bluuebunny/crossref_metadata_2025 huggingface dataset:
Dismantling and personalising task-sharing psychosocial interventions for common mental disorders: a study protocol for an individual participant data component network meta-analysis
Authors: Papola Davide , Karyotaki Eirini , Purgato Marianna , Sijbrandij Marit , Tedeschi Federico , Cuijpers Pim , Orestis Efthimiou , Furukawa Toshi A , Patel Vikram , Barbui Corrado
Published: November 2023

Introduction

Common mental disorders, including depression, anxiety and related somatic health symptoms, are leading causes of disability worldwide. Especially in low-resource settings, psychosocial interventions delivered by non-specialist providers through task-sharing modalities proved to be valid options to expand access to mental healthcare. However, such interventions are usually eclectic multicomponent interventions consisting of different combinations of evidence-based therapeutic strategies. Which of these various components (or combinations thereof) are more efficacious (and for whom) to reduce common mental disorder symptomatology is yet to be substantiated by evidence.

Methods and analysis

Comprehensive search was performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials—CENTRAL from database inception to 15 March 2023 to systematically identify all randomised controlled trials that compared any single component or multicomponent psychosocial intervention delivered through the task-sharing modality against any active or inactive control condition in the treatment of adults suffering from common mental disorders. From these trials, individual participant data (IPD) of all measured outcomes and covariates will be collected. We will dismantle psychosocial interventions creating a taxonomy of components and then apply the IPD component network meta-analysis (IPD-cNMA) methodology to assess the efficacy of individual components (or combinations thereof) according to participant-level prognostic factors and effect modifiers.

Ethics and dissemination

Ethics approval is not applicable for this study since no original data will be collected. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.
Susceptibility vessel sign, a predictor of long-term outcome in patients with stroke treated with mechanical thrombectomy
Authors: Beyeler Morin , Rea Erich , Weber Loris , Belachew Nebiyat Filate , Barvulsky Aleman Enrique , Kielkopf Moritz , Kurmann Christoph C , Grunder Lorenz , Piechowiak Eike Immo I , Meinel Thomas R , Heldner Mirjam R , Seiffge David , Pilgram-Pastor Sara , Dobrocky Tomas , Pabst Thomas , Berger Martin D , Jung Simon , Arnold Marcel , Gralla Jan , Fischer Urs , Kaesmacher Johannes , Mujanovic Adnan
Published: November 2023

Background

The absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients.

Methods

SVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively.

Results

Of the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P
=
0.003) and diabetes mellitus (P
<
0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533–1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55).

Conclusion

MT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.
The m6A reader IGF2BP2 promotes the progression of esophageal squamous cell carcinoma cells by increasing the stability of OCT4 mRNA
Authors: Zhao Rong , Li Ting , Zhao Xinran , Yang Ziyi , Ma Liying , Wang Xiaoxia
Published: November 2023

Esophageal squamous cell carcinoma (ESCC) is a common malignancy with high morbidity and mortality. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) serves as a reader of RNA m6A (N6 methyladenosine) modification to regulate gene expression at the post-transcriptional level. Emerging evidence suggests that IGF2BP2 plays critical roles in tumorigenesis and malignant development. However, the biological function and molecular mechanism of IGF2BP2 in ESCC are not well understood. Here, we found that IGF2BP2 expression was upregulated in esophageal cancer tissues and ESCC cells, and IGF2BP2 overexpression enhanced proliferation, migration, invasion, and stem cell-like properties of ESCC cells. Conversely, the knockdown of IGF2BP2 expression inhibited malignant phenotype of ESCC cells. Mechanistically, IGF2BP2 upregulated octomer-binding transcription factor 4 (OCT4) mRNA expression, and RNA immunoprecipitation (RIP) assay proved that IGF2BP2 could interact with OCT4 mRNA. Moreover, OCT4 was modified at m6A confirmed by methylated m6A RNA immunoprecipitation (Me-RIP)-qPCR assay, and IGF2BP2 knockdown reduced OCT4 mRNA stability. These results suggested that IGF2BP2 served as a reader for m6A-modified OCT4, thus increased OCT4 mRNA expression by regulating its stability. Furthermore, the knockdown of OCT4 could reverse the effects of IGF2BP2 on ESCC cells. In conclusion, these data indicate that IGF2BP2, as a reader for m6A, plays an oncogenic role by regulating OCT4 expression in ESCC, which provides new insights into targeting IGF2BP2/OCT4 axis for the therapy of ESCC.
Chemical shift tensors as probes of chalcogen bonds: solid-state NMR study of telluradiazole-XCN− (X = O, S, Se) salt cocrystals
Authors: Almario Carina , Nag Tamali , Bryce David L.
Published: November 2023

We report experimental 125Te magic-angle spinning solid-state nuclear magnetic resonance (MAS NMR) measurements of the tellurium chemical shift (CS) tensors in three [K(18-crown-6)]+ 3,4-dicyano-1,2,5-telluradiazole-XCN− (X = O, S, Se) salt cocrystals featuring chalcogen bonds. These data are compared to those for pure 3,4-dicyano-1,2,5-telluradiazole (1). A reduction in the span of the 125Te CS tensor is consistently noted in the salt cocrystals compared to pure 1. Isotopically 15N-labelled [K(18-crown-6)]+[1-OC15N]−, which features a chalcogen bond between Te and the cyanate nitrogen atom, is synthesized using KOC15N, and the nitrogen CS tensors are measured for both samples via 15N slow MAS NMR spectroscopy. Possible dynamic disorder of the cyanate ions in KOCN is ruled out. Two crystallographically distinct nitrogen sites are resolved for the salt cocrystal. Upon formation of [K(18-crown-6)]+[1-OC15N]−, the 15N isotropic CS and CS tensor span both decrease relative to the values for pure KOC15N, and the axial symmetry of this tensor is lost. These findings are supplemented with a series of density functional theory calculations of magnetic shielding tensors using cluster models or periodic boundary conditions. Inclusion of spin–orbit relativistic effects in the calculation of tellurium shielding tensors is particularly important in achieving agreement with experiment.
Gravitational baryogenesis in non-minimal kinetic coupling model
Authors: Goodarzi Parviz
Published: November 2023

In this work, we consider the gravitational baryogenesis in the framework of non-minimal derivative coupling model. A mechanism to generate the baryon asymmetry based on the coupling between the derivative of the Ricci scalar curvature and the baryon current in context of non-minimal derivative coupling model is investigated. We show that, in this model, the temperature increases during the reheating periods to the end of reheating period or beginning of radiation dominated era. Therefore the reheating temperature is larger then decoupling temperature. It can be demonstrated that, the evaluation of baryon asymmetry is not depends on coupling constant. In this model we can generate baryon asymmetry at low and high reheating temperature, by considering the high friction constraint.
State Complexity of Permutation and the Language Inclusion Problem up to Parikh Equivalence on Alphabetical Pattern Constraints and Partially Ordered NFAs
Authors: Hoffmann Stefan
Published: November 2023

We investigate the state complexity of the permutation operation, or the commutative closure, on Alphabetical Pattern Constraints (APCs). This class corresponds to level [Formula: see text] of the Straubing-Thérien hierarchy and includes the finite, the piecewise testable, or [Formula: see text]-trivial, and the [Formula: see text]-trivial and [Formula: see text]-trivial languages. We give a sharp state complexity bound expressed in terms of the longest strings in the unary projection languages of an associated finite language. Additionally, for a subclass, we give sharp bounds expressed in terms of the size of a recognizing input automaton and the size of the alphabet. We also state a related state complexity bound for the commutative closure on finite languages. Lastly, we investigate the language inclusion, equivalence and universality problems on APCs up to permutational, or Parikh, equivalence. These problems are known to be [Formula: see text]-complete on APCs in general, even for fixed alphabets. We show them to be decidable in polynomial time for fixed alphabets if we only want to solve them up to Parikh equivalence. We also correct a mistake from the conference version in a bound on the size of recognizing automata for the commutative closure.
Automatic Tracking Method for 3D Human Motion Pose Using Contrastive Learning
Authors: Li Zhipeng , Wang Jun , Hua Lijun , Liu Honghui , Song Wenli
Published: November 2023

Automatic tracking of three-dimensional (3D) human motion pose has the potential to provide corresponding technical support in various fields. However, existing methods for tracking human motion pose suffer from significant errors, long tracking times and suboptimal tracking results. To address these issues, an automatic tracking method for 3D human motion pose using contrastive learning is proposed. By using the feature parameters of 3D human motion poses, threshold variation parameters of 3D human motion poses are computed. The golden section is introduced to transform the threshold variation parameters and extract the features of 3D human motion poses by comparing the feature parameters with the threshold of parameter variation. Under the supervision of contrastive learning, a constraint loss is added to the local–global deep supervision module of contrastive learning to extract local parameters of 3D human motion poses, combined with their local features. After normalizing the 3D human motion pose images, frame differences of the background image are calculated. By constructing an automatic tracking model for 3D human motion poses, automatic tracking of 3D human motion poses is achieved. Experimental results demonstrate that the highest tracking lag is 9%, there is no deviation in node tracking, the pixel contrast is maintained above 90% and only 6 sub-blocks have detail loss. This indicates that the proposed method effectively tracks 3D human motion poses, tracks all the nodes, achieves high accuracy in automatic tracking and produces good tracking results.
Streamlining Micro-Credentials Implementation in Higher Education Institutions: Considerations for Effective Implementation and Policy Development
Authors: Keoy Kay Hooi , Koh Yung Jing , Iqbal Javid , Anjum Shaik Shabana , Yeo Sook Fern , Cherukuri Aswani Kumar , Teoh Wai Yee , Piut Dayang Aidah Awang
Published: November 2023

The rise of online learning has brought about a close connection between micro-credentials and lifelong learning, employability, and new models of digital education. Micro-credentials are considered instrumental in transforming higher education today. This study aims to examine the extent to which micro-credentials have been adopted in Malaysia, focussing on the viewpoint of Higher Education Providers (HEPs). It seeks to identify the challenges faced by HEPs when offering micro-credentials, encompassing technological, organisational, and people-related obstacles. By analysing empirical data, this research intends to propose a conceptual framework that can guide the successful adoption and implementation of micro-credentials within educational institutions. By addressing these recommendations, HEPs in Malaysia can successfully adopt and implement micro-credentials within their institutions. This will not only enhance the learning experience for students but also contribute to the overall transformation of higher education, keeping pace with the demands of the digital age and fostering a culture of continuous learning and skill development.
Explainability in Deep Reinforcement Learning: A Review into Current Methods and Applications
Authors: Hickling Thomas , Zenati Abdelhafid , Aouf Nabil , Spencer Phillippa
Published: November 2023

The use of Deep Reinforcement Learning (DRL) schemes has increased dramatically since their first introduction in 2015. Though uses in many different applications are being found, they still have a problem with the lack of interpretability. This has bread a lack of understanding and trust in the use of DRL solutions from researchers and the general public. To solve this problem, the field of Explainable Artificial Intelligence has emerged. This entails a variety of different methods that look to open the DRL black boxes, ranging from the use of interpretable symbolic Decision Trees to numerical methods like Shapley Values. This review looks at which methods are being used and for which applications. This is done to identify which models are the best suited to each application or if a method is being underutilised.
Adaptive Adversarial Contrastive Learning for Cross-Domain Recommendation
Authors: Hsu Chi-Wei , Chen Chiao-Ting , Huang Szu-Hao
Published: November 2023

Graph-based cross-domain recommendations (CDRs) are useful for suggesting appropriate items because of their promising ability to extract features from user–item interactions and transfer knowledge across domains. Thus, the model can effectively alleviate cold start and data sparsity issues. Although the graph-based CDRs can capture valuable information, they still have some limitations. First, embeddings are highly vulnerable to noisy interactions, because the message aggregation in the graph convolutional network can further enlarge the impact. Second, because of the property of graph-structured data, the influence of high-degree nodes on representation learning is more than that of the long-tail items, and this can cause a poor recommendation performance. In this study, we devised a novel
A
daptive
A
dversarial
C
ontrastive
L
earning framework for graph-based
C
ross-
D
omain
R
ecommendation (
ACLCDR
). The ACLCDR introduces reinforcement learning to generate adaptive augmented samples for contrastive learning tasks. Then, we leveraged a multitask training strategy to jointly optimize the model with auxiliary tasks. Finally, we verified the effectiveness of the ACLCDR through nine real-world cross-domain tasks adopted from Amazon and Douban. We observed that ACLCDR exceeded the best state-of-the-art baseline by 25%, 42.5%, 16.3%, and 23.8% in terms of
HR@
10 and
NDCG@10
for the Music & Movie task from Amazon.
From Large Language Models to Databases and Back: A Discussion on Research and Education
Authors: Amer-Yahia Sihem , Bonifati Angela , Chen Lei , Li Guoliang , Shim Kyuseok , Xu Jianliang , Yang Xiaochun
Published: November 2023

In recent years, large language models (LLMs) have garnered increasing attention from both academia and industry due to their potential to facilitate natural language processing (NLP) and generate highquality text. Despite their benefits, however, the use of LLMs is raising concerns about the reliability of knowledge extraction. The combination of DB research and data science has advanced the state of the art in solving real-world problems, such as merchandise recommendation and hazard prevention [30]. In this discussion, we explore the challenges and opportunities related to LLMs in DB and data science research and education.
Analysis of participation rates in Poll Everywhere questions and academic performance in a veterinary biochemistry and metabolism course
Authors: Cardamone Carie , Schonhoff Christopher M.
Published: November 2023

Many professional schools (medical, dental, and veterinary) routinely record most lectures and do not require attendance. Although lecture recordings may provide a valuable study tool for students, these results suggest that students who do not actively engage with class material miss an opportunity to maximize learning.
Stratification of neurogenic bladder risk in spina bifida using the urinary peptidome
Authors: Fazelinia Hossein , Ding Hua , Taylor Deanne , Spruce Lynn , Roof Jennifer , Weiss Dana , Fesi Joanna , Ischiropoulos Harry , Zderic Stephen
Published: November 2023

This approach could help risk stratify the neurogenic bladder in patients with spina bifida and could allow us to safely defer on up to 1/3 of urodynamic studies. These pilot data justify a larger trial before this approach becomes a clinical tool.
Decision Fusion and Micro‐Doppler Effects in Moving Sonar Target Recognition
Authors: Alenizi Farhan A. , Alsalami Omar Mutab , Saffari Abbas , Zahiri Seyed Hamid , Mohammadi Mokhtar
Published: November 2023

This paper proposes a method for underwater target recognition based on micro‐Doppler effects (called STR_MD) using a majority voting ensemble classifier weighted with particle swarm optimization (PSO) (called MV‐PSO). The micro‐Doppler effect refers to amplitude/phase modulation of the received signal by rotating parts of a target such as propellers. Since different targets’ geometric and physical properties differ, their micro‐Doppler signature is different. This inconsistency can be considered an effective issue (especially in the frequency domain) for sonar target recognition. To demonstrate the effectiveness of the proposed method, both simulated and practical micro‐Doppler data are produced and applied to the designed STR_MD. Also, MV‐PSO with six well‐known basic classifiers, k‐nearest neighbors (k‐NN), Naive Bayes (NB), decision tree (DT), MLP_NN, support vector machine (SVM), and random forest (RF), has been used to evaluate the performance of the proposed method. This ensemble classifier assigns an instance to a class that most base classifiers agree on. However, basic classifiers in a set seldom work just as well. Therefore, in this case, one strategy is to weigh each classification depending on its performance using PSO. The performance parameters measured are the recognition score, reliability, and processing time. The simulation results showed that the correct recognition rate, reliability, and processing time for the simulated data at SNR = 5 dB and 10° viewing angle were 98.50, 98.89, and 9.81 s, respectively, and for the practical dataset with RPM = 1200, 100, 100, and 4.43, respectively. Thus, MV‐PSO has a more encouraging performance in STR_MD for simulated and practical micro‐Doppler sonar datasets.
Bayesian Disease Mapping to Identify High-Risk Population for Oral Cancer: A Retrospective Spatiotemporal Analysis
Authors: Ramamurthy Poornima , Sharma Dileep , Adeoye John , Choi Siu-Wai , Thomson Peter
Published: November 2023

Objectives. Bayesian mapping is an effective spatiotemporal approach to identify high-risk geographic areas for diseases and has not been used to identify oral cancer hotspots in Australia previously. This retrospective disease mapping study was undertaken to identify the oral cancer trends and patterns within the Queensland state in Australia. Methods. This study included data obtained from Queensland state Cancer Registry from 1982 to 2018. Domains mapped included the oral cancer incidence and mortality in Queensland (QLD). Local government areas (LGAs) and suburbs were utilized as geographical units for the estimation using Bayesian mapping approach. Results. Of the 78 LGAs, 21 showed high-oral cancer incidence as measured using higher median smoothed incidence risk (SIR), above the state average. Specifically, nine LGAs within predominantly rural areas had SIR above 100% of the state average. Of these, only one LGA (Mount Isa City) had a median smoothed SIR and 95% CI of 2.61 (2.14–3.15) which was constantly above 100% of the state average. Furthermore, mortality risk estimated using smoothed mortality risk (SMR), were significantly higher than the state average in 31 LGAs. Seventeen LGAs had a median SMR above 100% of the state average while three LGAs had the highest overall, 3- and 5-year mortality risks. Considering the 95% credible interval which is indicative of the uncertainty around the estimates, three LGAs had the highest overall mortality risks—Yarrabah Aboriginal Shire (3.80 (2.16–6.39)), Cook Shire (3.37 (2.21–5.06)), and Mount Isa City (3.04 (2.40–3.80)). Conclusion. Bayesian disease mapping approach identified multiple incidence and mortality hotspots within regional areas of the Queensland. Findings from our study can aid in designing targeted public health screening and interventions for primary prevention of oral cancer in regional and remote communities.
Figure 6 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: November 2023

A, Left: acid-extracted histone and protein lysates prepared from ex vivo GS lines derived from the two-hit de novo models (KP, H3.1KP, KF, and KN) were probed for K27M, K27me3, HA, and total H3.3 levels. NSCs derived from the LRL (LRL NSC) were used as controls. Middle: validation of FGFR1 overexpression in ex vivo KF cells; GAPDH was used as a loading control. Right: validation of p53 and NF1 downregulation in ex vivo cells by qRT-PCR. Data are presented as means ± SD from at least n = 3 replicates. ****, P < 0.0001 and ***, P = 0.0003 were calculated using unpaired t test and one-way ANOVA. B, Left: acid-extracted histone and protein lysates prepared from ex vivo GS lines derived from the three- and four-hit de novo models (KPP, KPD, KPAP, KPAD, KPPMPIK, H3.1KACVPIK, KNF, KPF, and KPC) were probed for K27M, K27me3, HA, and total H3.3 levels. LRL NSCs were used as controls. Validation of PDGFRA, PPM1D, PIK3CA, ACVR1, FGFR1, and CCND2 overexpression in ex vivo GS cells; GAPDH and tubulin were used as loading controls. Right: validation of p53, ATRX, and NF1 downregulation in ex vivo GS cells by qRT-PCR. Data are presented as means ± SD from at least n = 3 replicates. ****, P < 0.0001 and ***, P = 0.0003 were calculated using unpaired t test and one-way ANOVA. C, Left: IHC detection of hematoxylin and eosin (H&E), GFP, K27M, and Ki-67 in coronal hindbrain sections from orthotopically engrafted, symptomatic mice. Mice were injected in either the pons (H3K27M) or striatum (H3.3G34R) with 150,000 to 300,000 cells from each cell GS cell line (n = 5 mice per condition). Tumor cells are GFP+. Scale bars, 2 mm. Right: BLI of brainstem tumors in orthotopically engrafted C57BL/6J mice without shaving/depilation using Akaluc imaging. D, Kaplan–Meier curves depicting survival of mice orthotopically injected with GS cells derived from H3.3K27M (left), H3.1K27M (middle), and H3.3G34R (right) models. Note that the following samples are shown twice in A and B: LRL NSC, KF, and KN; these repetitions are indicated with an asterisk. The sole purpose of this repetition is to make it easier for the reader, by collating all the Western blot (WB) data describing the “two-hit” models in A and all the WB data describing the “three-hit or more” models in B.
Supplementary Tables 1-3, 7-9 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: November 2023

Tables describing statistical analyses, median survivals, IC50 values calculated from cell viability assays, primer sequences and antibodies.
Supplementary Table 5 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: November 2023

Cell type ontologies derived from snRNA-seq data.
Supplementary Table 4 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: November 2023

Quality control and filtering of snRNA-seq data.
Supplementary Figures 1-27 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: November 2023

Figures describing hindbrain vs ganglionic eminence targeting strategies, each of the 16 models generated and validation that they expressed the introduced mutations, survival of GE vs CTX-electroporated embryos, and cell viability data shown in bar graph format.
Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia
Authors: Varkaris Andreas , Pazolli Ermira , Gunaydin Hakan , Wang Qi , Pierce Levi , Boezio Alessandro A. , Bulku Artemisa , DiPietro Lucian , Fridrich Cary , Frost Adam , Giordanetto Fabrizio , Hamilton Erika P. , Harris Katherine , Holliday Michael , Hunter Tamieka L. , Iskandar Amanda , Ji Yongli , Larivée Alexandre , LaRochelle Jonathan R. , Lescarbeau André , Llambi Fabien , Lormil Brenda , Mader Mary M. , Mar Brenton G. , Martin Iain , McLean Thomas H. , Michelsen Klaus , Pechersky Yakov , Puente-Poushnejad Erika , Raynor Kevin , Rogala Dipali , Samadani Ramin , Schram Alison M. , Shortsleeves Kelley , Swaminathan Sweta , Tajmir Shahein , Tan Gege , Tang Yong , Valverde Roberto , Wehrenberg Bryan , Wilbur Jeremy , Williams Bret R. , Zeng Hongtao , Zhang Hanmo , Walters W. Patrick , Wolf Beni B. , Shaw David E. , Bergstrom Donald A. , Watters James , Fraser James S. , Fortin Pascal D. , Kipp D. Randal
Published: November 2023

PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor–positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor of PI3Kα. RLY-2608 inhibited tumor growth in PIK3CA-mutant xenograft models with minimal impact on insulin, a marker of dysregulated glucose homeostasis. RLY-2608 elicited objective tumor responses in two patients diagnosed with advanced hormone receptor–positive breast cancer with kinase or helical domain PIK3CA mutations, with no observed WT PI3Kα-related toxicities.

Significance:

Treatments for PIK3CA-mutant cancers are limited by toxicities associated with the inhibition of WT PI3Kα. Molecular dynamics, cryo-electron microscopy, and DNA-encoded libraries were used to develop RLY-2608, a first-in-class inhibitor that demonstrates mutant selectivity in patients. This marks the advance of clinical mutant-selective inhibition that overcomes limitations of orthosteric PI3Kα inhibitors.

See related commentary by Gong and Vanhaesebroeck, p. 204 .

See related article by Varkaris et al., p. 227 .

This article is featured in Selected Articles from This Issue, p. 201
Supplementary Methods from Antitumor Effects of PRMT5 Inhibition in Sarcomas
Authors: Verbeke Stéphanie , Bourdon Aurélien , Guegan Jean-Philippe , Leroy Laura , Chaire Vanessa , Richard Elodie , Bessede Alban , Italiano Antoine
Published: November 2023

supplementary methods for apoptosis and cell cycle analysis and Western blot
FIGURE 5 from Antitumor Effects of PRMT5 Inhibition in Sarcomas
Authors: Verbeke Stéphanie , Bourdon Aurélien , Guegan Jean-Philippe , Leroy Laura , Chaire Vanessa , Richard Elodie , Bessede Alban , Italiano Antoine
Published: November 2023

Schematic representation of glycolysis impaired by PRMT5 inhibition in STSs. The red and green arrows show the decrease and increase observed upon GSK595 treatment, respectively. Adapted from Grasmann et al. Biochim Biophys Acta Rev Cancer. 2019. G6PC, glucose-6-phosphatase; HK, hexokinase; PFK, phosphofructokinase; FBP1, fructose-1,6-bisphosphatase 1; TIGAR, TP53-inducible glycolysis and apoptosis regulator; PPP, pentose phosphate pathway; GK, glycerol kinase; PCK1, cytosolic isoform of phosphoenolpyruvate carboxykinase; PCK2, mitochondrial isoform of phosphoenolpyruvate carboxykinase; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase; PYK, pyruvate kinase; GLUD, glutamate dehydrogenase; GA, glutaminase; LDHD, D-lactate dehydrogenase; and TCA cycle, tricarboxylic acid cycle.
FIGURE 1 from Antitumor Effects of PRMT5 Inhibition in Sarcomas
Authors: Verbeke Stéphanie , Bourdon Aurélien , Guegan Jean-Philippe , Leroy Laura , Chaire Vanessa , Richard Elodie , Bessede Alban , Italiano Antoine
Published: November 2023

Prognostic impact of PRMT5 gene expression in STSs. A, GEPIA dot plot showing PRMT5 expression in sarcomas and normal samples, with each dot representing a distinct tumor (n = 262) or normal sample (n = 2). B, Kaplan‒Meier curves of overall survival according to PRMT5 gene expression in 262 STSs from TCGA consortium (http://gepia.cancer-pku.cn/index.html). C, Kaplan‒Meier curves of metastasis-free survival in 255 patients with translocation-related sarcomas according to PRMT5 expression (green line: low expression; red line: high expression: n = 135). D, Kaplan‒Meier curves of metastasis-free survival in 389 patients with complex genomic sarcomas according to PRMT5 expression (green line: low expression, n = 159; red line: high expression: n = 180).
Data from Antitumor Effects of PRMT5 Inhibition in Sarcomas
Authors: Verbeke Stéphanie , Bourdon Aurélien , Guegan Jean-Philippe , Leroy Laura , Chaire Vanessa , Richard Elodie , Bessede Alban , Italiano Antoine
Published: November 2023

Abstract
Patients with advanced soft-tissue sarcomas (STS) have few therapeutic options. Protein arginine methyltransferase 5 (PRMT5), an anticancer target, has been extensively investigated in recent years in epithelial tumors. To date, no data related to the biological role of PRMT5 inhibition and its potential effect as a treatment in STS have been reported.

To investigate the therapeutic potential of PRMT5 targeting in STS, we first evaluated the prognostic value of PRMT5 expression in two different cohorts of patients with STS. We then used the potent and selective GSK3326595 (GSK595) compound to investigate the antitumor effect of the pharmacologic inhibition of PRMT5 in vitro via MTT, apoptosis, cell cycle, clonogenicity, and proliferation assays. In vivo studies were performed with two animal models to evaluate the effects of GSK595 on tumor growth. The mechanisms of action were investigated by RNA sequencing, metabolic pathway analysis, Western blotting, and glucose uptake/lactate production assays.

High PRMT5 gene expression levels were significantly associated with worsened metastasis-free survival of patients with STS. GSK595 decreased the global symmetric dimethylarginine level, the proliferation rate and clonogenicity of STS cell lines in vitro and tumor growth in vivo. Moreover, PRMT5 inhibition regulated aerobic glycolysis through downregulation of key enzymes of glycolysis as well as glucose uptake and lactate production.

The current study demonstrated that PRMT5 regulates STS cell metabolism and thus represents a potential therapeutic target for STS. Additional studies in diverse sarcoma subtypes will be essential to confirm and expand upon these findings.
Significance:
STSs have limited therapeutic options. We show here the poor prognostic value of high PRMT5 expression in STS. Moreover, we demonstrate that the pharmacologic inhibition of PRMT5 has significant antitumor activity through the downregulation of glycolysis. Our findings support the clinical investigation of PRMT5 inhibition in STSs.
Sobre o tempo sampleado e o espaço intermedial: pós-produção, vídeo-instalação e The Clock de Christian Marclay
Authors: Bouman Margot
Published: November 2023

Like other postproduction work by contemporary artists and purveyors of popular culture, the videos of artist, musician and composer Christian Marclay use accumulations of cultural data extracted from thousands of films (and television shows) as raw material for the diegesis. What sets Marclay’s installation The Clock (2010) apart from other installations and films in this category is the interrelationship established between its postproduction aesthetic and its specific display conditions. By matching on-screen time with actual time in a carefully designed exhibition context, The Clock simultaneously reifies the psychosomatic transformation of the moviegoer identified by Roland Barthes and dismantles the hermetic nature of the cinematic apparatus. In so doing, Marclay mobilizes latent aspects of video installation to produce new phenomenological experiences and reorganize the relationship between aesthetics and everyday life.
Description of Tobriloides sinensis sp. n. (Nematoda: Triplonchida: Tobrilidae) from Shanxi province, north China
Authors: Yang Gurong , Liu Meina , Ma Yibing , Zhao Zengqi , Wang Jianming , Xu Yumei
Published: November 2023

Tobriloides sinensis sp. n. is described from Shanxi province, China. It is characterised by relatively long body (1620-1935 m), two subventral teeth posterior to dorsal tooth, a short pharynx (b = 4.2-5.0), cardia three times longer than wide (91-98 μm long and 30-37 μm wide), female reproductive system amphidelphic, the vulva situated slightly posterior to mid-body (V = 59.0-69.9), and the tail relatively short (c = 8.4-9.7 and c′ = 4.6-5.7). The phylogenetic relationships of the new species were analysed using data from the near full length small subunit (SSU) and D2-D3 segments of large subunit (LSU) of rRNA genes. The status of T. sinensis sp. n. is discussed based on both morphological and molecular characteristics.
The Gentleman, the Detective, and the Housewife
Authors: Hsiung Hansun
Published: November 2023

This article examines Japanese experiments concerning the power of “thoughtography,” demonstrating how sensory disagreements between psychologists and physicists were concretized through divergent gendered personae within contested spaces of experiment. Specifically, I analyze thoughtography as a story of conflicts between personae of “gentleman” and “detective” within the private, nuclear-familial home of the “housewife.” In the early twentieth century, the psychological laboratory had yet to establish its authority in Japan. Successful experiment thus required visiting subjects and navigating the intersensorial spaces of their homes. The strategies through which researchers adapted to homes, and the strategies by which housewives manipulated homes to their advantage, reveal contestations over how to look, touch, and feel in the presence of others. They furthermore reveal that the drive to emulate “Western science” met with contradictions in “Westernization” itself, particularly between demands concerning new protocols of masculine scholarly sociability and the prerogatives of the bourgeois wife and mother.
Speaking Xhosa multilingually
Authors: Mesthrie Rajend , Mfazwe-Mojapelo Lulu
Published: November 2023

Although code-switching has been quite well studied as a worldwide phenomenon, closer attention to effects on the more localized language involved is needed, especially in the repertoires of younger, well-educated speakers speaking in a multilingual mode. We argue that their language shows creativity going well beyond older instances of borrowing and code-switching into a “third space” grammar, which shows an active and creative synthesis of at least two languages. This study is based on interview data with 37 speakers of Xhosa in Soweto, South Africa. It focuses on (a) the verb suffix -isha as a marker of multilingual Xhosa par excellence, (b) a new lease of life given to the class 14 prefix ubu- in connection with (mainly) Latinate adjectives from English, and (c) the interchangeability of logical connectors across the third space.
Taxonomic review of Thoracostomopsidae (Nematoda, Enoplida): state of the art, list of valid species and dichotomous keys
Authors: SOUZA JOÃO V. DE , MARIA TATIANA F.
Published: November 2023

Thoracostomopsidae is a family of free-living marine nematodes that has three subfamilies (Thoracostomopsinae, Trileptiinae and Enoplolaiminae). Most species descriptions within this family are very old and lack indication of important morphological details, so this article aims to fill this gap in the literature. This taxonomic review provides a list of all valid species, as well as species inquirenda, nomina nuda and synonyms, for each genus. Our review recognizes 16 valid genera, 193 valid species, 47 species inquirendae and three species as nomen nudum. Additionally, taxonomic dichotomous keys were constructed, modified or updated for each genus, as well to the subfamilies, using the most important diagnostic characters.
CHECK LIST OF ARMENIAN APHIDS (HEMIPTERA: APHIDOMORPHA)
Authors: STEPANYAN ILONA , BARJADZE SHALVA , KARAGYAN GAYANE , KALASHIAN MARK
Published: November 2023

This paper presents a checklist of aphids of Armenia. Nowadays, 203 species of aphids belonging to 83 genera, 10 subfamilies, two families and two superfamilies are known, of which nine species are recognized in Armenia for the first time: Aphis cephalariae Barjadze, A. chloris Koch, A. solanella Theobald, A. urticata Gmelin, A. wellensteini (Börner), Brachyunguis harmalae Das, Macrosiphoniella millefolii (De Geer), Microlophium carnosum (Buckton), and Metopeurum buryatica (Pashtshenko). Twelve alien aphid species are cited in the paper.
Diversity of Leptoceroidea (Insecta: Trichoptera) in Pará State, Brazil: A new species of Oecetis McLachlan 1877 and new records
Authors: MOURA LAISSE , QUINTEIRO FÁBIO B.
Published: November 2023

The order Trichoptera contains approximately 17,250 described species and their individuals are important freshwater environment components, frequently used as bioindicators of environmental quality. Despite recent advances in the knowledge of caddisflies in the Neotropical region, there are gaps to be filled, especially in critically endangered biomes, such as the Amazon rainforest, which has its largest area in the North Region of Brazil. In this region of Brazil, the state of Pará presents a promising scenario for biodiversity studies, since a great portion of its area is covered by the Amazon rainforest and distinct environments (e.g., mangroves and rainforest). Knowledge about Trichoptera in the state includes 97 species records, 12 of them belonging to Leptoceroidea. To improve knowledge regarding the Amazon fauna, we record nine species of Leptoceroidea for the first time in Pará State: Marilia alata, Nectopsyche muhni, Nectopsyche multilineata, Oecetis bidigitata, Oecetis cassicoleata, Oecetis doesburgi, Oecetis iguazu, Phylloicus auratus, and Triplectides maranhensis; we also describe and illustrate one new species: Oecetis ancorospina n. sp. which belongs to the Oecetis testacea Species Group.
From Wounds to Scars: The Embodiment of a Forwarded Past through the Body Marks of Jesus in John 20
Authors: Wong Edward
Published: November 2023

This article draws attention to the narrative development of the body marks of the resurrected Johannine Jesus and explores what these marks might signify about John’s reappropriation of Jesus’s suffering. Drawing on the work of Candida R. Moss, who has argued that the resurrection body marks of the Johannine Jesus should be understood as closed scars rather than open wounds, this article re-envisages the implications of Jesus’s textured skin in Jn 20 and examines how John’s gospel mediates and ascribes meaning to Jesus’s body as an inscription surface in response to the crucifixion. By discussing how marked skins serve as privileged facilities to convey meanings and interacting with an exemplary ancient scar narrative from Homer’s Odyssey, I argue that the crucifixion wounds of the Johannine Jesus undergo a narrative transformation in Jn 20 in which the forming of the scars signifies a process of ‘working through’ the trauma and violence of the cross.
The ‘Galilean Q Community’ and the Orientalist Legacy in 2DH Scholarship
Authors: Kirk Alan
Published: November 2023

Contemporary Q scholarship imagines the existence of a ‘Galilean Q Community’ furnished with a simple religious piety standing over against Judean/Jerusalem-centered Judaism with its narrow ethnic particularism, its cult ritualism, and its scribal legalism. The ‘Galilean Q community’ plays the same role vis-à-vis Judean Judaism in the imaginary of contemporary Q scholarship that Sufi Islam does in past and present western Orientalist discourses on Islam: in G. A. Lipton’s words, as embodying ‘a type of philosophical Protestantism freed from all outward prescriptions of religious law’, as an ‘Oriental version of a Kantian universal faith’ over against Islamic orthodoxy, which is Semitic, legalistic, obsessed with Sharia, dogmatic, ritualistic, intolerant, coercive, and politicized. This essay explores the roots of this Orientalist paradigm in nineteenth-century Synoptic source criticism and its continued influence in circles of 2DH scholarship.
Nonverbal social behavior generation for social robots using end-to-end learning
Authors: Ko Woo-Ri , Jang Minsu , Lee Jaeyeon , Kim Jaehong
Published: November 2023

Social robots facilitate improved human–robot interactions through nonverbal behaviors such as handshakes or hugs. However, the traditional methods, which rely on precoded motions, are predictable and can detract from the perception of robots as interactive agents. To address this issue, we have introduced a Seq2Seq-based neural network model that learns social behaviors from human–human interactions in an end-to-end manner. To mitigate the risk of invalid pose sequences during long-term behavior generation, we incorporated a generative adversarial network (GAN). This proposed method was tested using the humanoid robot, Pepper, in a simulated environment. Given the challenges in assessing the success of social behavior generation, we devised novel metrics to quantify the discrepancy between the generated and ground-truth behaviors. Our analysis reveals the impact of different networks on behavior generation performance and compares the efficacy of learning multiple behaviors versus a single behavior. We anticipate that our method will find application in various sectors, including home service, guide, delivery, educational, and virtual robots, thereby enhancing user interaction and enjoyment.
Damage assessment of laminated composites using unsupervised autonomous features
Authors: Khan Asif , Kim Heung Soo
Published: November 2023

This article proposes a framework for the damage assessment of and effect of temperature variations in laminated composites using Lamb waves and unsupervised autonomous features. A network of piezoelectric transducers is employed to generate data for 18 health states of a laminated composite plate. The data is processed with sparse autoencoder (SAE) for unsupervised autonomous features. The discriminative capabilities of the extracted features are confirmed by processing the feature space in the supervised and unsupervised frameworks of machine learning. The confusion matrices of supervised learning provided physical insights into the problem. The feature space was also visualized in two dimensions in an unsupervised manner through principal component analysis (PCA), which revealed physically consistent results for the effect of temperature variations, damage of different severity levels, and the undamaged paths between the actuator and sensors. The healthy state data and information on the paths between the actuator and sensors was processed via SAE for damage localization. The proposed approach can be employed for the autonomous assessment of composite structures for the presence of damage and variations of operating temperatures while using both supervised and unsupervised machine learning algorithms.
Representations of mental health and mental health problems in content published by female social media influencers
Authors: Lind Judith , Wickström Anette
Published: November 2023

When social media influencers (SMIs) describe their experiences of mental health problems, they contribute to the circulation of representations of mental health. The aim of this article is to analyse the ways of talking about mental health problems that are made accessible to a wider audience through the YouTube videos published by four Swedish female SMIs. Our analysis shows that much content related to mental health contains traces of, and contributes to discourses informed by, positive psychology. Mostly, mental health problems are represented as manageable, if only the individual assumes responsibility for her mental wellbeing, but a few videos also contain displays of negativity and resignation. In addition to avoiding association with the unattractiveness associated with negativity, the four SMIs navigate expectations placed on them to encourage confidence and self-love while at the same time expressing modesty. The result is representations of mental health that are multi-layered and complex.