bluuebunny/crossref_metadata_2025 huggingface dataset:
A single centre prospective study of three device-assisted therapies for Parkinson’s disease
Authors: Morales-Briceño Hugo , Ha Ainhi D. , Chiang Han-Lin , Tai Yicheng , Chang Florence C. F. , Tsui David S. , Griffith Jane , Galea Donna , Kim Samuel D. , Cruse Belinda , Mahant Neil , Fung Victor S. C.
Published: June 2023

Comparative studies assessing outcomes with the three device-assisted therapies could help to individualise treatment for patients living with Parkinson’s disease. We designed a single-centre non-randomised prospective observational study assessing the quality of life (QoL), motor and non-motor outcomes at 6 and 12-months in patients treated with subcutaneous apomorphine continuous 16-hours infusion (APO), levodopa-carbidopa intestinal gel (LCIG) or subthalamic nucleus deep brain stimulation (STN-DBS). In this study, 66 patients were included (13 APO; 19 LCIG; 34 STN-DBS). At baseline, cognitive, non-motor and motor scores were significantly less severe in the STN-DBS group, whereas the LCIG group had a longer disease duration and higher non-motor scores. In the APO group, there were no statistically significant changes in non-motor, motor and QoL scales. The LCIG group had significant changes in QoL and motor scales that were significant after multiple comparison analysis at 6 and 12-months. The STN-DBS group showed improvement in QoL scores and non-motor and motor scores at 6 and 12-months after multiple comparison analysis. In this real-life prospective study, device-assisted therapies showed differences in their effects on QoL and motor and non-motor function at 12-months. However, there were also differences in baseline characteristics of the patient groups that were not based on pre-determined selection criteria. Differences in characteristics of patients offered and/or treatment with different device-assisted therapies may reflect within-centre biases that may, in turn, influence perceptions of treatment efficacy or outcomes. Treatment centres should be aware of this potential confounder when assessing and offering device-assisted treatment options to their patients and potential baseline differences need to be taken into consideration when comparing the results of non-randomised studies.
Predictive value of abbreviated olfactory tests in prodromal Parkinson disease
Authors: Vaswani Pavan A. , Morley James F. , Jennings Danna , Siderowf Andrew , Marek Kenneth ,   the PARS Investigators, Seibyl John , Stern Matthew , Russell David , Sethi Kapil , Frank Samuel , Simuni Tanya , Hauser Robert , Ravina Bernard , Richards Irene , Liang Grace , Adler Charles , Saunders-Pullman Rachel , Evatt Marian L. , Lai Eugene , Subramanian Indu , Hogarth Penelope , Chung Kathryn
Published: June 2023

There is disagreement in the literature whether olfaction may show specific impairments in Parkinson Disease (PD) and if olfactory tests comprised of selected odors could be more specific for diagnosis. We sought to validate previously proposed subsets of the University of Pennsylvania Smell Identification Test (UPSIT) odors for predicting conversion to PD in an independent, prodromal cohort. Conversion to PD was assessed in 229 participants in the Parkinson At Risk Study who completed baseline olfactory testing with the UPSIT and up to 12 years of clinical and imaging evaluations. No commercially available or proposed subset performed better than the full 40-item UPSIT. The proposed “PD-specific” subsets also did not perform better than expected by chance. We did not find evidence for selective olfactory impairment in Parkinson disease. Shorter odor identification tests, including commercially available 10–12 item tests, may have utility for ease of use and cost, but not for superior predictive value.
Genome-wide case-only analysis of gene-gene interactions with known Parkinson’s disease risk variants reveals link between LRRK2 and SYT10
Authors: Aleknonytė-Resch Milda , Trinh Joanne , Leonard Hampton , Delcambre Sylvie , Leitão Elsa , Lai Dongbing , Smajić Semra , Orr-Urtreger Avi , Thaler Avner , Blauwendraat Cornelis , Sharma Arunabh , Makarious Mary B. , Kim Jonggeol Jeff , Lake Julie , Rahmati Pegah , Freitag-Wolf Sandra , Seibler Philip , Foroud Tatiana , Singleton Andrew B. ,   The International Parkinson Disease Genomics Consortium, Grünewald Anne , Kaiser Frank , Klein Christine , Krawczak Michael , Dempfle Astrid
Published: June 2023

The effects of one genetic factor upon Parkinson’s disease (PD) risk may be modified by other genetic factors. Such gene-gene interaction (G×G) could explain some of the ‘missing heritability’ of PD and the reduced penetrance of known PD risk variants. Using the largest single nucleotide polymorphism (SNP) genotype data set currently available for PD (18,688 patients), provided by the International Parkinson’s Disease Genomics Consortium, we studied G×G with a case-only (CO) design. To this end, we paired each of 90 SNPs previously reported to be associated with PD with one of 7.8 million quality-controlled SNPs from a genome-wide panel. Support of any putative G×G interactions found was sought by the analysis of independent genotype-phenotype and experimental data. A total of 116 significant pairwise SNP genotype associations were identified in PD cases, pointing towards G×G. The most prominent associations involved a region on chromosome 12q containing SNP rs76904798, which is a non-coding variant of the LRRK2 gene. It yielded the lowest interaction p-value overall with SNP rs1007709 in the promoter region of the SYT10 gene (interaction OR = 1.80, 95% CI: 1.65–1.95, p = 2.7 × 10−43). SNPs around SYT10 were also associated with the age-at-onset of PD in an independent cohort of carriers of LRRK2 mutation p.G2019S. Moreover, SYT10 gene expression during neuronal development was found to differ between cells from affected and non-affected p.G2019S carriers. G×G interaction on PD risk, involving the LRRK2 and SYT10 gene regions, is biologically plausible owing to the known link between PD and LRRK2, its involvement in neural plasticity, and the contribution of SYT10 to the exocytosis of secretory vesicles in neurons.
Multicomponent intranasal adjuvant for mucosal and durable systemic SARS-CoV-2 immunity in young and aged mice
Authors: Jangra Sonia , Landers Jeffrey J. , Laghlali Gabriel , Rathnasinghe Raveen , Warang Prajakta , Park Seok-Chan , O’Konek Jessica. J. , Singh Gagandeep , Janczak Katarzyna W. , García-Sastre Adolfo , Arya Nandini , Karadag Dilara , Baker James R. , Schotsaert Michael , Wong Pamela T.
Published: June 2023

Multiple FDA-approved SARS-CoV-2 vaccines currently provide excellent protection against severe disease. Despite this, immunity can wane relatively fast, particularly in the elderly and novel viral variants capable of evading infection- and vaccination-induced immunity continue to emerge. Intranasal (IN) vaccination more effectively induces mucosal immune responses than parenteral vaccines, which would improve protection and reduce viral transmission. Here, we developed a rationally designed IN adjuvant consisting of a combined nanoemulsion (NE)-based adjuvant and an RNA-based RIG-I agonist (IVT DI) to drive more robust, broadly protective antibody and T cell responses. We previously demonstrated this combination adjuvant (NE/IVT) potently induces protective immunity through synergistic activation of an array of innate receptors. We now demonstrate that NE/IVT with the SARS-CoV-2 receptor binding domain (RBD), induces robust and durable humoral, mucosal, and cellular immune responses of equivalent magnitude and quality in young and aged mice. This contrasted with the MF59-like intramuscular adjuvant, Addavax, which showed a decrease in immunogenicity with age. Robust antigen-specific IFN-γ/IL-2/TNF-α was induced in both young and aged NE/IVT-immunized animals, which is significant as their reduced production is associated with suboptimal protective immunity in the elderly. These findings highlight the potential of adjuvanted mucosal vaccines for improving protection against COVID-19.
mTORC2–NDRG1–CDC42 axis couples fasting to mitochondrial fission
Authors: Martinez-Lopez Nuria , Mattar Pamela , Toledo Miriam , Bains Henrietta , Kalyani Manu , Aoun Marie Louise , Sharma Mridul , McIntire Laura Beth J. , Gunther-Cummins Leslie , Macaluso Frank P. , Aguilan Jennifer T. , Sidoli Simone , Bourdenx Mathieu , Singh Rajat
Published: June 2023

Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at serine 336 sustains mitochondrial fission and respiratory sufficiency. Time-lapse imaging shows that NDRG1, but not the phosphorylation-deficient NDRG1Ser336Alamutant, engages with mitochondria to facilitate fission in control cells, as well as in those lacking DRP1. Using proteomics, a small interfering RNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase CDC42 and effectors and regulators of CDC42 to orchestrate fission. Accordingly,RictorKO, NDRG1Ser336Alamutants andCdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.
Material category of visual objects computed from specular image structure
Authors: Schmid Alexandra C. , Barla Pascal , Doerschner Katja
Published: June 2023

Recognizing materials and their properties visually is vital for successful interactions with our environment, from avoiding slippery floors to handling fragile objects. Yet there is no simple mapping of retinal image intensities to physical properties. Here, we investigated what image information drives material perception by collecting human psychophysical judgements about complex glossy objects. Variations in specular image structure—produced either by manipulating reflectance properties or visual features directly—caused categorical shifts in material appearance, suggesting that specular reflections provide diagnostic information about a wide range of material classes. Perceived material category appeared to mediate cues for surface gloss, providing evidence against a purely feedforward view of neural processing. Our results suggest that the image structure that triggers our perception of surface gloss plays a direct role in visual categorization, and that the perception and neural processing of stimulus properties should be studied in the context of recognition, not in isolation.
Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci
Authors: Mignogna Gianmarco , Carey Caitlin E. , Wedow Robbee , Baya Nikolas , Cordioli Mattia , Pirastu Nicola , Bellocco Rino , Malerbi Kathryn Fiuza , Nivard Michel G. , Neale Benjamin M. , Walters Raymond K. , Ganna Andrea
Published: June 2023

Response to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We examined item nonresponse behaviour across 109 questionnaire items in the UK Biobank (N = 360,628). Phenotypic factor scores for two participant-selected nonresponse answers, ‘Prefer not to answer’ (PNA) and ‘I don’t know’ (IDK), each predicted participant nonresponse in follow-up surveys (incremental pseudo-R2 = 0.056), even when controlling for education and self-reported health (incremental pseudo-R2 = 0.046). After performing genome-wide association studies of our factors, PNA and IDK were highly genetically correlated with one another (rg = 0.73 (s.e. = 0.03)) and with education (rg,PNA = −0.51 (s.e. = 0.03); rg,IDK = −0.38 (s.e. = 0.02)), health (rg,PNA = 0.51 (s.e. = 0.03); rg,IDK = 0.49 (s.e. = 0.02)) and income (rg,PNA = –0.57 (s.e. = 0.04); rg,IDK = −0.46 (s.e. = 0.02)), with additional unique genetic associations observed for both PNA and IDK (P < 5 × 10−8). We discuss how these associations may bias studies of traits correlated with item nonresponse and demonstrate how this bias may substantially affect genome-wide association studies. While the UK Biobank data are deidentified, we further protected participant privacy by avoiding exploring non-response behaviour to single questions, assuring that no information can be used to associate results with any particular respondents.
Elimination of charge-carrier trapping by molecular design
Authors: Sachnik Oskar , Tan Xiao , Dou Dehai , Haese Constantin , Kinaret Naomi , Lin Kun-Han , Andrienko Denis , Baumgarten Martin , Graf Robert , Wetzelaer Gert-Jan A. H. , Michels Jasper J. , Blom Paul W. M.
Published: June 2023

A common obstacle of many organic semiconductors is that they show highly unipolar charge transport. This unipolarity is caused by trapping of either electrons or holes by extrinsic impurities, such as water or oxygen. For devices that benefit from balanced transport, such as organic light-emitting diodes, organic solar cells and organic ambipolar transistors, the energy levels of the organic semiconductors are ideally situated within an energetic window with a width of 2.5 eV where charge trapping is strongly suppressed. However, for semiconductors with a band gap larger than this window, as used in blue-emitting organic light-emitting diodes, the removal or disabling of charge traps poses a longstanding challenge. Here we demonstrate a molecular strategy where the highest occupied molecular orbital and lowest unoccupied molecular orbital are spatially separated on different parts of the molecules. By tuning their stacking by modification of the chemical structure, the lowest unoccupied molecular orbitals can be spatially protected from impurities that cause electron trapping, increasing the electron current by orders of magnitude. In this way, the trap-free window can be substantially broadened, opening a path towards large band gap organic semiconductors with balanced and trap-free transport.
Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
Authors: Han Xikun , Gharahkhani Puya , Hamel Andrew R. , Ong Jue Sheng , Rentería Miguel E. , Mehta Puja , Dong Xianjun , Pasutto Francesca , Hammond Christopher , Young Terri L. , Hysi Pirro , Lotery Andrew J. , Jorgenson Eric , Choquet Hélène , Hauser Michael , Cooke Bailey Jessica N. , Nakazawa Toru , Akiyama Masato , Shiga Yukihiro , Fuller Zachary L. , Wang Xin , Hewitt Alex W. , Craig Jamie E. , Pasquale Louis R. , Mackey David A. , Wiggs Janey L. , Khawaja Anthony P. , Segrè Ayellet V. ,   23andMe Research Team,   International Glaucoma Genetics Consortium, MacGregor Stuart
Published: June 2023

Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total sample size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach, which increased the number of independent risk loci to 312, with the vast majority replicating in a large independent cohort from 23andMe, Inc. (total sample size over 2.8 million; 296 loci replicated atP < 0.05, 240 after Bonferroni correction). Leveraging multiomics datasets, we identified many potential druggable genes, including neuro-protection targets likely to act via the optic nerve, a key advance for glaucoma because all existing drugs only target intraocular pressure. We further used Mendelian randomization and genetic correlation-based approaches to identify novel links to other complex traits, including immune-related diseases such as multiple sclerosis and systemic lupus erythematosus.
Immunomodulatory response in an experimental model of brain death
Authors: Santana Alexandre Chagas , Andraus Wellington , Zimelewicz Oberman Dan , Rabelo Nícollas Nunes , Silva Filipe Miranda Oliveira , Dellê Humberto , Pepineli Rafael , de Moraes Edvaldo Leal , Scavone Cristoforo , de Sá Lima Larissa , Degaspari Sabrina , Brasil Sérgio , Solla Davi Jorge Fontoura , Ruiz Liliane Moreira , de Oliveira-Braga Karina Andrighetti , Nepomuceno Natalia Aparecida , Pêgo-Fernandes Paulo Manuel , Tullius Stefan Gunther , Figueiredo Eberval Gadelha
Published: June 2023

Liver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.
Non-contrast CT synthesis using patch-based cycle-consistent generative adversarial network (Cycle-GAN) for radiomics and deep learning in the era of COVID-19
Authors: Kalantar Reza , Hindocha Sumeet , Hunter Benjamin , Sharma Bhupinder , Khan Nasir , Koh Dow-Mu , Ahmed Merina , Aboagye Eric O. , Lee Richard W. , Blackledge Matthew D.
Published: June 2023

Handcrafted and deep learning (DL) radiomics are popular techniques used to develop computed tomography (CT) imaging-based artificial intelligence models for COVID-19 research. However, contrast heterogeneity from real-world datasets may impair model performance. Contrast-homogenous datasets present a potential solution. We developed a 3D patch-based cycle-consistent generative adversarial network (cycle-GAN) to synthesize non-contrast images from contrast CTs, as a data homogenization tool. We used a multi-centre dataset of 2078 scans from 1,650 patients with COVID-19. Few studies have previously evaluated GAN-generated images with handcrafted radiomics, DL and human assessment tasks. We evaluated the performance of our cycle-GAN with these three approaches. In a modified Turing-test, human experts identified synthetic vs acquired images, with a false positive rate of 67% and Fleiss’ Kappa 0.06, attesting to the photorealism of the synthetic images. However, on testing performance of machine learning classifiers with radiomic features, performance decreased with use of synthetic images. Marked percentage difference was noted in feature values between pre- and post-GAN non-contrast images. With DL classification, deterioration in performance was observed with synthetic images. Our results show that whilst GANs can produce images sufficient to pass human assessment, caution is advised before GAN-synthesized images are used in medical imaging applications.
Performance optimization of efficient PbS quantum dots solar cells through numerical simulation
Authors: Kumar Sandeep , Bharti Pragya , Pradhan Basudev
Published: June 2023

Colloidal quantum dots (CQDs) solar cells are less efficient because of the carrier recombination within the material. The electron and hole transport layers have high impact on the performance of CQDs based solar cells which makes its investigation a very important component of the development of the more efficient devices. In this work, we have tried performance optimization in tetrabutyl ammonium iodide capped lead sulfide (PbS) CQDs (PbS-TBAI) as absorber layers based solar cells by incorporating different hole transport layers (HTLs) to achieve better power conversion efficiency (PCE) in different device architectures by SCAPS—1D numerical simulation software. It was observed from the simulation that the ITO/TiO2/PbS-TBAI/HTL/Au device architecture shows higher power conversion efficiency as compared to the conventional experimentally realized device architecture of ITO/TiO2/PbS-TBAI/PbS-EDT/HTL/Au. The influence of interface defect density (IDD) at the interface TiO2/PbS-TBAI has also been studied where IDD is varied from 1 × 1013 cm−2 to 1 × 1018 cm−2 while keeping the rest of the device parameters intact. The result shows a noteworthy reduction in the PV performance of the device at higher IDD. This modelled device structure provides a new direction toward the experimental realization in high efficiency PbS QDs solar cells.
Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes
Authors: Vaváková Magdaléna , Hofwimmer Kaisa , Laurencikiene Jurga , Göransson Olga
Published: June 2023

Salt-inducible kinase 2 (SIK2) is highly expressed in white adipocytes, but downregulated in individuals with obesity and insulin resistance. These conditions are often associated with a low-grade inflammation in adipose tissue. We and others have previously shown that SIK2 is downregulated by tumor necrosis factor α (TNFα), however, involvement of other pro-inflammatory cytokines, or the mechanisms underlying TNFα-induced SIK2 downregulation, remain to be elucidated. In this study we have shown that TNFα downregulates SIK2 protein expression not only in 3T3L1- but also in human in vitro differentiated adipocytes. Furthermore, monocyte chemoattractant protein-1 and interleukin (IL)-1β, but not IL-6, might also contribute to SIK2 downregulation during inflammation. We observed that TNFα-induced SIK2 downregulation occurred also in the presence of pharmacological inhibitors against several kinases involved in inflammation, namely c-Jun N-terminal kinase, mitogen activated protein kinase kinase 1, p38 mitogen activated protein kinase or inhibitor of nuclear factor kappa-B kinase (IKK). However, IKK may be involved in SIK2 regulation as we detected an increase of SIK2 when inhibiting IKK in the absence of TNFα. Increased knowledge about inflammation-induced downregulation of SIK2 could ultimately be used to develop strategies for the reinstalment of SIK2 expression in insulin resistance.
Image quality assessment using deep learning in high b-value diffusion-weighted breast MRI
Authors: Kapsner Lorenz A. , Balbach Eva L. , Folle Lukas , Laun Frederik B. , Nagel Armin M. , Liebert Andrzej , Emons Julius , Ohlmeyer Sabine , Uder Michael , Wenkel Evelyn , Bickelhaupt Sebastian
Published: June 2023

The objective of this IRB approved retrospective study was to apply deep learning to identify magnetic resonance imaging (MRI) artifacts on maximum intensity projections (MIP) of the breast, which were derived from diffusion weighted imaging (DWI) protocols. The dataset consisted of 1309 clinically indicated breast MRI examinations of 1158 individuals (median age [IQR]: 50 years [16.75 years]) acquired between March 2017 and June 2020, in which a DWI sequence with a high b-value equal to 1500 s/mm2 was acquired. From these, 2D MIP images were computed and the left and right breast were cropped out as regions of interest (ROI). The presence of MRI image artifacts on the ROIs was rated by three independent observers. Artifact prevalence in the dataset was 37% (961 out of 2618 images). A DenseNet was trained with a fivefold cross-validation to identify artifacts on these images. In an independent holdout test dataset (n = 350 images) artifacts were detected by the neural network with an area under the precision-recall curve of 0.921 and a positive predictive value of 0.981. Our results show that a deep learning algorithm is capable to identify MRI artifacts in breast DWI-derived MIPs, which could help to improve quality assurance approaches for DWI sequences of breast examinations in the future.
Reduction in disialyl-T antigen levels in mice deficient for both St6galnac3 and St6galnac4 results in blood filling of lymph nodes
Authors: Fuseya Sayaka , Izumi Hiroyuki , Hamano Ayane , Murakami Yuka , Suzuki Riku , Koiwai Rikako , Hayashi Takuto , Kuno Atsushi , Takahashi Satoru , Kudo Takashi
Published: June 2023

Sialic acid (SA) is present at the terminal ends of carbohydrate chains in glycoproteins and glycolipids and is involved in various biological phenomena. The biological function of the disialyl-T (SAα2-3Galβ1-3(SAα2-6)GalNAcα1-O-Ser/Thr) structure is largely unknown. To elucidate the role of disialyl-T structure and determine the key enzyme from the N-acetylgalactosaminide α2,6-sialyltransferase (St6galnac) family involved in its in vivo synthesis, we generated St6galnac3- and St6galnac4-deficient mice. Both single-knockout mice developed normally without any prominent phenotypic abnormalities. However, the St6galnac3::St6galnact4 double knockout (DKO) mice showed spontaneous hemorrhage of the lymph nodes (LN). To identify the cause of bleeding in the LN, we examined podoplanin, which modifies the disialyl-T structures. The protein expression of podoplanin in the LN of DKO mice was similar to that in wild-type mice. However, the reactivity of MALII lectin, which recognizes disialyl-T, in podoplanin immunoprecipitated from DKO LN was completely abolished. Moreover, the expression of vascular endothelial cadherin was reduced on the cell surface of high endothelial venule (HEV) in the LN, suggesting that hemorrhage was caused by the structural disruption of HEV. These results suggest that podoplanin possesses disialyl-T structure in mice LN and that both St6galnac3 and St6galnac4 are required for disialyl-T synthesis.
Measurements and predictions of diffusible hydrogen escape and absorption in catholically charged 316LN austenitic stainless steel
Authors: Weihrauch Melissa , Patel Maulik , Patterson Eann A.
Published: June 2023

Hydrogen can have an impact on the service life of safety critical components, such as coolant pipes in nuclear reactors, where it may interact with other factors including irradiation. Hence, it is important to characterise such behaviour which in turn requires the capability to charge representative material specimens with hydrogen and to quantity the levels of hydrogen present. Hydrogen concentrations resulting from cathodic charging of 316LN stainless steel over short time periods (< 2 h) were estimated from hydrogen release rates obtained from potentiostatic discharge measurements and used to calibrate simulations based on Fick’s second law of diffusion in order to predict the hydrogen concentration after 24 h of charging. Leave-one-out cross-validation was used to establish confidence in results which were also validated using measurements from the melt extraction technique. The success of Fick’s second law for estimating escape rates showed that a majority of the absorbed hydrogen was diffusible rather than trapped. These results confirmed that the potentiostatic discharge technique can be used on materials with low diffusivity, and provide a new method through which hydrogen concentrations within a sample can be estimated after cathodic charging non-destructively without the need to remove samples from solution.
Improved sustainability of solar panels by improving stability of amorphous silicon solar cells
Authors: Ganguly Gautam
Published: June 2023

As the world grapples with global warming, it becomes imperative to carefully examine the sustainable energy technology choices. Solar is the fastest growing clean energy source but today it contributes little to the electricity generated, so future installations will dwarf the existing installed base. There is a factor of 2–4 decrease in the energy payback time from the dominant crystalline silicon technology to thin film technologies. Essential criteria like use of abundant materials and simple but mature production technology point to amorphous silicon (a-Si) technology. Here we delve into the primary issue impeding adoption of a-Si technology—the Staebler Wronski Effect (SWE), that generates metastable, light induced defects which reduce the performance of a-Si based solar cells. We demonstrate that a simple change leads to a significant reduction in SWE power loss and define a clear path to elimination of SWE, allowing the technology to be widely adopted.
Enhancing human resilience beyond COVID-19-related stress: public responses to multi-benefits of home gardening
Authors: Wu Chen-Fa , Trac Luu Van Thong , Chen Szu-Hung , Menakanit Alisara , Le Quoc Tuan , Tu Hung-Ming , Tsou Chih-Peng , Huang Hsi-Chih , Chookoh Nittaya , Weng Chih-Cheng , Chou Li-Wei , Chen Chiu-Chuan
Published: June 2023

The SARS-CoV-2 virus has caused a public health crisis globally. Against the backdrop of global resilience, studies have demonstrated the therapeutic value of home gardening as a measure to strengthen human health. However, there is a lack of comparative studies on its benefits across countries. Studies need to examine the role of home gardening in improving public health in various societies to understand and encourage this practice broadly and effectively. We chose Taiwan, Thailand, and Vietnam as case studies, which have suffered substantial pandemic impacts, with millions of infections and thousands of deaths. We explored and compared the perceptions of people on home gardening and its health benefits during the COVID-19 pandemic. We conducted online surveys in three countries between May 1 and September 30, 2022, with a total of 1172 participants. Data were collated on perceived pandemic stress, challenges and solutions in gardening, home gardening intentions, and mental and physical health benefits. In these countries, we found that perceived pandemic stress positively affects home gardening intentions, whereby the motivation of Vietnamese people is the highest. Challenges hinder gardening intentions, while the solutions only positively affect gardening intentions in Taiwan and Vietnam. Home gardening intentions positively affect mental and physical health, whereby there are higher mental health benefits in Taiwanese people than in Thai people. Our findings potentially support public health recovery and promote healthy lifestyles during the COVID-19 pandemic.
Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics
Authors: Arora Abishek , Becker Martin , Marques Cátia , Oksanen Marika , Li Danyang , Mastropasqua Francesca , Watts Michelle Evelyn , Arora Manish , Falk Anna , Daub Carsten Oliver , Lanekoff Ingela , Tammimies Kristiina
Published: June 2023

Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors (lead, valproic acid, bisphenol A, ethanol, fluoxetine hydrochloride and zinc deficiency) and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after 5-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. Moreover, fluoxetine exposure elevated several fatty acids when validated using mass spectrometry-based metabolomics. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.
Machine learning assists in increasing the time resolution of X-ray computed tomography applied to mineral precipitation in porous media
Authors: Lee Dongwon , Weinhardt Felix , Hommel Johannes , Piotrowski Joseph , Class Holger , Steeb Holger
Published: June 2023

Many subsurface engineering technologies or natural processes cause porous medium properties, such as porosity or permeability, to evolve in time. Studying and understanding such processes on the pore scale is strongly aided by visualizing the details of geometric and morphological changes in the pores. For realistic 3D porous media, X-Ray Computed Tomography (XRCT) is the method of choice for visualization. However, the necessary high spatial resolution requires either access to limited high-energy synchrotron facilities or data acquisition times which are considerably longer (e.g. hours) than the time scales of the processes causing the pore geometry change (e.g. minutes). Thus, so far, conventional benchtop XRCT technologies are often too slow to allow for studying dynamic processes. Interrupting experiments for performing XRCT scans is also in many instances no viable approach. We propose a novel workflow for investigating dynamic precipitation processes in porous media systems in 3D using a conventional XRCT technology. Our workflow is based on limiting the data acquisition time by reducing the number of projections and enhancing the lower-quality reconstructed images using machine-learning algorithms trained on images reconstructed from high-quality initial- and final-stage scans. We apply the proposed workflow to induced carbonate precipitation within a porous-media sample of sintered glass-beads. So we were able to increase the temporal resolution sufficiently to study the temporal evolution of the precipitate accumulation using an available benchtop XRCT device.
Assessing the impact of protonating acid combinations in e-cigarette liquids: a randomised, crossover study on nicotine pharmacokinetics
Authors: Frosina Justin , McEwan Michael , Ebajemito James , Thissen Jesse , Taluskie Karen , Baxter-Wright Sarah , Hardie George
Published: June 2023

The addition of protonating acids to e-cigarette liquid formulations (e-liquids) enhances nicotine bioavailability in e-cigarette use. However, little is known about the impact of different combinations of protonating acid on nicotine pharmacokinetics. The objectives of this study were to compare pharmacokinetics of nicotine absorption following use of a closed-system e-cigarette, containing e-liquids with two different nicotine levels and with different ratios of three common protonating acids—lactic, benzoic and levulinic. In a randomised, controlled, crossover study, nicotine pharmacokinetics and product liking were assessed for prototype e-liquids used in a Vuse e-cigarette containing either 3.5% or 5% nicotine and varying ratios of lactic, benzoic and/or levulinic acid. During an 8-day confinement period, 32 healthy adult current cigarette smokers/e-cigarette dual users used a single study e-liquid each day during 10-min fixed and ad libitum use periods after overnight nicotine abstinence. For most comparisons, Cmax and AUC0–60 following both fixed and ad libitum puffing were significantly higher for e-liquids containing 5% nicotine compared with 3.5% nicotine. However, Cmax and AUC0–60 were not statistically different for 5% nicotine e-liquids containing varying ratios of lactic, levulinic and benzoic acid when compared to an e-liquid containing lactic acid only. Mean scores for product liking were similar for all e-liquid formulations assessed, regardless of nicotine concentration, acid content, and whether the product was used in a fixed or ad libitum puffing regimen. While e-liquid nicotine concentration significantly affected users’ nicotine uptake, the different combinations of benzoic, levulinic and lactic acid in the e-liquids assessed had limited impact on nicotine pharmacokinetics and product liking scores.
Different incidences of diabetic retinopathy requiring treatment since diagnosis according to the course of diabetes diagnosis: a retrospective cohort study
Authors: Sugiyama Takehiro , Yanagisawa-Sugita Ayako , Tanaka Hirokazu , Ihana-Sugiyama Noriko , Imai Kenjiro , Ohsugi Mitsuru , Ueki Kohjiro , Tamiya Nanako , Kobayashi Yasuki
Published: June 2023

We aimed to estimate the cumulative incidence of treatment-requiring diabetic retinopathy since clinical diagnosis of diabetes based on the course of diagnosis in a retrospective cohort study using Japan’s medical claims and health checkup data (JMDC Claims Database; 2009–2020). We included patients whose diabetes was first diagnosed at medical facilities (hospitals/clinics). We grouped them by health checkup participation before diagnosis, health checkup results, and antidiabetic medication promptly after the diagnosis. The incidence of treatment-requiring diabetic retinopathy (laser photocoagulation, intraocular injection, or vitrectomy) was compared among the groups. Of 126,696 patients, those who started an antidiabetic medication promptly after diabetes diagnosis without a recent health checkup faced the highest risk of treatment-requiring diabetic retinopathy (1-/5-year cumulative incidence: 3.1%/6.0%). This increased risk was consistently observed across various analyses, including the Cox proportional hazard model, sensitivity analysis restricting to those with an eye examination, and sensitivity analysis using vitrectomy as the outcome. Among patients with HbA1c ≥ 6.5% at recent health checkups, those who promptly started an antidiabetic medication had a higher risk (1.4%/3.8%) than those who did not (0.7%/2.7%). Taking the information about the course of diabetes diagnosis is important to manage risk stratification for diabetic retinopathy appropriately.
Classification of head and neck cancer from PET images using convolutional neural networks
Authors: Hellström Henri , Liedes Joonas , Rainio Oona , Malaspina Simona , Kemppainen Jukka , Klén Riku
Published: June 2023

The aim of this study was to develop a convolutional neural network (CNN) for classifying positron emission tomography (PET) images of patients with and without head and neck squamous cell carcinoma (HNSCC) and other types of head and neck cancer. A PET/magnetic resonance imaging scan with 18F-fluorodeoxyglucose (18F-FDG) was performed for 200 head and neck cancer patients, 182 of which were diagnosed with HNSCC, and the location of cancer tumors was marked to the images with a binary mask by a medical doctor. The models were trained and tested with five-fold cross-validation with the primary data set of 1990 2D images obtained by dividing the original 3D images of 178 HNSCC patients into transaxial slices and with an additional test set with 238 images from the patients with head and neck cancer other than HNSCC. A shallow and a deep CNN were built by using the U-Net architecture for classifying the data into two groups based on whether an image contains cancer or not. The impact of data augmentation on the performance of the two CNNs was also considered. According to our results, the best model for this task in terms of area under receiver operator characteristic curve (AUC) is a deep augmented model with a median AUC of 85.1%. The four models had highest sensitivity for HNSCC tumors on the root of the tongue (median sensitivities of 83.3–97.7%), in fossa piriformis (80.2–93.3%), and in the oral cavity (70.4–81.7%). Despite the fact that the models were trained with only HNSCC data, they had also very good sensitivity for detecting follicular and papillary carcinoma of thyroid gland and mucoepidermoid carcinoma of the parotid gland (91.7–100%).
Microbial hydrogen consumption leads to a significant pH increase under high-saline-conditions: implications for hydrogen storage in salt caverns
Authors: Dopffel Nicole , Mayers Kyle , Kedir Abduljelil , Alagic Edin , An-Stepec Biwen Annie , Djurhuus Ketil , Boldt Daniel , Beeder Janiche , Hoth Silvan
Published: June 2023

Salt caverns have been successfully used for natural gas storage globally since the 1940s and are now under consideration for hydrogen (H2) storage, which is needed in large quantities to decarbonize the economy to finally reach a net zero by 2050. Salt caverns are not sterile and H2 is a ubiquitous electron donor for microorganisms. This could entail that the injected H2 will be microbially consumed, leading to a volumetric loss and potential production of toxic H2S. However, the extent and rates of this microbial H2 consumption under high-saline cavern conditions are not yet understood. To investigate microbial consumption rates, we cultured the halophilic sulphate-reducing bacteria Desulfohalobium retbaense and the halophilic methanogen Methanocalculus halotolerans under different H2 partial pressures. Both strains consumed H2, but consumption rates slowed down significantly over time. The activity loss correlated with a significant pH increase (up to pH 9) in the media due to intense proton- and bicarbonate consumption. In the case of sulphate reduction, this pH increase led to dissolution of all produced H2S in the liquid phase. We compared these observations to a brine retrieved from a salt cavern located in Northern Germany, which was then incubated with 100% H2 over several months. We again observed a H2 loss (up to 12%) with a concurrent increase in pH of up to 8.5 especially when additional nutrients were added to the brine. Our results clearly show that sulphate-reducing microbes present in salt caverns consume H2, which will be accompanied by a significant pH increase, resulting in reduced activity over time. This potentially self-limiting process of pH increase during sulphate-reduction will be advantageous for H2 storage in low-buffering environments like salt caverns.
The full-body illusion changes visual depth perception
Authors: Bayer Manuel , Betka Sophie , Herbelin Bruno , Blanke Olaf , Zimmermann Eckart
Published: June 2023

Knowing where objects are relative to us implies knowing where we are relative to the external world. Here, we investigated whether space perception can be influenced by an experimentally induced change in perceived self-location. To dissociate real and apparent body positions, we used the full-body illusion. In this illusion, participants see a distant avatar being stroked in virtual reality while their own physical back is simultaneously stroked. After experiencing the discrepancy between the seen and the felt location of the stroking, participants report a forward drift in self-location toward the avatar. We wondered whether this illusion-induced forward drift in self-location would affect where we perceive objects in depth. We applied a psychometric measurement in which participants compared the position of a probe against a reference sphere in a two-alternative forced choice task. We found a significant improvement in task performance for the right visual field, indicated by lower just-noticeable differences, i.e., participants were better at judging the differences of the two spheres in depth. Our results suggest that the full-body illusion is able to facilitate depth perception at least unilaterally, implying that depth perception is influenced by perceived self-location.
Activated volcanism of Mount Fuji by the 2011 Japanese large earthquakes
Authors: Nanjo K. Z. , Yukutake Y. , Kumazawa T.
Published: June 2023

The relation between earthquakes and volcanic eruptions, each of which is manifested by large-scale tectonic plate and mantle motions, has been widely discussed. Mount Fuji, in Japan, last erupted in 1707, paired with a magnitude (M)-9-class earthquake 49 days prior. Motivated by this pairing, previous studies investigated its effect on Mount Fuji after both the 2011 M9 Tohoku megaquake and a triggered M5.9 Shizuoka earthquake 4 days later at the foot of the volcano, but reported no potential to erupt. More than 300 years have already passed since the 1707 eruption, and even though consequences to society caused by the next eruption are already being considered, the implications for future volcanism remain uncertain. This study shows how volcanic low-frequency earthquakes (LFEs) in the deep part of the volcano revealed unrecognized activation after the Shizuoka earthquake. Our analyses also show that despite an increase in the rate of occurrence of LFEs, these did not return to pre-earthquake levels, indicating a change in the magma system. Our results demonstrate that the volcanism of Mount Fuji was reactivated by the Shizuoka earthquake, implying that this volcano is sufficiently sensitive to external events that are considered to be enough to trigger eruptions.
The NK cell checkpoint NKG2A maintains expansion capacity of human NK cells
Authors: Kaulfuss Meike , Mietz Juliane , Fabri Astrid , vom Berg Johannes , Münz Christian , Chijioke Obinna
Published: June 2023

Human natural killer (NK) cells are cytotoxic effector cells that are increasingly harnessed in cancer immunotherapy. NKG2A/CD94 is an inhibitory receptor on NK cells that has established regulatory functions in the direct interaction with target cells when engaged with its ligand, the non-classical HLA class I molecule HLA-E. Here, we confirmed NKG2A as a checkpoint molecule in primary human NK cells and identified a novel role for NKG2A in maintaining NK cell expansion capacity by dampening both proliferative activity and excessive activation-induced cell death. Maintenance of NK cell expansion capacity might contribute to the preferential accumulation of human NKG2A+ NK cells after hematopoietic cell transplantation and enrichment of functionally impaired NK cells in human cancers. Functional silencing of NKG2A for cancer immunotherapy is highly attractive but will need to consider that this might also lead to a reduced survival by driving activation-induced cell death in targeted NK cells.
Flexible aqueous Zn–S battery based on an S-decorated Ti3C2Tx cathode
Authors: Sonigara Keval K. , Vaghasiya Jayraj V. , Mayorga-Martinez Carmen C. , Pumera Martin
Published: June 2023

Flexible aqueous zinc-ion batteries can store energy safely and at a low cost, which benefits wearable electronic gadgets; however, currently used cathodes restrict these devices with a low specific capacity and energy density. Herein, we developed a flexible zinc-sulfur (Zn–S) battery constructed by Ti3C2Txdecorated with sulfur (S@Ti3C2Tx) as a cathode and Zn metal anode with iodine-added amphiphilic gel electrolyte (AGE). Benefiting from the confinement synergy of S@Ti3C2Txcathode, the Zn-S battery exhibited a high storage capacity of 772.7 mAh g−1at 300 mA g−1, which is higher than a conventional S-decorated carbon cathode (491.7 mAh g−1). More specially, the flexible device offers good cycling stability (82.7%) and excellent mechanical stability with 91% capacity retention after 90° bending (500 cycles). To demonstrate real applications, the flexible Zn–S batteries were integrated in series to power electrical gadgets (e.g., digital clock, light-emitting diode, and robot). It exhibits exceptional flexibility to sustain different deformations and maintains a steady supply of power to run the wearable electronic gadget. These findings offer a fresh starting point for flexible energy storage technologies and show the promising potential of the Zn–S battery in real-world applications.