consistency‐driven multimodal sentiment analysis method is proposed in this paper. This proposed system examines the correlation among the text, audio and video followed by multimodal sentiment analysis. A different set of features are extracted and then the extracted features are chosen optimally by employing a new hybrid grass bee optimization algorithm (HGBEE) thus obtaining a feature set containing an optimal value for better precision and low computational time. Then an utterance level multimodular fusion regarding text, audio, and video features is developed. Finally, the proposed multikernal extreme learning classifier (MKELM) is employed for sentiment classification. Then the proposed system is evaluated by testing with three multimodal datasets in terms of precision, accuracy, recall, and F‐measure, respectively. From the simulation, it is clear that the proposed system accomplishes the maximum classification accuracy value of 98.3% with minimum computation time. The implementation of our proposed approach is done under the MATLAB platform.
The insular herpetofauna of Mexico: Composition, conservation, and biogeographic patterns
Authors: Pliego‐Sánchez Juan Valentín , Blair Christopher , Díaz de la Vega‐Pérez Aníbal H. , Jiménez‐Arcos Víctor H.
Published: April 2021

We compile a Mexican insular herpetofaunal checklist to estimate endemism, conservation status, island threats, net taxonomic turnover among six biogeographic provinces belonging to the Nearctic and Neotropical regions, and the relationships between island area and mainland distance versus species richness. We compile a checklist of insular herpetofaunal through performing a literature and collection review. We define the conservation status according to conservation Mexican law, the Red List of International Union for Conservation of Nature, and Environmental Vulnerability Scores. We determine threat percentages on islands according to the 11 major classes of threats to biodiversity. We estimate the net taxonomic turnover with beta diversity analysis between the Nearctic and Neotropical provinces. The Mexican insular herpetofauna is composed of 18 amphibian species, 204 species with 101 subspecies of reptiles, and 263 taxa in total. Endemism levels are 11.76% in amphibians, 53.57% in reptiles, and 27.91% being insular endemic taxa. Two conservation status systems classify the species at high extinction risk, while the remaining system suggests less concern. However, all systems indicate species lacking assessment. Human activities and exotic alien species are present on 60% of 131 islands. The taxonomic turnover value is high (0.89), with a clear herpetofaunal differentiation between the two biogeographic regions. The species–area and species–mainland distance relationships are positive. Insular herpetofauna faces a high percentage of threats, with the Neotropical provinces more heavily impacted. It is urgent to explore the remaining islands (3,079 islands) and better incorporate insular populations and species in ecological, evolutionary, and systematic studies. In the face of the biodiversity crisis, islands will play a leading role as a model to apply restoration and conservation strategies.
Solutions proposed for socio‐environmental conflicts and concerning multiple‐use hydroelectric reservoirs in Brazil
Authors: Siqueira Fernanda B. , dos Santos Marco Aurélio
Published: April 2021

Hydropower reservoirs designed and/or operated to provide multiple services beyond power generation are called multiple‐use reservoirs. However, their construction has social and environmental impacts that require technical knowledge, social discussion, and acceptance by the public. The present paper analyzes the roles of the strategic environmental assessment and the hydroelectric inventory studies, as well as proposes alternatives for water distribution. The purpose of this study is to focus on the initial phases of hydropower planning, with the aid of the SHARE concept, in order to avoid future conflicts in the use of water resources. Although the instruments analyzed provide for the participation of different sectors, there is still little integration and alignment with sectoral policies (electrical and environmental) or there is no institutionalization of them, which makes this an urgent problem. The diagnosis resulting from this study is that the situation of multiple‐uses reservoirs in Brazil still deserves significant advances. As a proposal for improving the framework, this study claims that the use of integrated planning between sectors that use water resources should be improved by applying new concepts of integrated planning, such as the SHARE concept.
Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis: A 2-Year Randomized Study
Authors: Sølling Anne Sophie , Harsløf Torben , Langdahl Bente
Published: April 2021

Increased bone turnover and rapid bone loss follow discontinuation of denosumab. We investigated the long-term efficacy of zoledronate (ZOL) in maintaining bone mineral density (BMD) after discontinuation of denosumab. In this randomized, open-label, interventional study, we included 61 postmenopausal women and men older than 50 years discontinuing denosumab after 4.6 ± 1.6 years. We administered ZOL 6 months (6 M) or 9 months (9 M) after the last denosumab or when bone turnover had increased (observation group [OBS]). ZOL was readministrated if p-cross-linked C-terminal telopeptide (p-CTX) increased ≥1.26 μg/L or BMD decreased ≥5%. The results after 12 months have previously been published; here we report the outcome after 24 months (ClinicalTrials NCT03087851). Fifty-eight patients completed the study. From 12 to 24 months after the initial ZOL, lumbar spine (LS) BMD was maintained: 0.9 ± 0.9%, 0.4 ± 0.8%, and 0.3 ± 0.7% in the 6 M, 9 M, and OBS groups, respectively (p > .05, no between-group differences). Similarly, total hip (TH) and femoral neck (FN) BMD did not change in any group during year 2. From baseline to 24 months after ZOL, LS BMD decreased by 4.0 ± 0.8%, 4.1 ± 0.8%, and 4.3 ± 1.5% in the 6 M, 9 M, and OBS groups, respectively (p < .001, no between-group differences). Significant bone loss (LS, TH, or FN) was found in all groups 24 months after ZOL: 6 M group: n = 12 (60%), 9 M group: n = 7 (37%), and OBS group: n = 10 (53%). P-CTX did not change significantly during the second year (p > .05, no between-group differences). No patient fulfilled the CTX or fracture criteria for retreatment during year 2; however, 9 patients were retreated at M24 due to BMD loss ≥5%. Two patients sustained a non-vertebral fracture during year 2. Treatment with ZOL subsequent to long-term denosumab did not fully prevent increased bone turnover and bone loss during the first year; however, CTX remained with the reference range and BMD was maintained during the second year. © 2021 American Society for Bone and Mineral Research (ASBMR).
A combination of ssGSEA and mass cytometry identifies immune microenvironment in muscle‐invasive bladder cancer
Authors: Wang Xi , Pan Lixin , Lu Qinchen , Huang Haoxuan , Feng Chao , Tao Yuting , Li Zhijian , Hu Jiaxin , Lai Zhiyong , Wang Qiuyan , Tang Zhong , Xie Yuanliang , Li Tianyu
Published: April 2021

Background

Muscle‐invasive bladder cancer (MIBC) is a heterogeneous disease with varying clinical courses and responses to treatment. To improve the prognosis of patients, it is necessary to understand such heterogeneity.

Methods

We used single‐sample gene set enrichment analysis to classify 35 MIBC cases into immunity‐high and immunity‐low groups. Bioinformatics analyses were conducted to compare the differences between these groups. Eventually, single‐cell mass cytometry (CyTOF) was used to compare the characteristics of the immune microenvironment between the patients in the two groups.

Results

Compared with patients in the immunity‐low group, patients in the immunity‐high group had a higher number of tumor‐infiltrating immune cells and greater enrichment of gene sets associated with antitumor immune activity. Furthermore, positive immune response‐related pathways were more enriched in the immunity‐high group. We identified 26 immune cell subsets, including cytotoxic T cells (Tcs), helper T cells (Ths), regulatory T cells (Tregs), B cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs) using CyTOF. Furthermore, there was a higher proportion of CD45+ lymphocytes and enrichment of one Tc subset in the immunity‐high group. Additionally, M2 macrophages were highly enriched in the immunity‐low group. Finally, there was higher expression of PD‐1 and Tim‐3 on Tregs as well as a higher proportion of PD‐1+ Tregs in the immunity‐low group than in the immunity‐high group.

Conclusion

In summary, the immune microenvironments of the immunity‐high and immunity‐low groups of patients with MIBC are heterogeneous. Specifically, immune suppression was observed in the immune microenvironment of the patients in the immunity‐low group.
Persistent bilateral breast pain treated with traditional Kampo medicine
Authors: Iwata Kentaro , Nishimoto Takashi
Published: April 2021

A 45‐year‐old woman presented with persistent bilateral breast and axillary pain lasting for more than 3 months. Lengthy work‐up failed to identify the etiology. Physical examination was entirely normal, including breast examination. A traditional Kampo medicine, Goshaku‐san, was tried, and the symptoms began to improve gradually. This case is characterized by persistent regional pain syndrome mainly on her breast yet not accompanied by other symptoms, and we would like to propose the current case as a novel unique disease entity. We also discuss the potential benefit of Kampo medicine for the symptoms.
Balanced supersaturation for some degenerate hypergraphs
Authors: Corsten Jan , Tran Tuan
Published: April 2021

A classical theorem of Simonovits from the 1980s asserts that every graph satisfying must contain copies of . Recently, Morris and Saxton established a balanced version of Simonovits' theorem, showing that such has copies of , which are “uniformly distributed” over the edges of . Moreover, they used this result to obtain a sharp bound on the number of ‐free graphs via the method of hypergraph containers. In this article, we generalise Morris–Saxton's results for even cycles to ‐graphs. We also prove analogous results for complete ‐partite ‐graphs.
Revisiting Mednick’s (1962) Theory of Creativity with a Composite Measure of Creativity: The Effect of Stimulus Type on Word Association Production
Authors: Vitrano Deana , Altarriba Jeanette , Leblebici‐Basar Deniz
Published: April 2021

S.A. Mednick (1962) proposed a theory of creativity suggesting that highly creative individuals can produce more word associations to a stimulus than less creative individuals. Numerous studies have supported this theory using the Remote Associates Test (RAT) as the measure of creativity. Additionally, some studies have suggested that high‐frequency words elicit more word associations overall than low‐frequency words, and concrete words elicit more associations overall than abstract words. The current study further investigated Mednick’s theory by (a) creating controlled lists of stimuli that can better uncover how word type (abstract versus concrete) and word frequency (high versus low) affect the number of word associations produced to a stimulus, (b) including several creativity tasks besides the RAT, and (c) examining the role of other factors in creative thinking, including intelligence and verbal fluency. Participants first completed a word association task with four different types of words (i.e., high‐frequency concrete, low‐frequency concrete, high‐frequency abstract, and low‐frequency abstract), and then completed a variety of tasks, including several creativity tasks. Participants were categorized as highly creative or less creative based on a composite measure of the creativity tasks. Highly creative individuals produced more associations overall, supporting Mednick’s theory. Furthermore, high‐frequency stimuli resulted in higher overall associative responses compared to low‐frequency stimuli, but contrary to previous research, no differences emerged for concrete versus abstract stimuli. There was also no difference in intelligence scores between the two creativity groups, and only a marginally significant difference in verbal fluency scores.
Reduced pests, improved grain quality and greater total income: benefits of intercropping rice with Pontederia cordata
Authors: Xiang Huimin , Lan Ni , Wang Fugang , Zhao Benliang , Wei Hui , Zhang Jiaen
Published: April 2021

BACKGROUND

Intercropping, which is growing two or more different crops in the same field simultaneously, is an effective traditional agricultural practice for productivity, resource utilization, and pest control. However, study on intercropping in paddy fields is limited. So in this study, field experiments of 2 years/four seasons (early and late seasons in 2016 and 2017) were conducted to examine the effects of rice‐Pontederia cordata intercropping on rice plant growth, pest control, yield, income, and grain quality.

RESULTS

We found rice‐P. cordata intercropping significantly decreased the occurrence of rice diseases and pests, with a 22.0–45.9% reduction in sheath blight and a 33.8–34.4% reduction in leaf folders. The mean land equivalent ratio (LER) (1.09) result indicates that intercropping rice and P. cordata generated positive yield effects. In addition, due to the economic profit from the replacement stripe of P. cordata in the rice paddy field, intercropping rice with P. cordata could greatly enhance farmer income. The average total income of rice intercropped with P. cordata was 2.5‐fold higher than that of rice monoculture. Furthermore, intercropping significantly improved grain quality compared with the rice monoculture. It significantly increased the milled rice rate and whole milled rice rate by 11.2% and 12.8%, respectively, but decreased the chalky rice rate by 30.9–39.8% and chalkiness degree by 32.2%.

CONCLUSIONS

We suggest that rice‐P. cordata intercropping provides an environmentally effective way to control rice diseases and pests, results in higher overall productivity and total income, and improves grain quality. © 2021 Society of Chemical Industry.
Screening of semi‐volatile compounds in plants treated with coated cerium oxide nanoparticles by comprehensive two‐dimensional gas chromatography
Authors: Milenković Ivana , Radotić Ksenija , Trifković Jelena , Vujisić Ljubodrag , Beškoski Vladimir P.
Published: April 2021

Literature data about semi‐volatile organic compounds in plants and the effect of cerium oxide nanoparticles on them are scarce. Surface modification of nanoparticles may change nanoparticle‐environment interaction, and therefore affects compounds in plants. In this research, uncoated and glucose‐, levan‐, and pullulan‐coated cerium oxide nanoparticles were used for wheat and pea treatment during the growth. The aim was the screening of semi‐volatile organic compounds from plants’ shoots using comprehensive two‐dimensional gas chromatography–mass spectrometry, a powerful separation technique allowing to reach unique separation resolution, and investigation of qualitative changes after the treatment with coated cerium oxide nanoparticles. The results were analyzed by the identification of individual peaks and fingerprint analysis by image processing. Wheat samples contained a higher number of semi‐volatile organic compounds (108) compared to pea (77) but were less affected by the treatments with coated nanoparticles. The highest number of compounds was detected in wheat after the treatment with levan‐ and pullulan‐coated nanoparticles, and in pea after treatment with levan‐coated nanoparticles. This article reports a successful application of a semi‐volatile organic compounds profile presented only as categorical variables and unique fingerprint images for the inter‐cultivar recognition. This method may be useful in screening nanoparticles’ effects on different plants.
Changes in carbon stocks and its economic valuation under a changing land use pattern—A multitemporal study in Konar catchment, India
Authors: Rajbanshi Joy , Das Sharmistha
Published: April 2021

Land use and land cover (LULC) changes influence the global terrestrial carbon pools and carbon sequestration processes to great extents. Therefore, the understanding of the soil carbon dynamics under the dire pressure of LULC changes is highly necessary. The subhumid tropical catchment of Konar, India, has endured immense LULC transitions over the years and this is likely to promote altered carbon exchanges with atmosphere and, thus, has a significant impact on climate regulation and ecosystem services. Our study analyzed the change in total carbon storage in the past (1992–2004 and 2004–2016) and predicted the future (2030) with respect to the changing land use scenario in the catchment. In addition, the monetary valuation of the carbon loss and/or gain in that area has been performed considering its economic value in the society. The Markov chain model was used in this work in order to predict the LULC map for the future period, and integrated valuation of ecosystem services and trade‐offs (InVEST) model was applied to measure the changes in total carbon stocks. The results show that 129,273.75 Mg carbon has already been lost from 2004 to 2016 that is worth of $US 20.06 million ($US 212.69 ha−1), and another 66,050.25 Mg of carbon which is worth of $US 9.73 million ($US 103.21 ha−1) is expected to be lost in future by 2030. A thorough understanding of the carbon scenario of the study area may help to promote feasible mitigation actions to conserve the carbon pools.
Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models
Authors: Ueda Jun , Uemura Norihito , Sawamura Masanori , Taguchi Tomoyuki , Ikuno Masashi , Kaji Seiji , Taruno Yosuke , Matsuzawa Shuichi , Yamakado Hodaka , Takahashi Ryosuke
Published: April 2021

Background

The intercellular transmission of pathogenic proteins plays a key role in the clinicopathological progression of neurodegenerative diseases. Previous studies have demonstrated that this uptake and release process is regulated by neuronal activity.

Objective

The objective of this study was to examine the effect of perampanel, an antiepileptic drug, on α‐synuclein transmission in cultured cells and mouse models of Parkinson's disease.

Methods

Mouse primary hippocampal neurons were transduced with α‐synuclein preformed fibrils to examine the effect of perampanel on the development of α‐synuclein pathology and its mechanisms of action. An α‐synuclein preformed fibril‐injected mouse model was used to validate the effect of oral administration of perampanel on the α‐synuclein pathology in vivo.

Results

Perampanel inhibited the development of α‐synuclein pathology in mouse hippocampal neurons transduced with α‐synuclein preformed fibrils. Interestingly, perampanel blocked the neuronal uptake of α‐synuclein preformed fibrils by inhibiting macropinocytosis in a neuronal activity‐dependent manner. We confirmed that oral administration of perampanel ameliorated the development of α‐synuclein pathology in wild‐type mice inoculated with α‐synuclein preformed fibrils.

Conclusion

Modulation of neuronal activity could be a promising therapeutic target for Parkinson's disease, and perampanel could be a novel disease‐modifying drug for Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society
Latent variable Gaussian process models: A rank‐based analysis and an alternative approach
Authors: Tao Siyu , Apley Daniel W. , Plumlee Matthew , Chen Wei
Published: April 2021

Gaussian process (GP) models have been extended to emulate expensive computer simulations with both qualitative/categorical and quantitative/continuous variables. Latent variable (LV) GP models, which have been recently developed to map each qualitative variable to some underlying numerical LVs, have strong physics‐based justification and have achieved promising performance. Two versions use LVs in Cartesian (LV‐Car) space and hyperspherical (LV‐sph) space, respectively. Despite their success, the effects of these different LV structures are still poorly understood. This article illuminates this issue with two contributions. First, we develop a theorem on the effect of the ranks of the qualitative factor correlation matrices of mixed‐variable GP models, from which we conclude that the LV‐sph model restricts the interactions between the input variables and thus restricts the types of response surface data with which the model can be consistent. Second, following a rank‐based perspective like in the theorem, we propose a new alternative model named LV‐mix that combines the LV‐based correlation structures from both LV‐Car and LV‐sph models to achieve better model flexibility than them. Through extensive case studies, we show that LV‐mix achieves higher average accuracy compared with the existing two.
Unwanted isolation: An obstacle to constructive interaction between oncology nurses and their patients
Authors: Pishgooie Amir Hossain , Mohtashami Jamileh , Atashzadeh‐Shoorideh Foroozan , Sanaie Neda , Fathollahzadeh Ensieh , Skerrett Victoria
Published: April 2021

Aim

The current study was carried out to investigate the obstacles faced by oncology nurses in their interactions with their patients.

Design

This research is a descriptive qualitative study.

Methods

In this study, conventional content analysis was used for analysing the data collected from 26 oncology nurses. The participants were selected through purposive sampling. Semi‐structured interviews were used for collecting data. Data analysis was conducted with Elo and Kyngäs's approach.

Results

The results included three categories: “role conflict,” “role overload” and “inefficient interaction,” and 10 subcategories.
Premedication practices for neonatal tracheal intubation: Results from the EPIPPAIN 2 prospective cohort study and comparison with EPIPPAIN 1
Authors: Walter‐Nicolet Elizabeth , Marchand‐Martin Laetitia , Guellec Isabelle , Biran Valérie , Moktari Mostafa , Zana‐Taieb Elodie , Magny Jean‐François , Desfrère Luc , Waszak Paul , Boileau Pascal , Chauvin Gilles , de Saint Blanquat Laure , Borrhomée Suzanne , Droutman Stéphanie , Merhi Mona , Zupan Véronique , Karoui Leila , Cimerman Patricia , Carbajal Ricardo , Durrmeyer Xavier
Published: April 2021

To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty‐one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49‐20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12‐11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46‐8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.
Combined assessment of early and late‐phase outcomes in orphan drug development
Authors: Pateras Konstantinos , Nikolakopoulos Stavros , Roes Kit C. B.
Published: April 2021

In drug development programs, proof‐of‐concept Phase II clinical trials typically have a biomarker as a primary outcome, or an outcome that can be observed with relatively short follow‐up. Subsequently, the Phase III clinical trials aim to demonstrate the treatment effect based on a clinical outcome that often needs a longer follow‐up to be assessed. Early‐phase outcomes or biomarkers are typically associated with late‐phase outcomes and they are often included in Phase III trials. The decision to proceed to Phase III development is based on analysis of the early‐Phase II outcome data. In rare diseases, it is likely that only one Phase II trial and one Phase III trial are available. In such cases and before drug marketing authorization requests, positive results of the early‐phase outcome of Phase II trials are then likely seen as supporting (or even replicating) positive Phase III results on the late‐phase outcome, without a formal retrospective combined assessment and without accounting for between‐study differences. We used double‐regression modeling applied to the Phase II and Phase III results to numerically mimic this informal retrospective assessment. We provide an analytical solution for the bias and mean square error of the overall effect that leads to a corrected double‐regression. We further propose a flexible Bayesian double‐regression approach that minimizes the bias by accounting for between‐study differences via discounting the Phase II early‐phase outcome when they are not in line with the Phase III biomarker outcome results. We illustrate all methods with an orphan drug example for Fabry disease.
Local application reduces number of needed EPC for beneficial effects on wound healing compared to systemic treatment in mice
Authors: Sommer Katharina , Jakob Heike , Kisch Tobias , Henrich Dirk , Marzi Ingo , Frank Johannes , Sander Anna L.
Published: April 2021

Introduction

Stem cell transplantation is one of the most promising strategies to improve healing in chronic wounds as systemic administration of endothelial progenitor cells (EPC) enhances healing by promoting neovascularization and homing though a high amount of cells is needed. In the following study, we analysed whether local application can reduce the number of EPC needed achieving the same beneficial effect on wound healing.

Material and Methods

Wound healing after local or systemic treatment with EPC was monitored in vivo by creating standardized wounds on the dorsum of hairless mice measuring wound closure every second day. Systemic group received 2 × 106 EPC i.v. and locally treated group 2 × 105 EPC, locally injected. As control PBS injection was performed the same way. Expression of CD31, VEGF, CD90 and, SDF-1α was analysed immunohistochemically for evaluation of neovascularisation and amelioration of homing.

Results

Local (7.1 ± 0.45 SD) as well as systemic (6.1 ± 0.23 SD) EPC transplantation led to a significant acceleration of wound closure compared to controls (PBS local: 9.7 ± 0.5 SD, PBS systemic 10.9 ± 0.38 SD). Systemic application enhanced CD31 expression on day 6 after wounding and local EPC on 6 and 9 in comparison to control. VEGF expression was not significantly affected. Systemic and local EPC treatment resulted in a significantly enhanced SDF-1α and CD90 expression on all days investigated.

Conclusion

Local as well as systemic EPC treatment enhances wound healing. Moreover, beneficial effects are obtained with a tenfold decrease number of EPC when applied locally. Thus, local EPC treatment might be more convenient way to enhance wound healing as number of progenitor cells is limited.
Discrimination in the age of artificial intelligence
Authors: Heinrichs Bert
Published: April 2021

In this paper, I examine whether the use of artificial intelligence (AI) and automated decision-making (ADM) aggravates issues of discrimination as has been argued by several authors. For this purpose, I first take up the lively philosophical debate on discrimination and present my own definition of the concept. Equipped with this account, I subsequently review some of the recent literature on the use AI/ADM and discrimination. I explain how my account of discrimination helps to understand that the general claim in view of the aggravation of discrimination is unwarranted. Finally, I argue that the use of AI/ADM can, in fact, increase issues of discrimination, but in a different way than most critics assume: it is due to its epistemic opacity that AI/ADM threatens to undermine our moral deliberation which is essential for reaching a common understanding of what should count as discrimination. As a consequence, it turns out that algorithms may actually help to detect hidden forms of discrimination.
Relationship between pancreatic parenchyma loss and early postoperative hyperglycemia in patients with benign pancreatic diseases
Authors: Wen Kan , Cen Chunyuan , Wu Leidi , Huang Mengting , Yang Hongli , Yue Xiaofei , Zhang Yu , Ma Guina , Li Xin , Han Ping
Published: April 2021

Objective

To evaluate the relationship between pancreatic parenchyma loss and early postoperative hyperglycemia in patients with benign pancreatic diseases.

Methods

A total of 171 patients with benign pancreatic tumors or chronic pancreatitis, whose preoperative fasting blood glucose (FBG) was normal and who underwent partial pancreatectomy were reviewed. The pancreatic volume was measured by CT imaging before and after the operation. According to their different pancreatic resection volume (PRV), 171 patients were divided into five groups: < 30%, 30%–39%, 40%–49%, 50%–59%, and ≥ 60%. The correlation between the PRV and postoperative FBG was investigated. According to the postoperative FBG value, the patients were divided into a hyperglycemia group (HG) and nonhyperglycemia group (non-HG) to explore the best cutoff value of the PRV between the two groups.

Results

There were significant differences in the postoperative FBG among the five groups (PRV < 30%, 30%–39%, 40%–49%, 50%–59%, and ≥ 60%). The PRV was positively correlated with postoperative FBG in the benign tumor group and chronic pancreatitis group (R = 0.727 and 0.651, respectively). ROC curve analysis showed that the best cutoff value of the PRV between the HG (n = 84) and non-HG (n = 87) was 39.95% with an AUC = 0.898; the sensitivity was 89.29%, and the specificity was 82.76%.

Conclusion

There was a linear positive correlation between the postoperative FBG level and PRV. Patients with a PRV ≥ 40% are more likely to develop early postoperative hyperglycemia.
Health-economic evaluation of collaborative orthogeriatric care for patients with a hip fracture in Germany: a retrospective cohort study using health and long-term care insurance claims data
Authors: Schulz Claudia , Büchele Gisela , Peter Raphael S. , Rothenbacher Dietrich , Brettschneider Christian , Liener Ulrich C. , Becker Clemens , Rapp Kilian , König Hans-Helmut
Published: April 2021

Background

Evidence suggests benefits of orthogeriatric co-management (OGCM) for hip fracture patients. Yet, evidence on cost-effectiveness is limited and based on small datasets. The aim of our study was to conduct an economic evaluation of the German OGCM for geriatric hip fracture patients.

Methods

This retrospective cohort study was based on German health and long-term care insurance data. Individuals were 80 years and older, sustained a hip fracture in 2014, and were treated in hospitals providing OGCM (OGCM group) or standard care (control group). Health care costs from payer and societal perspective, life years gained (LYG) and cost-effectiveness were investigated within 1 year. We applied weighted gamma and two-part models, and entropy balancing to account for the lack of randomisation. We calculated incremental cost-effectiveness ratios (ICER) and employed the net-benefit approach to construct cost-effectiveness acceptability curves.

Results

14,005 patients were treated in OGCM, and 10,512 in standard care hospitals. Total average health care costs per patient were higher in the OGCM group: €1181.53 (p < 0.001) from payer perspective, and €1408.21 (p < 0.001) from societal perspective. The ICER equalled €52,378.12/ LYG from payer and €75,703.44/ LYG from societal perspective. The probability for cost-effectiveness would be 95% if the willingness-to-pay was higher than €82,000/ LYG from payer, and €95,000/ LYG from societal perspective.

Conclusion

Survival improved in hospitals providing OGCM. Costs were found to increase, driven by inpatient and long-term care. The cost-effectiveness depends on the willingness-to-pay. The ICER is likely to improve with a longer follow-up.
Modelling interaction patterns in a predator-prey system of two freshwater organisms in discrete time: an identified structural VAR approach
Authors: Herwartz Helmut
Published: April 2021

In ecology, the concept of predation describes interdependent patterns of having one species (called the predator) killing and consuming another (the prey). Specifying the so-called functional response of prey populations to predation is an important matter of debate which is typically addressed by means of continuous time models. Empirical regression or autoregression models applied to discrete predator-prey population data promise feasible steady state approximations of often complicated dynamic patterns of population growth and interaction. Ewing et al. (Ecol Econ 60:605–612, 2007) argue in favour of the informational content of so-called vector autoregressive models for the dynamic analysis of predator-prey systems. In this work we reconsider their analysis of dynamic interaction of two freshwater organisms, and design a structural model that allows to approximate the functional response in causal form. Results from an unrestricted structural model are in line with core axiomatic assumptions of predator-prey models. Conditional on population growth lagged up to three periods (i.e., 36 h), the semi-daily population growth of the preyParamecium aureliadiminishes, on average, by 1.2 percentage points in response to an increase of the population growth of the predatorDidinium nasutumby one percentage point.
Evidence linking calcium to increased organo-mineral association in soils
Authors: Rowley Mike C. , Grand Stephanie , Spangenberg Jorge E. , Verrecchia Eric P.
Published: April 2021

Geochemical indicators are emerging as important predictors of soil organic carbon (SOC) dynamics, but evidence concerning the role of calcium (Ca) is scarce. This study investigates the role of Ca prevalence in SOC accumulation by comparing otherwise similar sites with (CaCO3-bearing) or without carbonates (CaCO3-free). We measured the SOC content and indicators of organic matter quality (C stable isotope composition, expressed as δ13C values, and thermal stability) in bulk soil samples. We then used sequential sonication and density fractionation (DF) to separate two occluded pools from free and mineral-associated SOC. The SOC content, mass, and δ13C values were determined in all the fractions. X-ray photoelectron spectroscopy was used to investigate the surface chemistry of selected fractions. Our hypothesis was that occlusion would be more prevalent at the CaCO3-bearing site due to the influence of Ca on aggregation, inhibiting oxidative transformation, and preserving lower δ13C values. Bulk SOC content was twice as high in the CaCO3-bearing profiles, which also had lower bulk δ13C values, and more occluded SOC. Yet, contrary to our hypothesis, occlusion only accounted for a small proportion of total SOC (< 10%). Instead, it was the heavy fraction (HF), containing mineral-associated organic C, which accounted for the majority of total SOC and for the lower bulk δ13C values. Overall, an increased Ca prevalence was associated with a near-doubling of mineral-associated SOC content. Future investigations should now aim to isolate Ca-mediated complexation processes that increase organo-mineral association and preserve organic matter with lower δ13C values.
Read, spot and translate
Authors: Specia Lucia , Wang Josiah , Lee Sun Jae , Ostapenko Alissa , Madhyastha Pranava
Published: April 2021

We propose multimodal machine translation (MMT) approaches that exploit the correspondences between words and image regions. In contrast to existing work, our referential grounding method considers objects as the visual unit for grounding, rather than whole images or abstract image regions, and performs visual grounding in the source language, rather than at the decoding stage via attention. We explore two referential grounding approaches: (i) implicit grounding, where the model jointly learns how to ground the source language in the visual representation and to translate; and (ii) explicit grounding, where grounding is performed independent of the translation model, and is subsequently used to guide machine translation. We performed experiments on the Multi30K dataset for three language pairs: English–German, English–French and English–Czech. Our referential grounding models outperform existing MMT models according to automatic and human evaluation metrics.