bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulfa drugs–based Norbornenyl imides and reductive Heck reactions: Synthesis and antimicrobial screening
Authors: Bagdatli Emine , Cil Elif
Published: October 2021

In the field of our research interest, we designed new sulfa drugs–substituted norbornyl imides as prospective bioactive scaffolds by the reaction of endo‐endic anhydride with sulfa drugs followed by reductive Heck reactions of these products. Norbornenyl imides, as starting compounds, and their Heck products were achieved in good yields. Molecular characterization and stereochemistry of the compounds were investigated using Fourier transform infrared, liquid chromatography time‐of‐flight mass spectrometry, proton nuclear magnetic resonance, carbon 13 attached proton test, H‐H correlation spevtroscopy, and nuclear overhauser enhancement spectroscopy experiments. The Heck products of norbornenyl imides showed exo‐selectivity. All eight novel synthesized compounds, including two sulfa drugs–based norbornenyl imides and six exo‐5‐aryl‐ substituted norbornyl imides, as well as standard sulfonamides, were evaluated for antimicrobial activity against nine microorganisms consisting of Gram‐negative bacteria, Gram‐positive nonactinobacteria, actinobacteria, and yeast. The most active compound was 3a against actinobacteria. The efficacy of 2 and its derivatives against the studied strains were weaker than 3 and its derivatives, but all the studied samples exhibited antifungal potency.
Machine learning to predict in‐hospital mortality among patients with severe obesity: Proof of concept study
Authors: Soffer Shelly , Zimlichman Eyal , Levin Matthew A. , Zebrowski Alexis M. , Glicksberg Benjamin S. , Freeman Robert , Reich David L. , Klang Eyal
Published: October 2021

Objectives

Hospitalized patients with severe obesity require adapted hospital management. The aim of this study was to evaluate a machine learning model to predict in‐hospital mortality among this population.

Methods

Data of unselected consecutive emergency department admissions of hospitalized patients with severe obesity (BMI ≥ 40 kg/m2) was analyzed. Data was retrieved from five hospitals from the Mount Sinai health system, New York. The study time frame was between January 2011 and December 2019. Data was used to train a gradient‐boosting machine learning model to identify in‐hospital mortality. The model was trained and evaluated based on the data from four hospitals and externally validated on held‐out data from the fifth hospital.

Results

A total of 14,078 hospital admissions of inpatients with severe obesity were included. The in‐hospital mortality rate was 297/14,078 (2.1%). In univariate analysis, albumin (area under the curve [AUC] = 0.77), blood urea nitrogen (AUC = 0.76), acuity level (AUC = 0.73), lactate (AUC = 0.72), and chief complaint (AUC = 0.72) were the best single predictors. For Youden’s index, the model had a sensitivity of 0.77 (95% CI: 0.67–0.86) with a false positive rate of 1:9.

Conclusion

A machine learning model trained on clinical measures provides proof of concept performance in predicting mortality in patients with severe obesity. This implies that such models may help to adopt specific decision support tools for this population.
Semiparametric regression analysis of clustered interval‐censored failure time data with a cured subgroup
Authors: Yang Dian , Du Mingyue , Sun Jianguo
Published: October 2021

This article discusses regression analysis of clustered interval‐censored failure time data in the presence of a cured fraction or subgroup. Such data often occur in many areas, including epidemiological studies, medical studies, and social sciences. For the problem, a class of semiparametric transformation nonmixture cure models is presented and for estimation, the maximum likelihood estimation procedure is derived. For the implementation of the proposed method, we develop a novel EM algorithm based on a Poisson variable‐based augmentation. An extensive simulation study is conducted and suggests that the proposed approach works well in practical situations. Finally the method is applied to an example that motivated this study.
Si/SiOC/Carbon Lithium‐Ion Battery Negative Electrode with Multiple Buffer Media Derived from Cross‐Linked Dimethacrylate and Poly (dimethyl siloxane)
Authors: Wang Meimei , Cheng Ya‐Jun , Xia Yonggao
Published: October 2021

Silicon holds a great promise for next generation lithium‐ion battery negative electrode. However, drastic volume expansion and huge mechanical stress lead to poor cyclic stability, which has been one of the major drawbacks to prevent its practical applications. In this work, difunctional methacrylate monomers and vinyl terminated poly (dimethyl siloxane) have been cross‐linked via a facile scalable thermal polymerization process, where SiOC (silicon oxycarbide) and carbon network are formed upon calcination. With the multiple buffer media of SiOC and carbon, the electrochemical properties of the Si/SiOC/C (silicon/silicon oxycarbide/carbon) nanohybrid have been effectively improved in terms of both cyclic and rate performance. After one hundred cycles the discharge capacities of Si/SiOC/C composite is also 443 mAhg−1 while the capacity retention is 83.4 %. Through charge and discharge in higher current density, the capacities can also recover to the similar level.
Maximum likelihood estimation and the local asymptotic mixed normality in a second‐order branching process with continuous state space
Authors: Ramtirthkar Mukund , Kale Mohan
Published: October 2021

A second‐order branching process with continuous state space (SOBPCS) is considered. Maximum likelihood (ML) estimation in SOBPCS is studied under the assumption that the underlying subordinators are gamma processes. This estimation is discussed under two sampling schemes. In the first scheme, we assume that all generation sizes as well as the contributions of lag 1 and lag 2 in each generation are observable. In the second scheme, we assume that only generation sizes are observable. The derived estimators under each scheme are shown to be consistent and asymptotically normal (CAN). Also, it is shown that the SOBPCS belongs to the local asymptotic mixed normal (LAMN) family of models. A simulation study is carried out to verify the results. We apply our results to the optical density data emerging through growth of Bacilllus subtilis bacteria.
A stochastic locally diffusive model with neural network‐based deformations for global sea surface temperature
Authors: Hu Wenjing , Fuglstad Geir‐Arne , Castruccio Stefano
Published: October 2021

In this work, we propose a new approach to model large, irregularly distributed spatio‐temporal global data via a locally diffusive stochastic partial differential equation (SPDE). The proposed model assumes a local deformation of the SPDE with non‐linear dependence on the covariates through a neural network. The proposed model can be fit in a computationally efficient manner using a triangulation over the sphere and sparsity of the precision matrix, as shown in an application with a large data set of simulated multi‐decadal monthly sea surface temperature.
Risk factors for mortality in preterm infants with necrotizing enterocolitis: a retrospective multicenter analysis
Authors: Kordasz Marcin , Racine Michaël , Szavay Philipp , Lehner Markus , Krebs Thomas , Luckert Christian , Hau Eva-Maria , Berger Steffen , Kessler Ulf
Published: October 2021

It is difficult to predict the risk of mortality in necrotizing enterocolitis (NEC). This study aimed at identifying risk factors for severe NEC (Bell stage III) and mortality in preterm children with NEC. In this multicenter retrospective study, we analyzed multiple data from 157 premature children with confirmed NEC in the period from January 2007 to October 2018. We performed univariate, multivariate, stepwise logistic regression, and receiver operator characteristics (ROC) analyses. We were able to demonstrate that low Apgar scores (notably at 1′ and 5′), low hemoglobin concentration (Hgb), and high lactate level at disease onset and during disease correlated with NEC severity and mortality (P < 0.05, respectively). Severe NEC was related to congenital heart disease (CHD — OR 2.6, CI95% 1.2–5.8, P 0.015) and patent ductus arteriosus (PDA — OR 3.3, CI95% 1.6–6.9, P 0.0012), whereas death was related to the presence of PDA (OR 5.5, CI95% 2.3–14, P < 0.001).

Conclusion: Low Apgar scores, low Hgb, high lactate levels, and the presence of CHD or PDA correlated with severe NEC or mortality in children with NEC.

What is Known:• It remains difficult to predict which infant that suffers from necrotizing enterocolitis at risk of death.• Several clinical and laboratory parameters tools to predict fatal outcome in NEC.

What is New:• The following laboratory parameters were associated with the risk of death from NEC: Hemoglobin concentration, base excess and lactate level.• The following clinical variables were associated with the risk of death from NEC: Apgar scores, as well as the presence of congenital heart disease and patent ductus arteriosus.
Combined use of multimodal techniques for the resection of glioblastoma involving corpus callosum
Authors: Cui Meng , Chen Hewen , Sun Guochen , Liu Jialin , Zhang Meng , Lin Hepu , Sun Caihong , Ma Xiaodong
Published: October 2021

Purpose

To compare the multimodal techniques (including neuronavigation, intraoperative MRI [iMRI], and neuromonitoring [IONM]) and conventional approach (only guided by neuronavigation) in removing glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM), their effectiveness and safety were analyzed and compared.

Methods

Electronic medical records were retrospectively reviewed for ccGBM cases treated in our hospital between January 2016 and July 2020. Patient demographics, tumor characteristics, clinical outcomes, extent of resection (EOR), progression-free survival (PFS), and overall survival (OS) were obtained and compared between the multimodal group (used multimodal techniques) and the conventional group (only used neuronavigation). Both groups only included patients that had maximal safe resection (not biopsy). Postoperative radiochemotherapy was also performed or not. Univariate and multivariate analyses were performed to identify significant prognostic factors and optimal EOR threshold.

Results

Finally 56 cases of the multimodal group and 21 cases of the conventional group were included. The multimodal group achieved a higher median EOR (100% versus 96.1%, P = 0.036) and gross total resection rate (60.7% versus 33.3%, P = 0.032) and a lower rate of permanent motor deficits (5.4% versus 23.8%, P = 0.052) than the conventional approach. The multimodal group had the longer median PFS (10.9 versus 7.0 months, P = 0.023) and OS (16.1 versus 11.6 months, P = 0.044) than the conventional group. Postoperative language and cognitive function were similar between the two groups. In multivariate analysis, a higher EOR, radiotherapy, and longer cycles of temozolomide chemotherapy were positive prognostic factors for survival of ccGBM. An optimal EOR threshold of 92% was found to significantly benefit the PFS (HR = 0.51, P = 0.036) and OS (HR = 0.49, P = 0.025) of ccGBM.

Conclusion

Combined use of multimodal techniques can optimize the safe removal of ccGBM. Aggressive resection of EOR > 92% using multimodal techniques combined with postoperative radiochemotherapy should be suggested for ccGBM.
Glycan characteristics of human heart constituent cells maintaining organ function: relatively stable glycan profiles in cellular senescence
Authors: Itakura Yoko , Sasaki Norihiko , Toyoda Masashi
Published: October 2021

Cell surface glycoproteins, which are good indicators of cellular types and biological function; are suited for cell evaluation. Tissue remodeling using various cells is a key feature of regenerative therapy. For artificial heart remodeling, a mixture of heart constituent cells has been investigated for organ assembly, however, the cellular characteristics remain unclear. In this study, the glycan profiles of human cardiomyocytes (HCMs), human cardiac fibroblasts (HCFs), and human vascular endothelial cells (ECs) were analyzed using evanescent-field lectin microarray analysis, a tool of glycan profiling, to clarify the required cellular characteristics. We found that ECs had more “α1-2fucose” and “core α1-6fucose” residues than other cells, and that “α2-6sialic acid” residue was more abundant in ECs and HCMs than in HCFs. HCFs showed higher abundance of “β-galactose” and “β-N-acetylgalactosamine” residues on N-glycan and O-glycan, respectively, compared to other cells. Interestingly, cardiac glycan profiles were insignificantly changed with cellular senescence. The residues identified in this study may participate in organ maintenance by contributing to the preservation of glycan components. Therefore, future studies should investigate the roles of glycans in optimal tissue remodeling since identifying cellular characteristics is important for the development of regenerative therapies.
Developing a Social Evolutionary Measure of Child and Adolescent Hedonic and Eudaimonic Wellbeing in Rural Sierra Leone
Authors: Symonds Jennifer E. , Sloan Seaneen , Kearns Michelle , Devine Dympna , Sugrue Ciaran , Suryanaryan Sachita , Capistrano Daniel , Samonova Elena
Published: October 2021

The study establishes the validity of a new measure of child and adolescent hedonic and eudaimonic wellbeing designed for international use and based on social evolutionary theory. The measure advances the fields of psychometrics and happiness studies by providing the first a-contextual assessment of both hedonic and eudaimonic wellbeing that is suitable for use with children and adolescents. The Child and Adolescent Personal and Social Assessment of Wellbeing contains a brief measure (8-items) of children’s global hedonia and eudaimonia, and domain specific measures (8-items each) of children’s wellbeing in relation to peers, teachers, and families. To develop the measure, we conducted a mixed methods investigation in rural Sierra Leone. We researched the ecological validity of the conceptual framework in a qualitative study of 40 participants (19 children and 21 adults) living in two communities. We developed the quantitative items through a two-phase pilot study of 200 children living in ten communities. We examined the psychometric properties of the measure in the pilot study data, and in a larger dataset generated with 2324 children living in 95 communities. The qualitative results showed that the participants experienced the framework components (e.g., social acceptance) in their daily lives, and that each component was intertwined with indigenous perspectives on child wellbeing. The quantitative results demonstrated that the measure had good dimensional, concurrent, and predictive validity.
Implementation of ACTS into sPHENIX Track Reconstruction
Authors: Osborn Joseph D. , Frawley Anthony D. , Huang Jin , Lee Sookhyun , Costa Hugo Pereira Da , Peters Michael , Pinkenburg Christopher , Roland Christof , Yu Haiwang
Published: October 2021

sPHENIX is a high energy nuclear physics experiment under construction at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory (BNL). The primary physics goals of sPHENIX are to study the quark-gluon-plasma, as well as the partonic structure of protons and nuclei, by measuring jets, their substructure, and heavy flavor hadrons in $$p$$
p
$$+$$
+
$$p$$
p
, p + Au, and Au + Au collisions. sPHENIX will collect approximately 300 PB of data over three run periods, to be analyzed using available computing resources at BNL; thus, performing track reconstruction in a timely manner is a challenge due to the high occupancy of heavy ion collision events. The sPHENIX experiment has recently implemented the A Common Tracking Software (ACTS) track reconstruction toolkit with the goal of reconstructing tracks with high efficiency and within a computational budget of 5 s per minimum bias event. This paper reports the performance status of ACTS as the default track fitting tool within sPHENIX, including discussion of the first implementation of a time projection chamber geometry within ACTS.
Negativity Spreads More than Positivity on Twitter After Both Positive and Negative Political Situations
Authors: Schöne Jonas Paul , Parkinson Brian , Goldenberg Amit
Published: October 2021

What type of emotional language spreads further in political discourses on social media? Previous research has focused on situations that primarily elicited negative emotions, showing that negative language tended to spread further. The current project extends existing knowledge by examining the spread of emotional language in response to both predominantly positive and negative political situations. In Study 1, we examined the spread of emotional language in tweets related to the winning and losing parties in the 2016 US elections, finding that increased negativity (but not positivity) predicted content sharing in both situations. In Study 2, we compared the spread of emotional language in two separate situations: the celebration of the US Supreme Court approval of same-sex marriage (positive) and the Ferguson unrest (negative), finding again that negativity spread further. These results shed light on the nature of political discourse and engagement.
The Role of Long Term Label-Retaining Cells in the Treatment of Erectile Dysfunction by Vacuum Erectile Device
Authors: Yang Baibing , Luse Dustin , Cao Yanna , Ko Tien , Wang Run
Published: October 2021

Introduction

Vacuum erectile device (VED) therapy is commonly used for penile rehabilitation after radical prostatectomy, however, the underlying mechanism of this effect is not fully understood.

Aim

To evaluate the presence of label-retaining cells (LRCs), cells with long-term retention of 5-ethynyl-2-deoxyuridine (EdU) labeling and recognized as adult stem cells or progenitor-like cells, in cavernous tissue after VED treatment using a BCNC rat model.

Methods

Postnatal pups (1 day old) of Sprague Dawley (SD) rats were intraperitoneally injected with EdU (50 ug/g, BID for 3 days) and BCNC surgery was conducted at 6 weeks old (designated as natal-labeled rats). Adult SD rats underwent BCNC surgery and EdU injection (50 ug/g, once) after surgery (designated as adult-labeled rats). One week after surgery, both natal- and adult-labeled rats received daily VED treatment for 4 weeks. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured for all rats and then the penile tissue was harvested. The ratio of ICP/MAP was calculated to represent erectile function. Penile tissue was examined by immunofluorescence staining to detect EdU positive cells.

Main Outcome Measures

The ratio of Intracavernous pressure (ICP) /MAP and the percentage of EdU positive cells were measured.

Results

The erectile function was impaired after BCNC and partially restored after VED treatment in both natal- and adult-labeled rats (P < .05). There was no difference in the percentage of EdU positive cells in natal-labeled rat cavernous tissue in BCNC group compared with VED group. Among the adult-labeled rats, the percentage of EdU positive cells increased in BCNC group (P < .05) but didn't change significantly after VED treatment (P = .35).

Conclusion

LRCs may play a limited role in the restoration of erectile dysfunction through VED treatment after BCNC.
Exploring posthuman ethics: opening new spaces for postqualitative inquiry within pedagogies of the circular economy
Authors: Kopnina Helen
Published: October 2021

This article discusses closed-loop systems, namely Cradle to Cradle and circular economy, in the context of sustainable education. These circular models, at least ideally, promise absolute decoupling of resource consumption from the economy. This article presents student assignments applying these models to Hennes & Mauritz, a clothing retail company, and insect food producer, Protix.

While the discussion of circular economy revolves around the economic benefits of closed-loop systems, it rarely addresses posthumanism. Posthumanism is related to postqualitative theory, inspired by Gilles Deleuze and Felix Guattari. Deleuze and Guattari emphasize that nature has become intertwined with technology and culture. In the cases discussed, combining both techno- and organic materials produces ‘monstrous hybrids’. It appears that fully circular solutions are rare as absolute decoupling is limited by thermodynamic (im)possibilities. This realization still has to be developed in environmental education. Within this posthumanist inquiry, the larger lesson from the case studies is the necessity of teaching about degrowth in production, consumption and corporate strategy. In pedagogical terms, this article aims to generate a more critical discussion within the environmental education community about how postqualitative inquiry can provide different and distinct perspectives from qualitative inquiry in the context of the circular economy.
Is Virtual Team-Based Learning Feasible and Effective in Teaching Neurolocalisation?
Authors: Ong Kim Yao , Gan Adelia Shin Ping , Rajalingam Preman , Tan Nigel C.K. , Tan Kevin
Published: October 2021

We investigated the feasibility and effectiveness of virtual team-based learning (TBL) in teaching neurolocalisation (NL) in a sample of 18 student volunteers. Student satisfaction and knowledge outcomes were evaluated using the modified TBL Student Assessment Instrument and Extended Matching Questionnaire (EMQ), respectively. Mean student satisfaction rating was good at 3.9 out of 5.0 (SD 0.3). Participants achieved high mean EMQ scores of 84.2% (SD 2.9) with moderate correlation between individual assessment scores and EMQ scores (ρ = 0.587, p = 0.01). Virtual TBL is feasible for teaching NL with good student satisfaction and knowledge outcomes.
Aménagement d'ambons dans une église rurale récemment découverte à Koustilya (Sud-ouest de la Tunisie)
Authors: Chetoui Mourad
Published: October 2021

There were two excavation missions at the site of Koustilya, in 2017 and in 2018, to investigate the remains of a late rural church. The excavations identified the monument as a building for Christian worship. The architecture of this monument (three aisles and an apse and associated rooms) suggests a Christian church. This church enriches the list of rural Christian churches in Tunisia and additionally has some special features: among the architectural components discovered in this church are two fixed ambons built into the masonry. These give this church a particular importance, somewhat unique when compared to other Christian churches in the ancient Maghreb.
The feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet in established community groups at increased CVD risk: the TEAM-MED EXTEND study: a pilot cluster randomised controlled trial
Authors: O’Neill Roisin F. , McGowan Laura , McEvoy Claire T. , Wallace Sara Megan , Moore Sarah E. , McKinley Michelle C. , Kee Frank , Cupples Margaret E. , Young Ian S. , Woodside Jayne V.
Published: October 2021

This study aimed to evaluate the feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet (MD) in established community groups where existing social support may assist the behaviour change process. Four established community groups with members at increased Cardiovascular Disease (CVD) risk and homogenous in gender were recruited and randomised to receive either a 12-month Peer Support (PS) intervention (PSG) (n 2) or a Minimal Support intervention (educational materials only) (MSG) (n 2). The feasibility of the intervention was assessed using recruitment and retention rates, assessing the variability of outcome measures (primary outcome: adoption of an MD at 6 months (using a Mediterranean Diet Score (MDS)) and process evaluation measures including qualitative interviews. Recruitment rates for community groups (n 4/8), participants (n 31/51) and peer supporters (n 6/14) were 50 %, 61 % and 43 %, respectively. The recruitment strategy faced several challenges with recruitment and retention of participants, leading to a smaller sample than intended. At 12 months, a 65 % and 76·5 % retention rate for PSG and MSG participants was observed, respectively. A > 2-point increase in MDS was observed in both the PSG and the MSG at 6 months, maintained at 12 months. An increase in MD adherence was evident in both groups during follow-up; however, the challenges faced in recruitment and retention suggest a definitive study of the peer support intervention using current methods is not feasible and refinement based on the current feasibility study should be incorporated. Lessons learned during the implementation of this intervention will help inform future interventions in this area.
Sustainable Green Finance towards a Green Belt and Road
Authors: GOH Allison
Published: October 2021

At the second Belt and Road forum in 2019, the Chinese government set out its intentions to develop a “Green Belt and Road”. This paper will examine critical issues arising from green-financed projects under the Belt and Road. In particular, the root issue of the lack of harmonized sustainability standards for green bonds globally. While there are positive regulatory developments, there is still a big gap between companies’ reporting metrics and investors’ growing expectations of what constitutes “green”—constituting “green washing”. This issue compounds as green projects under the Belt and Road are often complex infrastructure projects, where unexpected (and negative) externalities may sometimes occur on the ground. In this regard, this paper advocates for robust risk management, where accurate forecasting of environmental harm and stakeholder engagement are implemented actively throughout the project's life cycle. Finally, adequate dispute resolution and avoidance measures should be adopted to protect stakeholders.
Coevolution of Weathering Front and Water Table
Authors: Wang Wei , Chen Po , Dueker Ken , Zhang Ye , Lee En‐jui , Mu Dawei , Keifer Ian , Jiao Jianying
Published: October 2021

Water is known to play an essential role in initiating and maintaining subsurface weathering reactions. However, the interaction between the weathering front and the water table is unclear and under intense debate. Here, we present a high‐fidelity, 3D image of a variably saturated weathering front beneath a granite terrain in the Laramie Range, Wyoming, constructed using full‐3D ambient‐noise adjoint tomography and calibrated with data from an extensive drilling and hydraulic well testing effort. The imaged weathering front between saprolite and weathered bedrock is overall shallower than the water table under ridge but deeper than water table under valleys. We propose that downward‐advancing weathering front coevolves with water table in a positive cycle that gradually flattens the water table, enhances the rate of groundwater drainage, and exposes underlying bedrock to weathering. As a result, we expect this cycle to become “sluggish” with time as water table gradient decreases.
Photon-counting distributed free-space spectroscopy
Authors: Yu Saifen , Zhang Zhen , Xia Haiyun , Dou Xiankang , Wu Tengfei , Hu Yihua , Li Manyi , Shangguan Mingjia , Wei Tianwen , Zhao Lijie , Wang Lu , Jiang Pu , Zhang Chengjun , You Lixing , Tao Leigang , Qiu Jiawei
Published: October 2021

Spectroscopy is a well-established nonintrusive tool that has played an important role in identifying and quantifying substances, from quantum descriptions to chemical and biomedical diagnostics. Challenges exist in accurate spectrum analysis in free space, which hinders us from understanding the composition of multiple gases and the chemical processes in the atmosphere. A photon-counting distributed free-space spectroscopy is proposed and demonstrated using lidar technique, incorporating a comb-referenced frequency-scanning laser and a superconducting nanowire single-photon detector. It is suitable for remote spectrum analysis with a range resolution over a wide band. As an example, a continuous field experiment is carried out over 72 h to obtain the spectra of carbon dioxide (CO2) and semi-heavy water (HDO, isotopic water vapor) in 6 km, with a range resolution of 60 m and a time resolution of 10 min. Compared to the methods that obtain only column-integrated spectra over kilometer-scale, the range resolution is improved by 2–3 orders of magnitude in this work. The CO2 and HDO concentrations are retrieved from the spectra acquired with uncertainties as low as ±1.2% and ±14.3%, respectively. This method holds much promise for increasing knowledge of atmospheric environment and chemistry researches, especially in terms of the evolution of complex molecular spectra in open areas.
Foveated glasses-free 3D display with ultrawide field of view via a large-scale 2D-metagrating complex
Authors: Hua Jianyu , Hua Erkai , Zhou Fengbin , Shi Jiacheng , Wang Chinhua , Duan Huigao , Hu Yueqiang , Qiao Wen , Chen Linsen
Published: October 2021

Glasses-free three-dimensional (3D) displays are one of the game-changing technologies that will redefine the display industry in portable electronic devices. However, because of the limited resolution in state-of-the-art display panels, current 3D displays suffer from a critical trade-off among the spatial resolution, angular resolution, and viewing angle. Inspired by the so-called spatially variant resolution imaging found in vertebrate eyes, we propose 3D display with spatially variant information density. Stereoscopic experiences with smooth motion parallax are maintained at the central view, while the viewing angle is enlarged at the periphery view. It is enabled by a large-scale 2D-metagrating complex to manipulate dot/linear/rectangular hybrid shaped views. Furthermore, a video rate full-color 3D display with an unprecedented 160° horizontal viewing angle is demonstrated. With thin and light form factors, the proposed 3D system can be integrated with off-the-shelf purchased flat panels, making it promising for applications in portable electronics.
Clinico-genetic findings in 509 frontotemporal dementia patients
Authors: Wagner Matias , Lorenz Georg , Volk Alexander E. , Brunet Theresa , Edbauer Dieter , Berutti Riccardo , Zhao Chen , Anderl-Straub Sarah , Bertram Lars , Danek Adrian , Deschauer Marcus , Dill Veronika , Fassbender Klaus , Fliessbach Klaus , Götze Katharina S. , Jahn Holger , Kornhuber Johannes , Landwehrmeyer Bernhard , Lauer Martin , Obrig Hellmuth , Prudlo Johannes , Schneider Anja , Schroeter Matthias L. , Uttner Ingo , Vukovich Ruth , Wiltfang Jens , Winkler Andrea S. , Zhou Qihui , Ludolph Albert C. ,   The German FTLD consortium, Oexle Konrad , Otto Markus , Diehl-Schmid Janine , Winkelmann Juliane
Published: October 2021

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
Astrocytes in the ventral pallidum extinguish heroin seeking through GAT-3 upregulation and morphological plasticity at D1-MSN terminals
Authors: Kruyer Anna , Dixon Danielle , Angelis Ariana , Amato Davide , Kalivas Peter W.
Published: October 2021

GABAergic projections from the nucleus accumbens core to the dorsolateral ventral pallidum are necessary for drug-conditioned cues to initiate relapse-like drug seeking. Astrocytes in the ventral pallidum are situated perisynaptically and regulate GABA transmission through expression of GABA uptake transporters, but whether they are involved in regulating drug seeking is unknown. To determine the contribution of ventral pallidal astrocytes to heroin seeking, we labeled astrocytes in male and female rats with a membrane-bound fluorescent tag and used confocal microscopy to quantify astroglial expression of the GABA transporter GAT-3 and astrocyte synaptic proximity after withdrawal from heroin self-administration and during 15 min of cued heroin seeking. We found that GAT-3 was upregulated in rats that had extinguished heroin seeking, but not in animals that were withdrawn from heroin without extinction training or in rats that extinguished sucrose seeking. When GAT-3 upregulation was reversed using a vivo-morpholino oligo, heroin seeking was restored in the extinguished context and extinction of cued heroin seeking was disrupted compared to control animals. Although astrocyte synaptic proximity was not altered overall after heroin withdrawal, examination of astrocyte proximity to accumbens D1- or D2-expressing afferents revealed a selective increase in astrocyte proximity with D1-expressing terminals during extinction of heroin self-administration. Experimentally-induced reduction of astrocyte synaptic proximity through knockdown of the astrocyte-selective actin-binding protein ezrin also markedly disrupted extinction of heroin seeking. Notably, GAT-3 or ezrin knockdown had no impact on context- or cue-induced seeking in sucrose-trained animals. These data show that astrocytes in the ventral pallidum undergo plasticity after extinction of heroin use that reduces seeking and highlight the importance of astrocyte-neuron interactions in shaping behaviors associated with opioid use disorder.
Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials
Authors: Kishi Taro , Ikuta Toshikazu , Matsuda Yuki , Sakuma Kenji , Okuya Makoto , Nomura Ikuo , Hatano Masakazu , Iwata Nakao
Published: October 2021

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks,n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56,n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70,n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61,n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50,n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
LncRNA RP11-465B22.8 triggers esophageal cancer progression by targeting miR-765/KLK4 axis
Authors: Hu Rui , Bi Rui , Jiang Lianyong , Xiao Haibo , Xie Xiao , Liu Hongtao , Hu Fengqing
Published: October 2021

LncRNAs play an important role in tumorigenesis and progression; however, the function and mechanisms of lncRNAs in esophageal cancer (EC) remain largely unclear. In this study, we screened the differentially expressed lncRNAs in EC by using RNA-seq and one of the most upregulated lncRNAs, lncRNA RP11-465B22.8, was further characterized. LncRNA RP11-465B22.8 was upregulated in EC tissues and high lncRNA RP11-465B22.8 expression was associated with poor survival of EC patients. Ectopic expression of lncRNA RP11-465B22.8 enhanced the proliferation, migration, and invasion of EC cells, whereas knockdown of lncRNA RP11-465B22.8 led to the opposite effects. Mechanistically, lncRNA RP11-465B22.8 sponged miR-765 to increase the expression of KLK4. Moreover, LncRNA RP11-465B22.8 could be delivered from EC cells to macrophages via exosomes and subsequently induced M2 macrophage-induced cell migration and invasion. Our findings revealed a novel lncRNA RP11-465B22.8/miR-765/KLK4 pathway in EC and indicated that lncRNA RP11-465B22.8 might be a potential target for EC therapy.
Phosphorylated α-synuclein aggregated in Schwann cells exacerbates peripheral neuroinflammation and nerve dysfunction in Parkinson’s disease through TLR2/NF-κB pathway
Authors: Sun Li , Jiang Wen-Wen , Wang Ye , Yuan Yong-Sheng , Rong Zhe , Wu Jing , Fan Yi , Lu Ming , Zhang Ke-Zhong
Published: October 2021

To investigate the mechanism of peripheral neuropathy in Parkinson’s disease (PD), we prepared a PD mice model by long-term exposure of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic PD pathology in humans and the sciatic nerves were taken for further research. It turned out that phosphorylated α-synuclein (p-α-syn) was significantly deposited in Schwann cells (SCs) of sciatic nerves possibly contributing to degenerated myelin SCs and atrophied axons in MPTP group. Further analysis confirmed that toll-like receptors (TLRs) were implicated with PD peripheral neuropathy, in which TLR2 exhibits the predominant expression. Increased expression of inflammatory factors about TLR2/nuclear factor kappa-B (NF-κB) pathway was noted in MPTP group compared to saline group, with proteins on other pathways showing no changes. Moreover, MPTP-challenged mice exhibited worse motor ability and damaged nerve conduction, implicating that p-α-syn neurotoxicity might be relevant to impairments of motor and sensory nerves. After the treatment of CU-CPT22, a TLR2 antagonist, p-α-syn accumulation, motor and sensory function were ameliorated in CU-CPT22 combined with MPTP group. Thus, we demonstrated that pathological p-α-syn might combine TLR2 to affect SCs activation, inflammatory response as well as motor and sensory function through TLR2/nuclear factor kappa-B (NF-κB) signaling pathway. This study firstly demonstrates a novel mechanism of p-α-syn accumulated in SCs of peripheral nerves, which extends our understanding on SCs-mediated peripheral neuroinflammation related to TLR2/NF-κB signaling pathway and sheds light on potential new therapeutic avenues for PD.
Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer
Authors: Gyamfi Jones , Yeo Joo Hye , Kwon Doru , Min Byung Soh , Cha Yoon Jin , Koo Ja Seung , Jeong Joon , Lee Jinu , Choi Junjeong
Published: October 2021

Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.
Evolution of HER2-low expression from primary to recurrent breast cancer
Authors: Miglietta Federica , Griguolo Gaia , Bottosso Michele , Giarratano Tommaso , Lo Mele Marcello , Fassan Matteo , Cacciatore Matilde , Genovesi Elisa , De Bartolo Debora , Vernaci Grazia , Amato Ottavia , Conte PierFranco , Guarneri Valentina , Dieci Maria Vittoria
Published: October 2021

About a half of HER2-negative breast cancer (BC) show HER2-low expression that can be targeted by new antibody-drug conjugates. The main aim of this study is to describe the evolution of HER2 expression from primary BC to relapse by including HER2-low category in both primary and recurrent BC samples. Patients with matched primary and relapse BC samples were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. A cutoff of >10% cells staining for HER2-positivity was applied. HER2-negative cases were sub-classified as HER2-low (IHC = 1 + /2+ and ISH not amplified), or HER2-0 (IHC-0). 547 patients were included. The proportion of HER2-low cases was 34.2% on the primary tumor and 37.3% on the relapse samples. Among HER2-negative cases, HER2-low status was more frequent in HR-positive vs triple-negative tumors (47.3% vs 35.4% on primary tumor samples, 53.8% vs 36.2% on relapse samples). The overall rate of HER2 discordance was 38.0%, mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). Among patients with a primary HER2-negative tumor, the rate of HER2 discordance was higher in HR-positive/HER2-negative vs triple-negative cases (45.5% vs 36.7% p = 0.170). This difference was mostly driven by cases switching from HER2-0 to HER2-low. HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new therapeutic opportunities in a relevant proportion of patients.
Hydrogel-based flexible materials for diabetes diagnosis, treatment, and management
Authors: Song Jiang , Zhang Yanni , Chan Siew Yin , Du Zhaoyi , Yan Yinjia , Wang Tengjiao , Li Peng , Huang Wei
Published: October 2021

Diabetes is a chronic metabolic disease characterized by high glucose concentration in blood. Conventional management of diabetes requires skin pricking and subcutaneous injection, causing physical pain and physiological issues to diabetic individuals. Hydrogels possess unique advantages such as lightweight, stretchability, biocompatibility, and biodegradability, offering the opportunities to be integrated as flexible devices for diabetes management. This review highlights the development of hydrogels as flexible materials for diabetes applications in glucose monitoring, insulin delivery, wound care, and cell transplantation in recent years. Challenges and prospects in the development of hydrogel-based flexible devices for personalized management of diabetes are discussed as well.
Optimising classification of Parkinson’s disease based on motor, olfactory, neuropsychiatric and sleep features
Authors: Bestwick Jonathan P. , Auger Stephen D. , Schrag Anette E. , Grosset Donald G. , Kanavou Sofia , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Noyce Alastair J.
Published: October 2021

Olfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson’s disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. PD patient data on smell (UPSIT), possible RBD (RBD Screening Questionnaire), and anxiety/depression (LADS) were taken from the Tracking Parkinson’s study (n = 1046). For motor impairment (BRAIN test) in PD cases, published data were supplemented (n = 87). Control data (HADS for anxiety/depression) were taken from the PREDICT-PD pilot study (n = 1314). UPSIT, RBDSQ, and anxiety/depression data were analysed using logistic regression to determine which items were associated with PD. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated. Sixteen odours were associated with PD; LRs for this set ranged from 0.005 to 5511. Six RBDSQ and seven anxiety/depression questions were associated with PD; LRs ranged from 0.35 to 69 and from 0.002 to 402, respectively. BRAIN test LRs ranged from 0.16 to 1311. For a 70% DR, the FPR was 2.4% for the 16 odours, 4.6% for anxiety/depression, 16.0% for the BRAIN test, and 20.0% for the RBDSQ. Specific selections of (prodromal) PD marker features rather than dichotomized marker test results optimize PD classification. Such optimized classification models could improve the ability of algorithms to detect prodromal PD; however, prospective studies are needed to investigate their value for PD-prediction models.
A cognitive fingerprint in human random number generation
Authors: Schulz Marc-André , Baier Sebastian , Timmermann Benjamin , Bzdok Danilo , Witt Karsten
Published: October 2021

Is the cognitive process of random number generation implemented via person-specific strategies corresponding to highly individual random generation behaviour? We examined random number sequences of 115 healthy participants and developed a method to quantify the similarity between two number sequences on the basis of Damerau and Levenshtein’s edit distance. “Same-author” and “different author” sequence pairs could be distinguished (96.5% AUC) based on 300 pseudo-random digits alone. We show that this phenomenon is driven by individual preference and inhibition of patterns and stays constant over a period of 1 week, forming a cognitive fingerprint.