bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired activation of succinate-induced type 2 immunity and secretory cell production in the small intestines of Ptk6−/− male mice
Authors: Vlajic Katarina , Bie Wenjun , Gilic Milica B. , Tyner Angela L.
Published: October 2024

Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that is distantly related to the SRC family of tyrosine kinases. It is expressed in epithelial linings and regulates regeneration and repair of the intestinal epithelium. Analysis of publicly available datasets showed Ptk6 is upregulated in tuft cells upon activation of type 2 immunity. We found that disruption of Ptk6 influences gene expression involved in intestinal immune responses. Administration of succinate, which mimics infection and activates tuft cells, revealed PTK6-dependent activation of innate immune responses in male but not female mice. In contrast to all wild type and Ptk6−/− female mice, Ptk6−/− male mice do not activate innate immunity or upregulate differentiation of the tuft and goblet secretory cell lineages following succinate treatment. Mechanistically, we found that PTK6 regulates Il25 and Irag2, genes that are required for tuft cell effector functions and activation of type 2 innate immunity, in organoids derived from intestines of male but not female mice. In patients with Crohn’s disease, PTK6 is upregulated in tuft cells in noninflamed regions of intestine. These data highlight roles for PTK6 in contributing to sex differences in intestinal innate immunity and provide new insights into the regulation of IL-25.
Defining ethical criteria to guide the expanded use of Noninvasive Prenatal Screening (NIPS): Lessons about severity from preimplantation genetic testing
Authors: Gallois Hortense , Ravitsky Vardit , Roy Marie-Christine , Laberge Anne-Marie
Published: October 2024

We hypothesized that ethical criteria that guide the use of preimplantation genetic testing (PGT) could be used to inform policies about expanded use of non-invasive prenatal screening (NIPS). We used a systematic review of reasons approach to assess ethical criteria used to justify using (or not using) PGT for genetic conditions. Out of 1135 identified documents, we retained and analyzed 216 relevant documents. Results show a clear distinction in acceptability of PGT for medical vs. non-medical conditions. Criteria to decide on use of PGT for medical conditions are largely based on their severity, but there is no clear definition of “severity”. Instead, characteristics of the condition that relate to severity are used as sub-criteria to assess severity. We found that characteristics that are used as sub-criteria for assessing severity include monogenic etiology, high penetrance, absence of treatment, early age of onset, shortened lifespan, and reduced quality of life. Consensus about the use of PGT is highest for conditions that meet most of these criteria. There is no consensus around the acceptability of using PGT to detect non-medical conditions. We propose that the same severity criteria could be used by policymakers to assess the acceptability of using other genetic tests in screening and practice, including for the use of NIPS for additional conditions as indications broaden.
Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project
Authors: Ní Leathlobhair Máire , Frangou Anna , Kinnersley Ben , Cornish Alex J. , Chubb Daniel , Lakatos Eszter , Arumugam Prabhu , Gruber Andreas J. , Law Philip , Tapinos Avraam , Jakobsdottir G. Maria , Peneva Iliana , Sahli Atef , Smyth Evie M. , Ball Richard Y. , Sylva Rushan , Benes Ksenija , Stark Dan , Young Robin J. , Lee Alexander T. J. , Wolverson Vincent , Houlston Richard S. , Sosinsky Alona , Protheroe Andrew , Murray Matthew J. , Wedge David C. , Verrill Clare ,   Testicular Cancer Genomics England Clinical Interpretation Partnership Consortium,   Genomics England Research Consortium
Published: October 2024

Testicular germ cell tumours (TGCT), which comprise seminoma and non-seminoma subtypes, are the most common cancers in young men. In this study, we present a comprehensive whole genome sequencing analysis of adult TGCTs. Leveraging samples from participants recruited via the UK National Health Service and data from the Genomics England 100,000 Genomes Project, our results provide an extended description of genomic elements underlying TGCT pathogenesis. This catalogue offers a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genome features, including mutational signatures and analysis of extrachromosomal DNA amplification. This study establishes correlations between genomic alterations and histological diversification, revealing divergent evolutionary trajectories among TGCT subtypes. By reconstructing the chronological order of driver events, we identify a subgroup of adult TGCTs undergoing relatively late whole genome duplication. Additionally, we present evidence that human leukocyte antigen loss is a more prevalent mechanism of immune disruption in seminomas. Collectively, our findings provide valuable insights into the developmental and immune modulatory processes implicated in TGCT pathogenesis and progression.
DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits
Authors: Hwang Liang-Dar , Cuellar-Partida Gabriel , Yengo Loic , Zeng Jian , Toivonen Jarkko , Arvas Mikko , Beaumont Robin N. , Freathy Rachel M. , Moen Gunn-Helen , Warrington Nicole M. , Evans David M.
Published: October 2024

Perinatal traits are influenced by fetal and maternal genomes. We investigate the performance of three strategies to detect loci in maternal and fetal genome-wide association studies (GWASs) of the same quantitative trait: (i) the traditional strategy of analysing maternal and fetal GWASs separately; (ii) a two-degree-of-freedom test which combines information from maternal and fetal GWASs; and (iii) a one-degree-of-freedom test where signals from maternal and fetal GWASs are meta-analysed together conditional on estimated sample overlap. We demonstrate that the optimal strategy depends on the extent of sample overlap, correlation between phenotypes, whether loci exhibit fetal and/or maternal effects, and whether these effects are directionally concordant. We apply our methods to summary statistics from a recent GWAS meta-analysis of birth weight. Both the two-degree-of-freedom and meta-analytic approaches increase the number of genetic loci for birth weight relative to separately analysing the scans. Our best strategy identifies an additional 62 loci compared to the most recently published meta-analysis of birth weight. We conclude that whilst the two-degree-of-freedom test may be useful for the analysis of certain perinatal phenotypes, for most phenotypes, a simple meta-analytic strategy is likely to perform best, particularly in situations where maternal and fetal GWASs only partially overlap.
Deletion upstream of MAB21L2 highlights the importance of evolutionarily conserved non-coding sequences for eye development
Authors: Ceroni Fabiola , Cicekdal Munevver B. , Holt Richard , Sorokina Elena , Chassaing Nicolas , Clokie Samuel , Naert Thomas , Talbot Lidiya V. , Muheisen Sanaa , Bax Dorine A. , Kesim Yesim , Kivuva Emma C. , Vincent-Delorme Catherine , Lienkamp Soeren S. , Plaisancié Julie , De Baere Elfride , Calvas Patrick , Vleminckx Kris , Semina Elena V. , Ragge Nicola K.
Published: October 2024

Anophthalmia, microphthalmia and coloboma (AMC) comprise a spectrum of developmental eye disorders, accounting for approximately 20% of childhood visual impairment. While non-coding regulatory sequences are increasingly recognised as contributing to disease burden, characterising their impact on gene function and phenotype remains challenging. Furthermore, little is known of the nature and extent of their contribution to AMC phenotypes. We report two families with variants in or near MAB21L2, a gene where genetic variants are known to cause AMC in humans and animal models. The first proband, presenting with microphthalmia and coloboma, has a likely pathogenic missense variant (c.338 G > C; p.[Trp113Ser]), segregating within the family. The second individual, presenting with microphthalmia, carries an ~ 113.5 kb homozygous deletion 19.38 kb upstream of MAB21L2. Modelling of the deletion results in transient small lens and coloboma as well as midbrain anomalies in zebrafish, and microphthalmia and coloboma in Xenopus tropicalis. Using conservation analysis, we identify 15 non-coding conserved elements (CEs) within the deleted region, while ChIP-seq data from mouse embryonic stem cells demonstrates that two of these (CE13 and 14) bind Otx2, a protein with an established role in eye development. Targeted disruption of CE14 in Xenopus tropicalis recapitulates an ocular coloboma phenotype, supporting its role in eye development. Together, our data provides insights into regulatory mechanisms underlying eye development and highlights the importance of non-coding sequences as a source of genetic diagnoses in AMC.
DGCNN approach links metagenome-derived taxon and functional information providing insight into global soil organic carbon
Authors: Gardiner Laura-Jayne , Marshall Matthew , Reusch Katharina , Dearden Chris , Birmingham Mark , Carrieri Anna Paola , Pyzer-Knapp Edward O. , Krishna Ritesh , Neal Andrew L.
Published: October 2024

Metagenomics can provide insight into the microbial taxa present in a sample and, through gene identification, the functional potential of the community. However, taxonomic and functional information are typically considered separately in downstream analyses. We develop interpretable machine learning (ML) approaches for modelling metagenomic data, combining the biological representation of species with their associated genetically encoded functions within models. We apply our methods to investigate soil organic carbon (SOC) stocks. First, we combine a diverse global set of soil microbiome samples with environmental data, improving the predictive performance of classic ML and providing new insights into the role of soil microbiomes in global carbon cycling. Our network analysis of predictive taxa identified by classical ML models provides context for their ecological significance, extending the focus beyond just the most predictive taxa to ‘hidden’ features within the model that might be considered less predictive using standard methods for explainability. We next develop unique graph representations for individual microbiomes, linking microbial taxa to their associated functions directly, enabling predictions of SOC via deep graph convolutional neural networks (DGCNNs). Interpretation of the DGCNNs distinguished between the importance of functions of key individual species, providing genome sequence differences, e.g., gene loss/acquisition, that associate with SOC. These approaches identify several members of the Verrucomicrobiaceae family and a range of genetically encoded functions, e.g., related to carbohydrate metabolism, as important for SOC stocks and effective global SOC predictors. These relatively understudied but widespread organisms could play an important role in SOC dynamics globally.
Extending radiowave frequency detection range with dressed states of solid-state spin ensembles
Authors: Hermann Jens C. , Rizzato Roberto , Bruckmaier Fleming , Allert Robin D. , Blank Aharon , Bucher Dominik B.
Published: October 2024

Quantum sensors using solid-state spin defects excel in the detection of radiofrequency (RF) fields, serving various applications in communication, ranging, and sensing. For this purpose, pulsed dynamical decoupling (PDD) protocols are typically applied, which enhance sensitivity to RF signals. However, these methods are limited to frequencies of a few megahertz, which poses a challenge for sensing higher frequencies. We introduce an alternative approach based on a continuous dynamical decoupling (CDD) scheme involving dressed states of nitrogen vacancy (NV) ensemble spins driven within a microwave resonator. We compare the CDD methods to established PDD protocols and demonstrate the detection of RF signals up to ~85 MHz, about ten times the current limit imposed by the PDD approach under identical conditions. Implementing the CDD method in a heterodyne/synchronized protocol combines the high-frequency detection with high spectral resolution. This advancement extends to various domains requiring detection in the high frequency (HF) and very high frequency (VHF) ranges of the RF spectrum, including spin sensor-based magnetic resonance spectroscopy at high magnetic fields.
Robust projective measurements through measuring code-inspired observables
Authors: Ouyang Yingkai
Published: October 2024

Quantum measurements are ubiquitous in quantum information processing tasks, but errors can render their outputs unreliable. Here, we present a scheme that implements a robust projective measurement through measuring code-inspired observables. Namely, given a projective POVM, a classical code, and a constraint on the number of measurement outcomes each observable can have, we construct commuting observables whose measurement is equivalent to the projective measurement in the noiseless setting. Moreover, we can correct t errors on the classical outcomes of the observables’ measurement if the classical code corrects t errors. Since our scheme does not require the encoding of quantum data onto a quantum error correction code, it can help construct robust measurements for near-term quantum algorithms that do not use quantum error correction. Moreover, our scheme works for any projective POVM, and hence can allow robust syndrome extraction procedures in non-stabilizer quantum error correction codes.
Tunable magnonic crystal in a hybrid superconductor–ferrimagnet nanostructure
Authors: Kharlan Julia , Szulc Krzysztof , Kłos Jarosław W. , Centała Grzegorz
Published: October 2024

One of the most intriguing properties of magnonic systems is their reconfigurability, where an external magnetic field alters the static magnetic configuration to influence magnetization dynamics. In this paper, we present an alternative approach to tunable magnonic systems. We studied theoretically and numerically a magnonic crystal induced within a uniform magnetic layer by a periodic magnetic field pattern created by the sequence of superconducting strips. We showed that the spin-wave spectrum can be tuned by the inhomogeneous stray field of the superconductor in response to a small uniform external magnetic field. Additionally, we demonstrated that modifying the width of superconducting strips and separation between them leads to the changes in the internal field which are unprecedented in conventional magnonic structures. The paper presents the results of semi-analytical calculations for realistic structures, which are verified by finite-element method computations.
Knowledge graph driven medicine recommendation system using graph neural networks on longitudinal medical records
Authors: Mishra Rajat , Shridevi S.
Published: October 2024

Medicine recommendation systems are designed to aid healthcare professionals by analysing a patient’s admission data to recommend safe and effective medications. These systems are categorised into two types: instance-based and longitudinal-based. Instance-based models only consider the current admission, while longitudinal models consider the patient’s medical history. Electronic Health Records are used to incorporate medical history into longitudinal models. This project proposes a novel Knowledge Graph-Driven Medicine Recommendation System using Graph Neural Networks, KGDNet, that utilises longitudinal EHR data along with ontologies and Drug-Drug Interaction knowledge to construct admission-wise clinical and medicine Knowledge Graphs for every patient. Recurrent Neural Networks are employed to model a patient’s historical data, and Graph Neural Networks are used to learn embeddings from the Knowledge Graphs. A Transformer-based Attention mechanism is then used to generate medication recommendations for the patient, considering their current clinical state, medication history, and joint medical records. The model is evaluated on the MIMIC-IV EHR data and outperforms existing methods in terms of precision, recall, F1 score, Jaccard score, and Drug-Drug Interaction control. An ablation study on our models various inputs and components to provide evidence for the importance of each component in providing the best performance. Case study is also performed to demonstrate the real-world effectiveness of KGDNet.
Histamine stimulates human microglia to alter cellular prion protein expression via the HRH2 histamine receptor
Authors: Pehar Marcus , Hewitt Melissa , Wagner Ashley , Sandhu Jagdeep K. , Khalili Aria , Wang Xinyu , Cho Jae-Young , Sim Valerie L. , Kulka Marianna
Published: October 2024

Although the cellular prion protein (PrPC) has been evolutionarily conserved, the role of this protein remains elusive. Recent evidence indicates that PrPC may be involved in neuroinflammation and the immune response in the brain, and its expression may be modified via various mechanisms. Histamine is a proinflammatory mediator and neurotransmitter that stimulates numerous cells via interactions with histamine receptors 1-4 (HRH1-4). Since microglia are the innate immune cells of the central nervous system, we hypothesized that histamine-induced stimulation regulates the expression of PrPC in human-derived microglia. The human microglial clone 3 (HMC3) cell line was treated with histamine, and intracellular calcium levels were measured via a calcium flux assay. Cytokine production was monitored by enzyme-linked immunosorbent assay (ELISA). Western blotting and quantitative reverse transcription-polymerase chain reaction were used to determine protein and gene expression of HRH1-4. Flow cytometry and western blotting were used to measure PrPC expression levels. Fluorescence microscopy was used to examine Iba-1 and PrPC localization. HMC3 cells stimulated by histamine exhibited increased intracellular calcium levels and increased release of IL-6 and IL-8, while also modifying PrPC localization. HMC3 stimulated with histamine for 6 and 24 hours exhibited increased surface PrPC expression. Specifically, we found that stimulation of the HRH2 receptor was responsible for changes in surface PrPC. Histamine-induced increases in surface PrPC were attenuated following inhibition of the HRH2 receptor via the HRH2 antagonist ranitidine. These changes were unique to HRH2 activation, as stimulation of HRH1, HRH3, or HRH4 did not alter surface PrPC. Prolonged stimulation of HMC3 decreased PrPC expression following 48 and 72 hours of histamine stimulation. HMC3 cells can be stimulated by histamine to undergo intracellular calcium influx. Surface expression levels of PrPC on HMC3 cells are altered by histamine exposure, primarily mediated by HRH2. While histamine exposure also increases release of IL-6 and IL-8 in these cells, this cytokine release is not fully dependent on PrPC levels, as IL-6 release is only partially reduced and IL-8 release is unchanged under the conditions of HRH2 blockade that prevent PrPC changes. Overall, this suggests that PrPC may play a role in modulating microglial responses.
Spatial analysis and soft computational modeling for hazard assessment of potential toxic elements in potable groundwater
Authors: Aswal R. S. , Prasad Mukesh , Singh Jaswinder , Singh Hakam , Shrivastava Utpal , Wadhwa Manoj , Pandey Om Prakash , Egbueri Johnbosco C.
Published: October 2024

Swiftly increasing population and industrial developments of urban areas has accelerated the worsening of the water quality in recent years. Groundwater samples from different locations of the Doon valley, Garhwal Himalaya were analyzed to measure concentrations of six potential toxic elements (PTEs) viz. chromium (Cr), nickel (Ni), arsenic (As), molybdenum (Mo), cadmium (Cd), and lead (Pb) using Inductively Coupled Plasma Mass Spectrometer (ICP-MS) with the aim to study the spatial distribution and associated hazards. In addition, machine learning algorithms have been used for prediction of water quality and identification of influencing PTEs. The results inferred that the mean values (in the units of µg L−1) of analyzed PTEs were observed in the order of Mo (1.066) > Ni (0.744) > Pb (0.337) > As (0.186) > Cr (0.180) > Cd (0.026). The levels and computed risks of PTEs were found below the safe limits. The radial basis function neural network (RBF-NN) algorithms showed high level of accuracy in the predictions of heavy metal pollution index (HPI), heavy metal evaluation index (HEI), non-carcinogenic (N-CR) and carcinogenic (CR) parameters with determination coefficient values ranged from 0.912 to 0.976. However, the modified heavy metal pollution index (m-HPI) and contamination index (CI) predictions showed comparatively lower coefficient values as 0.753 and 0.657, respectively. The multilayer perceptron neural network (MLP-NN) demonstrated fluctuation in precision with determination coefficient between 0.167 and 0.954 for the prediction of computed indices (HPI, HEI, CI, m-HPI). In contrast, the proficiency in forecasting of non-carcinogenic and carcinogenic hazards for both sub-groups showcased coefficient values ranged from 0.887 to 0.995. As compared to each other, the radial basis function (RBF) model indicated closer alignments between predicted and actual values for pollution indices, while multilayer perceptron (MLP) model portrayed greater precision in prediction of health risk indices.
Association of visceral fat area with early-stage locomotive syndrome across various age groups: a cross-sectional study
Authors: Miyazaki Tadashi , Ozato Naoki , Yamaguchi Tohru , Sugiura Yoko , Kawada Hiromitsu , Katsuragi Yoshihisa , Osaki Noriko , Mikami Tatsuya , Ito Ken , Murashita Koichi , Nakaji Shigeyuki , Tamada Yoshinori
Published: October 2024

The association between visceral fat area (VFA) and locomotive syndrome (LS) has been extensively studied in the older population; however, the association between VFA and early-stage LS (stage 1 [LS1]) remains unclear. In this cross-sectional study, we investigated this association across different age groups. The study involved 1,236 (524 male and 712 female) participants (aged 20–85 years). Multiple regression analysis adjusted for sex, body mass index, skeletal muscle mass index, T-score, exercise habits, smoking status, and alcohol consumption revealed a significant association between LS1 and VFA across all VFA quartiles. The adjusted odds ratio OR for quartiles 2, 3, and 4 was 1.84, 2.68, and 4.12, respectively. The association between LS1 and VFA across the age groups—high VFA (> 73 cm2) and non-older (< 65 years) (OR, 1.87; 95% CI, 1.28–2.72; p = 0.001), low VFA (≤ 73 cm2) and older (≥ 65 years) (OR, 3.16; 95% CI, 1.94–5.14; p < 0.001), and high VFA and older groups (OR, 6.43; 95% CI, 3.98–10.4; p < 0.001)—was significantly stronger than that in the low VFA and non-older group. In summary, our findings suggest that managing VFA through diet and exercise is crucial for preventing LS1 across all age groups.
The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin
Authors: Dubaissi Eamon , Hilton Emma N. , Lilley Sarah , Collins Richard , Holt Charlotte , March Peter , Danahay Henry , Gosling Martin , Grencis Richard K , Roberts Ian S , Thornton David J
Published: October 2024

The TMEM16A chloride channel is proposed as a therapeutic target in cystic fibrosis, where activation of this ion channel might restore airway surface hydration and mitigate respiratory symptoms. While TMEM16A is associated with increased mucin production under stimulated or pro-inflammatory conditions, its role in baseline mucin production, secretion and/or maturation is less well understood. Here, we use the Xenopus tadpole skin mucociliary surface as a model of human upper airway epithelium to study Tmem16a function in mucus production. We found that Xenopus tropicalis Tmem16a is present at the apical membrane surface of tadpole skin small secretory cells that express canonical markers of mammalian “goblet cells” such as Foxa1 and spdef. X. tropicalis Tmem16a functions as a voltage-gated, calcium-activated chloride channel when transfected into mammalian cells in culture. Depletion of Tmem16a from the tadpole skin results in dysregulated mucin maturation post-secretion, with secreted mucins having a disrupted molecular size distribution and altered morphology assessed by sucrose gradient centrifugation and electron microscopy, respectively. Our results show that in the Xenopus tadpole skin, Tmem16a is necessary for normal mucus barrier formation and demonstrate the utility of this model system to discover new biology relevant to human mucosal biology in health and disease.
Characteristics and predictors of persistent somatic symptoms in patients with cardiac disease
Authors: Clifford Caroline , Löwe Bernd , Kohlmann Sebastian
Published: October 2024

Persistent somatic symptoms (PSS) are a diagnostic core criterion of the somatic symptom disorder. This longitudinal study aims to determine the frequency of PSS in patients with cardiac disease, identify potential predictive factors, and investigate its impact on healthcare utilization. Somatic symptoms were assessed with the Somatic Symptom Scale-8 four times over the course of three months in consecutively approached cardiac outpatients. Patients were grouped having PSS vs. not having PSS following a psychometric-driven approach based on the SSS-8 cut-off score and a data-driven approach applying cluster analysis. T-tests were performed to compare the characteristics between patients having vs. not having PSS. To identify predictors of group affiliation, we conducted multivariable logistic regressions. Additionally, analyses of covariance were used to further examine associations between healthcare utilization and group affiliation. The study included 95 patients (30.5% female) with a mean age of 60.5 years (SD = 8.7). All patients had at least one of the following cardiac diseases recorded in their medical history: coronary heart disease (n = 51), myocardial infarction (n = 21), valve disease (n = 22), cardiomyopathy (n = 15), cardiac dysrhythmia (n = 43), and heart failure (n = 12). 30 (32%) were grouped having PSS according to the psychometric-driven approach and 27 (28%) according to the data-driven approach. For both approaches, patients with PSS were more likely to be female, unemployed, reporting angina pectoris, having higher depression, and higher anxiety severity (for all: p ≤ 0.05). Predictors of PSS group affiliation were female gender, higher age, depression severity, and angina pectoris (for all: p ≤ 0.015). Patients with PSS more frequently visited general practitioners and cardiologists compared to patients without PSS (p ≤ 0.013). Enhancing our knowledge of PSS in patients with cardiac disease could help to improve identification of patients’ specific needs and the factors to consider in diagnosis and individualized treatment.
Efficiency of multivariate tests in trials in progressive supranuclear palsy
Authors: Yousefi Elham , Gewily Mohamed , König Franz , Höglinger Günter , Hopfner Franziska , Karlsson Mats O. , Ristl Robin , Zehetmayer Sonja , Posch Martin
Published: October 2024

Measuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as progressive supranuclear palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes as measured by the items of the progressive supranuclear palsy rating scale (PSPRS). We consider several statistical approaches, including sum scores, a modified PSPRS rating scale that had been recommended by FDA in a pre-IND meeting, multivariate tests, and analysis approaches based on multiple comparisons of the individual items. In addition, we propose two novel approaches which measure disease status based on Item Response Theory models. We assess the performance of these tests under various scenarios in an extensive simulation study and illustrate their use with a re-analysis of the ABBV-8E12 clinical trial. Furthermore, we discuss the impact of the FDA-recommended scoring of item scores on the power of the statistical tests. We find that classical approaches as the PSPRS sum score demonstrate moderate to high power when treatment effects are consistent across the individual items. The tests based on Item Response Theory (IRT) models yield the highest power when the simulated data are generated from an IRT model. The multiple testing based approaches have a higher power in settings where the treatment effect is limited to certain domains or items. The study demonstrates that there is no one-size-fits-all testing procedure for evaluating treatment effects using PSPRS items; the optimal method varies based on the specific effect size patterns. The efficiency of the PSPRS sum score, while generally robust and straightforward to apply, varies depending on the specific patterns of effect sizes encountered and more powerful alternatives are available in specific settings. These findings can have important implications for the design of future clinical trials in PSP and similar multifaceted diseases.
Brain-to-blood transport of fluorescein in vitro
Authors: Schoknecht Karl , Eilers Jens
Published: October 2024

Investigating blood-brain barrier (BBB) dysfunction has become a pre-clinical and clinical research focus as it accompanies many neurological disorders. Nevertheless, knowledge of how diagnostic BBB tracers cross the endothelium from blood-to-brain or vice versa often remains incomplete. In particular, brain-to-blood transport (efflux) may reduce tracer extravasation of intravascularly (i.v.) applied tracers. Conversely, impaired efflux could mimic phenotypic extravasation. Both processes would affect conclusions on BBB properties primarily attributed to blood-to-brain leakage. Here, we specifically investigated efflux of fluorescent BBB tracers, focusing on the most common non-toxic marker, sodium fluorescein, which is applicable in patients. We used acute neocortical slices from mice and applied fluorescein, sulforhodamine-B, rhodamine-123, FITC dextran to the artificial cerebrospinal fluid. Anionic low molecular weight (MW) fluorescein and sulforhodamine-B, but not ~ 10-fold larger FITC-dextran and cationic low MW rhodamine-123, showed efflux into the lumen of blood vessels. Our data suggest that fluorescein efflux depends on organic anion transporter polypeptides (Oatp) rather than P-glycoprotein. Furthermore, sodium-potassium ATPase inhibition and incomplete oxygen-glucose deprivation (OGD, 20% O2) reduced fluorescein efflux, while complete OGD (0% O2) abolished efflux. We provide evidence for active efflux of fluorescein in vitro. Impaired efflux of fluorescein could thus contribute to the frequently observed BBB dysfunction in neuropathologies in addition to blood-to-brain leakage.
Risk factors for Ascaris lumbricoides infection and its association with nutritional status and IQ in 14-Year old adolescents in Chitwan, Nepal
Authors: Parajuli Rajendra Prasad , Bhandari Shristi , Ward Lauren Marie , Suarez-Lopez Jose Ricardo
Published: October 2024

Inconsistent results have been obtained from studies investigating the association between soil-transmitted helminths (STHs) and nutritional status and cognitive outcomes. This study aimed to investigate the influence of STHs and nutritional status on the intelligence quotient (IQ) of adolescents in the Chitwan Valley, Nepal. In this birth cohort study from the Chitwan district of Nepal, 74 cohort participants were followed up after 14 years. The presence and egg density of the STHs were investigated following the Kato–Katz method. Full-scale IQ was evaluated using the Wechsler Abbreviated Scale of Intelligence-II (WASI-II). Multivariate regression analysis was also conducted to examine the associations of STHs and nutritional status with IQ scores, adjusting for adverse childhood experiences (ACE) and demographic and socioeconomic factors. The only STHs detected was for Ascaris lumbricoides, which was detected in 16% (12/74) of the study participants. Similarly, 16% (12/73) of participants reported undernutrition (body mass index (BMI) Z score<-2SD), and 33% (25/74) of participants had a developmental deficit (WASI II FSIQ < 69). There were no significant associations between the presence of A. lumbricoides or egg density and IQ scores. However, undernutrition (BMIZ<-2SD) increased the odds of a developmental deficit according to both univariate and adjusted multivariate models [i.e., adjusted odds ratio (aOR) 9.41; 95% CI (2.23 to 39.80)]. While the study primarily examines the association of STHs and nutritional status with IQ, it is important to note that adolescents with educated mothers or higher incomes also showed better cognitive development. The prevalence of undernutrition and associated developmental deficits characterized by an IQ < 69 was alarmingly high in this cohort of adolescents from Chitwan, Nepal. Despite the high prevalence of A. lumbricoides, its infection was not identified as significantly associated with cognition. However, it is noteworthy that a consistent favorable impact of an enriching postnatal environment, approximated by maternal education and family income, may improve neurodevelopmental indicators.
Differential amino acid usage leads to ubiquitous edge effect in proteomes across domains of life that can be explained by amino acid secondary structure propensities
Authors: Morimoto Juliano , Pietras Zuzanna
Published: October 2024

Amino acids are the building blocks of proteins and enzymes which are essential for life. Understanding amino acid usage offers insights into protein function and molecular mechanisms underlying life histories. However, genome-wide patterns of amino acid usage across domains of life remain poorly understood. Here, we analysed the proteomes of 5590 species across four domains and found that only a few amino acids are consistently the most and least used. This differential usage results in lower amino acid usage diversity at the most and least frequent ranks, creating a ubiquitous inverted U-shape pattern of amino acid diversity and rank which we call an ‘edge effect’ across proteomes and domains of life. This effect likely stems from protein secondary structural constraints, not the evolutionary chronology of amino acid incorporation into the genetic code, highlighting the functional rather than evolutionary influences on amino acid usage. We also tested other contemporary hypotheses regarding amino acid usage in proteomes and found that amino acid usage varies across life’s domains and is only weakly influenced by growth temperature. Our findings reveal a novel and pervasive amino acid usage pattern across genomes with the potential to help us probe deep evolutionary relationships and advance synthetic biology.
Risk preference and rural livelihood transitions in the hilly and mountainous region of southern China: a case study in Ruijin City
Authors: Wu Zhilong , Chen Hao , Zeng Tian , Yan Yushan , Zhang Mengyuan
Published: October 2024

Rural livelihood transition towards non-agriculturalization, non-grainization and even anti-urbanization has become a thorny social problem that undermines farmland resources and worldwide food security. Based on a simulation survey, this study explored the risk preferences and the livelihood transition mechanisms of typical farmers in the hilly and mountainous region. The results indicated that: (1) 76.86% of rural households exhibited risk aversion tendencies, with 60.67% being highly risk-averse. The ranking of risk aversion among the three typical farmers is consistent with asset abundance, with non-agriculture oriented households > semi-farmer and semi-labour households > vocational farmer households. (2) The non-grainization of vocational farmer households is significantly and positively correlated with the family labour force, land management area, and housing assets, yet negatively correlated with risk preferences. Compared to traditional grain cultivation, non-grainization in the hilly and mountainous region possesses lower risks and higher profitability for vocational farmer households. (3) The total non-agriculturalization of semi-farmer and semi-labour households correlates negatively with land management area but positively with family income. (4) Anti-urbanization and returning hometowns for farming are still regarded as a livelihood fallback by the non-agriculture oriented households, but excessive gift expenditure has become a heavy burden in rural society. Therefore, practical and systematical countermeasures are proposed in this research to guide sustainable livelihood transition.
Controlling strain localization in thin films with nanoindenter tip sharpness
Authors: Zak Stanislav
Published: October 2024

Thin film nanoindentation has increased interest due to its usage in various applications. It is virtually impossible to measure thin film elastic modulus without the substrate influence. Several different methods exist to obtain the true thin film’s elastic modulus with no attention given to investigate what parameters can improve insight into thin film mechanical property measurement. A key parameter is the tip radius. This work is aimed at quantifying the influence of the tip radius on the strain field under the indenter. Three Berkovich indentation tips with different tip radii were used for thin multilayer nanoindentation with numerical modelling. The results confirm the existence of the large elastically deformed zone, with a strong localization under the tip. Comparison between the experiments and numerical model shows direct connection between the tip radius and strain localization affecting the experiment, emphasizing importance of knowing the tip radius.
ROI constrained optimal online allocation in sponsored search
Authors: Xu Wenjian , Liu Shui , Chen Zulong , Zhou Ying , Li Liangyue , Wang Yangyang , Lu Quan , Ji Yuyang , Wan Jian
Published: October 2024

Sponsored search plays a major role in the revenue contribution of e-commerce platforms. Advertising systems are designed to maximize platform revenue, but other goals also need to be considered, such as user experience, advertiser utility, and how to achieve the long-term revenue goal. A key component of a sponsored search system is online allocation, which makes real-time decisions to match users’ search requests with relevant ad campaigns to maximize platform revenue within constraints such as campaign budgets. Although much progress has been made, most of the research work on allocation problem has focused on satisfying guaranteed deals for display ads, and those challenges for allocation problems in sponsored search are not properly addressed. In this paper, we develop a framework to solve the large-scale sponsored search ad allocation problem, consisting of two main parts. One is an optimization problem solved offline by a parameter-server based architecture, and the other is an online strategy to alleviate the conflict with the auction mechanism during online service. Comprehensive offline evaluation on real production data and online A/B testing on real production system have been made. The experimental results demonstrate that through better allocating user queries to appropriate ads, the proposed model can significantly increase the platform’s revenue without sacrificing advertisers’ ROI.
Endogenous opioid receptor system mediates costly altruism in the human brain
Authors: Chen Jinglu , Putkinen Vesa , Seppälä Kerttu , Hirvonen Jussi , Ioumpa Kalliopi , Gazzola Valeria , Keysers Christian , Nummenmaa Lauri
Published: October 2024

Functional neuroimaging studies suggest that a large-scale brain network transforms others’ pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [11C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate’s pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others’ pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain.
Catalytic activity and stability of NiPt/C catalysts for the synthesis of iso-butanol from methanol/ethanol mixtures
Authors: Pasel Joachim , Häusler Johannes , Peters Ralf , Stolten Detlef
Published: October 2024

The uniqueness and innovation of the Ni99Pt1/C catalyst lies in the fact that a promising activity for iso-butanol synthesis was already observed at a low temperature of 165 °C in methanolic solution and at a very low precious metal mass fraction.
N-type Ag2S modified CZTSSe solar cell with lowest Voc,def
Authors: Yang Jin , Fu Junjie , Dong Weiwei , Ren Shu , Zhang Xin , Su Jingyi , Zhao Chaoliang , Wei Meng , Zhao Dandan , Zhang Yange , Wu Sixin , Zheng Zhi
Published: October 2024

The Sn, Zn-doped Ag2S plays a triple role in CZTSSe devices: p–n conversion, front-interface bandgap grading, and defect passivation. This strategy achieved an efficiency of 14.25%, with the Voc of 0.584 V and the lowest Voc,def of 0.228 V.
Robust calix[4]arene-polyethyleneimine coated iron oxide nanoparticles for enhanced recovery of gold and platinum chloride complexes
Authors: Moya Carlos , Brion Natacha , Troian-Gautier Ludovic , Jabin Ivan , Bruylants Gilles
Published: October 2024

Robust IONPs@X4C4@PEI samples designed for the efficient extraction of Au(iii) and Pt(iv) salts from synthetic solutions.
A MoS2 quantum dot functionalized TiO2 nanotube array for selective detection of xylene at low temperature
Authors: Bhardwaj Radha , Hazra Arnab
Published: October 2024

Electrochemically synthesized TiO2 nanotube array was functionalized with MoS2 quantum dots and transformed into metal–insulator–metal type sensor which exhibited xylene selectivity with high response magnitude at low operating temperature.
Impact of catalyst support on water-assisted CO oxidation over PdO/MO2 (M = Sn, Ti, and Si) catalysts: experimental and theoretical investigation
Authors: Liu Kun , Liao Luliang , Liao Guangfu
Published: October 2024

This study investigates the influence of different supports on PdO-based catalysts during CO oxidation, particularly under humid conditions.
Hydrogen spillover drives room temperature sensing on spark plasma sintered BaTiO3 with Pt electrodes
Authors: Bell Jon G. , Huangfu Shangxiong , Artiglia Luca , Graule Thomas , Stuer Michael
Published: October 2024

Change in BaTiO3 grain boundary resistance due to H2 dissociation on platinum and spillover and reaction of hydrogen with BaTiO3 surface hydroxyl species. This forms adsorbed water that desorbs to generate oxygen vacancies.
Local structural distortions and thermochromic properties of Cs2NaFeCl6 halide double perovskite
Authors: Sahoo Bikash Ranjan , Hathwar Venkatesha R. , Deshpande U. P. , Bhobe Preeti A.
Published: October 2024

The thermochromism shown by the Cs2NaFeCl6 perovskite is influenced by the strong electron–phonon coupling induced by octahedral distortion around the Fe atom.
Physicochemical properties and application of concentrated KN(SO2F)2/sulfolane solution in high-voltage high-power K-ion batteries
Authors: Igarashi Daisuke , Tatara Ryoichi , Yasuno Satoshi , Komaba Shinichi
Published: October 2024

A highly concentrated electrolyte of KN(SO2F)2 (KFSA) and sulfolane (SL) was developed as a K-ion battery electrolyte. The equimolar mixture solution of KFSA/SL exhibited a wide potential window and improved the rate capability of K2Mn[Fe(CN)6].
Influence of a diketopyrrolopyrrole spacer on the ultrafast nonlinear optical properties and excited state dynamics of dimeric zinc porphyrin molecules
Authors: Murali Rahul , Biswas Chinmoy , Nayak Sudhanshu Kumar , Wu Hanping , Peng Xiaobin , Kumar Vipin , Chetti Prabhakar , Soma Venugopal Rao , Raavi Sai Santosh Kumar
Published: October 2024

This work highlights the significance of adding a DPP unit to the zinc-porphyrin core with ethynylene bridges to enhance third-order NLO properties under femtosecond laser excitation.
An anti‐interference decision‐making method for communication waveform based on collaborative filtering
Authors: Li Wenji , Zheng Zhong , Zheng Hanyu , Guan Yundi
Published: October 2024

Aiming at the problem of efficient and reliable transmission for communication system in complex electromagnetic environment, an anti‐interference decision‐making method for communication waveform based on collaborative filtering (CF) is proposed here. The required minimum signal‐to‐noise ratio to meet a specific bit error rate is adopted as a key indicator to evaluate the performance of certain waveform–channel combinations. The main challenge that is solved is to predict transmission performance ratings that cannot be obtained in practice. With CF of waveform features and interference features, the missing training data can be accurately predicted. The convergence speed and prediction accuracy of the proposed algorithm are verified by simulation, and the influence of different feature quantities and different data deficiency degrees on the stability and accuracy of the algorithm is discussed.
Differential neural mechanisms underlie cortical gating of visual spatial attention mediated by alpha-band oscillations
Authors: Yang Xiaofang , Fiebelkorn Ian C. , Jensen Ole , Knight Robert T. , Kastner Sabine
Published: October 2024

Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval. Dorsal intraparietal areas contralateral to the attended hemifield primarily exhibited a delayed and sustained alpha desynchronization, while ventrolateral extrastriatal areas ipsilateral to the attended hemifield primarily exhibited an earlier and sustained alpha synchronization. Analyses of cross-frequency coupling between alpha phase and broadband high-frequency activity (HFA) further revealed cross-frequency interactions along the visual hierarchy contralateral to the attended locations. Directionality analyses indicate that alpha phase in early and extrastriatal visual areas modulated HFA power in downstream visual areas, thus potentially facilitating the feedforward processing of an upcoming, spatially predictable target. In contrast, in areas ipsilateral to the attended locations, HFA power modulated local alpha phase in early and extrastriatal visual areas, with suppressed interareal interactions, potentially attenuating the processing of distractors. Our findings reveal divergent alpha-mediated neural mechanisms underlying target enhancement and distractor suppression during the deployment of spatial attention, reflecting enhanced functional connectivity at attended locations, while suppressed functional connectivity at unattended locations. The collective dynamics of these alpha-mediated neural mechanisms play complementary roles in the efficient gating of sensory information.