bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S8 from TREM2-Expressing Multinucleated Giant Macrophages Are a Biomarker of Good Prognosis in Head and Neck Squamous Cell Carcinoma
Authors: Gessain Grégoire , Anzali Ahmed-Amine , Lerousseau Marvin , Mulder Kevin , Bied Mathilde , Auperin Anne , Stockholm Daniel , Signolle Nicolas , Sassi Farah , Marques Da Costa Maria Eugenia , Marchais Antonin , Sayadi Alexandre , Weidner Daniela , Uderhardt Stefan , Blampey Quentin , Nakkireddy Sumanth Reddy , Broutin Sophie , Dutertre Charles-Antoine , Busson Pierre , Walter Thomas , Marhic Alix , Moya-Plana Antoine , Guerlain Johanne , Breuskin Ingrid , Casiraghi Odile , Gorphe Philippe , Classe Marion , Scoazec Jean-Yves , Blériot Camille , Ginhoux Florent
Published: December 2024

CosMx protein panel showing stainings in MGC
Supplementary Table 2 from TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer
Authors: Kortleve Dian , Hammerl Dora , van Brakel Mandy , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke M. , Liao Chen-Yi , Huang Shaozhuo , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique T.A. , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W.M. , Abbott Rachel J.M. , Debets Reno
Published: December 2024

ROPN1/B peptides identified with immunopeptidomics.
Supplementary Figure 9 from TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer
Authors: Kortleve Dian , Hammerl Dora , van Brakel Mandy , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke M. , Liao Chen-Yi , Huang Shaozhuo , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique T.A. , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W.M. , Abbott Rachel J.M. , Debets Reno
Published: December 2024

Presence of ROPN1 and FLY-1A TCRβ in metastatic TNBC in relation to endogenous T cell phenotype and anti-PD1 response.
Supplementary Figure 5 from TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer
Authors: Kortleve Dian , Hammerl Dora , van Brakel Mandy , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke M. , Liao Chen-Yi , Huang Shaozhuo , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique T.A. , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W.M. , Abbott Rachel J.M. , Debets Reno
Published: December 2024

Extended phenotypes of intra-tumoral and peripheral T-cells following adoptive transfer of FLY-1A TCR T cells.
Figure S4 from Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells
Authors: Grossmann Liron D. , Chen Chia-Hui , Uzun Yasin , Thadi Anusha , Wolpaw Adam J. , Louault Kevin , Goldstein Yael , Surrey Lea F. , Martinez Daniel , Calafatti Matteo , Gerelus Mark , Gao Peng , Lee Lobin , Patel Khushbu , Kaufman Rebecca S. , Shani Guy , Farrel Alvin , Moshitch-Moshkovitz Sharon , Grimaldi Paris , Shapiro Matthew , Kendsersky Nathan M. , Lindsay Jarrett M. , Casey Colleen E. , Krytska Kateryna , Scolaro Laura , Tsang Matthew , Groff David , Matkar Smita , Kalna Josh R. , Mycek Emily , McDevitt Jayne , Runbeck Erin , Patel Tasleema , Bernt Kathrin M. , Asgharzadeh Shahab , DeClerck Yves A. , Mossé Yael P. , Tan Kai , Maris John M.
Published: December 2024

Supplementary Figure S4 differences in persister cell composition between diagnosis and definitive surgery as well as decrease in MYC/N protein level in human samples, PDX and cell lines following chemotherapy
Data from MARK2/MARK3 Kinases Are Catalytic Codependencies of YAP/TAZ in Human Cancer
Authors: Klingbeil Olaf , Skopelitis Damianos , Tonelli Claudia , Yoshimoto Toyoki , Alpsoy Aktan , Panepinto Maria C. , Minicozzi Francesca , Merrill Joseph R. , Cafiero Amanda M. , Aggarwal Disha , Russo Suzanne , Ha Taehoon , Demerdash Osama E. , Wee Tse-Luen , Spector David L. , Lyons Scott K. , Tuveson David A. , Cifani Paolo , Vakoc Christopher R.
Published: December 2024

Abstract
The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. In this study, we used paralog cotargeting CRISPR screens to identify kinases MARK2/3 as absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts. Underlying this observation is the direct MARK2/3-dependent phosphorylation of NF2 and YAP/TAZ, which effectively reverses the tumor suppressive activity of the Hippo module kinases LATS1/2. To simulate targeting of MARK2/3, we adapted the CagA protein from Helicobacter pylori as a catalytic inhibitor of MARK2/3, which we show can regress established tumors in vivo. Together, these findings reveal MARK2/3 as powerful codependencies of YAP/TAZ in human cancer, targets that may allow for pharmacology that restores Hippo pathway–mediated tumor suppression.

Significance: We show how genetic redundancy conceals tight functional relationships between signaling and transcriptional activation in cancer. Blocking the function of MARK2/3 kinases leads to the reactivation of the Hippo tumor suppressive pathway and may have therapeutic potential in YAP/TAZ-dysregulated carcinomas and sarcomas.

See related commentary by Gauthier-Coles and Sheltzer, p. 2312
Data from NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations
Authors: Lin Jessica J. , Horan Joshua C. , Tangpeerachaikul Anupong , Swalduz Aurélie , Valdivia Augusto , Johnson Melissa L. , Besse Benjamin , Camidge D. Ross , Fujino Toshio , Yoda Satoshi , Nguyen-Phuong Linh , Mizuta Hayato , Bigot Ludovic , Nobre Catline , Lee Jii Bum , Yu Mi Ra , Mente Scot , Sun Yuting , Kohl Nancy E. , Porter James R. , Shair Matthew D. , Zhu Viola W. , Felip Enriqueta , Cho Byoung Chul , Friboulet Luc , Hata Aaron N. , Pelish Henry E. , Drilon Alexander
Published: December 2024

Abstract
Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion–positive non–small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested. In vitro, NVL-655 inhibits diverse ALK fusions, activating alterations, and resistance mutations, showing ≥100-fold improved potency against ALKG1202R single and compound mutations over approved ALK TKIs. In vivo, it induces regression across 12 tumor models, including intracranial and patient-derived xenografts. NVL-655 inhibits ALK over TRK with 22-fold to >874-fold selectivity. These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion–positive non–small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations.

Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers.
Supplementary Table 1 from Dynamic Evolution of Fibroblasts Revealed by Single-Cell RNA Sequencing of Human Pancreatic Cancer
Authors: Dimitrieva Slavica , Harrison Jon M. , Chang Jonathan , Piquet Michelle , Mino-Kenudson Mari , Gabriel Millicent , Sagar Vivek , Horn Heiko , Lage Kasper , Kim Julie , Li Gang , Weng Shaobu , Harris Cynthia , Kulkarni Anupriya S. , Ting David T. , Qadan Motaz , Fagenholz Peter J. , Ferrone Cristina R. , Grauel Angelo L. , Laszewski Tyler , Raza Alina , Riester Markus , Somerville Tim , Wagner Joel P. , Dranoff Glenn , Engelman Jeffrey A. , Kauffmann Audrey , Leary Rebecca , Warshaw Andrew L. , Lillemoe Keith D. , Fernández-del Castillo Carlos , Ruddy David A. , Liss Andrew S. , Cremasco Viviana
Published: December 2024

Supplementary Table 1
Identification of Gene Candidates in Diterpenoid Biosynthesis of Curcuma longa: An mRNA Sequencing Approach
Authors: Fadhullah Hafizh , Purwoko Devit , Zulaeha Siti , Hanifah Nurul Fitri , Hartuti Endah Dwi , Rahmadara Gemilang , Safarrida Anna , Reninta Rikania , Evawati Evawati , Roza Irwan , Tajuddin Teuku
Published: December 2024

Curcuma longa is a medicinal plant renowned for its therapeutic properties and potential treatment of cancer. This study focused on the biosynthesis of diterpenoids in the rhizome and leaves of C. longa. The genes responsible for producing these medicinal compounds were analyzed using BLASTx, Gene Ontology (GO) annotation, differential expression, and homology. The substantial dataset was obtained from the National Center for Biotechnology Information (NCBI), comprising 151,730,334 clean reads and 167,264 transcripts for the analysis. The results of the BLASTx analysis were as follows: NR yielded 65.93%, Swiss-Prot yielded 44.52%, and COG yielded 17.35%. Subsequently, GO annotation was performed using Blast2GO, resulting in an annotation rate of 56.79%. Differential expression analysis revealed a total of 636 genes that were significantly differentiated between the rhizome and leaves. The homology analysis resulted in 11 proteins associated with diterpenoid biosynthesis and nine proteins related to CYP450. Approximately three class I proteins were highly expressed in the rhizome. Additionally, seven CYP450 enzymes from the CYP71D and CYP726 subfamilies were identified; three were highly expressed in the rhizome. The expression patterns of these enzymes were similar to the aforementioned three class I diTPSs, indicating their potential involvement in macroditerpenoid biosynthesis in C. longa. These findings provide valuable genomic resources for future functional genomics research on C. longa, facilitating targeted efforts to enhance the production of bioactive compounds.
In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development
Authors: Lindner Jonathan R. , Morello Matteo
Published: December 2024

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.
Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus
Authors: Fekete Éva M. , Gomez Javier , Ghobrial Mina , Kaminski Kathren , Muskus Patricia C. , Boychuk Carie R. , Hantke Guixa Ana , Vazirabad Ibrahim , Xie Michelle , Ganiyu Azeez , Golosova Daria , Mathieu Natalia M. , Wang Yoko B. , Lu Ko-Ting , Wackman Kelsey K. , Brozoski Daniel T. , Mouradian Gary C. , Hodges Matthew R. , Segar Jeffrey L. , Grobe Justin L. , Sigmund Curt D. , Nakagawa Pablo
Published: December 2024

BACKGROUND:

The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.

METHODS:

Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.

RESULTS:

We identified novel renin-expressing cholinergic neurons in the nucleus ambiguus (NuAm), a major vagal cardioinhibitory center in the brainstem. The expression of renin-angiotensin system genes was relatively abundant in the NuAm, implying that angiotensin II might mediate an important regulatory role in this nucleus and other regions with neural connectivity to the NuAm. Then, we generated conditional knockout mice lacking the classical renin isoform (Ren-a
ChAT-KO
), specifically in cholinergic neurons. Ablation of Ren-a in cholinergic neurons abrogated renin expression in the NuAm. Moreover, studies using radiotelemetry, heart rate variability analyses, and pharmacological approaches revealed that the parasympathetic nervous system is depressed in Ren-a
ChAT-KO
males while augmented in the Ren-a
ChAT-KO
females. Subsequently, transcriptomic approaches were used to infer putative genes and signaling pathways regulated by renin within the NuAm.

CONCLUSIONS:

This study revealed that renin in cholinergic neurons plays a fundamental role in preserving autonomic balance and cardiovascular homeostasis in a sex-dependent manner. These findings define the NuAm as an endogenous, local source of renin with biological function and serve as conclusive evidence for the presence and functionality of the brain renin-angiotensin system.
Neural Correlates of Different Randomization Tasks
Authors: Guseva Maja , Bogler Carsten , Allefeld Carsten , Ziya Ece Büşra , Haynes John-Dylan
Published: December 2024

In some cases, when we are making decisions, the available choices can appear to be equivalent. When this happens, our choices appear not to be constrained by external factors and, instead, we can believe to be selecting “randomly.” Furthermore, randomness is sometimes even explicitly required by task conditions such as in random sequence generation tasks. This is a challenging task that involves the coordination of multiple cognitive processes, which can include the inhibition of habitual choice patterns and monitoring of the running choice sequence. It has been shown that random choices are strongly influenced by the way they are instructed. This raises the question whether the brain mechanisms underlying random selection also differ between different task instructions. To assess this, we measured brain activity while participants were engaging in three different variations of a sequence generation task: On the basis of previous work, participants were instructed to either (1) “generate a random sequence of choices,” (2) “simulate a fair coin toss,” or (3) “choose freely.” Our results reveal a consistent frontoparietal activation pattern that is shared across all tasks. Specifically, increased activity was observed in bilateral inferior and right middle frontal gyrus, left pre-SMA, bilateral inferior parietal lobules, and portions of anterior insular cortex in both hemispheres. Activity in the mental coin toss condition was higher in right dorsolateral prefrontal cortex, left (pre-) SMA, a portion of right inferior frontal gyrus, bilateral superior parietal lobules, and bilateral anterior insula. In addition, our multivariate analysis revealed a distinct region in the right frontal pole to be predictive of the outcome of choices, but only when randomness was explicitly instructed. These results emphasize that different randomization tasks involve both shared and unique neural mechanisms. Thus, even seemingly similar randomization behavior can be produced by different neural pathways.
On the Compressive Power of Autoencoders With Linear and ReLU Activation Functions
Authors: Sun Liangjie , Wu Chenyao , Ching Wai-Ki , Akutsu Tatsuya
Published: December 2024

In this article, we mainly study the depth and width of autoencoders consisting of rectified linear unit (ReLU) activation functions. An autoencoder is a layered neural network consisting of an encoder, which compresses an input vector to a lower-dimensional vector, and a decoder, which transforms the low-dimensional vector back to the original input vector exactly (or approximately). In a previous study, Melkman et al. (2023) studied the depth and width of autoencoders using linear threshold activation functions with binary input and output vectors. We show that similar theoretical results hold if autoencoders using ReLU activation functions with real input and output vectors are used. Furthermore, we show that it is possible to compress input vectors to one-dimensional vectors using ReLU activation functions, although the size of compressed vectors is trivially Ω(log n) for autoencoders with linear threshold activation functions, where n is the number of input vectors. We also study the cases of linear activation functions. The results suggest that the compressive power of autoencoders using linear activation functions is considerably limited compared with those using ReLU activation functions.
Functional brain networks predicting sustained attention are not specific to perceptual modality
Authors: Corriveau Anna , Ke Jin , Terashima Hiroki , Kondo Hirohito M. , Rosenberg Monica D.
Published: December 2024

Sustained attention is essential for daily life and can be directed to information from different perceptual modalities, including audition and vision. Recently, cognitive neuroscience has aimed to identify neural predictors of behavior that generalize across datasets. Prior work has shown strong generalization of models trained to predict individual differences in sustained attention performance from patterns of fMRI functional connectivity. However, it is an open question whether predictions of sustained attention are specific to the perceptual modality in which they are trained. In the current study, we test whether connectome-based models predict performance on attention tasks performed in different modalities. We show first that a predefined network trained to predict adults’ visual sustained attention performance generalizes to predict auditory sustained attention performance in three independent datasets (N1 = 29, N2 = 60, N3 = 17). Next, we train new network models to predict performance on visual and auditory attention tasks separately. We find that functional networks are largely modality general, with both model-unique and shared model features predicting sustained attention performance in independent datasets regardless of task modality. Results support the supposition that visual and auditory sustained attention rely on shared neural mechanisms and demonstrate robust generalizability of whole-brain functional network models of sustained attention.
Individualized mouse brain network models produce asymmetric patterns of functional connectivity after simulated traumatic injury
Authors: Rayfield Adam C. , Wu Taotao , Rifkin Jared A. , Meaney David F.
Published: December 2024

The functional and cognitive effects of traumatic brain injury (TBI) are poorly understood, as even mild injuries (concussion) can lead to long-lasting, untreatable symptoms. Simplified brain dynamics models may help researchers better understand the relationship between brain injury patterns and functional outcomes. Properly developed, these computational models provide an approach to investigate the effects of both computational and in vivo injury on simulated dynamics and cognitive function, respectively, for model organisms. In this study, we apply the Kuramoto model and an existing mesoscale mouse brain structural network to develop a simplified computational model of mouse brain dynamics. We explore how to optimize our initial model to predict existing mouse brain functional connectivity collected from mice under various anesthetic protocols. Finally, to determine how strongly the changes in our optimized models’ dynamics can predict the extent of a brain injury, we investigate how our simulations respond to varying levels of structural network damage. Results predict a mixture of hypo- and hyperconnectivity after experimental TBI, similar to results in TBI survivors, and also suggest a compensatory remodeling of connections that may have an impact on functional outcomes after TBI.
Dynamic brain states underlying advanced concentrative absorption meditation: A 7-T fMRI-intensive case study
Authors: Treves Isaac N. , Yang Winson F. Z. , Sparby Terje , Sacchet Matthew D.
Published: December 2024

Advanced meditation consists of states and stages of practice that unfold with mastery and time. Dynamic functional connectivity (DFC) analysis of fMRI could identify brain states underlying advanced meditation. We conducted an intensive DFC case study of a meditator who completed 27 runs of jhāna advanced absorptive concentration meditation (ACAM-J), concurrently with 7-T fMRI and phenomenological reporting. We identified three brain states that marked differences between ACAM-J and nonmeditative control conditions. These states were characterized as a DMN-anticorrelated brain state, a hyperconnected brain state, and a sparsely connected brain state. Our analyses indicate higher prevalence of the DMN-anticorrelated brain state during ACAM-J than control states, and the prevalence increased significantly with deeper ACAM-J states. The hyperconnected brain state was also more common during ACAM-J and was characterized by elevated thalamocortical connectivity and somatomotor network connectivity. The hyperconnected brain state significantly decreased over the course of ACAM-J, associating with self-reports of wider attention and diminished physical sensations. This brain state may be related to sensory awareness. Advanced meditators have developed well-honed abilities to move in and out of different altered states of consciousness, and this study provides initial evidence that functional neuroimaging can objectively track their dynamics.
THE EDITOR’S NOTE: Math, mindset, and identity
Authors: Preston Teresa
Published: December 2024

Kappan editor-in-chief Teresa Preston reflects on common perceptions about math, developing a math identity, and the math education students need, as discussed in the December 2024/January 2025 issue of Kappan.
Building thinking classrooms in mathematics: A conversation with Peter Liljedahl
Authors: Vail Kathleen
Published: December 2024

Peter Liljedahl, a professor of education at Simon Fraser University in British Columbia, studied math classrooms and students for 15 years. His book, Building Thinking Classrooms in Mathematics, Grades K-12: 14 Teaching Practices for Enhancing Learning, is the result of that research. He found that by disrupting the norms of the classroom – having students work in small, randomized groups at vertical whiteboards or other erasable surface – students are more engaged and more likely to think, not simply mimic back what the teacher is saying.
The utility of homomorphism concepts in simulation: building families of models from base-lumped model pairs
Authors: Zeigler Bernard P , Koertje Christian , Zanni Cole
Published: December 2024

In this tutorial review paper we explain the concept of homomorphism and identify some principles that justify homomorphism construction based on the homogeneity of structure and coupling in systems with multiple components. We discuss some simple examples to show how these underlying justifying conditions can arise. Examples include brain simulation, combat attrition, and the greatly reduced computational complexity represented by Pascal’s triangle. Homomorphism is also shown to be fundamental for constructing approximate low-resolution models. Models that simplify complex time-demanding simulation models are often used as surrogate or metamodels in system optimization. However, such models are fitted typically to computationally derived response surfaces and not structurally related directly to the originals using homomorphisms as described here. Along these lines, we show how homomorphism plays an essential role in a novel approach being developed to strongly control tree expansion in state space explorations of stochastic system simulation.
Pope Francis, Dignitas Infinita, and an Evolving Catholic Anthropology: Doctrinal Implications
Authors: Salzman Todd A. , Lawler Michael G.
Published: December 2024

Dignitas Infinita highlights “the indispensable nature of the dignity of the human person in Christian anthropology” and warns of “ambivalent ways in which the concept is understood today.” Among those “ambivalent ways” are plural definitions of human dignity in official Catholic teaching. There is ambivalence in definitions of Catholic sexual human dignity and Catholic social human dignity, which lead to inconsistencies in the foundation and justification of moral doctrine. In this article, we first present Catholic definitions of social and sexual human dignity. Second, we explain Pope Francis’s anthropological nuances that provide an alternative definition of human dignity, which we label holistic human dignity. Third, we evaluate and describe the harm deriving from statements in the document and by Pope Francis, a harm that results from inconsistent definitions of human dignity in doctrinal teaching.
Multiple Imputation for Systematically Missing Partner Variables in Survey Data
Authors: Haensch Anna-Carolina , Schunck Reinhard
Published: December 2024

Systematically missing information on secondary respondents is a frequent problem in multiactor surveys. Budget and time constraints often prevent all variables collected for primary respondents (e.g., anchors) from being collected for secondary respondents (e.g., partners). Thus, a subset of variables are systematically missing for secondary respondents. This can severely limit the analysis potential of multiactor data, ruling out all research questions that would require (the same) information on primary and secondary respondents. The problem of systematically missing data is also present in other settings, for example, after changes in measurement instruments in repeated surveys or in ex post survey harmonization if one or more surveys did not include a specific variable. In these cases, using multiple imputation (MI) techniques to impute the missing variables is a common approach. The authors explore whether MI can be used when data on secondary respondents are systematically missing. Results from simulation studies show that imputation under the assumption of conditional independence for primary and secondary respondents variables leads to a strong bias toward zero in the estimated partial correlation between primary and secondary respondents. However, external data in the form of bridging studies can be used to estimate the partial correlation between the observed variable for the primary and the unobserved variable for the secondary respondent, leading to estimates with less bias after MI.
Reducing Behavioral Problems and Treatment Duration of Adolescents in Secure Residential Care: A Multiple Single-Case Experimental Design Study
Authors: Gutterswijk Raymond V. , Kuiper Chris H. Z. , Harder Annemiek T. , van der Horst Frank C. P. , Bocanegra Bruno R. , Prinzie Peter
Published: December 2024

Secure residential care (SRC) is criticized for several reasons. Therefore, in many countries, the general policy is to limit the length of stay of adolescents in SRC. However, research on length of stay and treatment effects of SRC on adolescents’ behavioral problems is sparse. Using single case experimental designs with time-series, forty adolescents referred to SRC completed a questionnaire on behavioral and attention problems every two weeks during a baseline (A) and treatment period (B). Two-level regression analyses were used to investigate the effects of SRC on behavioral and attention problems. In addition, we tested whether length of stay moderated effectiveness. On the individual level, the treatment showed a positive statistically significant effect on the behavioral problems of 0%–8% of the adolescents and a statistically significant negative effect on behavioral problems was found in 3%–10% of the adolescents. On the group level, adolescents showed no significant decrease in problem behavior or attention problems from baseline to discharge. Length of stay did not moderate the results. Based on the results we conclude that most adolescents fail to improve. In addition, length of stay was not associated with effectiveness, nor could it be explained by adolescents’ characteristics.
Justice and Personality: A Promissory Note
Authors: Ronell Avital
Published: December 2024

Drucilla Cornell located her work and alliances at contested borders of exchange, translation, prickly political showdowns, gender affiliation, and inherited jointures of enmity. Cornell made us think about what it means to live in America today, meaning yesterday and today, ceding to the destructive pull of a national death drive and the repeal of rights to which women and minorities never cease being susceptible. Her work “asks and answers” the question about the structural ground rules that make the rollback of rights inevitable, legally riding out a destiny on an exhausting loop with the dreary fatalism of Sisyphus, a relentless paring down of legal protection rigged to attack a determined portion of our citizenry, arriving not merely from a whim of a demented few. Though her analyses went to worldwide theaters of injustice, her grip was firmly on the United States and its regressive judiciary as well as legislative behaviors regarding reproductive restriction, voting rights, and specific axioms of civil rights. Her analyses saw us as structurally faltering—as being ever on the brink of losing acquired rights, a predicament that creates a political psychology of despairing repetition compulsion, promoting an inescapable losing streak, even when one pauses to “win” a few rounds and reshuffle gendered cards. Cornell understood an American civic tic that bore fatal consequences, given full view in the murder she and her cohorts mourn when wringing out their poignant contemplation of the destruction of Mary Joe Frug. Some of her strongest work on the injustices routinely dealt to women, mothers, and their allies comes forward as a tribute and an attribute of mourning, as tributary honoring. The grief she expressed over loss of rights, intimately bound up with loss of life, drives her North American passion. She kept her lynx eye on murderous habits that were sublimated to law and remain part of a sweeping exclusionary civic operation that won’t let up, going after minute corners and work spaces. To get a running start, she took her cues from Kant through Heidegger and Levinas when making critical assessments. They rode with elements of built-in racisms, a feature of philosophical inheritability and arrogant metaphysical say-so with which they each grappled, if, in some instances, testing posited limits to failure. This failure is our inheritance, still apportioning the cards we were dealt.
The mechanical behavior and deformation mode of multilayer composite structures based on triply periodic minimal surface elements
Authors: Liu Erqiang , Lv Yufeng , Hao Xin , Wang Yu , Xiao Gesheng , Lin Jinbao
Published: December 2024

In this paper, the mechanical behavior and compression deformation mode of three types of composite multilayer structures based on triply periodic minimal surfaces (TPMS) were conducted through experiments and finite element analysis. The results indicate that the load-displacement curves under varying stain rates manifest a double-platform characteristic for all three structure types. The P-G four-layer structure and P-G six-layer structure have no discernible extrusion of the structural layers during compression, and the entirety of the structure displays an almost regular cubic configuration after compression. Nevertheless, local separation was observed in the extruded portion of the P-H six-layer structure after the structural deformation at higher strain rates. For the other conditions, the structure exhibited a bulge but did not display any local detachment or separation phenomena. During the deformation of the P-H six-layer structure, a dome-shaped region emerges in the first and fifth layers. The “crown” layer displays an inverted bell-shaped failure mode for the first layer structure, exhibiting downward extrusion. In contrast, the fifth layer structure displays an upward extrusion and exhibits a bell-shaped failure mode. The P-H 6-layer structure has the best energy absorption performance under quasistatic compression conditions for the P-G 4-layer, P-G 6-layer and P-H 6-layer structure. However, the energy absorption performance of the identical structure remains largely consistent across varying strain rate conditions.
Perioperative real-life experiences and care needs of patients undergoing lung cancer ablation: A qualitative study
Authors: Huang Lihua , Pan Xiaojun , Li Jing , Zhang Hui , Mao Yanjun
Published: December 2024

Objective

To gain an in-depth understanding of the perioperative real experiences and care needs of patients undergoing lung cancer ablation, to make a reliable basis for the construction of care programs for perioperative complications of lung cancer ablation, and to further improve the quality of perioperative clinical care interventions for such patients.

Methods

Sixteen lung cancer patients undergoing lung cancer ablation who were hospitalized in the Department of Oncology of our hospital from April 2023 to October 2023 as well as six healthcare professionals of Shanghai Pulmonary Hospital were recruited by purposive sampling. Semi-structured interviews were conducted with the enrolled individuals by using a phenomenological approach, and the Colaizzi's 7-step analysis method was used to analyze, summarize and refine the themes of the interview data.

Results

A total of seven study themes were identified emotional reactions of ablation patients, financial stress, needs for information on treatment outcomes and health education during recovery, reassurance of living and care needs during hospitalization, concerns about the treatment of complications, correct and detailed preoperative assessment, and doctor-nurse collaboration for good management of patient complications.

Conclusion

In the clinical nursing of patients with lung cancer, we should construct standardized perioperative ablation nursing process as soon as possible, create diversified health guidance materials, strengthen the continuity of nursing after discharge, improve patients’ understanding of the disease, pay attention to their emotional changes, and provide more maintenance support, so as to reduce complications and improve the quality of life of patients with lung cancer ablation.
Personal Narratives From a Mental Health Community Art-Based Project: Insights From Collaborative Creation
Authors: Cases-Cunillera Jaume , del Río Sáez Ruben , Simó-Algado Salvador
Published: December 2024

Community arts interventions demonstrate positive effects on mental health recovery by fostering creativity, self-expression, and social interaction. This study explores the participation process in the Artistic Couples project, which provides collaborative spaces for artists with mental health conditions and local artists. We followed up six artistic couples participating in the project using a narrative-in-action process over 6 months in various community settings. Our aim was to understand the experiences of artists during their participation in Artistic Couples and to uncover the mental health benefits derived from their involvement. Coupled and individually semi-structured interviews and participant observation were employed. Data analysis was conducted using narrative analysis. The results of the collaborative process among participants are reflected in three primary areas: (1) Meeting, engagement, and connection; (2) Dialogue, teamwork, and creative process; and (3) Personal development and learning. The research findings suggest that participating in the Artistic Couples project facilitates self-expression, a sense of social connection, and improved artistic skills among participants, fostering mutual support and effective interpersonal communication. Moreover, participants reported experiences of learning and personal development. Consequently, the study advocates for creating new community spaces that encourage collaborative practices within mental health services. These spaces should promote free expression and facilitate discussions on personal matters, including mental health challenges.
Safety, efficacy, and tolerability of alemtuzumab in pediatric patients with active relapsing-remitting multiple sclerosis: The LemKids study
Authors: Chitnis Tanuja , Arnold Douglas L , Quartier Pierre , Chirieac Magdalena , Hu Wenruo , Jurgensen Stephanie , Havrdova Eva K
Published: December 2024

Background:

Limited licensed medications are available for multiple sclerosis (MS) in pediatric patients.

Objective:

To evaluate the efficacy, safety, and tolerability of alemtuzumab in pediatric patients with relapsing-remitting multiple sclerosis (RRMS) and disease activity on prior disease-modifying therapies (DMTs).

Methods:

LemKids was a multicenter, multinational, single-arm, open-label, switch (from ongoing DMT to alemtuzumab treatment) study in pediatric RRMS patients (aged 10–<18 years), with disease activity on DMT. The primary endpoint was a comparison of the number of new/enlarging T2 lesions on the magnetic resonance imaging of the brain between the prior-DMT period and alemtuzumab treatment.

Results:

This study was prematurely terminated due to low enrollment and an European Medicines Agency Article-20 pharmacovigilance review of alemtuzumab in adult RRMS. Of 46 screened patients, 16 were enrolled; 12 completed prior-DMT treatment period; 11 received alemtuzumab of whom 7 completed treatment. Patients on alemtuzumab developed fewer new/enlarging T2 lesions compared with prior-DMT (7 vs 178, relative risk (95% confidence interval): 0.04 (0.01-0.14)). No significant pharmacodynamic changes or safety concerns were noted in this limited dataset.

Conclusion:

Alemtuzumab treatment was associated with a low number of new/enlarging T2 lesions in pediatric patients with RRMS and was safe and well tolerated in seven patients during infusion and the initial 4 months.
Characteristics of spatial and temporal distribution of carbon emissions and influencing factors in Hefei City based on nighttime lighting data
Authors: Du Yipin , Su Wenshan , Wang Wei
Published: December 2024

Urban areas are significant contributors to global carbon emissions. Investigating the spatiotemporal distribution characteristics of urban carbon emissions and their influencing factors is essential for formulating effective carbon reduction policies and enhancing urban environmental quality. This study utilized nighttime light data to analyse the spatiotemporal distribution of carbon emissions in Hefei City. We employed a Random Forest regression model to explore the impact of urban spatial morphology on carbon emissions. The findings indicated that carbon emissions in Hefei have shown a consistent annual increase without a clear spatial pattern. Regression analysis revealed a nonlinear positive correlation between carbon emissions and factors such as floor area ratio, building density, architectural volume and staggered degree. Conversely, the body mass index and enclosure factor demonstrated a nonlinear negative correlation with carbon emissions. Amongst them, the body mass index was shown to have the highest impact weight on urban carbon emission, which was 0.195, followed by architectural volume and floor area ratio, which were 0.155 and 0.145, respectively. This research highlights the complex influence of urban spatial morphology on carbon emissions and provides valuable insights for the development of urban carbon reduction strategies.
P2RX7, an adaptive immune response gene, is associated with Parkinson's disease risk and age at onset
Authors: Shani Shachar , Gana-Weisz Mali , Bar-Shira Anat , Thaler Avner , Gurevich Tanya , Mirelman Anat , Giladi Nir , Alcalay Roy N. , Orr-Urtreger Avi , Goldstein Orly
Published: December 2024

Background

The adaptive immune response has a role in Parkinson's disease (PD). Patients with LRRK2 or GBA1 mutations often exhibit distinct clinical characteristics.

Objective

To evaluate the involvement of adaptive immune response genes in three PD groups: GBA1-PD, LRRK2-PD, and non-carrier (NC)-PD.

Methods

Differentially expressed genes (DEGs) associated with PD were identified using four datasets. Of them, adaptive immune response genes were evaluated using whole-genome-sequencing of 201 unrelated Ashkenazi-Jewish (AJ) PD patients. Potential pathogenic variants were identified, and P2RX7 variants were assessed in 1200 AJ-PD patients. Burden analysis of rare variants (allele frequencies (AF) < 0.01) on disease risk, and association analyses of common variants (AF ≥ 0.01) with disease risk and age-at-onset (AAO) were conducted. AFs were compared to AJ-non-neuro cases reported in gnomAD. Variants associated with PD were further examined in an independent AJ cohort from AMP-PD.

Results

Of the four adaptive immune DEGs identified, CD8B2, P2RX7, IL27RA, and ZC3H12A, three common variants in P2RX7 were statistically significant: Tyr155His was associated with NC-PD (allelic OR = 1.15, p = 0.015) ; Arg276His was associated with LRRK2-PD (allelic OR = 2.10, p = 0.037), while Glu496Ala was associated with earlier AAO in LRRK2-PD ( p = 0.014). Burden analysis showed no significant effect on PD-risk. In the AMP-PD cohort, odds ratios of the two risk variants were similar to the primary cohort, but did not reach significance, probably due to small control sample size (n = 263).

Conclusions

Common variants within P2RX7 are likely associated with PD-risk and earlier AAO. These findings further suggest P2RX7's involvement in PD and its potential interplay with LRRK2.
Anterior Cruciate Ligament Reconstruction in Patients Older Than 50 Years: A Descriptive Study With Minimum 10-Year Follow-up
Authors: Micicoi Grégoire , Fairag Rayan , Machado Axel , Douiri Adil , Bronsard Nicolas , Ernat Justin , Gonzalez Jean-François
Published: December 2024

Background:

Anterior cruciate ligament (ACL) reconstruction is increasingly being performed in patients >50 years old; however, the long-term outcomes are unclear.

Purpose:

To analyze the functional results, osteoarthritic progression, reoperation rate, and failure rate at minimum 10-year follow-up in patients >50 years old who have undergone primary ACL reconstruction.

Study Design:

Case series; Level of evidence, 4.

Methods:

Included in this study were patients >50 years old who underwent primary ACL reconstruction and had at least 10 years of follow-up data. All patients had instability with limitation of their activities, indicating the necessity of surgical intervention. Patients with revision surgeries, ACL repairs, and nonoperative treatment were excluded. Failure was defined as the presence of revision, high-grade Lachman, positive pivot shift (2+), or subjective instability. The Knee injury and Osteoarthritis Outcome Score (KOOS), subjective and objective functional scores, and osteoarthritic progression were analyzed at final follow-up.

Results:

A total of 38 patients were identified. The mean age at surgery was 56.8 ± 5.7 years (range, 50.6-70 years). The mean clinical follow-up was 16.2 ± 4.3 years (range, 10.9-23.3 years). The failure rate was 10.5% (4/38): 1 of the 4 patients had a recurrence of instability at 13 years postoperatively and underwent revision with a modified Lemaire extra-articular tenodesis, 1 patient had a positive pivot shift (2+) without subjective instability, and 2 patients underwent total knee arthroplasty. The overall KOOS was 74.2 ± 22.2, and 91.4% of patients were satisfied or very satisfied with the results of the procedure. Radiographic osteoarthritis was identified in 88.5% of patients at final follow-up; however, there was no statistical significance on clinical outcomes ( P > .05). Concomitant partial medial meniscectomy ( P < .01) and meniscal repair ( P < .01) were associated with the presence of Ahlbäck grade 3 or 4 osteoarthritic manifestations.

Conclusion:

In patients over the age of 50 years who underwent primary ACL reconstruction, there was a low long-term failure rate and a high level of patient satisfaction, despite osteoarthritic progression in 88.5% of cases. Concomitant meniscal procedures were associated with more severe osteoarthritic progression.
Von Hippel Lindau syndrome: A systematic review of pharmaceutical treatments
Authors: Galarza Fortuna Gliceida M , Ozay Zeynep Irem , Hage Chehade Chadi , Gebrael Georges , Li Haoran , Maughan Benjamin L
Published: December 2024

Background

Patients with von Hippel-Lindau syndrome (VHL) have an increased risk of developing multiple neoplasms. Recently, multiple pharmacologic interventions have been assessed for the treatment of these VHL-associated neoplasms.

Objectives

To identify current clinical trials evaluating pharmacological interventions in VHL-associated neoplasms, with an emphasis in renal cell carcinoma (RCC).

Methods

We conducted a systematic review of the literature utilising MEDLINE/PubMed and EMBASE databases. We searched for Clinical Trials in VHL and RCC to understand the current landscape of therapeutic interventions in this population.

Results

We identified five single-arms clinical trials assessing systemic interventions in patients with VHL and RCC. These therapeutic interventions consisted of three tyrosine kinase inhibitors (TKIs) – semaxinib, sunitinib, and pazopanib - and one hypoxia-inducible factor (HIF) inhibitor -belzutifan. Belzutifan therapy was associated with an overall response rate (ORR) of 49% in patients with VHL and RCC. Only 3% of patients experienced disease progression while on belzutifan, which resulted in an impressive 97% clinical benefit rate. Pazopanib was also associated with an ORR of 64%; no patients experienced disease progression while on therapy. Lastly, two studies investigated the role of sunitinib in patients with VHL and RCC. In these studies, sunitinib was associated with an ORR ranging from 33% to 66%.

Conclusions

Anti-angiogenic interventions such as TKI and HIF inhibitors have been shown to be effective in decreasing the rate of progression of VHL-associated neoplasms. Although only a few trials have evaluated different pharmaceutical interventions in VHL-associated neoplasms, understanding the molecular basis of this pathology has opened the opportunity for novel therapeutic approaches to improve outcomes in this population.