bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of immunochemotherapy with R‐bendamustine or R‐CHOP for treatment naïve advanced‐stage follicular lymphoma: A subset analysis of the FOLL12 trial by Fondazione Italiana Linfomi
Authors: Nizzoli Maria E. , Manni Martina , Ghiggi Chiara , Pulsoni Alessandro , Musuraca Gerardo , Merli Michele , Califano Catello , Bari Alessia , Massaia Massimo , Conconi Annarita , Musto Pellegrino , Mannina Donato , Perrone Tommasina , Re Francesca , Galimberti Sara , Gini Guido , Capponi Monia , Vitolo Umberto , Usai Sara V. , Stefani Piero M. , Ballerini Filippo , Liberati Anna M. , Pennese Elsa , Pastore Domenico , Skrypets Tetiana , Catellani Hillary , Marcheselli Luigi , Federico Massimo , Luminari Stefano
Published: May 2023

We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II–IV follicular lymphoma (FL) grade 1–3a and high tumor burden. Patients were randomized 1:1 to receive either standard ICT followed by rituximab maintenance (RM) or the same ICT followed by a response‐adapted approach. ICT consisted of rituximab‐bendamustine (RB) or rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHOP), per physician's decision. A total of 786 patients were included in this analysis, 341 of whom received RB and 445 R‐CHOP. RB was more frequently prescribed to older subjects, females, patients without bulky disease, and those with grade 1–2 FL. After a median of 56 months of follow‐up, R‐CHOP and RB had similar progression‐free survival (PFS) (Hazard Ratio for RB 1.11, 95% CI 0.87–1.42, p = 0.392). Standard RM was associated with improved PFS compared to response‐adapted management both after R‐CHOP and RB. Grade 3–4 hematologic adverse events were more frequent with R‐CHOP during induction treatment and more frequent with RB during RM. Grade 3–4 infections were more frequent with RB. RB was also associated with a higher incidence of transformed FL. R‐CHOP and RB showed similar activity and efficacy, but with different safety profiles and long‐term events, suggesting that the treating physician should carefully select the most appropriate chemotherapy regimen for each patient based on patient's individual characteristics, choices, and risk profile.
Harmonized Multisite MRI‐Based Quantification of Human Liver Fat and Stiffness: A Pilot Study
Authors: Carmichael Owen T. , Singh Maninder , Bashir Adil , Russell Anne M. , Bolding Mark , Redden David T. , Storrs Judd , Willoughby William R. , Howard‐Claudio Candace , Hsia Daniel S. , Kimberly Robert P. , Gray Meagan E. , Ravussin Eric , Denney Thomas S.
Published: May 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end‐stage liver disease. NAFLD diagnosis and follow‐up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments.

Purpose/Hypothesis

The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors.

Study Type

Cohort.

Subjects

Four community‐dwelling adults with obesity.

Field strength/Sequence

1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE.

Assessment

Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing.

Statistical Tests

Linear regression in MATLAB, ICC analyses using SAS 9.4, one‐sided 95% confidence intervals for the ICC.

Results

PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF.

Conclusions

We demonstrated harmonization of PDFF, MRS, and MRE‐based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD.

Level of Evidence

2

Technical Efficacy Stage

2
Localized model order reduction and domain decomposition methods for coupled heterogeneous systems
Authors: Discacciati Niccolò , Hesthaven Jan S.
Published: May 2023

We propose a model order reduction technique to accurately approximate the behavior of multi‐component systems without any a‐priori knowledge of the coupled model. In the offline phase, we construct independent surrogate models by solving the local problems with parametrized interface boundary conditions, while we combine them using domain decomposition techniques during the online phase. We show the potential of the proposed approach in terms of accuracy, computational performance and robustness in a series of test cases, including nonlinear and multi‐physics problems.
Energy harvesting by piezoelectric polyvinylidene fluoride/zinc oxide/carbon nanotubes composite under cyclic uniaxial tensile deformation
Authors: Kumar Ajeet , Jaiswal Satish , Joshi Rita , Yadav Siddharth , Dubey Anshu , Sharma Divyam , Lahiri Debrupa , Lahiri Indranil
Published: May 2023

In this study, polyvinylidene fluoride (PVDF)/zinc oxide (ZnO)/carbon nanotubes (CNT) nano‐reinforced composites were fabricated by solution casting method. Addition of ZnO and CNTs nanoparticles enhances the electroactive polar β‐phase of PVDF nanocomposites. Formation of β‐phase in the composites were examined by Fourier transform infrared spectroscopy and X‐ray diffraction analysis. Piezoelectric properties were investigated by applying uniaxial cyclic tensile deformation with the help of mechanical tensile tester device. The maximum generated voltage peak of 1.32 V was observed in the case of the nano‐reinforced composite having 15% ZnO, with maximum current of 0.61 μA and power of 0.66 μW. The fabricated PVDF/ZnO/CNTs nano‐reinforced composites can be a good candidate for human motion‐based energy harvesting applications during walking, running and so forth in which uniaxial deformation occurs.
Development of High‐Reflectivity and Antireflection Dielectric Multilayer Mirrors for AlGaN‐Based Ultraviolet‐B Laser Diodes and their Device Applications
Authors: Yabutani Ayumu , Hasegawa Ryota , Kondo Ryosuke , Matsubara Eri , Imai Daichi , Iwayama Sho , Jin Yoshito , Matsumoto Tatsuya , Toramaru Masamitsu , Torii Hironori , Takeuchi Tetsuya , Kamiyama Satoshi , Miyake Hideto , Iwaya Motoaki
Published: May 2023

Fabrication techniques for high‐reflectivity (HR) and antireflection (AR) dielectric multilayer mirrors for AlGaN‐based ultraviolet‐B (UV‐B) laser diodes are developed. After depositing several dielectric materials and evaluating their complex refractive indices via ellipsometry, it is determined that SiO2 as a low‐refractive‐index material and Ta2O5 as a high‐refractive‐index material are appropriate material combinations in the UV‐B region at a light wavelength of ≈300 nm due to their low extinction coefficients and large refractive index difference. Based on these results, HR mirror with a reflectance of >99% in the UV‐B region at a center wavelength of 310 nm and an AR mirror with a reflectance of ≈8% in the same wavelength range are demonstrated; a mirror with reflectance that is almost equal to the designed value is demonstrated. Furthermore, these mirrors are coated on the respective edge surfaces of the UV‐B laser diodes. A comparison of the characteristics of the same device before and after edge coating reveals a reduction in the threshold current density of laser oscillation, whereas, simultaneously, an increase in slope efficiency and external differential quantum efficiency is observed. The improvement of these device characteristics, estimated from the above reflectance values, is confirmed to be almost theoretically explainable.
A review on phytoestrogens: Current status and future direction
Authors: Patra Surendra , Gorai Sukhamoy , Pal Soumitra , Ghosh Kuntal , Pradhan Shrabani , Chakrabarti Sudipta
Published: May 2023

Phytoestrogens are plant secondary metabolite that is structurally and functionally similar to mammalian estrogens, which have been shown to have various health benefits in humans. Isoflavones, coumestans, and lignans are the three major bioactive classes of phytoestrogens. It has a complicated mechanism of action involving an interaction with the nuclear estrogen receptor isoforms ERα and ERβ, with estrogen agonist and estrogen antagonist effects. Depending on their concentration and bioavailability in various plant sources, phytoestrogens can act as estrogen agonist or antagonists. Menopausal vasomotor symptoms, breast cancer, cardiovascular disease, prostate cancer, menopausal symptoms, and osteoporosis/bone health have all been studied using phytoestrogens as an additional standard hormone supplemental remedy. The botanical sources, techniques of identification, classification, side effects, clinical implications, pharmacological and therapeutic effects of their proposed mode of action, safety issues, and future directions for phytoestrogens have all been highlighted in this review.
The effect of phytochemicals in prediabetic patients: A systematic review of randomized controlled trials
Authors: Kiani Zahra , Amini Sepide , Askari Gholamreza , Kesharwani Prashant , Bagherniya Mohammad , Sahebkar Amirhossein
Published: May 2023

This study aimed to perform a systematic review to evaluate the effect of phytochemical consumption on the cardiometabolic parameters of prediabetic patients. A comprehensive search was conducted in PubMed, Scopus and ISI Web of Science, and Google Scholar up to June 2022 to find randomized controlled trials investigating the effects of phytochemicals alone or in combination with other nutraceuticals on prediabetic patients. Twenty‐three studies with 31 treatment arms comprising 2177 individuals were included in this study. Totally, in 21 arms, phytochemicals had positive effects on at least one measured cardiometabolic factor. In 13 out of 25 arms, fasting blood glucose (FBG) and in 10 out of 22 arms, hemoglobin A1c (HbA1c) significantly decreased compared with the control group. Furthermore, phytochemicals had beneficial effects on 2‐h postprandial and postprandial glucose, serum insulin, insulin sensitivity, and insulin resistance as well as inflammatory factors including high‐sensitivity C‐reactive protein (hs‐CRP), tumor necrosis factor α (TNF‐α), and interleukin 6 (IL‐6). Triglyceride (TG) was the abundant improved factor in the lipid profile. However, no sufficient evidence for notable positive effects of phytochemicals on blood pressure and anthropometry indices was observed. Phytochemical supplementation may have beneficial impacts on prediabetic patients by ameliorating glycemic status.
Multivariate disease progression modeling with longitudinal ordinal data
Authors: Poulet Pierre‐Emmanuel , Durrleman Stanley
Published: May 2023

Disease modeling is an essential tool to describe disease progression and its heterogeneity across patients. Usual approaches use continuous data such as biomarkers to assess progression. Nevertheless, categorical or ordinal data such as item responses in questionnaires also provide insightful information about disease progression. In this work, we propose a disease progression model for ordinal and categorical data. We built it on the principles of disease course mapping, a technique that uniquely describes the variability in both the dynamics of progression and disease heterogeneity from multivariate longitudinal data. This extension can also be seen as an attempt to bridge the gap between longitudinal multivariate models and the field of item response theory. Application to the Parkinson's progression markers initiative cohort illustrates the benefits of our approach: a fine‐grained description of disease progression at the item level, as compared to the aggregated total score, together with improved predictions of the patient's future visits. The analysis of the heterogeneity across individual trajectories highlights known disease trends such as tremor dominant or postural instability and gait difficulties subtypes of Parkinson's disease.
Long‐Cycling‐Life Sodium‐Ion Battery Using Binary Metal Sulfide Hybrid Nanocages as Anode
Authors: Huang Xiaofei , Tao Kehao , Han Tianli , Li Jinjin , Zhang Huigang , Hu Chaoquan , Niu Junjie , Liu Jinyun
Published: May 2023

Due to the relatively high capacity and lower cost, transition metal sulfides (TMS) as anode show promising potential in sodium‐ion batteries (SIBs). Herein, a binary metal sulfide hybrid consisting of carbon encapsulated CoS/Cu2S nanocages (CoS/Cu2S@C‐NC) is constructed. The interlocked hetero‐architecture filled with conductive carbon accelerates the Na+/e− transfer, thus leading to improved electrochemical kinetics. Also the protective carbon layer can provide better volume accommondation upon charging/discharging. As a result, the battery with CoS/Cu2S@C‐NC as anode displays a high capacity of 435.3 mAh g−1 after 1000 cycles at 2.0 A g−1 (≈3.4 C). Under a higher rate of 10.0 A g−1 (≈17 C), a capacity of as high as 347.2 mAh g−1 is still remained after long 2300 cycles. The capacity decay per cycle is only 0.017%. The battery also exhibits a better temperature tolerance at 50 and −5 °C. A low internal impedance analyzed by X‐ray diffraction patterns and galvanostatic intermittent titration technique, narrow band gap, and high density of states obtained by first‐principle calculations of the binary sulfides, ensure the rapid Na+/e− transport. The long‐cycling‐life SIB using binary metal sulfide hybrid nanocages as anode shows promising applications in versatile electronic devices.
Heterostructured Interface Enables Uniform Zinc Deposition for High‐Performance Zinc‐Ion Batteries
Authors: Jiang Zhenjing , Yin Kuibo , Pan Rui , Zhang Guoju , Cui Fuhan , Luo Kailin , Xiong Yuwei , Sun Litao
Published: May 2023

Zinc metal has considerable potential as a high‐energy anode material for aqueous batteries due to its high theoretical capacity and environmental friendliness. However, dendrite growth and parasitic reactions at the electrode/electrolyte interface remain two serious problems for the Zn metal anode. Here, the heterostructured interface of ZnO rod array and CuZn5 layer is fabricated on the Zn substrate (ZnCu@Zn) to address these two issues. The zincophilic CuZn5 layer with abundant nucleation sites ensures the initial uniform Zn nucleation process during cycling. Meanwhile, the ZnO rod array grown on the surface of the CuZn5 layer can guide the subsequent homogeneous Zn deposition via spatial confinement and electrostatic attraction effects, leading to the dendrite‐free Zn electrodeposition process. Consequently, the derived ZnCu@Zn anode exhibits an ultra‐long lifespan of up to 2500 h with symmetric cells at the current density and capacity of 0.5 mA cm−2/0.5 mA h cm−2. Besides, a remarkable cyclability (75% retention for 2500 cycles at 2 A g−1) is achieved in the ZnCu@Zn||MnO2 full cell with a capacity of 139.7 mA h g−1. This heterostructured interface with specific functional layers provides a feasible strategy for the design of high‐performance metal anodes.
Diagnosis of Parkinson's Disease via the Metabolic Fingerprint in Saliva by Deep Learning
Authors: Xu Wei , Chen Lina , Cai Guoen , Gao Ming , Chen Yifan , Pu Jun , Chen Xiaochun , Liu Ning , Ye Qinyong , Qian Kun
Published: May 2023

Parkinson's disease (PD) is the second cause of the neurodegenerative disorder, affecting over 6 million people worldwide. The World Health Organization estimated that population aging will cause global PD prevalence to double in the coming 30 years. Optimal management of PD shall start at diagnosis and requires both a timely and accurate method. Conventional PD diagnosis needs observations and clinical signs assessment, which are time‐consuming and low‐throughput. A lack of body fluid diagnostic biomarkers for PD has been a significant challenge, although substantial progress has been made in genetic and imaging marker development. Herein, a platform that noninvasively collects saliva metabolic fingerprinting (SMF) by nanoparticle‐enhanced laser desorption–ionization mass spectrometry with high‐reproducibility and high‐throughput, using ultra‐small sample volume (down to 10 nL), is developed. Further, excellent diagnostic performance is achieved with an area‐under‐the‐curve of 0.8496 (95% CI: 0.7393–0.8625) by constructing deep learning model from 312 participants. In conclusion, an alternative solution is provided for the molecular diagnostics of PD with SMF and metabolic biomarker screening for therapeutic intervention.
Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result
Authors: Scott F. , Smet M.‐E. , Elhindi J. , Mogra R. , Sunderland L. , Ferreira A. , Menezes M. , Meagher S. , McLennan A.
Published: May 2023

Objective

To evaluate the impact of detailed late first‐trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high‐risk non‐invasive prenatal test (NIPT) result for various chromosomal abnormalities.

Methods

This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first‐line screening test. Data were collected from pre‐NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome‐wide analysis for the last 2 years.

Results

Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high‐risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high‐risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively.

Conclusions

LFTU after a high‐risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at‐risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high‐risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Road Network Representation Learning with Vehicle Trajectories
Authors: Schestakov Stefan , Heinemeyer Paul , Demidova Elena
Published: May 2023

Spatio-temporal traffic patterns reflecting the mobility behavior of road users are essential for learning effective general-purpose road representations. Such patterns are largely neglected in state-of-the-art road representation learning, mainly focusing on modeling road topology and static road features. Incorporating traffic patterns into road network representation learning is particularly challenging due to the complex relationship between road network structure and mobility behavior of road users. In this paper, we present TrajRNE – a novel trajectory-based road embedding model incorporating vehicle trajectory information into road network representation learning. Our experiments on two real-world datasets demonstrate that TrajRNE outperforms state-of-the-art road representation learning baselines on various downstream tasks.
A Composite Indicator to Describe Digital Technology in Europe
Authors: Tebala Domenico , Marino Domenico , Bianchino Antonella
Published: May 2023

The “Digital Europe” program is a central element of the Commission's comprehensive response to the challenge of digital transformation and is included in the proposal on the Multiannual Financial Framework (MFF) for the period 2021–2027. Its aim is to provide a spending instrument adapted to the operational requirements of capacity building in the areas identified by the European Council, as well as to exploit the synergies between them. The program aims, among other things, to develop and strengthen basic skills in artificial intelligence, such as data resources and archives of artificial intelligence algorithms and make them accessible to all enterprises and public administrations; ensure that the essential capabilities needed to secure the EU's digital economy, society and democracy are available and accessible to the EU public sector and businesses, as well as improve the competitiveness of the EU cybersecurity industry; expand the optimal use of digital capabilities, in particular high-performance computing, artificial intelligence and cyber-security, in all sectors of the economy, in sectors of public interest and in society, including the implementation of interoperable solutions in areas of public interest, as well as facilitating access to technology and know-how for all enterprises.

To better understand the phenomenon, this study aims to analyse the use of digital technology among European enterprises through a composite index of artificial intelligence (AI) and information technologies (ICT) (using the Wellness Methodology Fair and Sustainable) to measure the territorial gaps and to know the European countries more or less inclined to use it.

For this purpose, this contribution develops with the following structure:

description of the theoretical reference framework and the indicators used to regard “artificial intelligence” and “information technologies”;

description of the methodology for the construction of the composite indicator;

description of the results, also through a geo-referenced map of European countries willing to use digital technology;

conclusions
Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19
Authors: Poma Anello Marcello , Bonuccelli Diana , Macerola Elisabetta , Niballi Sara , Basolo Alessio , Santini Ferruccio , Basolo Fulvio , Toniolo Antonio
Published: May 2023

Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes.

Key messages

• SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid.

• Infection of endocrine organs induces interferon response.

• Interferon response is observed in adipose tissue independently of virus presence.

• Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19.

• Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
Ultra-short-term prediction of LOD using LSTM neural networks
Authors: Gou Junyang , Kiani Shahvandi Mostafa , Hohensinn Roland , Soja Benedikt
Published: May 2023

Earth orientation parameters (EOPs) are essential in geodesy, linking the terrestrial and celestial reference frames. Due to the time needed for data processing and combining different space geodetic techniques, EOPs of the highest quality suffer latencies from several days to several weeks. However, real-time EOPs are needed for multiple geodetic and geophysical applications. Predictions of EOPs in the ultra-short term can overcome the latency of EOP products to a certain extent. Traditionally, predictions are performed using statistical methods. With the rapid expansion of computing capacity and data volume, the application of deep learning in geodesy has become increasingly promising in recent years. In particular, the Long Short-Term Memory (LSTM) neural networks, one of the most popular Recurrent Neural Network varieties, are promising for geodetic time series prediction. In this study, we investigate the potential of using LSTM to predict daily length of day (LOD) variations up to ten days in advance, accounting for the contribution of effective angular momentum (EAM). The data are first preprocessed to obtain residuals by combining physical and statistical models. Then, we employ LSTM networks to predict the LOD residuals using both LOD and EAM residuals as input features. Our methods outperform all other state-of-the-art methods in the first eight days with an improvement of up to 43% under the first EOP Prediction Comparison Campaign conditions. In addition, we assess the performance of LOD predictions using more extended time series to consider the improvements of EOP products over the last decade. The results show that extending data volume significantly increases the performance of the methods.
New Quantum Invariants of Planar Knotoids
Authors: Moltmaker Wout , van der Veen Roland
Published: May 2023

In this paper we discuss the applications of knotoids to modelling knots in open curves and produce new knotoid invariants. We show how invariants of knotoids generally give rise to well-behaved measures of how much an open curve is knotted. We define biframed planar knotoids, and construct new invariants of these objects that can be computed in polynomial time. As an application of these invariants we improve the classification of planar knotoids with up to five crossings by distinguishing two pairs of prime knotoids that were conjectured to be distinct by Goundaroulis et al.
Patterns of small involuntary fixation saccades (SIFSs) in different neurodegenerative diseases: the role of noise
Authors: Becker Wolfgang , Behler Anna , Vintonyak Olga , Kassubek Jan
Published: May 2023

During the attempt to steadily fixate at a single spot, sequences of small involuntary fixation saccades (SIFSs, known also as microsaccades οr intrusions) occur which form spatio-temporal patterns such as square wave jerks (SWJs), a pattern characterised by alternating centrifugal and centripetal movements of similar magnitude. In many neurodegenerative disorders, SIFSs exhibit elevated amplitudes and frequencies. Elevated SIFS amplitudes have been shown to favour the occurrence of SWJs (“SWJ coupling”). We analysed SIFSs in different subject groups comprising both healthy controls (CTR) and patients with amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP), i.e. two neurodegenerative diseases with completely different neuropathological basis and different clinical phenotypes. We show that, across these groups, the relations between SIFS amplitude and the relative frequency of SWJ-like patterns and other SIFS characteristics follow a common law. As an explanation, we propose that physiological and technical noise comprises a small, amplitude-independent component that has little effect on large SIFSs, but causes considerable deviations from the intended amplitude and direction of small ones. Therefore, in contrast to large SIFSs, successive small SIFSs have a lower chance to meet the SWJ similarity criteria. In principle, every measurement of SIFSs is affected by an amplitude-independent noise background. Therefore, the dependence of SWJ coupling on SIFS amplitude will probably be encountered in almost any group of subjects. In addition, we find a positive correlation between SIFS amplitude and frequency in ALS, but none in PSP, suggesting that the elevated amplitudes might arise at different sites in the two disorders.
Importance of coastal vegetated habitats for tropical marine fishes in the Red Sea
Authors: Dunne Aislinn , Coker Darren J. , Kattan Alexander , Tietbohl Matthew D. , Ellis Joanne I. , Jones Burton , Berumen Michael
Published: May 2023

Marine vegetated habitats such as seagrass, mangroves, and macroalgae are common along tropical coastlines globally and provide habitats for a diversity of fishes, including juvenile fish and species found on coral reefs. Understanding the use of these habitats by different fish species and life stages is fundamental to spatial planning, fisheries management, and conservation. While previous studies have focused on the habitat potential of seagrass, macroalgae, or mangroves for coral reef fish independently, it is important to consider their combined roles, as tropical seascapes are often mosaics of such habitats. In this study, we evaluated habitat associations across life stages for fish species in coral reefs, seagrasses, macroalgae, and mangroves in Saudi Arabia’s central Red Sea. Through in situ visual surveys, we documented 36% of local coral reef fish species in one or more vegetated habitats, with the fraction of coral reef species utilizing macroalgae or seagrass much greater than that of mangroves (29%, 18%, and 6%, respectively). Mangroves hosted mainly juvenile fish (83% of observed population) and macroalgae hosted the largest proportion of herbivores (39% of observed population), suggesting that each environment offers different combinations of resources (food and shelter), and a mix of these habitats could support biological connectivity across a seascape. Species targeted by local fisheries made up 37% of the species documented in vegetated habitats. The use of multiple habitat types by juvenile and commercially important fishes in the Red Sea underscores the need for a holistic approach to habitat protection.

Graphical abstract
Mesenchymal and induced pluripotent stem cell–based therapeutics: a comparison
Authors: Teale Misha A. , Schneider Samuel , Eibl Dieter , van den Bos Christian , Neubauer Peter , Eibl Regine
Published: May 2023

Stem cell–based cell therapeutics and especially those based on human mesenchymal stem cells (hMSCs) and induced pluripotent stem cells (hiPSCs) are said to have enormous developmental potential in the coming years. Their applications range from the treatment of orthopedic disorders and cardiovascular diseases to autoimmune diseases and even cancer. However, while more than 27 hMSC-derived therapeutics are currently commercially available, hiPSC-based therapeutics have yet to complete the regulatory approval process. Based on a review of the current commercially available hMSC-derived therapeutic products and upcoming hiPSC-derived products in phase 2 and 3, this paper compares the cell therapy manufacturing process between these two cell types. Moreover, the similarities as well as differences are highlighted and the resulting impact on the production process discussed. Here, emphasis is placed on (i) hMSC and hiPSC characteristics, safety, and ethical aspects, (ii) their morphology and process requirements, as well as (iii) their 2- and 3-dimensional cultivations in dependence of the applied culture medium and process mode. In doing so, also downstream processing aspects are covered and the role of single-use technology is discussed.

Key points

• Mesenchymal and induced pluripotent stem cells exhibit distinct behaviors during cultivation

• Single-use stirred bioreactor systems are preferred for the cultivation of both cell types

• Future research should adapt and modify downstream processes to available single-use devices
Formamide-based production of amines by metabolically engineering Corynebacterium glutamicum
Authors: Schwardmann Lynn S. , Wu Tong , Dransfeld Aron K. , Lindner Steffen N. , Wendisch Volker F.
Published: May 2023

Formamide is rarely used as nitrogen source
by microorganisms. Therefore, formamide and formamidase have been used as protection system to allow for growth under non-sterile conditions and for non-sterile production of acetoin, a product lacking nitrogen. Here, we equipped Corynebacterium glutamicum, a renowned workhorse for industrial amino acid production for 60 years, with formamidase from Helicobacter pylori 26695, enabling growth with formamide as sole nitrogen source. Thereupon, the formamide/formamidase system was exploited for efficient formamide-based production of the nitrogenous compounds L-glutamate, L-lysine, N-methylphenylalanine, and dipicolinic acid by transfer of the formamide/formamidase system to established producer strains. Stable isotope labeling verified the incorporation of nitrogen from formamide into biomass and the representative product L-lysine. Moreover, we showed ammonium leakage during formamidase-based access of formamide to be exploitable to support growth of formamidase-deficient C. glutamicum in co-cultivation and demonstrated that efficient utilization of formamide as sole nitrogen source benefitted from overexpression of formate dehydrogenase.

Key points

• C. glutamicum was engineered to access formamide.

• Formamide-based production of nitrogenous compounds was established.

• Nitrogen cross-feeding supported growth of a formamidase-negative strain.
Effects of different fracture parameters on microseisms induced by hydraulic fracturing
Authors: Shan Kun , Zheng Yanhao , Zhang Yanjun , Shan Zhigang , Li Zhihai
Published: May 2023

The microseism induced by hydraulic fracturing is of great significance to the development of geothermal reservoirs and the site selection of geothermal systems. In this study, taking geothermal field data from Qiabuqia as a geological reference, several models are developed for hydraulic fracturing simulations based on the models included in the commercial FracMan™ software suit. A series of numerical simulations are carried out to explore the effects of different fracture parameters, including the existence of faults, in-situ stress state, fracture occurrence, and fracture distribution near faults, on the induced microseisms. The results show that during hydraulic fracturing, the existence of faults does affect the propagation direction of the newly generated fractures, causing the fractures to extend toward the fault. The faults also increase the magnitude of microseismic events and make the distribution of microseismic events farther. Under three different in-situ stress states, the magnitudes of induced microseisms and the distance between microseismic events and injection wells are different, mainly due to the different forms of energy release. The total energy of induced microseisms under the reverse faulting stress state (RF) is the largest. Under the normal faulting stress state (NF), the number of microseismic events is the least, with only 28, and these microseismic events are concentrated near the well, with the farthest distribution distance of only 150 m. The fracture occurrence has a significant effect on induced microseisms, mainly affecting the number and distribution range of induced microseisms. With the same number of fractures, as the fracture concentration to the fault increases, both the maximum magnitude and the farthest distribution distance of the induced microseisms increase.
137Cs and isotopic ratios of Pu and U in lichens and mosses from Russian Arctic areas
Authors: Dutheil Paul , Paatero Jussi , Rodushkin Ilia , Sundström Timo , Leppänen Ari-Pekka , Salminen-Paatero Susanna
Published: May 2023

Knowledge of past anthropogenic sources of radionuclide contamination in Russian Arctic areas is important to assess the radioecological situation of these less-studied regions. Therefore, we investigated the sources of radionuclide contamination in Russian Arctic in the 1990s. Lichen and moss samples were collected from 1993 to 1996 in Kola Peninsula, Franz Josef Land, and few other locations. The activity concentration of 137Cs was determined from the archived samples by gamma spectrometry in 2020. After radiochemical separation of Pu and U isotopes from the lichens and mosses, mass ratios 240Pu/239Pu, 234U/238U, 235U/238U, and 236U/238U were determined by mass spectrometry. 137Cs activity concentrations at the sampling date were found to vary from 3.1 ± 1.4 (Inari, Finnish-Russian border) to 303 ± 7 (Kola Peninsula) Bq/kg. The ranges of isotopic ratios were 0.0592 ± 0.0007 to 0.253 ± 0.082 for 240Pu/239Pu, (4.89 ± 3.91) × 10−5 to (6.86 ± 0.04) × 10−5 for 234U/238U, 0.0072104(21) to 0.007376(41) for 235U/238U, and from below 1 × 10−7 to (2.65 ± 0.19) × 10−6 for 236U/238U, respectively. Based on the measured isotopic ratios and characteristic isotopic ratios of known contamination sources, the main Pu and U sources in the sampled lichens and mosses are global fallout, the Chernobyl accident, and possibly local nuclear activities. These results contribute to further understanding of past nuclear events and resulting nuclear contamination in Russian Arctic terrestrial areas.
Identifying Novel Drug Targets for Epilepsy Through a Brain Transcriptome-Wide Association Study and Protein-Wide Association Study with Chemical-Gene-Interaction Analysis
Authors: Lu Mengnan , Feng Ruoyang , Zhang Chenglin , Xiao Yanfeng , Yin Chunyan
Published: May 2023

Epilepsy is a severe neurological condition affecting 50–65 million individuals worldwide that can lead to brain damage. Nevertheless, the etiology of epilepsy remains poorly understood. Meta-analyses of genome-wide association studies involving 15,212 epilepsy cases and 29,677 controls of the ILAE Consortium cohort were used to conduct transcriptome-wide association studies (TWAS) and protein-wide association studies (PWAS). Furthermore, a protein-protein interaction (PPI) network was generated using the STRING database, and significant epilepsy-susceptible genes were verified using chip data. Chemical-related gene set enrichment analysis (CGSEA) was performed to determine novel drug targets for epilepsy. TWAS analysis identified 21,170 genes, of which 58 were significant (TWASfdr < 0.05) in ten brain regions, and 16 differentially expressed genes were verified based on mRNA expression profiles. The PWAS identified 2249 genes, of which 2 were significant (PWASfdr < 0.05). Through chemical-gene set enrichment analysis, 287 environmental chemicals associated with epilepsy were identified. We identified five significant genes (WIPF1, IQSEC1, JAM2, ICAM3, and ZNF143) that had causal relationships with epilepsy. CGSEA identified 159 chemicals that were significantly correlated with epilepsy (Pcgsea < 0.05), such as pentobarbital, ketone bodies, and polychlorinated biphenyl. In summary, we performed TWAS, PWAS (for genetic factors), and CGSEA (for environmental factors) analyses and identified several epilepsy-associated genes and chemicals. The results of this study will contribute to our understanding of genetic and environmental factors for epilepsy and may predict novel drug targets.
A biologically inspired decision-making system for the autonomous adaptive behavior of social robots
Authors: Maroto-Gómez Marcos , Castro-González Álvaro , Malfaz María , Salichs Miguel Ángel
Published: May 2023

The decisions made by social robots while they fulfill their tasks have a strong influence on their performance. In these contexts, autonomous social robots must exhibit adaptive and social-based behavior to make appropriate decisions and operate correctly in complex and dynamic scenarios. This paper presents a Decision-Making System for social robots working on long-term interactions like cognitive stimulation or entertainment. The Decision-making System employs the robot’s sensors, user information, and a biologically inspired module to replicate how human behavior emerges in the robot. Besides, the system personalizes the interaction to maintain the users’ engagement while adapting to their features and preferences, overcoming possible interaction limitations. The system evaluation was in terms of usability, performance metrics, and user perceptions. We used the Mini social robot as the device where we integrated the architecture and carried out the experimentation. The usability evaluation consisted of 30 participants interacting with the autonomous robot in 30 min sessions. Then, 19 participants evaluated their perceptions of robot attributes of the Godspeed questionnaire by playing with the robot in 30 min sessions. The participants rated the Decision-making System with excellent usability (81.08 out of 100 points), perceiving the robot as intelligent (4.28 out of 5), animated (4.07 out of 5), and likable (4.16 out of 5). However, they also rated Mini as unsafe (security perceived as 3.15 out of 5), probably because users could not influence the robot’s decisions.
All-Polymer Solar Cells and Photodetectors with Improved Stability Enabled by Terpolymers Containing Antioxidant Side Chains
Authors: Zhang Chunyang , Song Ao , Huang Qiri , Cao Yunhao , Zhong Zuiyi , Liang Youcai , Zhang Kai , Liu Chunchen , Huang Fei , Cao Yong
Published: May 2023

It is of vital importance to improve the long-term and photostability of organic photovoltaics, including organic solar cells (OSCs) and organic photodetectors (OPDs), for their ultimate industrialization. Herein, two series of terpolymers featuring with an antioxidant butylated hydroxytoluene (BHT)-terminated side chain, PTzBI-EHp-BTBHTx and N2200-BTBHTx (x = 0.05, 0.1, 0.2), are designed and synthesized. It was found that incorporating appropriate ratio of benzothiadiazole (BT) with BHT side chains on the conjugated backbone would induce negligible effect on the molecular weight, absorption spectra and energy levels of polymers, however, which would obviously enhance the photostability of these polymers. Consequently, all-polymer solar cells (all-PSCs) and photodetectors were fabricated, and the all-PSC based on PTzBI-EHp-BTBHT0.05: N2200 realized an optimal power conversion efficiency (PCE) approaching ~ 10%, outperforming the device based on pristine PTzBI-EHp: N2200. Impressively, the all-PSCs based on BHT-featuring terpolymers displayed alleviated PCEs degradation under continuous irradiation for 300 h due to the improved morphological and photostability of active layers. The OPDs based on BHT-featuring terpolymers achieved a lower dark current at − 0.1 bias, which could be stabilized even after irradiation over 400 h. This study provides a feasible approach to develop terpolymers with antioxidant efficacy for improving the lifetime of OSCs and OPDs.
Response of Salmonella enterica serovar Typhimurium to alginate oligosaccharides fermented with fecal inoculum: integrated transcriptomic and metabolomic analyses
Authors: Cheng Jiaying , Xiao Mengshi , Ren Xinmiao , Secundo Francesco , Yu Ying , Nan Shihao , Chen Weimiao , Zhu Changliang , Kong Qing , Huang Youtao , Fu Xiaodan , Mou Haijin
Published: May 2023

Alginate oligosaccharides (AOS), extracted from marine brown algae, are a common functional feed additive; however, it remains unclear whether they modulate the gut microbiota and microbial metabolites. The response of Salmonella enterica serovar Typhimurium, a common poultry pathogen, to AOS fermented with chicken fecal inocula was investigated using metabolomic and transcriptomic analyses. Single-strain cultivation tests showed that AOS did not directly inhibit the growth of S. Typhimurium. However, when AOS were fermented by chicken fecal microbiota, the supernatant of fermented AOS (F-AOS) exhibited remarkable antibacterial activity against S. Typhimurium, decreasing the abundance ratio of S. Typhimurium in the fecal microbiota from 18.94 to 2.94%. Transcriptomic analyses showed that the 855 differentially expressed genes induced by F-AOS were mainly enriched in porphyrin and chlorophyll metabolism, oxidative phosphorylation, and Salmonella infection-related pathways. RT-qPCR confirmed that F-AOS downregulated key genes involved in flagellar assembly and the type III secretory system of S. Typhimurium, indicating metabolites in F-AOS can influence the growth and metabolism of S. Typhimurium. Metabolomic analyses showed that 205 microbial metabolites were significantly altered in F-AOS. Among them, the increase in indolelactic acid and 3-indolepropionic acid levels were further confirmed using HPLC. This study provides a new perspective for the application of AOS as a feed additive against pathogenic intestinal bacteria.
Variation in eye lenses of two new Late Devonian phacopid trilobites from western Junggar, NW China
Authors: Zong Rui-Wen
Published: May 2023

The suborder Phacopina, characterized by schizochroal eyes, is among the most common groups of trilobites in Devonian strata. The marine sediments of the Famennian in western Junggar, Xinjiang, contain abundant low-disparity phacopids, which have previously been designated toOmegops accipitrinus mobilis,Phacops circumspectans tuberculosus, andOmegops corneliuson the basis of small numbers of poorly preserved specimens. In this study, these phacopids were identified as two new species ofOmegops,O. honggulelengensisn. sp. andO. xiangin. sp., on the basis of nearly 200 well-preserved specimens. The intraspecific variations of eye lenses of these specimens were quantitatively analyzed. On the basis of differences in the total number, number of dorsoventral files, and arrangement of the eye lenses, the absence of lenses in the middle part of the visual surface, and asymmetry of the number and/or arrangement of lenses in the two eyes, it was concluded that the reasons for intraspecific variation in eye lenses of Late DevonianOmegopsfrom western Junggar were different from previously described factors but were likely genetic or embryological malfunctions or abnormalities caused by pathological conditions. Diversity of lenses in the schizochroal eyes shows that the number and arrangement of eye lenses was not stable in Phacopina. Therefore, many specimens are needed for quantitative study to determine the true characteristics of the number or arrangement of eye lenses when these features are used in the systematic taxonomy of Phacopina.

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