bluuebunny/crossref_metadata_2025 huggingface dataset:
Injectable Platelet-Rich Fibrin in Contact with Bone Substitutes, Porous Zirconia, or Laser-Textured Implant Surfaces: A Detailed Morphological Analysis
Authors: Oliveira Miguel Noronha , Varela Hugo Almeida , Nascimento Rubens M. , Sahoo Narayan , Carvalho Oscar , Henriques Bruno , Souza Júlio C. M.
Published: June 2023

The aim of the present study was to perform a detailed morphological analysis of an injectable platelet rich fibrin after combination with two different particulate hydroxyapatite-based granules, a porous zirconia block, and laser-textured zirconia or titanium surfaces. Blood samples were harvested from three participants to prepare the flowable injectable PRF in contact or not with particulate hydroxyapatite (Hap), bone mineral granules (DBBM), porous zirconia blocks, laser-textured titanium or zirconia surfaces. Optical and scanning electron microscopy (SEM) were used to evaluate the fibrin network density, fibrin fibers’ diameter, blood cells, and the interaction of PRF with the biomaterials. Histomorphometry of the flowable PRF was also performed using the hematoxylin–eosin staining protocol. Specimens were independently evaluated by two blinded and well-trained researchers in histomorphometry and microscopy. Particulate Hap and DBBM shown different morphological aspects by SEM analyses since DBBM revealed macro- and micro-scale pores while Hap revealed a dense structure. Hydroxyapatite and DBBM granules were entirely embedded by the fibrin-network in the presence of leukocytes and blood platelets. The zirconia porous structured was filled with PRF and its components. Also, the laser-structured zirconia or implant surfaces were entirely coated with the PRF fibrin network embedding leukocytes and blood platelets. Laser-textured titanium surfaces revealed macro- and micro-scale irregularities that increase the surface area and retention of the injectable PRF. Histomorphometric analyses revealed complementary details on the distribution of lymphocytes, red blood cells, and fibrin associated with platelet aggregation. The flowing and viscosity of an injectable platelet rich fibrin provided an agglomeration of synthetic or xenogeneic particulate bone substitutes and the coating of porous zirconia and textured implant surfaces as inspected by scanning electron microscopy. A cross-linked 3D-fibrin network was noticed involving the particulate bone substitutes and clogging the spaces into porous blocks as well as at macro-/micro-scale valleys on laser-textured implant surfaces. On the reconstruction of larger bone defects, platelet rich fibrin should be mixed with inorganic bone substitutes and implant surfaces to speed up the early events of the bone ingrowth. In addition, the particulate bioactive ceramics, porous zirconia, and textured implant surfaces provide the mechanical stability of the bone tissues and the 3D-fibrin network for further stimulation of osteogenic cells leading to an enhanced bone healing.
Neural Monte Carlo rendering of finite-time Lyapunov exponent fields
Authors: Xi Yang , Luan Wanna , Tao Jun
Published: June 2023

The finite-time Lyapunov exponent (FTLE) is widely used for understanding the Lagrangian behavior of unsteady flow fields. The FTLE field contains many important fine-level structures (e.g., Lagrangian coherent structures). These structures are often thin in depth, requiring Monte Carlo rendering for unbiased visualization. However, Monte Carlo rendering requires hundreds of billions of samples for a high-resolution FTLE visualization, which may cost up to hundreds of hours for rendering a single frame on a multi-core CPU. In this paper, we propose a neural representation of the flow map and FTLE field to reduce the cost of expensive FTLE computation. We demonstrate that a simple multi-layer perceptron (MLP)-based network can accelerate the FTLE computation by up to hundreds of times, and speed up the rendering by tens of times, while producing satisfactory rendering results. We also study the impact of the network size, the amount of training, and the predicted property, which may serve as guidance for selecting appropriate network structures.
Temporal variability of precipitation isotopes in Damascus, Syria — implications for regional climate change
Authors: Kattan Zuhair , Nasser Saeid
Published: June 2023

Records of stable isotopes (2H and 18O), deuterium excess (d-excess) and tritium (3H) values in precipitation (P) during 1990–2022, together with long-term time series (1919–2022) of air temperature (T) and P-amount values at the Damascus station, were analysed to explore the seasonal and annual variability patterns of those parameters in P and assess the vulnerability to climate change in this area. Variation of the annual average air T values over the period 1919–1969 shows an increase gradient of ≈ + 0.1 °C/decade. However, a remarkable much higher gradient (+ 0.64 °C/decade) is calculated for the period 1990–2022. The average P-amount value calculated for the last three decades (≈185 mm) was lower by ≈28 mm, compared to the value (≈213 mm), relative to the reference period (1919–1969). This significant decline in the annual P-amount value by ≈11–13%, accompanied by an annual heating of 0.2–0.6 °C/decade in the annual air T, is likely the result of the climate change affecting this area. The linear relationships between annual average δ18O and annual average δ2H values versus time over the period 1990–2019 indicate increased gradients in both stable isotopes (≈0.3–0.5‰ and ≈1.1–3.2‰ per decade for δ18O and δ2H, respectively), accompanied with a decrease gradient of ≈0.9–1.1‰ per decade in d-excess values. Variability of annual 3H concentrations towards low levels (< 6 TU) during the later years strongly suggests the return back towards the cosmogenic production of this radioisotope in the upper atmosphere. Information gained from this work would offer new insights to improve the understanding of the temporal variability of P isotopes and assess the risks associated with climate change on the natural water resources in the Eastern Mediterranean region.
Investigation on the opposing jet penetration mode transition mechanism in the hypersonic flow
Authors: Long L. , Liu B. , Meng Y.-s. , Huang W. , Li S.-b. , Tian S.-s.
Published: June 2023

As an effective drag reduction and thermal protection technology, the opposing jet can guarantee the flight safety of the hypersonic vehicle. In this paper, the jet mode transition is realised by controlling the total jet pressure ratio value (PR) with a function. The jet mode transition from the long penetration mode (LPM) to the short penetration mode (SPM) uses an increasing function. However, the jet mode transition from SPM to LPM uses a decreasing function. The flow field reconstruction process of a two-dimensional axisymmetric blunt body model in the hypersonic flow is studied when the jet mode transition between SPM and LPM changes into each other. The flow field structures and wall parameters of the LPM and SPM transition processes are obtained. The results indicate that the drag and Stanton number both decrease in the transition stage from LPM to SPM, and this is beneficial for the improvement of the drag reduction and thermal protection effect. The peak values of drag and Stanton number fall by 36.39% and 46.40%, respectively. When the jet mode transforms from SPM to LPM, the Stanton number increases, and the drag force first increases and then decreases. However, the final drag reduction effect is not obvious. With the increase in the change rate of the total pressure ratio of the two jet transformation modes, the jet mode transition time is advanced, and the flow field changes more violently.
Security Professionals’ Perceptions of Crime at the Oliver Reginald Tambo International Airport: Towards Sustainable Solutions
Authors: Panyapanya Michael , Jansen van Rensburg Shandré Kim
Published: June 2023

Across the globe, airports are regarded as essential infrastructure needing protection. One of the major goals of an airport, as encouraged by the regulatory bodies and evoked through public expectation, is safety. However, a public environment, such as an airport, is vulnerable to crime. The Oliver Reginald Tambo International Airport (ORTIA) is Africa’s biggest and busiest airport, servicing approximately 19 million passengers annually. Moreover, tourism is a key component of a healthy economy. Therefore, safety and security are significant for sustainable tourism in South Africa. Thus, this paper used a quantitative inquiry to determine security professionals’ perceptions of crime at ORTIA. A non-experimental and randomized cross-sectional research design was used. Through random sampling, a total of 100 participants contributed to the study and yielded a representative percentage of 36%. Data were collected through online self-administered questionnaires from security personnel employed at ORTIA and analysed through descriptive analysis. The findings revealed that the most problematic crimes taking place at ORTIA were reported to be theft, mishandled baggage, automated teller machine (ATM) crimes, burglary, robbery, illegal immigrants and smuggling of drugs. Furthermore, most participants had witnessed a crime taking place at the airport. As informed by the participants, sustainable solutions are proposed in terms of crime prevention and intervention.
Relationship between asset ownership and women's empowerment? Evidence from DHS data from 18 developing countries
Authors: Amir-ud-Din Rafi , Naz Lubna , Ali Hafeez
Published: June 2023

This study identifies the link between women's asset ownership and women's empowerment. Women's empowerment is measured by their decision-making role related to their health, large household purchases, and their social interaction. Using Demographic and Health Surveys data for 18 countries from South Asia, the Middle East, and sub-Saharan Africa, we found that the women who owned assets were 14% more likely to be empowered compared with the women who did not own any asset (odds ratio: 1.14, 95% confidence interval: 1.10–1.185). At a disaggregated country level, asset ownership was positively and significantly associated with women's empowerment in nine countries, negatively associated in one country, and had no significant association in the other eight countries. This study provides important insights into the link between women's asset ownership and empowerment and may inform public policy related to gender equality through women's empowerment.
Power of inclusive leadership: exploring the mediating role of identity-related processes and conditional effects of synergy diversity climate in nurturing positive employee behaviors
Authors: Naseer Saima , Bouckenooghe Dave , Syed Fauzia , Haider Aisha
Published: June 2023

Based on the fundamental principles of social identity theory, this study examines how inclusive leadership can help build employees' organizational identification, stimulate leader-directed helping behavior, and improve task performance by facilitating insider status and relational coordination. Furthermore, we explored how these relationships are conditional on the synergy diversity climate in a moderated mediation model. We collected temporally segregated data (n = 300) from employees in diverse workforces at three time intervals with a 2-week gap between intervals. The results support the indirect effects of inclusive leadership on employee outcomes through the development of perceived insider status and relational coordination. Additionally, these indirect effects are more pronounced at higher levels of a synergy diversity climate. In conclusion, our study offers critical insights into the diversity and leadership literature by answering why and under what conditions an inclusive leader can generate favorable employee outcomes.
VISUALIZING THE COMPLEX PROBLEM OF CHILDREN'S DIGITAL WELLBEING IN SOUTH KOREA: A SYSTEMS THINKING APPROACH
Authors: Widjaja Shannen Patricia , Baek Joon Sang
Published: June 2023

Considering the prevalence of digital interaction within the Generation Alpha, this study focuses on the digital wellbeing of elementary school-aged children in South Korea. By taking into account the multi-faceted nature, this study frames the issue that exists within children's digital wellbeing as a complex problem and aims to have a better comprehensive understanding of the system using a designerly and systems thinking approach. Thus, this study conducts a Systematic literature review and thematic analysis to get grasp of the current situation which then is translated using a systems thinking-based visualization tool to convey the causal relationships that exist within the system. Therefore, the outcome of this study presents a concept map that consolidates the findings to communicate a holistic perspective of children's digital wellbeing which can be used in design activities and decision-making processes which contribute to future design solutions and conversations.
B-SPLINE BASED METAMODEL OF THE THERMAL ANALYSIS OF THE WIRE ARC ADDITIVE MANUFACTURING PROCESS
Authors: Zani Mathilde , Montemurro Marco , Panettieri Enrico , Marin Philippe
Published: June 2023

Among additive manufacturing processes, wire arc additive manufacturing (WAAM) is one of the most promising methods for manufacturing complex near-net-shape parts, as it allows the layer-by-layer deposition of welded material at a high deposition rate. However, this technology is highly dependent on deposition conditions and thermomechanical phenomena during the process. Therefore, process simulation could be used to analyse the effects of different deposition parameters on the thermomechanical results to optimise the process. However, as the computing time required for this study may become prohibitive, a dedicated strategy is needed to reduce it while maintaining a good level of accuracy. In this study, only the thermal analysis of the process is investigated. An efficient metamodel based on B-spline entities is developed to emulate the thermal response of the WAAM process when building a mild steel four-layer wall structure. Thanks to B-spline entities, the temperature profile at different locations is approximated as a function of a subset of deposition parameters of WAAM process, and the results are compared with the simulated temperature profile resulting from a validation dataset.
Developmental trajectories of anger and sadness dysregulation in childhood differentially predict later borderline symptoms
Authors: Vogel Alecia C. , Geselowitz Ben , Tillman Rebecca , Barch Deanna M. , Luby Joan L. , Whalen Diana J.
Published: June 2023

Difficulties with emotion regulation are integral to borderline personality disorder (BPD) and its hypothesized developmental pathway. Here, we prospectively assess trajectories of emotion processing across childhood, how BPD symptoms impact these trajectories, and whether developmental changes are transdiagnostic or specific to BPD, as major depressive (MDD) and conduct disorders (CD) are also characterized by emotion regulation difficulties. This study included 187 children enriched for those with early symptoms of depression and disruptive behaviors from a longitudinal study. We created multilevel models of multiple components of emotional processing from mean ages 9.05 to 18.55 years, and assessed the effect of late adolescent BPD, MDD, and CD symptoms on these trajectories. Linear trajectories of coping with sadness and anger, and quadratic trajectories of dysregulated expressions of sadness and anger were transdiagnostic, but also exhibited independent relationships with BPD symptoms. Only inhibition of sadness was related to BPD symptoms. The quadratic trajectories of poor emotional awareness and emotional reluctance were also independently related to BPD. Findings support examining separable components of emotion processing across development as potential precursors to BPD, underscoring the importance of understanding these trajectories as not only a marker of potential risk but also potential targets for prevention and intervention.
L’interrogative in situ à la lumière des principes de ‘End-Weight’ et ‘End-Focus’
Authors: Guryev Alexander , Delafontaine François
Published: June 2023

Partant de l’hypothèse de Coveney (1995) que la structure informationnelle influence la sélection de l’interrogative in situ ‘Tu fais quoi ?’ (SVQ), ce travail s’appuie sur les données du Corpus suisse de SMS (2009-2015) pour évaluer l’incidence des principes dits ‘End-Weight’ et ‘End-Focus’. En suivant l’étude de Coveney (1995), nous analyserons l’incidence des paramètres suivants : (i) longueur de la proforme Q et (ii) celle de la partie SVC; paramètres du (iii) Sujet, (iv) Verbe, (v) Complément; et (vi) identité du mot Q. Suite à l’analyse de 217 occurrences de SVQ (sur 425 QU), nos résultats corroborent, fût-ce avec quelques nuances, plusieurs tendances observées par Coveney (1995). En même temps, notre étude révèle que les tendances en cause, telles qu’elles s’observent dans le Corpus de SMS, prennent la forme plus extrême et tendent à fonctionner comme des environnements morphosyntaxiques à variabilité faible : en débouchant régulièrement sur l’emploi de SVQ, elles réduisent drastiquement les chances d’apparition d’autres variantes ex situ. Ces tendances s’expliqueraient par le fait qu’en français informel l’usage de SVQ est en train d’évincer d’autres variantes, principalement dans ces contextes linguistiques qui se sont avérés initialement propices à sa rapide propagation au 20e siècle (Farmer 2015).
Purchase of ultra-processed foods in Norway: a repeated cross-sectional analysis of food sales in 2013 and 2019
Authors: Bjøntegaard Marie Michaelsen , Molin Marianne , Kolby Marit , Torheim Liv Elin
Published: June 2023

Objective:

A dietary pattern dominated by ultra-processed foods has been associated with non-communicable diseases in several studies. A previous study from 2013 found a high share of ultra-processed foods in Norwegian food sales. This study aimed to investigate the current share of ultra-processed foods in Norway and the development in expenditure on ultra-processed foods from 2013.

Design:

A repeated cross-sectional analysis of scanner data from the Consumer Price Index from September 2013 and 2019 and an investigation of the processing degree according to the NOVA classification system.

Setting:

Food sales in Norway.

Participants:

Norwegian grocery stores (n180, for both time periods).

Results:

The share of expenditure in 2019 was highest for ultra-processed foods (46·5 %) and minimally or unprocessed foods (36·3 %), followed by processed foods (8·5 %) and processed culinary ingredients (1·3 %). An increasing degree of processing was found for several of the food groups between 2013 and 2019; however, most effect sizes were weak. In 2019, soft drinks became the most frequently purchased food item, surpassing milk and cheese, with the highest expenditure in Norwegian grocery stores. Increases in expenditure on ultra-processed foods were mainly due to increased expenditures on soft drinks, sweets and potato products.

Conclusions:

A high share of expenditure on ultra-processed food was found in Norway, which may imply a high consumption of these foods. The change in expenditure of NOVA groups between 2013 and 2019 was small. Carbonated and non-carbonated soft drinks were the most frequently purchased products in Norwegian grocery stores and contributed to most of the expenditures.
Tariff Flexibility Amid Formation of Preferential Trade Agreements: WTO Law vs. PTA Law
Authors: Kim Jong Bum , Yoo Li
Published: June 2023

This paper examines the legal ramifications of using tariff flexibility arising from GATT unbound tariff lines or tariff overhangs under both WTO and preferential trade agreement (PTA) law when flexibility is exercised preferentially for PTA partners. Under WTO law, a WTO member that is a party to a PTA under GATT Article XXIV is required to use tariff flexibility on a non-discriminatory basis. However, PTA obligations including tariff elimination commitments and a standstill clause prohibit the WTO member from raising applied tariffs on imports from the PTA parties, thereby preventing the use of tariff flexibility on a non-discriminatory manner. In contrast, a WTO member entering into a PTA under the Enabling Clause may use tariff flexibility discriminatorily without violating WTO law. A WTO member has greater legal latitude in utilizing tariff flexibility if it forms a PTA under the Enabling Clause rather than under GATT Article XXIV. The discriminatory exercise of tariff flexibility by some WTO members in conformity with PTA obligations, but in violation of WTO law, is further evidence of the fragmentation of the world trading system, where WTO law is facing its limits.
No Loss, No Gain? COVID-19 school closures and Swiss fifth-graders' competencies and self-concept in mathematics
Authors: Compagnoni Miriam , Rechsteiner Beat , Grob Urs , Bayer Nicole , Wullschleger Andrea , Maag Merki Katharina
Published: June 2023

Abstract: COVID-19-related school closures in spring 2020 interrupted learning routines and posed a great challenge for students' competencies acquisition and self-concepts. Concerns about possible learning losses due to school closures, especially for disadvantaged students, are justified, but the currently available empirical evidence is still scarce, varies greatly with regard to context, and neglects reciprocal effects of competencies and self-concept. To address these shortcomings, this paper first provides insights on the effect that the 8 weeks of school closures had on Swiss primary school students' math competencies. IRT-based math tests were used to cross-sectionally compare data from 1,299 students in Grade 5 in late spring 2020 shortly after the reopening of schools with data from a previous year's cohort ( n = 11,314) using propensity score matching. The results revealed no significant differences in math competencies and no evidence of an increase in inequality when children with not German (vs German) as their first language were studied. Second, changes in math self-concepts in the school year 2019/20, when the pandemic first hit, as well as reciprocal effects of math competencies and math self-concept were assessed longitudinally ( n = 1,299) using random intercept cross-lagged panel models based on three measurement points. Results showed that higher math self-concept and positive change in math self-concept over the time of school closures were related to higher learning gains. Different development trajectories for children with German (vs not German) first language emerged. The study therefore fosters a better understanding of the effect that pandemic-induced school closures had on learning and relativizes the feared negative effects on math competencies caused by short school closures.
Mongolian Dust Activity Over the Last 25 Kyr Predominantly Driven by the East Asian Winter Monsoon: Insights From the Geochemistry of Lake Tuofengling Sediments
Authors: Zhang Wenfang , Zhang Enlou , Liu Enfeng , Abell Jordan T. , Sun Weiwei , Ni Zhenyu , Chen Rong , Cai Yue , Meng Xianqiang
Published: June 2023

Dust deposition in northeastern Asia since the Last Glacial Maximum has previously been studied using a variety of archives. However, the mechanisms driving variability in dust are less well constrained. Here, we present records of the Nd‐Sr isotope and major element composition of sediments from Lake Tuofengling, a crater lake located in northeastern China, over the past ∼25 thousand years. The results indicate that the lithogenic fractions of the sediments are a mixture between aeolian dust and local volcanic detritus. Our provenance data suggest that the aeolian dust component is predominantly from the Mongolia Plateau, likely carried by the East Asian Winter Monsoon. Our isotope and calculated dust flux records exhibit similar changing patterns to proxies of global ice volume and the strength of Atlantic meridional overturning circulation, potentially implicating ice sheets and ocean circulation as the dominant drivers of the East Asian Winter Monsoon over this time interval.
Early life stress, low-grade systemic inflammation and weaker suppression of the default mode network (DMN) during face processing in Schizophrenia
Authors: King Sinead , Mothersill David , Holleran Laurena , Patlola Saahithh Redddi , Burke Tom , McManus Ross , Kenyon Marcus , McDonald Colm , Hallahan Brian , Corvin Aiden , Morris Derek W. , Kelly John P. , McKernan Declan P. , Donohoe Gary
Published: June 2023

Childhood trauma (CT) is associated with lower cognitive and social cognitive function in schizophrenia. Recent evidence suggests that the relationship between CT and cognition is mediated by both low-grade systemic inflammation and reduced connectivity of the default mode network (DMN) during resting state. This study sought to test whether the same pattern of associations was observed for DMN connectivity during task based activity. Fifty-three individuals with schizophrenia (SZ) or schizoaffective disorder (SZA) and one hundred and seventy six healthy participants were recruited from the Immune Response and Social Cognition (iRELATE) project. A panel of pro-inflammatory markers that included IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNFa), and C-reactive protein (CRP), were measured in plasma using ELISA. DMN connectivity was measured during an fMRI social cognitive face processing task. Patients showed evidence of low grade systemic inflammation and significantly increased connectivity between the left lateral parietal (LLP) cortex-cerebellum and LLP-left angular gyrus compared to healthy participants. Across the entire sample, IL-6 predicted increased connectivity between LLP-cerebellum, LLP-precuneus, and mPFC-bilateral-precentral-gyri and left postcentral gyrus. In turn, and again in the entire sample, IL-6 (but no other inflammatory marker) mediated the relationship between childhood physical neglect and LLP-cerebellum. Physical neglect scores also significantly predicted the positive association between IL-6 and LLP-precuneus connectivity. This is to our knowledge the first study that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during task based activity. Consistent with our hypothesis, exposure to trauma is associated with weaker suppression of the DMN during a face processing task, and this association was mediated via increased inflammatory response. The findings may represent part of the biological mechanism by which CT and cognitive performance are related.
Structure-function coupling in white matter uncovers the abnormal brain connectivity in Schizophrenia
Authors: Zhao Jiajia , Huang Chu-Chung , Zhang Yajuan , Liu Yuchen , Tsai Shih-Jen , Lin Ching-Po , Lo Chun-Yi Zac
Published: June 2023

Schizophrenia is characterized by dysconnectivity syndrome. Evidence of widespread impairment of structural and functional integration has been demonstrated in schizophrenia. Although white matter (WM) microstructural abnormalities have been commonly reported in schizophrenia, the dysfunction of WM as well as the relationship between structure and function in WM remains uncertain. In this study, we proposed a novel structure-function coupling measurement to reflect neuronal information transfer, which combined spatial-temporal correlations of functional signals with diffusion tensor orientations in the WM circuit from functional and diffusion magnetic resonance images (MRI). By analyzing MRI data from 75 individuals with schizophrenia (SZ) and 89 healthy volunteers (HV), the associations between structure and function in WM regions in schizophrenia were examined. Randomized validation of the measurement was performed in the HV group to confirm the capacity of the neural signal transferring along the WM tracts, referring to quantifying the association between structure and function. Compared to HV, SZ showed a widespread decrease in the structure-function coupling within WM regions, involving the corticospinal tract and the superior longitudinal fasciculus. Additionally, the structure-function coupling in the WM tracts was found to be significantly correlated with psychotic symptoms and illness duration in schizophrenia, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of the neuropathology of schizophrenia. This work supports the dysconnectivity hypothesis of schizophrenia from the aspect of circuit function, and highlights the critical role of WM networks in the pathophysiology of schizophrenia.
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells
Authors: Yan Yuelong , Teng Hongqi , Hang Qinglei , Kondiparthi Lavanya , Lei Guang , Horbath Amber , Liu Xiaoguang , Mao Chao , Wu Shiqi , Zhuang Li , James You M. , Poyurovsky Masha V. , Ma Li , Olszewski Kellen , Gan Boyi
Published: June 2023

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H2O2, a common oxidative stress inducer, its high overexpression dramatically increases H2O2-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H2O2 treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). We further show that high overexpression of SLC7A11 promotes tumor growth but suppresses tumor metastasis, likely because metastasizing cancer cells with high expression of SLC7A11 are particularly susceptible to oxidative stress. Our findings reveal that SLC7A11 expression level dictates cancer cells’ sensitivity to oxidative stress and suggests a context-dependent role for SLC7A11 in tumor biology.
Phase III study of HR-positive/HER2-negative/lymph node-positive breast cancer non-responsive to primary chemotherapy: a randomized trial
Authors: Yang Yang , He Yingjian , Fan Zhaoqing , Chen Xue , Liu Yiqiang , Zhang Chao , Jiang Hongchuan , Wang Xin , Wang Xiang , Xie Fei , Wang Shu , Luo Bin , Kang Hua , Wang Tao , Jiang Zefei , Yuan Peng , Xu Binhe , Xu Ling , Liu Yinhua , Li Jinfeng , Xie Yuntao , Wang Tianfeng , Ouyang Tao
Published: June 2023

There are few studies focus on post-neoadjuvant treatment in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-positive (LN+) breast cancer, a multi-center, open-label, randomized, controlled phase III trial was conducted to evaluate pathological response-guided non-cross-resistant adjuvant chemotherapy in patients with HR+/HER2-/LN+ breast cancer who were non-responsive to primary chemotherapy. Patients received four cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (ET), or ET alone. Forty patients responsive to neoadjuvant chemotherapy and with Miller and Payne G4 or G5 and LN- status were assigned to the observation group. Distant disease-free survival was the primary endpoint. The final intention-to-treat analysis comprised 379 patients. After a median follow-up period of 72.4 months, the 5-year distant disease-free survival was 92% and 90% in the chemotherapy plus ET and ET-alone groups, respectively. Comparatively, the observation group showed a trend towards better distant disease-free survival. For patients non-responsive to neoadjuvant chemotherapy, adjuvant non-cross-resistant chemotherapy did not significantly improve distant disease-free survival compared to ET alone.
The value of a spaceflight clinical decision support system for earth-independent medical operations
Authors: Russell Brian K. , Burian Barbara K. , Hilmers David C. , Beard Bettina L. , Martin Kara , Pletcher David L. , Easter Ben , Lehnhardt Kris , Levin Dana
Published: June 2023

As NASA prepares for crewed lunar missions over the next several years, plans are also underway to journey farther into deep space. Deep space exploration will require a paradigm shift in astronaut medical support toward progressively earth-independent medical operations (EIMO). The Exploration Medical Capability (ExMC) element of NASA’s Human Research Program (HRP) is investigating the feasibility and value of advanced capabilities to promote and enhance EIMO. Currently, astronauts rely on real-time communication with ground-based medical providers. However, as the distance from Earth increases, so do communication delays and disruptions. Moreover, resupply and evacuation will become increasingly complex, if not impossible, on deep space missions. In contrast to today’s missions in low earth orbit (LEO), where most medical expertise and decision-making are ground-based, an exploration crew will need to autonomously detect, diagnose, treat, and prevent medical events. Due to the sheer amount of pre-mission training required to execute a human spaceflight mission, there is often little time to devote exclusively to medical training. One potential solution is to augment the long duration exploration crew’s knowledge, skills, and abilities with a clinical decision support system (CDSS). An analysis of preliminary data indicates the potential benefits of a CDSS to mission outcomes when augmenting cognitive and procedural performance of an autonomous crew performing medical operations, and we provide an illustrative scenario of how such a CDSS might function.
A 3-year natural history of orthostatic blood pressure dysregulation in early Parkinson’s disease
Authors: Yoo Sang-Won , Oh Yoon-Sang , Ryu Dong-Woo , Ha Seunggyun , Kim Yuna , Yoo Ji-Yeon , Kim Joong-Seok
Published: June 2023

In Parkinson’s disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.
A randomized controlled trial on the digital socio-emotional competence training Zirkus Empathico for preschoolers
Authors: Naumann Sandra , Bayer Mareike , Kirst Simone , van der Meer Elke , Dziobek Isabel
Published: June 2023

In this randomized controlled trial (RCT), the digital socio-emotional competence training Zirkus Empathico was tested in 74 Central European children (5.1 (0.9) years; 34 females) within a longitudinal design (three time points: T1 = pre-training; T2 = immediately following 6-week training, T3 = 3-month follow-up). The pre-registered primary outcome was empathy, secondary outcomes included emotion recognition, prosocial behavior, and behavioral problem reduction; furthermore, children’s neural sensitivity to facial expressions quantified with event-related potentials. Compared to controls (N = 38), Zirkus Empathico participants (N = 36) showed increases in empathy (d = 0.28 [−0.17, 0.76]), emotion recognition (d = 0.57 [0.01, 1.06]), prosocial behavior (d = 0.51 [0.05, 0.99]) and reduced behavioral problems (d = 0.54 [0.08, 1.03]). They also showed larger P3 amplitudes to happy vs. angry and neutral facial expressions post-training. Thus, Zirkus Empathico may be a promising digital training for social competence in preschoolers.
A better alignment between chronotype and school timing is associated with lower grade retention in adolescents
Authors: Rodríguez Ferrante Guadalupe , Goldin Andrea P. , Sigman Mariano , Leone María Juliana
Published: June 2023

Schools start early in the morning all over the world, contrasting with adolescents’ late chronotype. Interestingly, lower academic performance (i.e. grades or qualifications) was associated with later chronotypes. However, it is unclear whether it is a direct effect of chronotype or because students attend school too early to perform at their best. Moreover, little is known about how this affects students’ academic success beyond their grades. To address this gap in knowledge, we studied how school timing and chronotype affect grade retention (i.e. repeat a year) in a unique sample of students randomly assigned to one of three different school timings (starting at 07:45, 12:40, or 17:20). Even when controlling for academic performance, we found that later chronotypes exhibit higher odds of grade retention only in the morning, but not in later school timings. Altogether, ensuring a better alignment between school timing and students’ biological rhythms might enhance future opportunities of adolescents.
Early porosity generation in organic-sulfur-rich mudstones
Authors: Knapp Levi J. , Ardakani Omid H. , Reyes Julito , Ishikawa Kazuaki
Published: June 2023

High total organic sulfur (TOS) content (i.e., Type IIS kerogen) is well known to significantly influence kerogen transformation but the effect of TOS content on the evolution of organic porosity has only rarely and indirectly been investigated. This study demonstrates that organic porosity is generated at lower thermal maturity in mudstones containing Type IIS kerogen relative to those with Type II kerogen. To our knowledge this phenomenon has not been previously demonstrated. The implications are relevant for the characterization of organic-rich mudstones as cap rocks, hydrocarbon reservoirs, and disposal reservoirs for CO2 or nuclear waste because pore systems control storage volumes and matrix fluid flow. Five thermally immature core samples were selected from three organic-rich mudstone units with low to high TOS content: the late Devonian Duvernay Formation (Canada), middle late Miocene Onnagawa Formation (Japan), and early Jurassic Gordondale member of the Fernie Formation (Canada). Hydrous pyrolysis was used to artificially mature splits of the immature samples to four maturity stages, upon which petrophysical and organic geochemical properties were measured and compared to baseline immature samples. Most porosity growth in Type IIS samples occurred below 0.70% VRoeqv, but in Type II samples was broader and robust until 1.1% VRoeqv.
A new method of alternating shooting of two different seismic sources for deep geophysical surveys
Authors: Liu ChenGuang , Fu JinZhong , Hua QingFeng , Liu Kai , Zhi PengYao , Pei YanLiang , Zhou QingJie , Li XiShuang , Liu BaoHua
Published: June 2023

In the latest geophysical survey crossing the Ninety East Ridge of the Indian Ocean, a new method was employed to perform proportional double seismic source excitation and synchronously receive signals from the sea surface and the seabed. The two seismic sources used for excitation were two sets of gun arrays with different energies and dominant frequencies, a G gun array and a Bolt gun array. The G gun array consisted of 3 G.II guns with a total capacity of 450 in3 and a dominant frequency of 20–100 Hz. The Bolt gun array consisted of 4 Bolt 1500LL air guns with a total capacity of 6000 in3 and a dominant frequency of 10–40 Hz. The seismic receiving system comprised a 480-channel seismic streamer towed from the sea surface and 21 ocean bottom seismometers (OBS). During offshore operations, the integrated navigation system produced equidistant trigger signals at an interval of 50 m. The trigger signals were distributed to the G gun array and Bolt gun array at a ratio of 3:1 after passing through a pulse signal proportional distributor. The two sets of gun arrays fired alternatingly at a given ratio. The receiving equipment on the sea surface and seabed simultaneously received the seismic signals excited by the two sets of gun arrays. After targeted data processing, in addition to the seismic profile generated by the conventional G gun seismic source, the deep seismic profile generated by the Bolt gun seismic source and the survey profile of the active-source OBS were obtained simultaneously. The penetration depths of the three sets of profiles reach 2 km, 6 km, and 30 km, respectively, greatly improving the efficiency of offshore deep-sea seismic surveys.
A universal tool for stability predictions of biotherapeutics, vaccines and in vitro diagnostic products
Authors: Huelsmeyer M. , Kuzman D. , Bončina M. , Martinez J. , Steinbrugger C. , Weusten J. , Calero-Rubio C. , Roche W. , Niederhaus B. , VanHaelst Y. , Hrynyk M. , Ballesta P. , Achard H. , Augusto S. , Guillois M. , Pszczolinski C. , Gerasimov M. , Neyra C. , Ponduri D. , Ramesh S. , Clénet D.
Published: June 2023

It is of particular interest for biopharmaceutical companies developing and distributing fragile biomolecules to warrant the stability and activity of their products during long-term storage and shipment. In accordance with quality by design principles, advanced kinetic modeling (AKM) has been successfully used to predict long-term product shelf-life and relies on data from short-term accelerated stability studies that are used to generate Arrhenius-based kinetic models that can, in turn, be exploited for stability forecasts. The AKM methodology was evaluated through a cross-company perspective on stability modeling for key stability indicating attributes of different types of biotherapeutics, vaccines and biomolecules combined in in vitro diagnostic kits. It is demonstrated that stability predictions up to 3 years for products maintained under recommended storage conditions (2–8 °C) or for products that have experienced temperature excursions outside the cold-chain show excellent agreement with experimental real-time data, thus confirming AKM as a universal and reliable tool for stability predictions for a wide range of product types.
The development of laying hen locomotion in 3D space is affected by early environmental complexity and genetic strain
Authors: Rentsch Ana K. , Ross Erin , Harlander Alexandra , Niel Lee , Siegford Janice M. , Widowski Tina M.
Published: June 2023

Adult laying hens are increasingly housed in spatially complex systems, e.g., non-cage aviaries, where locomotion between elevated structures can be challenging for these gallinaceous birds. This study assessed the effect of early environmental complexity on spatial skills in two genetic strains. Brown (B) and white (W) feathered birds were raised in: Conventional cages with minimal complexity (Conv) or rearing aviaries with low (Low), intermediate (Mid), or high complexity (High). Birds from each housing treatment were challenged at three different time points in three different, age-appropriate vertical spatial tasks. Whites performed better than brown birds in all tests regardless of rearing environment. In chicks, test performance was predominantly explained by variation between replicates and differences in motivation for test participation. Treatment effects were seen in pubertal birds (pullets), with pullets from aviaries performing better than those from Conv. White High pullets performed better than white Mid or Low, an effect that was not found in browns. Pullets preferred to use a ramp to move downwards, but only when ramps had previously been experienced and when the ramp was not too steep. Overall, early environmental complexity affected spatial skills of laying hen pullets with stronger effects in white than brown feathered birds.
The effect of blocking immune checkpoints LAG-3 and PD-1 on human invariant Natural Killer T cell function
Authors: Balasko Allison L. , Kowatsch Monika M. , Graydon Colin , Lajoie Julie , Fowke Keith R.
Published: June 2023

Invariant Natural Killer T (iNKT) cells undergo immune exhaustion during chronic activation caused by cancer and viral infections, such as HIV. Exhaustion is marked by cell dysfunction and increased expression of immune checkpoint proteins programmed cell-death-1 (PD-1) and lymphocyte-activation-gene-3 (LAG-3). We hypothesize that blockade of PD-1 and/or LAG-3 will enhance iNKT cell function. Utilizing peripheral blood mononuclear cells from healthy donors, LAG-3 and PD-1 expression on iNKT cells was assessed using flow cytometry following in vitro stimulation with iNKT-specific stimulant α-galactosylceramide (n = 4). Efficacy of anti-LAG-3 and/or anti-PD-1 antibody blockades in enhancing iNKT cell function was assessed by determining proliferative capacity and IFN-γ production (n = 9). LAG-3 and PD-1 expression on iNKT cells peaked at Day 4 (98.8%; p ≤ 0.0001 and 98.8%; p = 0.005, respectively), followed by steep decrease by Day 10, coinciding with peak iNKT cell proliferation. In a 10-day blocking assay, both the anti-PD-1 alone and dual anti-PD-1 and anti-LAG-3 significantly increased iNKT proliferation (6 and 6.29 log2 fold-change respectively) compared to the no blockade control (ANOVA-p = 0.0005) with the dual blockade system being more effective (t-test-p = 0.013). This provides proof-of-concept for LAG-3 and PD-1 as immunotherapeutic targets to enhance human iNKT cell function, with the long-term goal of addressing immune exhaustion.
Impact of urban spatial structure elements on carbon emissions efficiency in growing megacities: the case of Chengdu
Authors: Feng Tian , Zhou Bo
Published: June 2023

Quantitative research on the impact weight and impact of regional heterogeneity of urban spatial structure elements on carbon emissions efficiency can provide a scientific basis and practical guidance for low-carbon and sustainable urban development. This study uses the megacity of Chengdu as an example to measure and analyze the spatial carbon emission efficiency and multidimensional spatial structure elements by building a high-resolution grid and identifying the main spatial structure elements that affect urban carbon emissions and their impact weights via the Ordinary Least Squares regression (OLS) and Geographically Weighted Regression (GWR). The spatial heterogeneity of the impact of each element is also explored. The results show that the overall carbon emission efficiency of Chengdu is high in the center and low on the sides, which is related to urban density, functional mix, land use, and traffic structure. However, the influence of each spatial structure element is different in the developed central areas, developing areas of the plain, mountainous developing areas, underdeveloped areas of the plain, and mountainous underdeveloped areas. Thus, it is appropriate to form differentiated urban planning strategies based on the characteristics of the development of each zone. The findings provide inspiration and a scientific basis for formulating policies and practice to the future low-carbon development of Chengdu, while provide a reference for other growing megacities.