bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning model to predict tensile properties of annealed Ti6Al4V parts prepared by selective laser melting
Authors: Yang Zhaotong , Yang Mei , Sisson Richard , Li Yanhua , Liang Jianyu
Published: September 2022

In this work, an artificial neural network model is established to understand the relationship among the tensile properties of as-printed Ti6Al4V parts, annealing parameters, and the tensile properties of annealed Ti6Al4V parts. The database was established by collecting published reports on the annealing treatment of selective laser melting (SLM) Ti6Al4V, from 2006 to 2020. Using the established model, it is possible to prescribe annealing parameters and predict properties after annealing for SLM Ti-6Al-4V parts with high confidence. The model shows high accuracy in the prediction of yield strength (YS) and ultimate tensile strength (UTS). It is found that the YS and UTS are sensitive to the annealing parameters, including temperature and holding time. The YS and UTS are also sensitive to initial YS and UTS of as-printed parts. The model suggests that an annealing process of the holding time of fewer than 4 h and the holding temperature lower than 850°C is desirable for as-printed Ti6Al4V parts to reach the YS required by the ASTM standard. By studying the collected data of microstructure and tensile properties of annealed Ti6Al4V, a new Hall-Petch relationship is proposed to correlate grain size and YS for annealed SLM Ti6Al4V parts in this work. The prediction of strain to failure shows lower accuracy compared with the predictions of YS and UTS due to the large scattering of the experimental data collected from the published reports.
Gamification of design thinking: a way to enhance effectiveness of learning
Authors: Bhatt Apoorv Naresh , Chakrabarti Amaresh
Published: September 2022

The goal of this paper is to develop and test a gamified design thinking framework, including its pedagogical elements, for supporting various learning objectives for school students. By synthesizing the elements and principles of design, learning and games, the authors propose a framework for a learning tool for school students to fulfil a number of learning objectives; the framework includes a design thinking process called “IISC Design Thinking” and its gamified version called “IISC DBox”. The effectiveness of the framework as a learning tool has been evaluated by conducting workshops that involved 77 school students. The results suggest that the gamification used had a positive effect on the design outcomes, fulfilment of learning objectives, and learners' achievements, indicating the potential of the framework for offering an effective, gamified tool for promoting design thinking in school education. In addition to presenting results from empirical studies for fulfilment of the objectives, this paper also proposes an approach that can be used for identifying appropriate learning objectives, selecting appropriate game elements to fulfil these objectives, and integrating appropriate game elements with design and learning elements. The paper also proposes a general approach for assessing the effectiveness of a gamified version for attaining a given set of learning objectives. The methodology used in this paper thus can be used as a reference for developing and evaluating a gamified version of design thinking course suitable not only for school education but also for other domains (e.g., engineering, management) with minimal changes.
Can a new role, the (Trainee) Associate Psychological Practitioner (T/APP), add value in General Practice? Results from the pilot year evaluation
Authors: Budd Miranda , Gardner Rebecca , Bhutani Gita , Gardner Kathryn , Iqbal Ameera , Harding Charlotte , Baguley Clare , Chauhan Umesh
Published: September 2022

Background:

The deployment of (Trainee) Associate Psychological Practitioners (T/APPs) to deliver brief psychological interventions focusing on preventing mental health deterioration and promoting emotional wellbeing in General Practice settings is a novel development in the North West of England. As the need and demand for psychological practitioners increases, new workforce supply routes are required to meet this growth.

Aims:

To evaluate the clinical impact and efficacy of the mental health prevention and promotion service, provided by the T/APPs and the acceptability of the role from the perspective of the workforce and the role to T/APPs, patients and services.

Methods:

A mixed-methods design was used. To evaluate clinical outcomes, patients completed measures of wellbeing (WEMWBS), depression (PHQ-9), anxiety (GAD-7) and resilience (BRS) at the first session, final session and at a 4–6 week follow-up. Paired-samples t-tests were conducted comparing scores from session 1 and session 4, and session 1 and follow-up for each of the four outcome measures. To evaluate acceptability, questionnaires were sent to General Practice staff, T/APPs and patients to gather qualitative and quantitative feedback on their views of the T/APP role. Quantitative responses were collated and summarised. Qualitative responses were analysed using inductive summative content analysis to identify themes.

Results:

T-test analysis revealed clinically and statistically significant reductions in depression and anxiety and elevations in wellbeing and resiliency between session 1 and session 4, and at follow-up. Moderate–large effect sizes were recorded. Acceptability of the T/APP role was established across General Practice staff, T/APPs and patients. Content analysis revealed two main themes: positive feedback and constructive feedback. Positive sub-themes included accessibility of support, type of support, patient benefit and primary care network benefit. Constructive sub-themes included integration of the role and limitations to the support.

Conclusions:

The introduction of T/APPs into General Practice settings to deliver brief mental health prevention and promotion interventions is both clinically effective and acceptable to patients, General Practice staff and psychology graduates.
Compton Camera Imaging of a Gamma‐Ray Glow From a Thunderstorm
Authors: Kuriyama E. , Masubuchi M. , Koshikawa N. , Iwashita R. , Omata A. , Kanda T. , Kataoka J. , Tsurumi M. , Diniz G. , Enoto T. , Wada Y.
Published: September 2022

Gamma‐ray glows associated with thunderclouds have been observed since the 1980s, however it remains unclear how, and at which thunderstorms gamma‐ray glows are generated in dense atmospheres. In this study, we report the first Compton camera imaging of a gamma‐ray glow from a winter thundercloud. On 14 January 2022, using two identical Bi4Ge3O12 scintillators in energy range of 0.05–5 MeV, we detected two gamma‐ray glows lasting ∼4 min in a mountain area 25 km from the Japan Sea and 410 m above sea level. The same events were also observed by the Compton camera, where the first glow we observed suggested statistically significant (4.0 and 5.9 σ level) signals of two enhanced concentrations in gamma‐ray photon images in a range of 0.15–1.5 MeV. These concentrations were most clearly observed in a time window of Δt = 50 s around the peak intensity of the gamma‐ray glow.
A New Mechanism for Early‐Time Plasmaspheric Refilling: The Role of Charge Exchange Reactions in the Transport of Energy and Mass Throughout the Ring Current—Plasmasphere System
Authors: Liu Jianghuai , Ilie Raluca , Borovsky Joseph E. , Liemohn Michael W.
Published: September 2022

Cold H+ produced via charge exchange reactions between ring current ions and exospheric neutral hydrogen constitutes an additional source of cold plasma that further contributes to the plasmasphere and affects the plasma dynamics in the Earth's magnetosphere system; however, its production and associated effects on the plasmasphere dynamics have not been fully assessed and quantified. In this study, we perform numerical simulations mimicking an idealized three‐phase geomagnetic storm to investigate the role of heavy ion composition in the ring current (O+ vs. N+) and exospheric neutral hydrogen density in the production of cold H+ via charge exchange reactions. It is found that ring current heavy ions produce more than 50% of the total cold H+ via charge exchange reactions, and energetic N+ is more efficient in producing cold H+ via charge exchange reactions than O+. Furthermore, the density structure of the cold H+ is highly dependent on the mass of the parent ion; that is, cold H+ deriving from charge exchange reactions involving energetic O+ with neutral hydrogen, populates the lower L‐shells, while cold H+ deriving from charge exchange reactions involving energetic N+ with neutral hydrogen populates the higher L‐shells. In addition, the density of cold H+ produced via charge exchange reactions involving N+ can be peak at values up to one order of magnitude larger than the local plasmaspheric density, suggesting that solely considering the supply of cold plasma from the ionosphere to the plasmasphere can lead to a significant underestimation of plasmasphere density.
Effects of Increasing the Category Resolution of the Sea Ice Thickness Distribution in a Coupled Climate Model on Arctic and Antarctic Sea Ice Mean State
Authors: Smith Madison M. , Holland Marika M. , Petty Alek A. , Light Bonnie , Bailey David A.
Published: September 2022

Many modern sea ice models used in global climate models represent the subgrid‐scale heterogeneity in sea ice thickness with an ice thickness distribution (ITD), which improves model realism by representing the significant impact of the high spatial heterogeneity of sea ice thickness on thermodynamic and dynamic processes. Most models default to five thickness categories. However, little has been done to explore the effects of the resolution of this distribution (number of categories) on sea‐ice feedbacks in a coupled model framework and resulting representation of the sea ice mean state. Here, we explore this using sensitivity experiments in CESM2 with the standard 5 ice thickness categories and 15 ice thickness categories. Increasing the resolution of the ITD in a run with preindustrial climate forcing results in substantially thicker Arctic sea ice year‐round. Analyses show that this is a result of the ITD influence on ice strength. With 15 ITD categories, weaker ice occurs for the same average thickness, resulting in a higher fraction of ridged sea ice. In contrast, the higher resolution of thin ice categories results in enhanced heat conduction and bottom growth and leads to only somewhat increased winter Antarctic sea ice volume. The spatial resolution of the ICESat‐2 satellite mission provides a new opportunity to compare model outputs with observations of seasonal evolution of the ITD in the Arctic (ICESat‐2; 2018–2021). Comparisons highlight significant differences from the ITD modeled with both runs over this period, likely pointing to underlying issues contributing to the representation of average thickness.
Implementation of Two Developmental Screening Programs in Sickle Cell Disease Specialty Care
Authors: Schlenz Alyssa M. , Schatz Jeffrey
Published: September 2022

Objective:

Developmental screening is a critical component of care for children with sickle cell disease (SCD), who are at elevated risk for neurodevelopmental disorders. This report describes the implementation of two related developmental screening programs implemented in different SCD specialty care settings with the purpose of describing screening protocols, outcomes, and lessons learned.

Methods:

Program 1 reviewed medical records for 201 children with SCD screened at ages 2 and 4 years. Program 2 reviewed program tracking and visit notes for 155 screenings across 67 children screened between 9 and 66 months of age. Key outcomes included characteristics of children screened, screening results, concordance between parent concerns and screening outcomes, and access to evaluation and intervention services.

Results:

Each program identified a substantial number of children with developmental concerns, including 42% of screenings in Program 1 and 36% of unique children screened in Program 2. Program 1 resulted in 56% of identified children receiving follow-up developmental services and 62% receiving developmental monitoring. Program 2 resulted in 58% of identified children receiving further evaluation following developmental screening, with 67–75% of children with neurodevelopmental diagnoses receiving intervention services following evaluation. While parent concerns were related to screening outcomes, screening instruments detected many children whose parents did not express developmental concerns.

Conclusions:

Routine developmental screening is a feasible, acceptable, and effective method for identifying concerns in children with SCD in specialty care. Flexible and collaborative care and sustainability are key considerations for effective programming, with pediatric psychologists uniquely positioned to provide optimal integrated care.

Implications for Impact Statement

Children with sickle cell disease are at high risk for neurodevelopmental disorders and benefit from early, high-quality identification and support for these concerns. Routine developmental screening delivered by a psychologist in specialty sickle cell disease care is a feasible, acceptable, and sustainable approach for meeting these important needs.
Establishment of a humanized animal model of systemic sclerosis in which T helper-17 cells from patients with systemic sclerosis infiltrate and cause fibrosis in the lungs and skin
Authors: Park Min-Jung , Park Youngjae , Choi Jeong Won , Baek Jin-Ah , Jeong Ha Yeon , Na Hyun Sik , Moon Young-Mee , Cho Mi-La , Park Sung-Hwan
Published: September 2022

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microangiopathy, and progressive fibrosis in the skin and internal organs. To evaluate the pathophysiologic mechanisms and efficacies of potential therapeutics for SSc, a preclinical model recapitulating the disease phenotypes is needed. Here, we introduce a novel animal model for SSc using immunodeficient mice injected with peripheral blood mononuclear cells (PBMCs) from SSc patients. Human PBMCs acquired from SSc patients and healthy controls were transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl (NSG) mice with concurrent bleomycin injection. Blood, skin, and lung tissues were acquired and analyzed after PBMC engraftment. In addition, we investigated whether the humanized murine model could be used to assess the efficacy of potential therapeutics for SSc. Human PBMCs from SSc patients and healthy controls were engrafted into the blood, skin, and lung tissues of NSG mice. Histological analysis of affected tissues from mice treated with SSc PBMCs (SSc hu-mice) demonstrated substantial inflammation, fibrosis and vasculopathy with human immune cell infiltration and increased expression of IL-17, TGF-β, CCL2, CCL3, and CXCL9. The proportions of circulating and tissue-infiltrating T helper 17 (Th17) cells were elevated in SSc hu-mice. These cells showed increased expression of CXCR3 and phosphorylated STAT3. SSc hu-mice treated with rebamipide and other potential Th17-cell-modulating drugs presented significantly reduced tissue fibrosis. Mice injected with patient-derived PBMCs show promise as an animal model of SSc.
Lanthanide-doped nanoscintillators
Authors: Bünzli Jean-Claude Georges
Published: September 2022

Lanthanide-doped nanoscintillators are taking the lead in several important fields including radiation detection, biomedicine, both at the level of diagnosis and therapy, and information encoding.
Measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts
Authors: Kann Samuel H. , Shaughnessey Erin M. , Coppeta Jonathan R. , Azizgolshani Hesham , Isenberg Brett C. , Vedula Else M. , Zhang Xin , Charest Joseph L.
Published: September 2022

Measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip (OOC) systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue models. However, current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints, require labels or added substrates, and lack real-time data. Here, we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer devices. Each membrane bilayer device supported a culture of human renal proximal tubule epithelial cells on a porous membrane suspended between two microchannels and exposed to controlled, unidirectional perfusion and physiologically relevant shear stress for several days. For the first time, we measured changes in oxygen in a membrane bilayer format and used a finite element analysis model to estimate cell oxygen consumption rates (OCRs), allowing comparison with OCRs from other cell culture systems. Finally, we demonstrated label-free detection of metabolic shifts in human renal proximal tubule cells following exposure to FCCP, a drug known for increasing cell oxygen consumption, as well as oligomycin and antimycin A, drugs known for decreasing cell oxygen consumption. The capability to measure cell OCRs and detect metabolic shifts in an array of membrane bilayer devices contained within an industry standard microtiter plate format will be valuable for analyzing flow-responsive and physiologically complex tissues during drug development and disease research.
A Japanese patient with neonatal biotin-responsive basal ganglia disease
Authors: Kobayashi Mizuki , Suzuki Yuichi , Nodera Maki , Matsunaga Ayako , Kohda Masakazu , Okazaki Yasushi , Murayama Kei , Yamagata Takanori , Osaka Hitoshi
Published: September 2022

Biotin-responsive basal ganglia disease (BBGD) with SLC19A3 mutation was first reported in 1998, and over 30 mutations have been reported. We report a neonatal BBGD case with sudden-onset feeding difficulty and impaired consciousness. Encephalopathy resolved after the initiation of biotin and thiamine treatment. Genetic testing revealed a novel heterozygous mutation [c.384_387del, p.Tyr128fs];[c.265 A > C, p.Ser89Arg] in SLC19A3. Early treatment for BBGD is essential, especially with onset in the neonatal or early infancy period.
The macroeconomic effects of adapting to high-end sea-level rise via protection and migration
Authors: Bachner Gabriel , Lincke Daniel , Hinkel Jochen
Published: September 2022

Climate change-induced sea level rise (SLR) is projected to be substantial, triggering human adaptation responses, including increasing protection and out-migration from coastlines. Yet, in macroeconomic assessments of SLR the latter option has been given little attention. We fill this gap by providing a global analysis of the macroeconomic effects of adaptation to SLR, including coastal migration, focusing on the higher end of SLR projections until 2050. We find that when adapting simultaneously via protection and coastal migration, macroeconomic costs can be lower than with protection alone. For some developing regions coastal migration is even less costly (in GDP) than protection. Additionally, we find that future macroeconomic costs are dominated by accumulated macroeconomic effects over time, rather than by future direct damages, implying the need for immediate adaptation. Finally, we demonstrate the importance of including autonomous adaptation in the reference scenario of economic assessment studies to avoid overestimation of adaptation benefits.
Control of electronic topology in a strongly correlated electron system
Authors: Dzsaber Sami , Zocco Diego A. , McCollam Alix , Weickert Franziska , McDonald Ross , Taupin Mathieu , Eguchi Gaku , Yan Xinlin , Prokofiev Andrey , Tang Lucas M. K. , Vlaar Bryan , Winter Laurel E. , Jaime Marcelo , Si Qimiao , Paschen Silke
Published: September 2022

It is becoming increasingly clear that breakthrough in quantum applications necessitates materials innovation. In high demand are conductors with robust topological states that can be manipulated at will. This is what we demonstrate in the present work. We discover that the pronounced topological response of a strongly correlated “Weyl-Kondo” semimetal can be genuinely manipulated—and ultimately fully suppressed—by magnetic fields. We understand this behavior as a Zeeman-driven motion of Weyl nodes in momentum space, up to the point where the nodes meet and annihilate in a topological quantum phase transition. The topologically trivial but correlated background remains unaffected across this transition, as is shown by our investigations up to much larger fields. Our work lays the ground for systematic explorations of electronic topology, and boosts the prospect for topological quantum devices.
A deeper understanding of system interactions can explain contradictory field results on pesticide impact on honey bees
Authors: Breda Dimitri , Frizzera Davide , Giordano Giulia , Seffin Elisa , Zanni Virginia , Annoscia Desiderato , Topping Christopher J. , Blanchini Franco , Nazzi Francesco
Published: September 2022

While there is widespread concern regarding the impact of pesticides on honey bees, well-replicated field experiments, to date, have failed to provide clear insights on pesticide effects. Here, we adopt a systems biology approach to gain insights into the web of interactions amongst the factors influencing honey bee health. We put the focus on the properties of the system that depend upon its architecture and not on the strength, often unknown, of each single interaction. Then we test in vivo, on caged honey bees, the predictions derived from this modelling analysis. We show that the impact of toxic compounds on honey bee health can be shaped by the concurrent stressors affecting bees. We demonstrate that the immune-suppressive capacity of the widespread pathogen of bees, deformed wing virus, can introduce a critical positive feed-back loop in the system causing bistability, i.e., two stable equilibria. Therefore, honey bees under similar initial conditions can experience different consequences when exposed to the same stressor, including prolonged survival or premature death. The latter can generate an increased vulnerability of the hive to dwindling and collapse. Our conclusions reconcile contrasting field-testing outcomes and have important implications for the application of field studies to complex systems.
Building up libraries and production line for single atom catalysts with precursor-atomization strategy
Authors: He Xiaohui , Zhang Hao , Zhang Xingcong , Zhang Ying , He Qian , Chen Hongyu , Cheng Yujie , Peng Mi , Qin Xuetao , Ji Hongbing , Ma Ding
Published: September 2022

Having the excellent catalytic performance, single atom catalysts (SACs) arouse extensive research interest. However, the application of SACs is hindered by the lack of versatile and scalable preparation approaches. Here, we show a precursor-atomization strategy to produce SACs, involving the spray of droplets of solutions containing metal precursors onto support surface through ultrasonic atomization and the subsequent calcination. This approach is versatile to successful synthesis of a series of catalysts, including 19 SACs with different metal sites and supports and 3 derivatives of SACs (single atom alloys, double atom catalysts and bi-metallic SACs). Furthermore, it can be scaled up by a homemade production line with productivity over 1 kg day−1, and the well-controlled catalyst uniformity is evidenced by the identical characterization results and catalytic properties in Suzuki-Miyaura cross-coupling. This strategy lays a foundation for further investigation and may accelerate the trend from basic research to industrial applications of SACs.
Synchronous quantitative analysis of chiral mesostructured inorganic crystals by 3D electron diffraction tomography
Authors: Ai Jing , Zhang Xueliang , Bai Te , Shen Qing , Oleynikov Peter , Duan Yingying , Terasaki Osamu , Che Shunai , Han Lu
Published: September 2022

Chiral mesostructures exhibit distinctive twisting and helical hierarchical stacking ranging from atomic to micrometre scales with fascinating structural-chiral anisotropy properties. However, the detailed determination of their multilevel chirality remains challenging due to the limited information from spectroscopy, diffraction techniques, scanning electron microscopy and the two-dimensional projections in transmission electron microscopy. Herein, we report a general approach to determine chiral hierarchical mesostructures based on three-dimensional electron diffraction tomography (3D EDT), by which the structure can be solved synchronously according to the quantitative measurement of diffraction spot deformations and their arrangement in reciprocal space. This method was verified on two samples—chiral mesostructured nickel molybdate and chiral mesostructured tin dioxide—revealing hierarchical chiral structures that cannot be determined by conventional techniques. This approach provides more precise and comprehensive identification of the hierarchical mesostructures, which is expected to advance our understanding of structural–chiral anisotropy at the fundamental level.
Genomic analyses of rice bean landraces reveal adaptation and yield related loci to accelerate breeding
Authors: Guan Jiantao , Zhang Jintao , Gong Dan , Zhang Zhengquan , Yu Yang , Luo Gaoling , Somta Prakit , Hu Zheng , Wang Suhua , Yuan Xingxing , Zhang Yaowen , Wang Yanlan , Chen Yanhua , Laosatit Kularb , Chen Xin , Chen Honglin , Sha Aihua , Cheng Xuzhen , Xie Hua , Wang Lixia
Published: September 2022

Rice bean (Vigna umbellata) is an underexploited domesticated legume crop consumed for dietary protein in Asia, yet little is known about the genetic diversity of this species. Here, we present a high-quality reference genome for a rice bean landrace (FF25) built using PacBio long-read data and a Hi-C chromatin interaction map, and assess the phylogenetic position and speciation time of rice bean within the Vigna genus. We sequence 440 landraces (two core collections), and GWAS based on data for growth sites at three widely divergent latitudes reveal loci associated with flowering and yield. Loci harboring orthologs of FUL (FRUITFULL), FT (FLOWERING LOCUS T), and PRR3 (PSEUDO-RESPONSE REGULATOR 3) contribute to the adaptation of rice bean from its low latitude center of origin towards higher latitudes, and the landraces which pyramid early-flowering alleles for these loci display maximally short flowering times. We also demonstrate that copy-number-variation for VumCYP78A6 can regulate seed-yield traits. Intriguingly, 32 landraces collected from a mountainous region in South-Central China harbor a recently acquired InDel in TFL1 (TERMINAL FLOWER1) affecting stem determinacy; these materials also have exceptionally high values for multiple human-desired traits and could therefore substantially advance breeding efforts to improve rice bean.
Emergent topological states via digital (001) oxide superlattices
Authors: Liu Zhiwei , Liu Hongquan , Ma Jiaji , Wang Xiaoxuan , Li Gang , Chen Hanghui
Published: September 2022

Oxide heterostructures exhibit many intriguing properties. Here we provide design principles for inducing multiple topological states in (001) (AMO3)1/($$AM^{\prime}$$

A

M

′

O3)1 oxide superlattices. Aided by first-principles calculations and model analysis, we show that a (SrMO3)1/(Sr$$M^{\prime}$$

M

′

O3)1 superlattice (M = Nb, Ta and $$M^{\prime}$$

M

′

= Rh, Ir) is a strong topological insulator with Z2 index (1;001). More remarkably, a (SrMoO3)1/(SrIrO3)1 superlattice exhibits multiple coexisting topological insulator (TI) and topological Dirac semi-metal (TDS) states. The TDS state has a pair of type-II Dirac points near the Fermi level and symmetry-protected Dirac node lines. The surface TDS Dirac cone is sandwiched by two surface TI Dirac cones in the energy-momentum space. The non-trivial topological properties arise from the band inversion between d orbitals of two dissimilar transition metal atoms and a particular parity property of (001) superlattice geometry. Our work demonstrates how to induce non-trivial topological states in (001) perovskite oxide heterostructures by rational design.
Nigral glucose metabolism as a diagnostic marker of neurodegenerative parkinsonian syndromes
Authors: Schröter Nils , Blazhenets Ganna , Frings Lars , Jost Wolfgang H. , Weiller Cornelius , Rijntjes Michel , Meyer Philipp T. , Brumberg Joachim
Published: September 2022

Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are characterized by nigrostriatal degeneration. We used [18F]FDG PET to assess glucose metabolism of the substantia nigra (SN) in patients with these diseases and evaluated its ability to discriminate neurodegenerative parkinsonian syndromes (NP) from controls. We retrospectively evaluated [18F]FDG PET scans of 171 patients with NP (n = 115 PD, n = 35 MSA, n = 21 PSP) and 48 controls (13 healthy controls [HC] and 35 control patients). Mean normalized bilateral [18F]FDG uptake in the SN was calculated and compared between groups with covariance and receiver operating characteristic (ROC) analyses (selection of the optimal cut-off required a minimum specificity of 90% to meet the clinical need of a confirmatory test). PD patients were additionally stratified by the expression of the well-established PD-related metabolic pattern (PDRP; elevated expression defined as 2 standard deviations above the mean value of HC). [18F]FDG uptake was significantly lower in NP (Cohen’s d = 1.09, p < 0.001) and its subgroups (PD, d = 1.10, p < 0.001; MSA, d = 0.97, p < 0.001; PSP, d = 1.79, p < 0.001) than in controls. ROC analysis for discriminating NP vs. controls revealed an area under the curve of 0.81 and a sensitivity and specificity of 56 and 92%. Moreover, nigral metabolism was below the cut-off in 60% of PD patients without elevated PDRP expression. Glucose metabolism of the SN can distinguish patients with NP from controls with good diagnostic accuracy and can be used as a marker of nigral degeneration. Its evaluation is particularly valuable in PD patients without elevated PDRP expression and may thus help to narrow the diagnostic gap of [18F]FDG PET in neurodegenerative parkinsonism (i.e., identification of patients with PD without cortical involvement).
Spironolactone alleviates schizophrenia-related reversal learning in Tcf4 transgenic mice subjected to social defeat
Authors: Stephan Marius , Schoeller Jonathan , Raabe Florian J. , Schmitt Andrea , Hasan Alkomiet , Falkai Peter , Jensen Niels , Rossner Moritz J.
Published: September 2022

Cognitive deficits are a hallmark of schizophrenia, for which no convincing pharmacological treatment option is currently available. Here, we tested spironolactone as a repurposed compound in Tcf4 transgenic mice subjected to psychosocial stress. In this ‘2-hit’ gene by environment mouse (GxE) model, the animals showed schizophrenia-related cognitive deficits. We had previously shown that spironolactone ameliorates working memory deficits and hyperactivity in a mouse model of cortical excitatory/inhibitory (E/I) dysbalance caused by an overactive NRG1-ERBB4 signaling pathway. In an add-on clinical study design, we used spironolactone as adjuvant medication to the standard antipsychotic drug aripiprazole. We characterized the compound effects using our previously established Platform for Systematic Semi-Automated Behavioral and Cognitive Profiling (PsyCoP). PsyCoP is a widely applicable analysis pipeline based on the Research Domain Criteria (RDoC) framework aiming at facilitating translation into the clinic. In addition, we use dimensional reduction to analyze and visualize overall treatment effect profiles. We found that spironolactone and aripiprazole improve deficits of several cognitive domains in Tcf4tg x SD mice but partially interfere with each other’s effect in the combination therapy. A similar interaction was detected for the modulation of novelty-induced activity. In addition to its strong activity-dampening effects, we found an increase in negative valence measures as a side effect of aripiprazole treatment in mice. We suggest that repurposed drug candidates should first be tested in an adequate preclinical setting before initiating clinical trials. In addition, a more specific and effective NRG1-ERBB4 pathway inhibitor or more potent E/I balancing drug might enhance the ameliorating effect on cognition even further.
Optical emissivity dataset of multi-material heterogeneous designs generated with automated figure extraction
Authors: Baibakova Viktoriia , Elzouka Mahmoud , Lubner Sean , Prasher Ravi , Jain Anubhav
Published: September 2022

Optical device design is typically an iterative optimization process based on a good initial guess from prior reports. Optical properties databases are useful in this process but difficult to compile because their parsing requires finding relevant papers and manually converting graphical emissivity curves to data tables. Here, we present two contributions: one is a dataset of thermal emissivity records with design-related parameters, and the other is a software tool for automated colored curve data extraction from scientific plots. We manually collected 64 papers with 176 figures reporting thermal emissivity and automatically retrieved 153 colored curve data records. The automated figure analysis software pipeline uses Faster R-CNN for axes and legend object detection, EasyOCR for axes numbering recognition, and k-means clustering for colored curve retrieval. Additionally, we manually extracted geometry, materials, and method information from the text to add necessary metadata to each emissivity curve. Finally, we analyzed the dataset to determine the dominant classes of emissivity curves and determine the underlying design parameters leading to a type of emissivity profile.
The dual neural effects of oxytocin in autistic youth: results from a randomized trial
Authors: Korisky Adi , Goldstein Abraham , Gordon Ilanit
Published: September 2022

Recent discoveries have highlighted the effects of oxytocin (OT) on social behavior and perception among autistic individuals. However, a gap persists in the literature regarding the potential effects of OT and the neural temporal dynamics due to OT administration. We explored the effect of OT on autistic individuals using magnetoencephalography (MEG), focusing on M100, M170, and M250, social perception-related components that tend to show atypical patterns in autistic individuals. Twenty-five autistic adolescents participated in this randomized, double-blind MEG study. Autistic individuals arrived at the lab twice and received an acute dose of intranasal OT or placebo in each session. During the scans, participants were asked to identify pictures of social and non-social stimuli. Additionally, 23 typically developing (TD) adolescents performed the same task in the MEG as a benchmark that allowed us to better characterize neural regions of interest and behavioral results for this age group in this task. A source-model beamformer analysis revealed that OT enhanced neural activity for social stimuli in frontal regions during M170. Additionally, in each of the preselected time windows, OT increased activation in the left hemisphere, regardless of the content of the presented stimuli. We suggest that OT increased the processing of social stimuli through two separate mechanisms. First, OT increased neural activity in a nonspecific manner, allowing increased allocation of attention toward the stimuli. Second, OT enhanced M170 activity in frontal regions only in response to social stimuli. These results reveal the temporal dynamics of the effects of OT on the early stages of social and non-social perception in autistic adolescents.

Trial registration: This study was a part of a project registered as clinical trial October 27th, 2021. ClinicalTrials.gov Identifier: NCT05096676.
A tree-based scan statistic for zero-inflated count data in post-market drug safety surveillance
Authors: Park Goeun , Jung Inkyung
Published: September 2022

After new drugs enter the market, adverse events (AE) induced by their use must be tracked; rare AEs may not be detected during clinical trials. Some organizations have been collecting information on suspected drugs and AEs via a spontaneous reporting system to conduct post-market drug safety surveillance. These organizations use the information to detect a signal representing potential causality between drugs and AEs. The drug and AE data are often hierarchically structured. Accordingly, the tree-based scan statistic can be used as a statistical data mining method for signal detection. Most of the AE databases contain a large number of zero-count cells. Notably, not only an observational zero from the Poisson distribution, but also a true zero exists in zero-count cells. True zeros represent theoretically impossible observations or possible but unreported observations. The existing tree-based scan statistic assumes that all zeros are zero-valued observations from the Poisson distribution. Therefore, true zeros are not considered in the modeling, which can lead to bias in the inferences. In this study, we propose a tree-based scan statistic for zero-inflated count data in a hierarchical structure. According to our simulation study, in the presence of excess zeros, our proposed tree-based scan statistic provides better performance than the existing tree-based scan statistic. The two methods were illustrated using Korea Adverse Event Reporting System data from the Korea Institute of Drug Safety and Risk Management.
Spontaneous activity in whisker-innervating region of neonatal mouse trigeminal ganglion
Authors: Banerjee Piu , Kubo Fumi , Nakaoka Hirofumi , Ajima Rieko , Sato Takuya , Hirata Tatsumi , Iwasato Takuji
Published: September 2022

Spontaneous activity during the early postnatal period is thought to be crucial for the establishment of mature neural circuits. It remains unclear if the peripheral structure of the developing somatosensory system exhibits spontaneous activity, similar to that observed in the retina and cochlea of developing mammals. By establishing an ex vivo calcium imaging system, here we found that neurons in the whisker-innervating region of the trigeminal ganglion (TG) of neonatal mice generate spontaneous activity. A small percentage of neurons showed some obvious correlated activity, and these neurons were mostly located close to one another. TG spontaneous activity was majorly exhibited by medium-to-large diameter neurons, a characteristic of mechanosensory neurons, and was blocked by chelation of extracellular calcium. Moreover, this activity was diminished by the adult stage. Spontaneous activity in the TG during the first postnatal week could be a source of spontaneous activity observed in the neonatal mouse barrel cortex.
Comparison of first versus second line sacrocolpopexies in terms of morbidity and mid-term efficacy
Authors: Lallemant Marine , Grob A. T. M. , Puyraveau M. , Perik M. A. G. , Alhafidh A. H. H. , Cosson M. , Ramanah R.
Published: September 2022

To compare pelvic organ prolapse (POP) recurrence and morbidity between first and second line sacrocolpopexies. We conducted a retrospective chart review of all laparoscopic or robotic sacrocolpopexies for POP-Q stage ≥ 2, with or without a history of previous prolapse repair, performed with a similar technique between January 2012 and June 2019 in 3 European Gynecologic Surgery Departments. Patients were separated into two groups: first line sacrocolpopexy (FLS) and second line sacrocolpopexy (SLS). Each patient from the SLS group was age-matched with a patient from the FLS group. The primary outcome measure was reoperation procedures for recurrent POP defined as a symptomatic POP-Q stage ≥ 2 POP in at least one vaginal compartment. Secondary outcomes included operative time, intraoperative organ trauma, intraoperative blood loss, postoperative POP recurrence (operated on or not), global reoperation and mesh-related complications. During this period, 332 patients were included. After age-matching, 170 patients were analyzed: 85 patients in the FLS and SLS groups, respectively. After a mean follow-up of 3 years, there was no statistically significant difference between the two groups in terms of recurrent POP (9.4% versus 10.6%, p = 0.7), recurrent POP reoperation (3.5% versus 5.9% p = 0.7), mesh-related reoperation (0% versus 2.4%, p = 0.5), global reoperation (3.5 versus 8.2%, p = 0.3), operative time (198 ± 67 min versus 193 ± 60 min, p = 0.5), intraoperative complications such as organ injury (4.7% versus 7.1%, p = 0.7) and blood loss > 500 mL (2.4% versus 0%, p = 0.5). Patients who underwent a first or a second line sacrocolpopexy seemed to have similar rates of prolapse recurrence and complications.
High frequency of Nichols-like strains and increased levels of macrolide resistance in Treponema pallidum in clinical samples from Buenos Aires, Argentina
Authors: Morando Nicolas , Vrbová Eliška , Melgar Asunta , Rabinovich Roberto Daniel , Šmajs David , Pando María A.
Published: September 2022

Globally, 94% of Treponema pallidum subsp. pallidum (TPA) clinical strains belong to the SS14-like group and 6% to the Nichols-like group, with a prevalence of macrolide resistance of 90%. Our goal was to determine whether local TPA strain distribution and macrolide resistance frequency have changed significantly since our last report, which revealed that Buenos Aires had a high frequency of Nichols-like strains (27%) and low levels of macrolide resistance (14%). Swab samples from patients with suspected syphilis were collected during 2015–2019 and loci TP0136, TP0548, TP0705 were sequenced in order to perform multilocus sequence typing. Strains were classified as Nichols-like or SS14-like. The presence of macrolide resistance-associated mutations was determined by examination of the 23S rDNA gene sequence. Of 46 typeable samples, 37% were classified as Nichols-like and 63% as SS14-like. Macrolide resistance prevalence was 45.7%. Seven allelic profiles were found, five were SS14-like and two were Nichols-like. The frequency of Nichols-like strains increased between studies (26.8% vs. 37%, p = 0.36). A dramatic increase was found in the frequency of macrolide resistant strains between studies (14.3% vs. 45.7%, p = 0.005). Our results are in agreement with international trends and underscore the need to pursue further TPA molecular typing studies in South America.
Artificial intelligence-enhanced volumetric laser endomicroscopy improves dysplasia detection in Barrett’s esophagus in a randomized cross-over study
Authors: Kahn Allon , McKinley Matthew J. , Stewart Molly , Wang Kenneth K. , Iyer Prasad G. , Leggett Cadman L. , Trindade Arvind J.
Published: September 2022

Volumetric laser endomicroscopy (VLE) is an advanced endoscopic imaging tool that can improve dysplasia detection in Barrett’s esophagus (BE). However, VLE scans generate 1200 cross-sectional images that can make interpretation difficult. The impact of a new VLE artificial intelligence algorithm called Intelligent Real-time Image Segmentation (IRIS) is not well-characterized. This is a randomized prospective cross-over study of BE patients undergoing endoscopy who were randomized to IRIS-enhanced or unenhanced VLE first followed by the other (IRIS-VLE vs. VLE-IRIS, respectively) at expert BE centers. The primary outcome was image interpretation time, which served as a surrogate measure for ease of interpretation. The secondary outcome was diagnostic yield of dysplasia for each imaging modality. 133 patients were enrolled. 67 patients were randomized to VLE-IRIS and 66 to IRIS-VLE. Total interpretation time did not differ significantly between groups (7.8 min VLE-IRIS vs. 7 min IRIS-VLE, P = 0.1), however unenhanced VLE interpretation time was significantly shorter in the IRIS-VLE group (2.4 min vs. 3.8 min, P < 0.01). When IRIS was used first, 100% of dysplastic areas were identified, compared with 76.9% when VLE was the first interpretation modality (P = 0.06). IRIS-enhanced VLE reduced the time of subsequent unenhanced VLE interpretation, suggesting heightened efficiency and improved dysplasia detection. It was also able to identify all endoscopically non-visible dysplastic areas.
High-efficiency near-infrared optical parametric amplifier for intense, narrowband THz pulses tunable in the 4 to 19 THz region
Authors: Seo Meenkyo , Mun Je-Hoi , Heo Jaeuk , Kim Dong Eon
Published: September 2022

Dynamic control of material properties using strong-field, narrowband THz sources has drawn attention because it allows selective manipulation of quantum states on demand by coherent excitation of specific low-energy modes in solids. Yet, the lack of powerful narrowband lasers with frequencies in the range of a few to a few tens of THz has restricted the exploration of hidden states in condensed matter. Here, we report the optimization of an optical parametric amplifier (OPA) and the efficient generation of a strong, narrowband THz field. The OPA has a total conversion efficiency of > 55%, which is the highest value reported to date, with an excellent energy-stability of 0.7% RMS over 3 h. We found that the injection of a high-energy signal beam to a power amplification stage in an OPA leads to high-efficiency and a super-Gaussian profile. By difference-frequency generation of two chirped OPA signal pulses in an organic nonlinear crystal, we obtained a THz pulse with an energy of 3.2 μJ, a bandwidth of 0.5 THz, and a pulse duration of 860 fs tunable between the 4 and 19 THz regions. This corresponds to an internal THz conversion efficiency of 0.4% and a THz field strength of 6.7 MV/cm. This approach demonstrates an effective way to generate narrow-bandwidth, intense THz fields.
Role of modified nasopharyngeal oxygen therapy in apnoeic oxygenation under general anaesthesia: a single-centre, randomized controlled clinical study
Authors: Geng Weilian , Chen Changxing , Chen Yaobing , Yu Xinhua , Huang Shaoqiang
Published: September 2022

Apnoeic oxygenation is not only important for patients who cannot be intubated/ventilated, but also can be routinely employed when planning to secure the airway.We aimed to compare safe apnoea times between patients receiving modified nasopharyngeal oxygen therapy and those receiving high-flow nasal oxygen therapy (HFNO) following the induction of general anaesthesia.This was a single-centre, randomized controlled clinical study. Eighty-four female patients undergoing elective laparoscopic gynaecological surgery under general anaesthesia were randomly assigned to the high-flow nasal oxygen therapy group (Group HFNO) or the modified nasopharyngeal oxygen therapy group (Group Naso). A Kaplan–Meier survival curve was used to describe the apnoeic oxygenation time.The safe apnoea time of the patients in the Group Naso was higher than that of the patients in the Group HFNO (20 (19.3 to 20.0) vs. 16.5 (12.9 to 20) minutes, P < 0.05). The incidence of SpO2 < 95% in the Group Naso was lower than that in the Group HFNO; hazard ratio 0.3 (95% confidence interval 0.2 to 0.6, P < 0.0001). Modified nasopharyngeal oxygen therapy which uses far less oxygen than HFNO is a convenient and effective method of apnoeic oxygenation in normal female patients.

Trial registration: https://www.chictr.org.cn, ChiCTR2000039433; date of registration: 28/10/2020.