bluuebunny/crossref_metadata_2025 huggingface dataset:
No difference between using short and long intervals for distributed proficiency-based laparoscopy simulator training: a randomized trial
Authors: Tang Diana Hai Yen , Østdal Theresa Bruun , Vamadevan Anishan , Konge Lars , Houlind Kim , Stadeager Morten , Bjerrum Flemming
Published: November 2023

Background

Simulation-based training is increasingly used to acquire basic laparoscopic skills. Multiple factors can influence training, e.g., distributed practice is superior to massed practice in terms of efficiency. However, the optimal interval between training sessions is unclear. The objective of this trial was to investigate if shorter intervals between sessions are more efficient than longer intervals during proficiency-based laparoscopy simulator training.

Methods

A randomized simulation-based trial where medical students (n = 39) were randomized to proficiency-based training with either 1–2 days (intervention group) or 6–8 days (control group) between training sessions. Both groups practiced a series of basic tasks and a procedural module until proficiency level on the LapSim® simulator. Both groups were given instructor feedback upon request. After reaching proficiency, participants were invited back for a retention test 3–5 weeks later and practiced the same tasks to proficiency again.

Results

The mean time to reach proficiency during training was 291 (SD 89) and 299 (SD 89) min in the intervention and control group, respectively (p = 0.81). During the retention test, the mean time to reach proficiency was 94 (SD 53) and 96 (SD 39) minutes in the intervention and control groups, respectively (p = 0.91).

Conclusion

We found no difference whether practicing with shorter intervals or longer intervals between training sessions when examining time to proficiency or retention.
Code verification of immersed boundary techniques using the method of manufactured solutions
Authors: Petö Márton , Gorji Mahan , Duvigneau Fabian , Düster Alexander , Juhre Daniel , Eisenträger Sascha
Published: November 2023

Code verification plays a crucial role for all finite element applications, especially for non-standard ones, such as immersed boundary approaches, which are typically based on novel algorithms and often error-prone in-house implementations. Instead of relying on rarely available analytical solutions or overkill FEM simulations, in this article, the capabilities of the method of manufactured solutions (MoMS) are explored, enabling an easy and straightforward derivation of closed-form reference solutions. The focus is kept on immersed problems, in particular, on the finite cell method (FCM), and manufactured solutions are derived for 2D and 3D problems involving voids and single/multiple inclusions. We propose several approaches for the construction of the manufactured solutions, where zero traction conditions for void regions and continuous normal stresses along material interfaces are directly fulfilled. Thus, no weak boundary conditions are required for reproducing the manufactured solution via FCM. This not only enables code verification for FCM implementations that lack the option of applying weak boundary conditions, but also keeps the simulation complexity low, when testing other relevant features, e.g., different integration schemes or the implementation of enrichment functions. The flexibility and wide application range of the MoMS in the context of immersed boundary simulations is demonstrated using static, quasi-static, and transient problems in the context of linear elasticity. Finally, the analytical derivations of the manufactured solutions used in this paper are provided as supplementary material.
Psychisch belastete Jugend?
Authors: Haselgruber Alexander , Weindl Dina , Sandra Schröter , Rusinek Monika , Maletzky Anna , Singer Verena , Zajec Karin , Noske Judith
Published: November 2023

Hintergrund

Seit Beginn der Covid-19 Pandemie wurde eine deutliche Zunahme der psychischen Belastung in der Allgemeinbevölkerung, besonders bei Kindern und Jugendlichen verzeichnet. Eine entsprechende Bedarfserhöhung an kinder- und jugendpsychiatrischer (KJP) Versorgung wurde berichtet. Zur Abbildung des gegenwärtigen Versorgungsbedarfs und der Akuität der Versorgungslage wurde erstmals für das Einzugsgebiet der KJPP Hinterbrühl (Industrieviertel und nördliches Burgenland) eine systematische Evaluation aller vorstellig gewordenen Patient:innen durchgeführt.

Methode

Von 1. Oktober 2022 bis 30. April 2023 wurden N = 714 Vorstellungen von tendenziell jugendlichen (Alter; M = 14,54, SD = 2,67) und weiblichen Patient:innen (63,0 %) verzeichnet. Die Einschätzung erfolgte durch Expert:innen mittels eines entwickelten Erhebungsinstruments. Auswertungen erfolgten über χ2-Tests, Korrelationsanalysen, Cohens Kappa, Mann-Whitney-U-Tests und logistische Regressionsanalysen.

Ergebnisse

Durchschnittlich erfolgten monatlich 104 Vorstellungen, davon 60,4 % akut, 66,8 % mit Selbst- oder Fremdgefährdung. 38,0 % aller Patient:innen wurden aufgenommen. Bei 63,5 % spielte Suizidalität eine Rolle. Weibliche Patientinnen wiesen häufiger F3-, F5- und F6-Diagnosen, sowie Selbstgefährdung und Suizidalität auf. Jugendliche waren häufiger selbstgefährdend und akut vorstellig und wurden häufiger aufgenommen. Die Vorstellung mit Einsatzkräften (OR = 2,41) und höhere Suizidalität nach Experteneinschätzung (OR = 3,90) erhöhten die Aufnahmechance signifikant.

Diskussion

In Österreich lässt sich seit der Covid-19 Pandemie eine Zunahme des KJP Versorgungsbedarfs mit einer markanten Verschiebung des Auftrags in den akutpsychiatrischen Bereich beobachten. Korrespondierend und übereinstimmend mit Vergleichsdaten anderer KJPs, zeigte sich an der KJPP Hinterbrühl ein konstant hohes Ausmaß an Vorstellungen, proportionalen Akutvorstellungen und stationären Aufnahmeraten. KJP Abteilungen müssen durch entsprechende Mittel und Personalversorgung befähigt werden, dieser anhaltenden Aus- und Belastung mittel- und langfristig standhalten zu können.
Comparing non-biodegradable plastic with environmentally friendly natural fibre composite on car front bumpers design
Authors: Sidde Sai Kiran , Cheung Wai Ming , Leung Pak Sing
Published: November 2023

Production of plastic is growing, and plastics are used in a variety of products. However, plastics are not biodegradable and do not decompose easily. To overcome the problems in decomposition of plastics, the use of a specific type of natural fibre composite (NFC) material for front-bumper in cars is considered in this investigation. NFCs have the advantages of being environmentally friendly, light weight and high strength. The use of jute fibre is adopted for the design of a car front bumper and compared with the plastic bumper through Finite Element Analysis. The aim is to identify their performances in terms of impact energy, strength and resilience. The results show that when both materials were simulated under the same impact force, jute fibre has a lower equivalent stress with 177.1 MPa compare with 293.18 MPa on plastic material. This finding indicates that jute fibre has greater yield limit and more resilient to fracture. The simulation result also shows that jute fibre has a higher equivalent stress of 65.55 MPa on the front bumper compare with a lower equivalent stress of 39.94 MPa on plastic. This suggests that plastic material will yield soon when an impact force is higher. The total deformation after the same impact force in jute fibre is 2.1 mm, which is significantly less than the deformation in plastic with 11.7 mm. Therefore, this research concludes that jute fibre can potentially replace plastic as a green composite material application to minimise environmental damages.

Graphical abstract
The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults
Authors: Arkenberg Per , Dittmar Manuela
Published: November 2023

It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, in particular to inflammaging, that is associated with increased levels of TNF-α. This study aimed (1) to investigate how 24-h profiles for OGG1 change during healthy aging and (2) to analyze the relationship of OGG1 with TNF-α, central body fat, cortisol and oxidative DNA/RNA damage. In a cross-sectional study in 20 healthy older and 20 young women, salivary levels of OGG1, TNF-α, cortisol and oxidative DNA/RNA damage were quantified by ELISAs every 4 h for a 24-h period. Trunk circumferences were taken as measures of central body fat. Older women, compared to young women, exhibited significantly lower protein levels of OGG1 throughout the whole 24-h period, a 2.5 times lower 24-h mean level for OGG1 (P < 0.00001) and loss of 24-h variation of OGG1. Both age groups demonstrated significant 24-h variation for TNF-alpha, cortisol and oxidative damage. The 24-h mean level for TNF-α was more than twice as high in older compared to young women (P = 0.011). Regression analysis detected that age, TNF-α and waist circumference were negative significant predictors of OGG1, explaining 56% of variance of OGG1 (P < 0.00001), while levels of cortisol and oxidative damage were no predictors of OGG1. Results indicate a strong decrease of protein levels of OGG1 and a loss of 24-h variation during natural cellular aging. The negative relationship, found between OGG1 and TNF-α and between OGG1 and waist circumference, suggests involvement of proinflammatory processes in DNA repair.
Einsatz von T-Zelltherapien in der soliden Onkologie
Authors: Müller Philipp Jie , Kobold Sebastian
Published: November 2023

Lately, cellular immunotherapies have emerged as a powerful tool in treating hematological malignancies. However, these therapeutic advances have not demonstrated sustained efficacy in solid oncology yet. The reasons are multi-layered and can be brought down to the missing antigen specificity, lack of immune cell infiltration into the tumor and the hostile tumor microenvironment, rendering immune cells dysfunctional. Here, we give an overview of current problems and solutions for cellular immunotherapies in solid tumors.
O2-sensitive Mikrokavitätenarrays: 3D-Zellkultursystem mit Sensorfunktion
Authors: Gottwald Eric , Grün Christoph , Liebsch Gregor
Published: November 2023

Oxygen is a crucial parameter for organotypic in vitro-cultures which are still performed under ambient atmosphere supplemented with 5 % CO2. This can lead to hyperoxia with its associated effects on signaling cascades and their effects on cellular behavior. Here, we describe a platform that enables real-time, label-free, optical oxygen (gradient) measurements in organotypic 3D-/organoid cultures thus allowing for physioxic culture and assay conditions in e. g. mito stress tests and substance testing.
Erzeugung menschlicher Nervengewebe in der Kulturschale
Authors: Rockel Anna F. , Ergün Süleyman , Wörsdörfer Philipp
Published: November 2023

Multiple protocols for organoid models of the human brain were developed over the last decade, representing different brain regions. Co-cultures of these organoids, referred to as assembloids, have further increased the complexity of these cultures. Our lab is working on neuro-mesodermal assembloids, which show incorporation of blood vessels and microglia-like cells into the nervous tissue. Moreover, these assembloids also contain neural crest cells and show peripheral nervous system development.
Assessment of stature in Iron Age populations of South Africa
Authors: Steyn Maryna
Published: November 2023

Worldwide and in South African Stone Age contexts, much research has been done on the relationship between stature of past populations and general well-being, as well as trends and patterns in stature through time. This research is aimed at collating and assessing all available stature and long bone data for Bantu-speaker individuals living in the South African Iron Age. Data for only 25 female and 32 male individuals, dating from circa AD 550 to AD 1823, could be found. In general, methods used to reconstruct stature were inconsistent and data were poorly reported. From the available data, no clear trends or patterns in stature through time could be observed and stature seems to be on a par relative to those of early twentieth century individuals. Recommendations are made as to which methods to use in stature estimations in this context. The data provided in this research can serve as reference material for future similar studies and can assist in interpreting individual stature estimations from bioarcheological research in the region.
On the consistency of relative facts
Authors: Cavalcanti Eric G. , Di Biagio Andrea , Rovelli Carlo
Published: November 2023

Lawrence et al. have presented an argument purporting to show that “relative facts do not exist” and, consequently, “Relational Quantum Mechanics is incompatible with quantum mechanics”. The argument is based on a GHZ-like contradiction between constraints satisfied by measurement outcomes in an extended Wigner’s friend scenario. Here we present a strengthened version of the argument, and show why, contrary to the claim by Lawrence et al., these arguments do not contradict the consistency of a theory of relative facts. Rather, considering this argument helps clarify how one should not think about a theory of relative facts, like RQM.
RETRACTED ARTICLE: Dual Siamese Anchor Points Adaptive Tracker with Transformer for RGBT Tracking
Authors: Fan Liangsong , Kim Pyeoungkee
Published: November 2023

Due to environmental conditions, such as rainy days, foggy days, and dim lighting, objects in visible light images are not prominently displayed, leading to an easy loss of targets during tracking. In recent years, many RGB visible light trackers have achieved significant success in addressing visual tracking challenges. However, these trackers perform poorly when tracking targets under special conditions, such as occlusions and low-light scenarios. In contrast, objects in thermal infrared images are more distinct in poor lighting conditions. Given this characteristic, researchers have shown increased interest in the development of trackers that combine thermal infrared and visible light imagery. However, some mainstream RGBT (red–green–blue and thermal) algorithms, such as MANET and ADNET, are based on the anchor-based theory, requiring consideration of anchor box sizes and introducing a substantial number of hyperparameters. This can lead to suboptimal performance when tracking dynamically changing targets. Moreover, these models rely on convolutional neural networks for feature extraction, which have limitations in capturing global features. In this paper, we introduce a novel training network model called DAPAT, which combines the anchor-free concept with Transformer theory. DAPAT differs from previous models in several ways. Specifically, we have designed a straightforward model to extract precise global features from template and search images. We have also incorporated two enhancement modules into the model to improve template and search images of different sizes while suppressing the impact of non-target images. We employ a dual-stream feature fusion network to reduce the loss of image feature information due to feature correlation operations. Finally, we compare the performance of the tracking model proposed in this paper with some advanced RGBT trackers on three data sets (RGBT234, RGBT210, and GTOT). The test results demonstrate that our tracker exhibits improvements in robustness and success rate, among other performance aspects.
Islam's Encounter with Modern Science
Authors: Edis Taner
Published: November 2023

Within Muslim populations, debates about the compatibility between science and religion tend to be framed by the long-standing competition between modernizing reformers, particularly westernizers, and theological conservatives. Much like their liberal Christian counterparts, reformers propose to embrace technical knowledge and reinterpret traditional beliefs undermined by modern science. Conservatives are more open to challenging the content of science, especially when science appears to support materialist views. Islamists promote an alternative, non-western style of modernity, nurturing a more pious professional class that contrasts with westernized elites. By scientific standards, westernizers appear to have the upper hand, especially as conservative apologetics is drawn toward distortions of science such as creationism, or fruitless attempts to Islamize science. But conservatives can also point to some success in defusing tensions between scientific and religious institutions without adopting the full secularization of science seen in post-Christian countries.
Customized Career Development Platform (CCDP) for clinical and translational researchers: A pragmatic cluster-randomized controlled trial
Authors: Rubio Doris M. , Mayowski Colleen , Meagher Emma A. , Patino Cecilia M. , Thakar Maya S. , Welch Julie L. , White Gretchen E.
Published: November 2023

Introduction:

Early-stage clinical and translational researchers who set and track career goals, milestones, and progress are successful in career development. We aimed to determine the effectiveness of the Customized Career Development Platform (CCDP), an online individual development plan (IDP), versus the traditional IDP template in improving research success and career satisfaction.

Methods:

We conducted a pragmatic cluster-randomized controlled trial of 340 scholars and trainees at 27 US academic healthcare institutions. The primary outcome was number of published manuscripts 24 months post-intervention. Secondary outcomes included the number of grant proposals submitted and funded, job satisfaction, and level of communication with mentors. An analysis of CCDP participants assessed proficiency level for the 14 Clinical and Translational Science Award (CTSA) competencies. Data were analyzed using intention-to-treat.

Results:

Participants were mostly female (60.3%) and Caucasian (67.2%); mean age was 34 years. Twenty-four months following the intervention, the CCDP versus traditional IDP groups showed a similar number of publications (9.4 vs 8.6), grants submitted (4.1 vs 4.4) and funded (1.3 vs 2.0), and job satisfaction score (3.6 vs 3.7). The CCDP group had higher odds of discussing communication (OR = 2.08) and leadership skills (OR = 2.62) and broadening their network (2.31) than the traditional IDP group. The CCDP arm reported improvements in 9 of the 14 CTSA competencies.

Conclusion:

The CCDP offers CTSA hubs an innovative alternative to traditional IDP tools. Future studies are needed to elucidate why the CCDP users did not fully appreciate or adopt the functionality of the online platform.
Is there really a healthy context paradox for victims of bullying? A longitudinal test of bidirectional within-and between-person associations between victimization and psychological problems
Authors: Laninga-Wijnen Lydia , Yanagida Takuya , Garandeau Claire F. , Malamut Sarah T. , Veenstra René , Salmivalli Christina
Published: November 2023

The finding that victims’ psychological problems tend to be exacerbated in lower-victimization classrooms has been referred to as the “healthy context paradox.” The current study has put the healthy context paradox to a strict test by examining whether classroom-level victimization moderates bidirectional within- and between-person associations between victimization and psychological adjustment. Across one school year, 3,470 Finnish 4th to 9th graders (Mage = 13.16, 46.1% boys) reported their victimization, depressive symptoms, anxiety, and self-esteem. Three types of multilevel models (cross-lagged panel, latent change score, and random-intercept cross-lagged panel) were estimated for each indicator of psychological adjustment. Findings indicated that the healthy context paradox emerges because classroom-level victimization moderates the prospective effect of victimization on psychological problems, rather than the effect of psychological problems on victimization. In classrooms with lower victimization, victims not only experience worse psychological maladjustment over time compared to others (between-person changes), but also higher maladjustment than before (absolute within-person changes).
A correct-by-construction conversion from lambda calculus to combinatory logic
Authors: SWIERSTRA WOUTER
Published: November 2023

This pearl defines a translation from well-typed lambda terms to combinatory logic, where both the preservation of types and the correctness of the translation are enforced statically.
“Baked bread to the people”: bread distribution and social and political networks at Pompeii
Authors: Tuck Steven L.
Published: November 2023

In 2017, archaeologists at Pompeii discovered by far the longest tomb inscription ever found at the city on a monumental tomb. This elogium provided insight into many aspects of the city's social, economic, and political world. One clause attests to the distribution of baked bread in the city. This note argues that the passage provides new evidence from Pompeii that answers two longstanding questions. The first is that of the subject of an often-reproduced Pompeian fresco. The identity of the main figure in the painting is debated: either a baker or a politician. The second is the status, political rank, and network of the owner of the property on which the fresco was discovered. Supported by the evidence of an electoral programma, the painting and inscription illuminate the mechanics of beneficence at Pompeii and serve to identify the residence of someone who operated in the political networks of the 1st-c. CE city at a sub-elite level.
γδ T cells: origin and fate, subsets, diseases and immunotherapy
Authors: Hu Yi , Hu Qinglin , Li Yongsheng , Lu Ligong , Xiang Zheng , Yin Zhinan , Kabelitz Dieter , Wu Yangzhe
Published: November 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2+ γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.
Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats
Authors: Creutzberg Kerstin Camile , Begni Veronica , Orso Rodrigo , Lumertz Francisco Sindermann , Wearick-Silva Luis Eduardo , Tractenberg Saulo Gantes , Marizzoni Moira , Cattaneo Annamaria , Grassi-Oliveira Rodrigo , Riva Marco Andrea
Published: November 2023

Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.
PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
Authors: Li Yaoyin , Ma Zeyi , Li Weiyu , Xu Xiaoqing , Shen Peiqi , Zhang Si-en , Cheng Bin , Xia Juan
Published: November 2023

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN+ CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN+ CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN+ CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN+ CAFs may serve as a novel potential therapeutic target for OSCC.
3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis
Authors: Cerrato Giulia , Alvarez-Lucena Carlota , Sauvat Allan , Hu Yanhua , Forveille Sabrina , Chen Guo , Durand Sylvère , Aprahamian Fanny , Leduc Marion , Motiño Omar , Boscá Lisardo , Xu Qingbo , Kepp Oliver , Kroemer Guido
Published: November 2023

Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposedApoE−/−mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity.
USP35 promotes HCC development by stabilizing ABHD17C and activating the PI3K/AKT signaling pathway
Authors: Wang Linpei , Wang Jiawei , Ma Xiaoqiu , Ju Guomin , Shi Chunfeng , Wang Wei , Wu Jian
Published: November 2023

S-palmitoylation is a reversible protein lipidation that controls the subcellular localization and function of targeted proteins, including oncogenes such as N-RAS. The depalmitoylation enzyme family ABHD17s can remove the S-palmitoylation from N-RAS to facilitate cancer development. We previously showed that ABHD17C has oncogenic roles in hepatocellular carcinoma (HCC) cells, and its mRNA stability is controlled by miR-145-5p. However, it is still unclear whether ABHD17C is regulated at the post-translational level. In the present study, we identified multiple ubiquitin-specific proteases (USPs) that can stabilize ABHD17C by inhibiting the ubiquitin-proteasome-mediated degradation. Among them, USP35 is the most potent stabilizer of ABHD17C. We found a positive correlation between the elevated expression levels of USP35 and ABHD17C, together with their association with increased PI3K/AKT pathway activity in HCCs. USP35 knockdown caused decreased ABHD17C protein level, impaired PI3K/AKT pathway, reduced proliferation, cell cycle arrest, increased apoptosis, and mitigated migration and invasion. USP35 can interact with and stabilize ABHD17C by inhibiting its ubiquitination. Overexpression of ABHD17C can rescue the defects caused by USP35 knockdown in HCC cells. In support of these in vitro observations, xenograft assay data also showed that USP35 deficiency repressed HCC development in vivo, characterized by reduced proliferation and disrupted PI3K/AKT signaling. Together, these findings demonstrate that USP35 may promote HCC development by stabilization of ABHD17C and activation of the PI3K/AKT pathway.
Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
Authors: Lin Jake , Moradi Elaheh , Salenius Karoliina , Lehtipuro Suvi , Häkkinen Tomi , Laiho Jutta E. , Oikarinen Sami , Randelin Sofia , Parikh Hemang M. , Krischer Jeffrey P. , Toppari Jorma , Lernmark Åke , Petrosino Joseph F. , Ajami Nadim J. , She Jin-Xiong , Hagopian William A. , Rewers Marian J. , Lloyd Richard E. , Rautajoki Kirsi J. , Hyöty Heikki , Nykter Matti ,   the TEDDY Study Group
Published: November 2023

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we observe increased monocyte and decreased B cell proportions 9-12 months prior to autoantibody positivity, especially in children who developed antibodies against insulin first. Lastly, we show that control children present transcriptional signatures consistent with robust immune responses to enterovirus infection, whereas children who later developed islet autoimmunity do not. These findings highlight distinct immune-related transcriptomic differences between case and control children prior to case progression to islet autoimmunity and uncover deficient antiviral response in children who later develop islet autoimmunity.
Structure of the DDB1-AMBRA1 E3 ligase receptor complex linked to cell cycle regulation
Authors: Liu Ming , Wang Yang , Teng Fei , Mai Xinyi , Wang Xi , Su Ming-Yuan , Stjepanovic Goran
Published: November 2023

AMBRA1 is a tumor suppressor protein that functions as a substrate receptor of the ubiquitin conjugation system with roles in autophagy and the cell cycle regulatory network. The intrinsic disorder of AMBRA1 has thus far precluded its structural determination. To solve this problem, we analyzed the dynamics of AMBRA1 using hydrogen deuterium exchange mass spectrometry (HDX-MS). The HDX results indicated that AMBRA1 is a highly flexible protein and can be stabilized upon interaction with DDB1, the adaptor of the Cullin4A/B E3 ligase. Here, we present the cryo-EM structure of AMBRA1 in complex with DDB1 at 3.08 Å resolution. The structure shows that parts of the N- and C-terminal structural regions in AMBRA1 fold together into the highly dynamic WD40 domain and reveals how DDB1 engages with AMBRA1 to create a binding scaffold for substrate recruitment. The N-terminal helix-loop-helix motif and WD40 domain of AMBRA1 associate with the double-propeller fold of DDB1. We also demonstrate that DDB1 binding-defective AMBRA1 mutants prevent ubiquitination of the substrate Cyclin D1 in vitro and increase cell cycle progression. Together, these results provide structural insights into the AMBRA1-ubiquitin ligase complex and suggest a mechanism by which AMBRA1 acts as a hub involved in various physiological processes.
Loss-of-function of an α-SNAP gene confers resistance to soybean cyst nematode
Authors: Usovsky Mariola , Gamage Vinavi A. , Meinhardt Clinton G. , Dietz Nicholas , Triller Marissa , Basnet Pawan , Gillman Jason D. , Bilyeu Kristin D. , Song Qijian , Dhital Bishnu , Nguyen Alice , Mitchum Melissa G. , Scaboo Andrew M.
Published: November 2023

Plant-parasitic nematodes are one of the most economically impactful pests in agriculture resulting in billions of dollars in realized annual losses worldwide. Soybean cyst nematode (SCN) is the number one biotic constraint on soybean production making it a priority for the discovery, validation and functional characterization of native plant resistance genes and genetic modes of action that can be deployed to improve soybean yield across the globe. Here, we present the discovery and functional characterization of a soybean resistance gene, GmSNAP02. We use unique bi-parental populations to fine-map the precise genomic location, and a combination of whole genome resequencing and gene fragment PCR amplifications to identify and confirm causal haplotypes. Lastly, we validate our candidate gene using CRISPR-Cas9 genome editing and observe a gain of resistance in edited plants. This demonstrates that the GmSNAP02 gene confers a unique mode of resistance to SCN through loss-of-function mutations that implicate GmSNAP02 as a nematode virulence target. We highlight the immediate impact of utilizing GmSNAP02 as a genome-editing-amenable target to diversify nematode resistance in commercially available cultivars.
Bony-fish-like scales in a Silurian maxillate placoderm
Authors: Cui Xindong , Friedman Matt , Yu Yilun , Zhu You-an , Zhu Min
Published: November 2023

Major groups of jawed vertebrates exhibit contrasting conditions of dermal plates and scales. But the transition between these conditions remains unclear due to rare information on taxa occupying key phylogenetic positions. The 425-million-year-old fishEntelognathuscombines an unusual mosaic of characters typically associated with jawed stem gnathostomes or crown gnathostomes. However, only the anterior part of the exoskeleton was previously known for this very crownward member of the gnathostome stem. Here, we report a near-complete post-thoracic exoskeleton ofEntelognathus. Strikingly, its scales are large and some are rhomboid, bearing distinctive peg-and-socket articulations; this combination was previously only known in osteichthyans and considered a synapomorphy of that group. The presence inEntelognathusof an anal fin spine, previously only found in some stem chondrichthyans, further illustrates that many characters previously thought to be restricted to specific lineages within the gnathostome crown likely arose before the common ancestor of living jawed vertebrates.
Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13
Authors: Jacob Prince , Lindelöf Hillevi , Rustad Cecilie F. , Sutton Vernon Reid , Moosa Shahida , Udupa Prajna , Hammarsjö Anna , Bhavani Gandham SriLakshmi , Batkovskyte Dominyka , Tveten Kristian , Dalal Ashwin , Horemuzova Eva , Nordgren Ann , Tham Emma , Shah Hitesh , Merckoll Else , Orellana Laura , Nishimura Gen , Girisha Katta M. , Grigelioniene Giedre
Published: November 2023

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2–64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, retaining the same radiographic pattern of spondylar- and epi-metaphyseal dysplasia, but with varying severity of the hip and knee deformities. Two new missense variants, c.548 G>A, p.(Arg183His) and c.569 G>T, p.(Arg190Leu), and a previously known splice variant c.477+1G>A were identified, confirming mutational clustering in a highly specific RNA binding motif. Structural analysis and interpretation of the variants’ impact on the protein suggests that disruption of extra-ribosomal functions of the protein through binding of mRNA may play a role in the skeletal phenotype of SEMD-RPL13. In addition, we present gonadal and somatic mosaicism for the condition.
De novo transcriptome assembly of Dalbergia sissoo Roxb. (Fabaceae) under Botryodiplodia theobromae-induced dieback disease
Authors: Zafar Ummul Buneen , Shahzaib Muhammad , Atif Rana Muhammad , Khan Sultan Habibullah , Niaz Muhammad Zeeshan , Shahzad Khalid , Chughtai Nighat , Awan Faisal Saeed , Azhar Muhammad Tehseen , Rana Iqrar Ahmad
Published: November 2023

Dalbergia sissooRoxb. (Shisham) is a timber-producing species of economic, cultural, and medicinal importance in the Indian subcontinent. In the past few decades, Shisham's dieback disease caused by the fungusBotryodiplodia theobromaehas become an evolving issue in the subcontinent endangering its survival. To gain insights into this issue, a standard transcriptome assembly was deployed to assess the response ofD. sissooat the transcriptomic level under the stress ofB. theobromaeinfection. For RNA isolation, the control and infected leaf tissue samples were taken from 1-year-old greenhouse-grownD. sissooplants after 20 days of stem-base spore inoculation. cDNA synthesis was performed from these freshly isolated RNA samples that were then sent for sequencing. About 18.14 Gb (Giga base) of data was generated using the BGISEQ-500 sequencing platform. In terms of Unigenes, 513,821 were identified after a combined assembly of all samples and then filtering the abundance. The total length of Unigenes, their average length, N50, and GC-content were 310,523,693 bp, 604 bp, 1,101 bp, and 39.95% respectively. The Unigenes were annotated using 7 functional databases i.e., 200,355 (NR: 38.99%), 164,973 (NT: 32.11%), 123,733 (Swissprot: 24.08%), 142,580 (KOG: 27.75%), 139,588 (KEGG: 27.17%), 99,752 (GO: 19.41%), and 137,281 (InterPro: 26.72%). Furthermore, the Transdecoder detected 115,762 CDS. In terms of SSR (Simple Sequence Repeat) markers, 62,863 of them were distributed on 51,508 Unigenes and on the predicted 4673 TF (Transcription Factor) coding Unigenes. A total of 16,018 up- and 19,530 down-regulated Differentially Expressed Genes (DEGs) were also identified. Moreover, the Plant Resistance Genes (PRGs) had a count of 9230. We are hopeful that in the future, these identified Unigenes, SSR markers, DEGs and PRGs will provide the prerequisites for managing Shisham dieback disease, its breeding, and in tree improvement programs.
Evaluation of the performance of GPT-3.5 and GPT-4 on the Polish Medical Final Examination
Authors: Rosoł Maciej , Gąsior Jakub S. , Łaba Jonasz , Korzeniewski Kacper , Młyńczak Marcel
Published: November 2023

The study aimed to evaluate the performance of two Large Language Models (LLMs): ChatGPT (based on GPT-3.5) and GPT-4 with two temperature parameter values, on the Polish Medical Final Examination (MFE). The models were tested on three editions of the MFE from: Spring 2022, Autumn 2022, and Spring 2023 in two language versions—English and Polish. The accuracies of both models were compared and the relationships between the correctness of answers with the answer’s metrics were investigated. The study demonstrated that GPT-4 outperformed GPT-3.5 in all three examinations regardless of the language used. GPT-4 achieved mean accuracies of 79.7% for both Polish and English versions, passing all MFE versions. GPT-3.5 had mean accuracies of 54.8% for Polish and 60.3% for English, passing none and 2 of 3 Polish versions for temperature parameter equal to 0 and 1 respectively while passing all English versions regardless of the temperature parameter value. GPT-4 score was mostly lower than the average score of a medical student. There was a statistically significant correlation between the correctness of the answers and the index of difficulty for both models. The overall accuracy of both models was still suboptimal and worse than the average for medical students. This emphasizes the need for further improvements in LLMs before they can be reliably deployed in medical settings. These findings suggest an increasing potential for the usage of LLMs in terms of medical education.
Evaluation of the surface water quality using global water quality index (WQI) models: perspective of river water pollution
Authors: Khan Md. Habibur Rahman Bejoy , Ahsan Amimul , Imteaz M. , Shafiquzzaman Md. , Al-Ansari Nadhir
Published: November 2023

Rapid industrialization, urbanization, global warming, and climate change are compromising surface water quality across the globe. Consequently, water conservation is essential for both environmental sustainability and human survival. This study assesses the water quality of the Jamuna River in Bangladesh at five distinct sites during wet and dry seasons. It employs six global water quality indices (WQIs) and contrasts the results with Bangladesh's Environmental Quality Standard (EQS) and the Department of Environment (DoE) criteria. The WQI models used are the Weighted Arithmetic WQI (WAWQI), British Columbia WQI (BCWQI), Canadian Council of Ministers of the Environment WQI (CWQI), Assigned WQI (AWQI), Malaysian WQI (MWQI), and Oregon WQI (OWQI). Fifteen physicochemical parameters were analyzed according to each WQI model's guidelines. The findings reveal that most parameters surpass the standard permissible values. The WQI model results indicate that the average water quality across the five sites falls into the lowest category. A comparison of the WQI models suggests potential correlations between WAWQI and AWQI, as well as between MWQI and OWQI. The straightforward presentation of the WQI models indicates that while the river water requires treatment for household and drinking use, it remains suitable for irrigation. The decline in water quality is likely attributable to human activities, urbanization, municipal waste disposal, and industrial effluents. Authorities must prioritize regular monitoring and assessment of water quality to address the identified challenges. Restoring the water to an acceptable standard will become increasingly difficult without proactive measures.
Robust in-vehicle respiratory rate detection using multimodal signal fusion
Authors: Warnecke Joana M. , Lasenby Joan , Deserno Thomas M.
Published: November 2023

Continuous health monitoring in private spaces such as the car is not yet fully exploited to detect diseases in an early stage. Therefore, we develop a redundant health monitoring sensor system and signal fusion approaches to determine the respiratory rate during driving. To recognise the breathing movements, we use a piezoelectric sensor, two accelerometers attached to the seat and the seat belt, and a camera behind the windscreen. We record data from 15 subjects during three driving scenarios (15 min each) city, highway, and countryside. An additional chest belt provides the ground truth. We compare the four convolutional neural network (CNN)-based fusion approaches: early, sensor-based late, signal-based late, and hybrid fusion. We evaluate the performance of fusing for all four signals to determine the portion of driving time and the signal combination. The hybrid algorithm fusing all four signals is most effective in detecting respiratory rates in the city ($$P = 62.42$$

P
=
62.42

), highway ($$P = 62.67$$

P
=
62.67

), and countryside ($$P = 60.94$$

P
=
60.94

). In summary, 60% of the total driving time can be used to measure the respiratory rate. The number of signals used in the multi-signal fusion improves reliability and enables continuous health monitoring in a driving vehicle.
Manufacturing of stretchable substrate with biaxial strain control for highly-efficient stretchable solar cells and displays
Authors: Kwak Ji-Youn , Jeong Ji-Young , Kwon Ye-Pil , Seo Dong-Hyun , Kang Chung-Mo , Kim Dong-Hyeon , Han Jun Sae , Gwak Eun-Ji , Choi Doo-Sun , Kim Ju-Young , Je Tae-Jin , Jeon Eun-chae
Published: November 2023

There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson’s ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 μm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays.