bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning highlights the importance of primary and secondary production in determining habitat for marine fish and macroinvertebrates
Authors: Friedland Kevin D. , Bachman Michelle , Davies Andrew , Frelat Romain , McManus M. Conor , Morse Ryan , Pickens Bradley A. , Smoliński Szymon , Tanaka Kisei
Published: February 2021

Species distribution models for marine organisms are increasingly used for a range of applications, including spatial planning, conservation, and fisheries management. These models have been constructed using a variety of mathematical forms and drawing on both physical and biological independent variables; however, what might be called first‐generation models have mainly followed the form of linear models, or smoothing splines, informed by data collected in the context of fish surveys.

The performance of different classes of variables were tested in a series of species occurrence models built with machine learning methods, specifically evaluating the potential contribution of lower trophic level data. Random forest models were fitted based on the classification of the absence/presence for fish and macroinvertebrates surveyed on the US Northeast Continental Shelf.

The potential variables included physical, primary production, secondary production, and terrain variables. For accepted model fits, six variable importance measures were computed, which collectively showed that physical and secondary production variables make the greatest contribution across all models. In contrast, terrain variables made the least contribution to these models.

Multivariable analyses that account for all performance measures reinforce the role of water depth and temperature in defining species presence and absence; however, chlorophyll concentration and some specific zooplankton taxa, such as Metridia lucens and Paracalanus parvus, also make important contributions with strong seasonal variations.

Our results suggest that lower trophic level variables, if available, are valuable in the creation of species distribution models for marine organisms.
Morphological, osteological, and genetic data support a new species of Madatyphlops (Serpentes: Typhlopidae) endemic to Mayotte Island, Comoros Archipelago
Authors: Hawlitschek Oliver , Scherz Mark D. , Webster Kathleen C. , Ineich Ivan , Glaw Frank
Published: February 2021

Blind snakes (Typhlopidae) are an enigmatic group of small burrowing snakes whose anatomy, phylogenetics, and biodiversity remain poorly known. Madatyphlops comorensis (Boulenger, 1889), endemic to the Comoros Archipelago in the Western Indian Ocean, is one of many species whose phylogenetic placement and generic assignment is unclear. We used DNA barcoding, external morphological examination, and osteological data from 3D reconstruction with micro‐CT to study specimens of Madatyphlops from the Comoros Archipelago. Our results support the placement of M. comorensis in Madatyphlops and the recognition of the specimens from Mayotte Island as a closely related but distinct species, which we describe as Madatyphlops eudelini sp. nov. In this context, we present the first detailed osteological descriptions of any species of Madatyphlops, which we hope will serve as groundwork for further osteological studies in this genus and contribute to our limited but growing understanding of the osteology of typhlopid snakes.
(+)‐Camphor and (−)‐borneol derivatives as potential anti‐orthopoxvirus agents
Authors: Sokolova Anastasiya S. , Kovaleva Kseniya S. , Yarovaya Olga I. , Bormotov Nikolay I. , Shishkina Larisa N. , Serova Olga A. , Sergeev Alexander A. , Agafonov Alexander P. , Maksuytov Rinat A. , Salakhutdinov Nariman F.
Published: February 2021

Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re‐emerge as natural infections. We have previously reported (+)‐camphor and (−)‐borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL‐2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4‐bromo‐Nʹ‐((1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC50 value of 13.9 μM and a selectivity index of 206. Also, (+)‐camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.
Bioeconomy and biofuels: the case of sugarcane ethanol in Brazil
Authors: Karp Susan G , Medina Jesus D C , Letti Luiz A J , Woiciechowski Adenise L , de Carvalho Júlio C , Schmitt Caroline C , de Oliveira Penha Rafaela , Kumlehn Gabriel S , Soccol Carlos R
Published: February 2021

Brazilian bioethanol is one of the most prominent biofuels produced on a large scale, representing 30% of the global fuel ethanol production share. Around 8.6 billion gallons were produced in 2019, second only to the US fuel ethanol production in the same period (15.8 billion gallons). Obtained from sugarcane in a highly energy‐efficient process, the biofuel, which can be used in Brazil as 100% ethanol (hydrated, minimum mass content of 92.5%) or in a volume proportion of 27% (anhydrous ethanol) in common gasoline, has contributed to the reduction of oil dependency and CO2 emissions, as well as to the development of an important economic sector. Pioneer biofuel policies and important advances in science and technology led to the establishment of a 46% renewable energy matrix. In this manuscript, an overview of the impacts of ethanol production and utilization will be given, with respect to environmental and socio‐economic concerns. The public policies and some technical aspects of sugarcane and ethanol production and energy cogeneration will be reviewed and discussed. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
Near‐term practical strategies to improve the life cycle techno‐economics, energy use and greenhouse gas emissions of corn stover supply system for biobased industries
Authors: Shah Ajay , Manandhar Ashish , Darr Matthew J.
Published: February 2021

Corn stover is predominantly used as the feedstock in the cellulosic biorefineries of the Midwestern USA; however, there are several opportunities to improve the performance of its supply chain. Thus, there is a need to optimize the corn stover supply system for the overall sustainability of the corn stover‐based industries. This paper presents three practical strategies that could be implemented in the near term to improve the performance of the corn stover supply chain. The first strategy involves reducing the corn stover collection area, which entails improving producers’ participation through enhanced knowledge transfer related to this industry, improving harvest ratio of biomass, and reducing dry matter loss during biomass handling and storage. The second strategy involves reducing the overall bale supply quantity, which primarily entails increasing bale density. The final suggested strategy involves reducing quantities of in‐field machinery, which is possible through improving the efficiency of field machinery, including windrowers, balers, and stackers, and increasing their harvest durations. By successfully implementing these strategies, the overall cost associated with the supply of corn stover, energy use, and greenhouse gas emissions could be reduced, on an average, by 34–35% from the current average benchmarks of $95.9/metric ton (t), 11% and greenhouse gas emissions is 58.4 kg CO2e/t, respectively. This can contribute toward creating a cost‐effective logistics system that is also environmentally sustainable. This will be critical for the long‐term success of the biorefineries using corn stover as the primary feedstock. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
Abnormal brain functional networks in end‐stage renal disease patients with cognitive impairment
Authors: Yue Zheng , Wang Pengming , Li Xuekun , Ren Jipeng , Wu Baolin
Published: February 2021

Introduction

Cognitive impairment (CI) is common in patients with end‐stage renal disease (ESRD). Neuroimaging studies have demonstrated structural and functional brain alterations underlying CI in patients with ESRD. However, the patterns of change in whole‐brain functional networks in ESRD patients with CI remain poorly understood.

Methods

We enrolled 66 patients with ESRD (36 patients with CI and 30 patients without CI) and 48 healthy control subjects (HCs). We calculated the topological properties using a graph theoretical analysis. An analysis of covariance (ANCOVA) was used to compare network metrics among the three groups. Moreover, we analyzed the relationships between altered network measures and clinical variables in ESRD patients with CI.

Results

Compared with HCs, both patient groups showed lower local efficiency and small‐worldness. ESRD patients had decreased nodal centralities in the default mode regions and right amygdala. Comparison of the two patient groups showed significantly decreased global (small‐worldness) and nodal (nodal centralities in the default mode regions) properties in the CI group. Altered nodal centralities in the bilateral medial part of the superior frontal gyrus, left posterior cingulate gyrus, and right precuneus were associated with cognitive performance in the CI group.

Conclusion

Disrupted brain functional networks were demonstrated in patients with ESRD, which were more severe in those with CI. Moreover, impaired nodal centralities in the default mode regions might underlie CI in patients with ESRD.
Circular business model evolution: Stakeholder matters for a self‐sufficient ecosystem
Authors: Moggi Sara , Dameri Renata Paola
Published: February 2021

Food waste is a key issue in the circular economy. A circular ecosystem results from the contributions of various stakeholders; however, the claims and value propositions of these stakeholders can differ, hampering long‐term sustainability of the ecosystem. This study analyses the case of RiCibo, a circular ecosystem based in Genoa, Italy. RiCibo collects surplus food and redistributes it to the needy in the local community. The study examines the conditions that facilitated RiCibo’s evolution from a simple project to a circular self‐sufficient ecosystem characterised by a co‐designed circular business model with a broad range of stakeholders. The results show that sharing people, infrastructure and knowledge, together with mutual trust among stakeholders, are the preconditions of a circular ecosystem. Long‐term continuity depends on additional tools that enhance financial self‐sufficiency, namely, participative governance, a co‐designed circular business model, accountability, frequent engagement, local actions and the development of advocacy power.
Involvement of long non‐coding RNAs in the progression of esophageal cancer
Authors: Xue Wenhua , Zheng Yuanyuan , Shen Zhibo , Li Lifeng , Fan Zhirui , Wang Wenbin , Zhu Zijia , Zhai Yunkai , Zhao Jie , Kan Quancheng
Published: February 2021

Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system with high incidence and mortality rate worldwide. Therefore, exploring the pathogenesis of EC and searching for new targeted therapies are the current research hotspot for EC treatment. Long non‐coding RNAs (lncRNAs) are endogenous RNAs with more than 200 nucleotides, but without protein‐coding function. In recent years, lncRNAs have gradually become the focuses in the field of non‐coding RNA. Some lncRNAs have been proved to be closely related to the pathogenesis of EC. Many lncRNAs are abnormally expressed in EC and participate in many biological processes including cell proliferation, apoptosis, and metastasis by inhibiting or promoting target gene expression. LncRNAs can also regulate the progression of EC through epithelial‐mesenchymal transformation (EMT), which is closely related to the occurrence, development, and prognosis of EC. In this article, we review and discuss the involvement of lncRNAs in the progression of EC.
Low‐grade chronic inflammation and immune alterations in childhood and adolescent cancer survivors: A contribution to accelerated aging?
Authors: Sulicka‐Grodzicka Joanna , Surdacki Andrzej , Seweryn Michał , Mikołajczyk Tomasz , Rewiuk Krzysztof , Guzik Tomasz , Grodzicki Tomasz
Published: February 2021

Background

The long‐term consequences of chemotherapy and radiotherapy result in a high prevalence and early onset of age‐related chronic diseases in survivors. We aimed to examine whether childhood and adolescent cancer survivors (CS) demonstrate biomarkers of accelerated aging.

Methods

We evaluated 50 young adult CS at 11 [8–15] years after cancer diagnosis, and 30 healthy, age and sex‐matched controls, who were unexposed to cancer therapy. Using a machine‐learning approach, we assessed factors discriminating CS from controls and compared selected biomarkers and lymphocyte subpopulations with data from the Framingham Heart Study (FHS) cohort and the Genotype Tissue Expression (GTEx) project.

Results

Survivors compared with controls had higher levels of C‐reactive protein and fibrinogen. The surface expression of CD38 on T cells was increased, and there was an increase in the percentage of memory T cells in survivors, compared with the unexposed group. The relationships between above cell subpopulations and age were consistent in CS, FHS, and GTEx cohorts, but not in controls.

Conclusions

Young pediatric cancer survivors differ from age‐related controls in terms of activation of the adaptive immune system and chronic, low‐grade inflammation. These changes resemble aging phenotype observed in older population. Further research in biomarkers of aging in young, adult childhood cancer survivors is warranted, as it may facilitate screening and prevention of comorbidities in this population.
Diagnostic value of sialyl‐Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge
Authors: Xu Feng , Gao Yue , Diao Xiaoli , Li Jie , Jiang Hongchuan , Zhao Hongying
Published: February 2021

Background

Mucin‐associated sialyl‐Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.

Methods

PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.

Results

PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2‐positive IDC (p = 0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p = 0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p = 0.037) were statistically significant independent risk factors for malignant PND.

Conclusions

Mucin‐associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.
Monolingual therapists’ views and experiences of working with multilingual clients: An exploratory study
Authors: Carmen Calvo‐Rodríguez M.
Published: February 2021

Although much attention has been paid in recent years to culture and diversity, cross‐lingual issues in the counselling room have not been given the consideration they deserve. This field is under‐researched in the UK, particularly from the monolingual counsellor's perspective, and often focuses on working with interpreters or addressing communication barriers. This brief study sets out to explore the experiences of monolingual therapists in the UK when working with proficient multilingual clients, trying to find out whether interventions such as ‘language switching’ are used therapeutically by monolinguals, and what their views are regarding supervision and training. A qualitative approach was taken, with a semi‐structured questionnaire collecting data from 50 participants. Thematic analysis was used to interpret their answers. The findings revealed that the majority of monolingual therapists had not reflected on the psychological and socio‐political implications of using English exclusively, the diverse roles of language and the specific needs of multilingual clients. The highest awareness was found among the most experienced counsellors, who perceived working with multilingual clients as an opportunity for personal and professional development and who showed as much linguistic empathy as multilingual counsellors. However, most participants placed a strong emphasis on communication barriers, which may indicate that, as counsellors, we could be overlooking the opportunities that cross‐lingual exchanges present therapeutically and, as a result, we may be failing to address the needs of multilinguals in our diverse community. The study concluded that there is a need to include this topic in counselling training and do further research.
The complex triad of congruence issues in influencer marketing
Authors: von Mettenheim Walter , Wiedmann Klaus‐Peter
Published: February 2021

Finding a fitting endorser has proven to be one of the most delicate and critical tasks of influencer marketing. This research explores the relevance of the congruency of the influencer personality with (1) brand personality and consumers' (2) actual/(3) ideal selves. Additionally, the (4) moderating role of involvement is considered, the impacts on post attitude/belief, brand trust and purchase intention are thereby studied. The novelty of this study lies in the integral examination of the types of congruencies and involvement in the context of influencer marketing as well as the consideration of their impact on the brand‐related variables. Based on an online survey with 547 participants analyzed by means of structural equation modeling in SmartPLS, partly counterintuitive findings were produced. When the involvement level rises, congruence with consumers' actual selves becomes more important. Under low‐involvement conditions, practitioners should pay more attention to influencers' fit with consumers' ideal selves. An adequate fit between brand and endorser is paramount and becomes even more important under high‐involvement conditions. Overall, this study reveals that the three types of congruency and involvement interact in a very unique way in the context of influencer marketing.
Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6‐NTRK3 gene fusion
Authors: Pitoia Fabián
Published: February 2021

Larotrectinib, a highly selective TRK inhibitor, was administered to a patient with rapidly progressing radioactive iodine‐refractory papillary NTRK3 fusion‐positive thyroid cancer. The patient achieved a durable (sustained for 11 months) complete response after 2 months of treatment and complete intracranial responses in metastatic brain lesions after 7 months of treatment.

Larotrectinib may provide a therapeutic route for patients with RAI‐R‐differentiated thyroid cancer who might otherwise have few treatment options.
Favism‐induced methemoglobinemia in a G6PD deficient male with a subsequent hemolytic cascade, a therapeutic challenge: Case report and review of literature
Authors: Ata Fateen , Javed Saad , Muthanna Bassam , dakhlia Ines , Bint I Bilal Ammara , Musa Motwakil , Uddin Mashuk , Yassin Mohamed A.
Published: February 2021

The co‐occurrence of acute hemolysis and methemoglobinemia secondary to favism in G6PD deficient individuals is rare. Identifying it promptly is of high clinical significance as treating methemoglobinemia (with methylene blue) can worsen hemolysis.
Fluorescent light energy combined with systemic isotretinoin: A 52‐week follow‐up evaluating efficacy and safety in treatment of moderate‐severe acne
Authors: Russo Antonio , Mellergaard Maiken , Pellacani Giovanni , Nisticò Steven , Nielsen Michael Canova Engelbrecht
Published: February 2021

Fluorescent light energy therapy combined with low‐dose isotretinoin or tetracycline show remarkable clinical effect on 12 cases of moderate‐to‐severe acne. Treatment was considered safe, well‐tolerated, and highly efficacious.
Anti‐Programmed death‐1 therapy in advanced hepatocellular carcinoma: A real‐world experience
Authors: Al jarroudi Ouissam , Chaabouni Hamed , Ulusakarya Ayhan , Almohamad Wathek , Gumus Yusuf , Goldschmidt Emma , Afqir Said , Morère Jean‐francois
Published: February 2021

Nivolumab is an effective and safe treatment in HCC.
Unexpected foreign body induced refractory maxillary sinusitis
Authors: Hallak Bassel , Teiga Pedro , Bühler Jean‐Pierre , Bouayed Salim
Published: February 2021

Maxillary sinusitis induced by ipsilateral dental manipulation often carries the risk of sinusal foreign body impaction. Adequate evaluation mandates radiological exploration of the sinus. Management requires complete foreign body removal, surgical drainage of the sinus, and closure of any oroantral communication or fistula.
Manipulating metal–sulfur interactions for achieving high‐performance S cathodes for room temperature Li/Na–sulfur batteries
Authors: Dai Ying‐Ying , Xu Chun‐Mei , Liu Xiao‐Hao , He Xiang‐Xi , Yang Zhuo , Lai Wei‐Hong , Li Li , Qiao Yun , Chou Shu‐Lei
Published: February 2021

Rechargeable lithium/sodium–sulfur batteries working at room temperature (RT‐Li/S, RT‐Na/S) appear to be a promising energy storage system in terms of high theoretical energy density, low cost, and abundant resources in nature. They are, thus, considered as highly attractive candidates for future application in energy storage devices. Nevertheless, the solubility of sulfur species, sluggish kinetics of lithium/sodium sulfide compounds, and high reactivity of metallic anodes render these cells unstable. As a consequence, metal–sulfur batteries present low reversible capacity and quick capacity loss, which hinder their practical application. Investigations to address these issues regarding S cathodes are critical to the increase of their performance and our fundamental understanding of RT‐Li/S and RT‐Na/S battery systems. Metal–sulfur interactions, recently, have attracted considerable attention, and there have been new insights on pathways to high‐performance RT‐Li/Na sulfur batteries, due to the following factors: (1) deliberate construction of metal–sulfur interactions can enable a leap in capacity; (2) metal–sulfur interactions can confine S species, as well as sodium sulfide compounds, to stop shuttle effects; (3) traces of metal species can help to encapsulate a high loading mass of sulfur with high‐cost efficiency; and (4) metal components make electrodes more conductive. In this review, we highlight the latest progress in sulfide immobilization via constructing metal bonding between various metals and S cathodes. Also, we summarize the storage mechanisms of Li/Na as well as the metal–sulfur interaction mechanisms. Furthermore, the current challenges and future remedies in terms of intact confinement and optimization of the electrochemical performance of RT‐Li/Na sulfur systems are discussed in this review.
Extraction and concentration of glutathione from yeast by membranes
Authors: Wang Yiran , Xiao Tonghu , Zhang Zhigen , Feng Xianshe
Published: February 2021

This study dealt with extraction of glutathione from yeast using hot water, followed by membrane separations. The supernatant of the yeast extract was subjected to ultrafiltration (UF) to remove macromolecules, and the glutathione in the resulting ultrafiltrate was concentrated using a nanofiltration (NF) membrane. The relationships between the permeation flux and volume concentration ratio (VCR) were investigated, and the resistance of the membrane fouling layer was analyzed. This study also investigated the effects of hot water extraction conditions (e.g., temperature and time) on the glutathione yield, as well as the stability of glutathione when exposed to light. The research findings suggest that the integrated UF and NF process is a promising approach to concentrating and purifying glutathione from yeast extract.
On statistical tests of functional connectome fingerprinting
Authors: Wang Zeyi , Sair Haris I. , Crainiceanu Ciprian , Lindquist Martin , Landman Bennett A. , Resnick Susan , Vogelstein Joshua T. , Caffo Brian
Published: February 2021

Fingerprinting of functional connectomes is an increasingly standard measure of reproducibility in functional magnetic resonance imaging connectomics. In such studies, one attempts to match a subject's first session image with their second, in a blinded fashion, in a group of subjects measured twice. The number or percentage of correct matches is usually reported as a statistic, which is then used in permutation tests. Despite the simplicity and increasing popularity of such procedures, the soundness of the statistical tests, the power, and the factors impacting the test are unstudied. In this article, we investigate the statistical tests of matching based on exchangeability assumption in the fingerprinting analysis. We show that a nearly universal Poisson(1) approximation applies for different matching schemes. We theoretically investigate the permutation tests and explore the issue that the test is overly sensitive to uninteresting directions in the alternative hypothesis, such as clustering due to familial status or demographics. We perform a numerical study on two functional magnetic resonance imaging (fMRI) resting‐state datasets, the Human Connectome Project (HCP) and the Baltimore Longitudinal Study of Aging (BLSA). These datasets are instructive, as the HCP includes technical replications of long scans and includes monozygotic and dizygotic twins, as well as non‐twin siblings. In contrast, the BLSA study incorporates more typical length resting‐state scans in a longitudinal study. Finally, a study of single regional connections is performed on the HCP data.
Long‐term outcomes of patients undergoing coronary sinus reducer implantation ‐ A multicenter study
Authors: Konigstein Maayan , Ponticelli Francesco , Zivelonghi Carlo , Merdler Ilan , Revivo Miri , Verheye Stefan , Giannini Francesco , Banai Shmuel
Published: February 2021

Background

Coronary sinus (CS) narrowing by reducer implantation has emerged as a safe and effective therapy for patients suffering from refractory angina. However, data regarding the clinical benefit of this treatment over time is lacking.

Methods

Patients undergoing successful reducer implantation were enrolled prospectively to clinical registries at three medical centers. Those with more than 2‐years of follow‐up were included in the present analysis. Peri‐procedural data, data regarding adverse events, and current evaluation of angina severity (Canadian Cardiovascular Society [CCS] class) were collected.

Results

Overall, 99 consecutive patients (77% males, mean age 69.8 ± 9.4) with severe angina were enrolled between September 2010 and October 2017 and included in the present analysis. No procedure‐related complications were recorded. During a median follow up time of 3.38 years (IQR 2.95–4.40), 15.1% of the patients died, 9% experienced myocardial infarction (MI) and 21% underwent percutaneous coronary intervention (PCI). Mean CCS class was 3.1 ± 0.5 at baseline, improved to 1.66 ± 0.8 at 1 year (p < .001), and remained low through 2‐years and at last follow up (1.72 ± 0.8 and 1.71 ± 0.8, p > 0.5 for both, in comparison to 1 year). At baseline 91% of patients reported severe disabling angina (CCS class 3–4), at 1 year only 17.9% suffered from disabling angina, p < .001, and this portion remained low overtime (19% at last follow up).

Conclusion

Long‐term mortality of patients undergoing reducer implantation is similar to that reported for patients with stable coronary artery disease. The previously reported short‐term efficacy of the reducer, reflected by significant improvement of angina symptoms, is maintained over time.
Evaluation of the Bioequivalence of Acarbose in Healthy Chinese People
Authors: Chen Yan , Guo Fahao , Wang Xin , Liu LuYao , Yang Can , Xiong YuQing , Zhang Hong
Published: February 2021

The purpose of this study was to determine whether the reference formulation and test formulation of acarbose are bioequivalent among healthy Chinese subjects based on evaluation of the pharmacodynamic end point. Two clinical trials with acarbose were conducted: study A, a pilot study (n = 12; 50 and 100 mg), and study B, a pivotal study (n = 60; 50 mg). In study A, there was a dose‐dependent relationship between 50 mg acarbose and 100 mg acarbose and a significant difference compared with sucrose alone. In study B, after logarithmic conversion, a linear mixed‐effects model was used to analyze the maximum serum glucose value and area under the serum glucose‐time curve from 0 to 2 hours. The geometric mean ratios (test formulation/reference formulation) were 92.68% and 95.70%, with 90% confidence intervals of 84.08%‐102.17% and 84.21%‐108.76%, respectively, falling between 80.00% and 125.00%. According to the geometric least‐squares mean, the test formulation (or reference formulation) was statistically significantly different as a single sucrose (P < .001). The effective dose of acarbose in healthy Chinese volunteers was 50 mg. The reference and test formulations were bioequivalent.
Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre‐analytical conditions
Authors: Simrén Joel , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik
Published: February 2021

Introduction

This study investigated alternative pre‐analytical handling of blood for neurofilament light (NfL) analysis where resources are limited.

Method

Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48‐hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters.

Results

Delayed centrifugation (R2 = 0.991) and DPS (discovery cohort, R2 = 0.954; confirmatory cohort, DPS: R2 = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2 = 0.995) and shaking (R2 = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS.

Discussion

DPS or delayed centrifugation are viable pre‐analytical procedures for the accurate quantification of plasma NfL.
Deep learning shows no morphological abnormalities in neutrophils in Alzheimer's disease
Authors: Chabrun Floris , Dieu Xavier , Doudeau Nicolas , Gautier Jennifer , Luque‐Paz Damien , Geneviève Franck , Ferré Marc , Mirebeau‐Prunier Delphine , Annweiler Cédric , Reynier Pascal
Published: February 2021

Introduction

Several studies have provided evidence of the key role of neutrophils in the pathophysiology of Alzheimer's disease (AD). Yet, no study to date has investigated the potential link between AD and morphologically abnormal neutrophils on blood smears.

Methods

Due to the complexity and subjectivity of the task by human analysis, deep learning models were trained to predict AD from neutrophil images. Control models were trained for a known feasible task (leukocyte subtype classification) and for detecting potential biases of overfitting (patient prediction).

Results

Deep learning models achieved state‐of‐the‐art results for leukocyte subtype classification but could not accurately predict AD.

Discussion

We found no evidence of morphological abnormalities of neutrophils in AD. Our results show that a solid deep learning pipeline with positive and bias control models with visualization techniques are helpful to support deep learning model results.
Differentiating traits and states identifies the importance of chronic neuropsychiatric symptoms for cognitive prognosis in mild dementia
Authors: Giil Lasse M. , Aarsland Dag , Vik‐Mo Audun Osland
Published: February 2021

Introduction

Neuropsychiatric symptoms (NPS) in dementia are associated with poor cognitive outcomes in longitudinal studies. Whether this is due to differences in symptom burden between persons (BP) or changes within persons (WP) is unknown.

Methods

Patients with mild Alzheimer's disease (AD, n = 111) and Lewy‐body dementia (LBD, n = 85) were assessed annually for 8 years. We modelled the association between NPS assessed by the Neuropsychiatric Inventory (NPI) and Mini‐Mental State Examinations (MMSE) using Tobit mixed‐effects model with NPS as individual means over time (BP) and its deviance (WP).

Results

The association between higher NPS and poorer cognitive outcomes was mostly due to BP differences for the NPI‐total score, and in particular for delusions, hallucinations, agitation, aberrant motor behavior, and apathy scores.

Discussion

The NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). Clinically, long‐term rather than episodic NPS better identifies patients with poor cognitive outcomes.
Single‐cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders
Authors: Kuan Pei‐Fen , Clouston Sean , Yang Xiaohua , Che Chang , Gandy Samuel , Kotov Roman , Bromet Evelyn , Luft Benjamin J.
Published: February 2021

Introduction

Recent research has found that World Trade Center (WTC) responders in their mid‐50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood.

Methods

The transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery: nine MCI and nine controls; replication: 11 MCI and 11 controls) using CITE‐Seq at single‐cell resolution in blood.

Results

Comparing the transcriptomic signatures across seven major cell subpopulations, the largest differences were observed in monocytes in which 226 genes were differentially expressed. Pathway analysis on the genes unique to monocytes identified processes associated with cerebral immune response.

Discussion

Our findings suggested monocytes may constitute a key cell type to target in blood‐based biomarker studies for early detection of risk of MCI and development of new interventions.
Insight into the genetic etiology of Alzheimer's disease: A comprehensive review of the role of rare variants
Authors: Hoogmartens Julie , Cacace Rita , Van Broeckhoven Christine
Published: February 2021

Early‐onset Alzheimer's disease (EOAD) is generally known as a dominant disease due to highly penetrant pathogenic mutations in the amyloid precursor protein, presenilin 1 and 2. However, they explain only a fraction of EOAD patients (5% to 10%). Furthermore, only 10% to 15% of EOAD families present with clear autosomal dominant inheritance. Studies showed that only 35% to 60% of EOAD patients have at least one affected first‐degree relative. Parent–offspring concordance in EOAD was estimated to be <10%, indicating that full penetrant dominant alleles are not the sole players in EOAD. We aim to summarize current knowledge of rare variants underlying familial and seemingly sporadic Alzheimer's disease (AD) patients. Genetic findings indicate that in addition to the amyloid beta pathway, other pathways are of importance in AD pathophysiology. We discuss the difficulties in interpreting the influence of rare variants on disease onset and we underline the value of carefully selected ethnicity‐matched cohorts in AD genetic research.
Differential blood DNA methylation across Lewy body dementias
Authors: Nasamran Chanond A. , Sachan Anubhav Nikunj Singh , Mott Jennifer , Kuras Yuliya I. , Scherzer Clemens R. , Study Harvard Biomarkers , Ricciardelli Eugenia , Jepsen Kristen , Edland Steven D. , Fisch Kathleen M. , Desplats Paula
Published: February 2021

Introduction

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.

Methods

We performed a cross‐sectional analysis of blood methylation in 42 DLB and 50 PDD cases applying linear models to compare groups and logistic least absolute shrinkage and selection operator regression to explore the discriminant power of methylation signals.

Results

DLB blood shows differential methylation compared to PDD. Some methylation changes associate with core features of LBD. Sets of probes show high predictive value to discriminate between variants.

Discussion

Our study is the first to explore LBD blood methylation. Despite overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.
Glioblastoma mimicking metastatic small cell carcinoma: A case report with ultrastructural findings
Authors: Maekawa Kazunari , Tokumitsu Takako , Noguchi Hiroshi , Nakamura Eriko , Gi Toshihiro , Horinouchi Shoichi , Yamashita Shinji , Takeshima Hideo , Asada Yujiro , Sato Yuichiro
Published: February 2021

It is often straightforward to distinguish glioblastoma (GBM) from metastatic carcinoma by cytology; however, small cell variants of GBM or GBM with primitive neuronal component (GBMPNC) can mimic metastatic small cell carcinoma (SCC). Herein, we report a case of GBMPNC mimicking metastatic SCC and present cytological and ultrastructural findings. A 65‐year‐old man with memory disturbance was hospitalized. Magnetic resonance imaging revealed the presence of a 6 cm sized tumor in the right anterior temporal lobe. Intraoperative cytology slides indicated that the tumor consisted of small‐sized cells with scant cytoplasm showing high cellularity. The initial intraoperative diagnosis was metastatic SCC; however, any primary visceral tumor was not detected clinically. Immunohistochemical and ultrastructural studies of postoperative histological sections revealed that the lesion was GBMPNC. This case shows that some GBMs may have the potential to closely mimic metastatic SCC, which expands the differential diagnosis and emphasizes the importance of clinical correlation.
Indigenous plants promote insect biodiversity in urban greenspaces
Authors: Mata Luis , Andersen Alan N. , Morán‐Ordóñez Alejandra , Hahs Amy K. , Backstrom Anna , Ives Christopher D. , Bickel Daniel , Duncan David , Palma Estibaliz , Thomas Freya , Cranney Kate , Walker Ken , Shears Ian , Semeraro Linda , Malipatil Mallik , Moir Melinda L. , Plein Michaela , Porch Nick , Vesk Peter A. , Smith Tessa R. , Lynch Yvonne
Published: February 2021

The contribution of urban greenspaces to support biodiversity and provide benefits for people is increasingly recognized. However, ongoing management practices favor vegetation oversimplification, often limiting greenspaces to lawns and tree canopy rather than multi‐layered vegetation that includes under‐ and midstorey, and the use of nonnative species. These practices hinder the potential of greenspaces to sustain indigenous biodiversity, particularly for taxa like insects that rely on plants for food and habitat. Yet, little is known about which plant species may maximize positive outcomes for taxonomically and functionally diverse insect communities in greenspaces. Additionally, while cities are expected to experience high rates of introductions, quantitative assessments of the relative occupancy of indigenous vs. introduced insect species in greenspace are rare, hindering understanding of how management may promote indigenous biodiversity while limiting the establishment of introduced insects. Using a hierarchically replicated study design across 15 public parks, we recorded occurrence data from 552 insect species on 133 plant species, differing in planting design element (lawn, midstorey, and tree canopy), midstorey growth form (forbs, lilioids, graminoids, and shrubs) and origin (nonnative, native, and indigenous), to assess (1) the relative contributions of indigenous and introduced insect species and (2) which plant species sustained the highest number of indigenous insects. We found that the insect community was overwhelmingly composed of indigenous rather than introduced species. Our findings further highlight the core role of multi‐layered vegetation in sustaining high insect biodiversity in urban areas, with indigenous midstorey and canopy representing key elements to maintain rich and functionally diverse indigenous insect communities. Intriguingly, graminoids supported the highest indigenous insect richness across all studied growth forms by plant origin groups. Our work highlights the opportunity presented by indigenous understory and midstorey plants, particularly indigenous graminoids, in our study area to promote indigenous insect biodiversity in urban greenspaces. Our study provides a blueprint and stimulus for architects, engineers, developers, designers, and planners to incorporate into their practice plant species palettes that foster a larger presence of indigenous over regionally native or nonnative plant species, while incorporating a broader mixture of midstorey growth forms.
Predictive scores for identifying patients with type 2 diabetes mellitus at risk of acute myocardial infarction and sudden cardiac death
Authors: Lee Sharen , Zhou Jiandong , Guo Cosmos Liutao , Wong Wing Tak , Liu Tong , Wong Ian Chi Kei , Jeevaratnam Kamalan , Zhang Qingpeng , Tse Gary
Published: February 2021

Introduction

The present study evaluated the application of incorporating non‐linear J/U‐shaped relationships between mean HbA1c and cholesterol levels into risk scores for predicting acute myocardial infarction (AMI) and non‐AMI‐related sudden cardiac death (SCD) respectively, amongst patients with type 2 diabetes mellitus.

Methods

This was a territory‐wide cohort study of patients with type 2 diabetes mellitus above the age 40 and free from prior AMI and SCD, with or without prescriptions of anti‐diabetic agents between January 1st, 2009 to December 31st, 2009 at government‐funded hospitals and clinics in Hong Kong. Patients recruited were followed up until 31 December 2019 or their date of death. Risk scores were developed for predicting incident AMI and non‐AMI‐related SCD. The performance of conditional inference survival forest (CISF) model compared to that of random survival forests (RSF) model and multivariate Cox model.

Results

This study included 261 308 patients (age = 66.0 ± 11.8 years old, male = 47.6%, follow‐up duration = 3552 ± 1201 days, diabetes duration = 4.77 ± 2.29 years). Mean HbA1c and low high‐density lipoprotein‐cholesterol (HDL‐C) were significant predictors of AMI on multivariate Cox regression. Mean HbA1c was linearly associated with AMI, whilst HDL‐C was inversely associated with AMI. Mean HbA1c and total cholesterol were significant multivariate predictors with a J‐shaped relationship with non‐AMI‐related SCD. The AMI and SCD risk scores had an area under the curve (AUC) of 0.666 (95% confidence interval (CI) = [0.662, 0.669]) and 0.677 (95% CI = [0.673, 0.682]), respectively. CISF significantly improves prediction performance of both outcomes compared to RSF and multivariate Cox models.

Conclusion

A holistic combination of demographic, clinical and laboratory indices can be used for the risk stratification of patients with type 2 diabetes mellitus for AMI and SCD.
Temporal trends in incidence, causes, use of mechanical circulatory support and mortality in cardiogenic shock
Authors: Schrage Benedikt , Becher Peter Moritz , Goßling Alina , Savarese Gianluigi , Dabboura Salim , Yan Isabell , Beer Benedikt , Söffker Gerold , Seiffert Moritz , Kluge Stefan , Kirchhof Paulus , Blankenberg Stefan , Westermann Dirk
Published: February 2021

Aim

The management of cardiogenic shock remains a clinical challenge even in well‐developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany.

Methods and results

Data on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005–07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014–17 (73 274 of 165 873 cases, 44.2%). Over time, intra‐aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal‐membrane‐oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction.

Conclusions

In this large, nation‐wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.