bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of a Virtual Group-Based Cognitive Behavioral Therapy Intervention for Adolescents With Disorders of Gut–Brain Interaction
Authors: Carmody Julia K. , Kramer Rebecca L. , Distel Laura M. L. , Davidson Ryan D. , Snyder Julie M. , Villa Manuela , Nemec Grace E. , Hale Amy E. 
Published: December 2023

Objective: Psychological intervention is an essential treatment component of disorders of gut–brain interaction (DGBIs), but engagement in evidence-based intervention is far from routine. A group-based treatment delivered via telehealth may expand access to evidence-based care for adolescents with DGBIs. The current study describes the development and initial feasibility and acceptability of the Gastroenterology psychology skills for adolescents (GPS-A), a five-session cognitive behavioral group intervention that teaches adolescents evidence-based skills to manage a range of DGBI symptoms. Method: Participants were 33 adolescents with a range of DGBI diagnoses who completed the intervention group and provided quantitative and qualitative feedback. Participant-reported outcomes (somatic symptoms, functional disability, quality of life [QoL]) were collected pre- and postintervention and at 1-month follow-up. Results: Fifty-one percent of patients contacted (30% of all potentially eligible patients) agreed to participate in the group intervention. Retention was high, with 100% of participants completing five sessions. Participants identified skills, community and interpersonal connections, and validation of their gastrointestinal condition and experience as the most helpful intervention components. There was a significant positive difference in overall and emotional QoL from preintervention to 1-month follow-up, though no significant differences were found in somatic symptoms or functional disability. Conclusions: Unlike previously developed cognitive behavioral therapy interventions, GPS-A was both specific to patients with DGBI symptoms and flexible enough to incorporate a range of disorders (e.g., Irritable Bowel Syndrome, functional dyspepsia, and functional abdominal pain). Future directions include testing preliminary effectiveness in a larger sample and expanding diversity of the sample (gender, race/ethnicity). Implications for Impact Statement Psychological interventions have gained recognition as an indispensable component in the treatment of disorders of gut–brain interaction (DGBIs) but access to evidence-based intervention is often challenging. The present study describes the development of a virtual, group-based, cognitive behavioral intervention for adolescents with DGBIs. Developed and piloted in a real-world clinical setting, the intervention proved feasible and acceptable, and as such represents a step toward increasing access to evidence-based care for adolescents with DGBIs.
A Topical Review of Conjunctive Heart Rate Variability Biofeedback and Acceptance and Commitment Therapy for Pediatric Disorders of Gut–Brain Interaction
Authors: Freeman Baez Katelyn , Lackey Nicholas S. , Ferdousian Vanoosheh , Fathi Moe , Clarke Dennis F. , Mathias Marisa S. , Wynveen Rachel , Weiss Lizabeth , Gevirtz Richard N. 
Published: December 2023

Objective: Disorders of gut–brain interaction (DGBI) affect a large segment of the pediatric population, significantly impacting quality of life and functioning. Recent findings indicate emerging psychological therapies targeting autonomic mechanisms may be effective treatment approaches. This article reviews utilization of conjunctive heart rate variability biofeedback (HRVB) alongside acceptance and commitment therapy (ACT) in the treatment of DGBI. Method: This study includes a topical review of HRVB as an adjunct to ACT in the context of autonomic regulation in DGBI intervention. An overview of our treatment model at the Center for Applied Biobehavioral Sciences (CABS) and procedures for future replication is provided. Clinic referrals, administrative processes, patient intake, education and measures, and treatment protocol are outlined. A review of previous studies at CABS and their outcomes are detailed. Results: Previous data suggests that utilization of HRVB as an adjunctive approach to psychological therapies which target autonomic regulation, such as ACT, alongside standard medical treatment should be considered in pediatric DGBI management. CABS outcomes support the inclusion of HRVB to target autonomic dysregulation in DGBI to improve symptomatology and functioning in this population. Conclusion: HRVB and ACT appear to be promising treatments for pediatric DGBI to be included in psychological and multidisciplinary clinical settings. Given the correlates of autonomic nervous system dysregulation in adults and preliminary findings in pediatric DGBI, these may be useful approaches for targeting the autonomic mechanisms of DGBI symptomatology. We address future directions for research to replicate and extend the findings for use in clinical settings. Implications for Impact Statement Heart rate variability biofeedback and acceptance and commitment therapy may be effective and promising treatments to be included in psychological and multidisciplinary clinical settings for pediatric disorders of gut–brain interaction (DGBI). These interventions may work by targeting the autonomic nervous system, potentially improving DGBI symptoms and functioning in the pediatric population. These treatments require further research and validation, which this article aims to demonstrate.
Toward Promotion of Health Equity in Pediatric Disorders of Gut–Brain Interaction: A Call to Action
Authors: Low Kapalu Christina , Wilkes Caroline D. 
Published: December 2023

Objectives: There has been increased attention to health equity, or the opportunity to obtain one’s health potential without disadvantage caused by discriminatory social systems, in recent years. The social determinants of health (SDoH), including economic stability, educational access and quality, healthcare access and quality, neighborhood and built environment, and social and community context, are the social, political, and systems-level factors that contribute to health inequities. Method: In this commentary, the authors will review the ways in which structural and systemic racism impact health, discuss what is known about SDoH in pediatric DGBIs and propose a call to action for pediatric psychologists to promote health equity via research, clinical work, teaching, and advocacy. Results: Unfortunately, very limited research on SDoH in pediatric disorders of gut–brain interaction (DGBIs) has been conducted to date. What we do know is that exposure to early life stressors influences DGBI prevalence and symptoms in both childhood and adulthood ( Chitkara et al., 2008 ). Thus, addressing SDoHs in pediatric gastroenterology has the potential to improve population health and reduce functional disability. Conclusion: Upstream, systems-level interventions are needed in order to make measurable change in health outcomes in pediatric DGBIs. Implications for Impact Statement Social determinants of health have been linked with health care disparities within pediatric disorders of gut–brain interaction. Pediatric psychologists are embedded members of medical teams, who possess the knowledge and skills needed to create upstream interventions to directly address social and systemic root causes of disparities.
Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer
Authors: Liu Xiaoxiao , Zhang Xing , Shao Zhiying , Zhong Xiaorong , Ding Xin , Wu Liang , Chen Jie , He Ping , Cheng Yan , Zhu Kunrui , Zheng Dan , Jing Jing , Luo Ting 
Published: December 2023

AbstractHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been the most challenging subtype of BC, consisting of 20% of BC with an apparent correlation with poor prognosis. Despite that pyrotinib, a new HER2 inhibitor, has led to dramatic improvements in prognosis, the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance. Therefore, identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity. Here, we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC. We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest, inhibit the proliferation of BT-474 and SK-BR-3 BC cells, and repress in vivo tumor growth in xenograft mice models. This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress. Furthermore, the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase (G6PD) degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16 (ZBTB16) in tumorigenesis of BC. Mechanistically, we identified that miR-16-5p was a potential upstream regulator of ZBTB16, and it showed a significant inverse correlation with ZBTB16. Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC. Together, these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.
Evidence for a shared genetic contribution to loneliness and borderline personality disorder
Authors: Schulze Anna , Streit Fabian , Zillich Lea , Awasthi Swapnil , Hall Alisha S. M. , Jungkunz Martin , Kleindienst Nikolaus , Frank Josef , Schwarze Cornelia E. , Dahmen Norbert , Schott Björn H. , Nöthen Markus , Mobascher Arian , Rujescu Dan , Lieb Klaus , Roepke Stefan , Herpertz Sabine C. , Schmahl Christian , Bohus Martin , Ripke Stephan , Rietschel Marcella , Lis Stefanie , Witt Stephanie 
Published: December 2023

AbstractLoneliness, influenced by genetic and environmental factors such as childhood maltreatment, is one aspect of interpersonal dysfunction in Borderline Personality Disorder (BPD). Numerous studies link loneliness and BPD and twin studies indicate a genetic contribution to this association. The aim of our study was to investigate whether genetic predisposition for loneliness and BPD risk overlap and whether genetic risk for loneliness contributes to higher loneliness reported by BPD patients, using genome-wide genotype data. We assessed the genetic correlation of genome-wide association studies (GWAS) of loneliness and BPD using linkage disequilibrium score regression and tested whether a polygenic score for loneliness (loneliness-PGS) was associated with case-control status in two independent genotyped samples of BPD patients and healthy controls (HC; Witt2017-sample: 998 BPD, 1545 HC; KFO-sample: 187 BPD, 261 HC). In the KFO-sample, we examined associations of loneliness-PGS with reported loneliness, and whether the loneliness-PGS influenced the association between childhood maltreatment and loneliness. We found a genetic correlation between the GWAS of loneliness and BPD in the Witt2017-sample (rg = 0.23, p = 0.015), a positive association of loneliness-PGS with BPD case-control status (Witt2017-sample: NkR² = 2.3%, p = 2.7*10–12; KFO-sample: NkR² = 6.6%, p = 4.4*10–6), and a positive association between loneliness-PGS and loneliness across patient and control groups in the KFO-sample (β = 0.186, p = 0.002). The loneliness-PGS did not moderate the association between childhood maltreatment and loneliness in BPD. Our study is the first to use genome-wide genotype data to show that the genetic factors underlying variation in loneliness in the general population and the risk for BPD overlap. The loneliness-PGS was associated with reported loneliness. Further research is needed to investigate which genetic mechanisms and pathways are involved in this association and whether a genetic predisposition for loneliness contributes to BPD risk.
Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated GPX4 ubiquitination
Authors: Sun Xiangfei , Zhang Qiang , Lin Xiaohan , Shu Ping , Gao Xiaodong , Shen Kuntang 
Published: December 2023

AbstractImatinib (IM) has significantly improved the prognosis of gastrointestinal stromal tumor (GIST) patients, but some patients still have primary resistance to IM, and approximately half of patients develop acquired drug resistance within 2 years of treatment, necessitating exploration of new treatment strategies. Targeting ferroptosis as a novel approach to tumor treatment has gained attention. Yet, there is limited research on ferroptosis in GIST, and the underlying mechanism remains unclear. In this study, we revealed that IM increased lipid reactive oxygen species and intracellular Fe2+ levels, and decreased glutathione levels in GIST. This effect could be partially inhibited by Ferrostatin-1. Additionally, knocking down STUB1 and overexpressing GPX4 reversed the IM-induced ferroptosis effect. Moreover, STUB1 was identified as a novel E3 ubiquitin ligase of GPX4, promoting the ubiquitination at site K191 of GPX4. The combination of the GPX4 inhibitor RSL3 and IM synergistically induces ferroptosis, inhibiting GIST proliferation both in vivo and in vitro. Furthermore, STUB1 and GPX4 expression serve as independent prognostic factors for GIST. In conclusion, This study is the first to demonstrate that IM induces ferroptosis by promoting STUB1-mediated GPX4 ubiquitination in GIST, and the combination of RSL3 and IM emerges as a promising therapeutic strategy for GIST.
Respiration modulates sleep oscillations and memory reactivation in humans
Authors: Schreiner Thomas , Petzka Marit , Staudigl Tobias , Staresina Bernhard P. 
Published: December 2023

AbstractThe beneficial effect of sleep on memory consolidation relies on the precise interplay of slow oscillations and spindles. However, whether these rhythms are orchestrated by an underlying pacemaker has remained elusive. Here, we tested the relationship between respiration, which has been shown to impact brain rhythms and cognition during wake, sleep-related oscillations and memory reactivation in humans. We re-analysed an existing dataset, where scalp electroencephalography and respiration were recorded throughout an experiment in which participants (N = 20) acquired associative memories before taking a nap. Our results reveal that respiration modulates the emergence of sleep oscillations. Specifically, slow oscillations, spindles as well as their interplay (i.e., slow-oscillation_spindle complexes) systematically increase towards inhalation peaks. Moreover, the strength of respiration - slow-oscillation_spindle coupling is linked to the extent of memory reactivation (i.e., classifier evidence in favour of the previously learned stimulus category) during slow-oscillation_spindles. Our results identify a clear association between respiration and memory consolidation in humans and highlight the role of brain-body interactions during sleep.
Capturing critical gem-diol intermediates and hydride transfer for anodic hydrogen production from 5-hydroxymethylfurfural
Authors: Fu Guodong , Kang Xiaomin , Zhang Yan , Guo Ying , Li Zhiwei , Liu Jianwen , Wang Lei , Zhang Jiujun , Fu Xian-Zhu , Luo Jing-Li 
Published: December 2023

AbstractThe non-classical anodic H2 production from 5-hydroxymethylfurfural (HMF) is very appealing for energy-saving H2 production with value-added chemical conversion due to the low working potential (~0.1 V vs RHE). However, the reaction mechanism is still not clear due to the lack of direct evidence for the critical intermediates. Herein, the detailed mechanisms are explored in-depth using in situ Raman and Infrared spectroscopy, isotope tracking, and density functional theory calculations. The HMF is observed to form two unique inter-convertible gem-diol intermediates in an alkaline medium: 5-(Dihydroxymethyl)furan-2-methanol anion (DHMFM−) and dianion (DHMFM2−). The DHMFM2− is easily oxidized to produce H2 via H− transfer, whereas the DHMFM− is readily oxidized to produce H2O via H+ transfer. The increases in potential considerably facilitate the DHMFM− oxidation rate, shifting the DHMFM− ↔ DHMFM2− equilibrium towards DHMFM− and therefore diminishing anodic H2 production until it terminates. This work captures the critical intermediate DHMFM2− leading to hydrogen production from aldehyde, unraveling a key point for designing higher performing systems.
Personalized functional brain network topography is associated with individual differences in youth cognition
Authors: Keller Arielle S. , Pines Adam R. , Shanmugan Sheila , Sydnor Valerie J. , Cui Zaixu , Bertolero Maxwell A. , Barzilay Ran , Alexander-Bloch Aaron F. , Byington Nora , Chen Andrew , Conan Gregory M. , Davatzikos Christos , Feczko Eric , Hendrickson Timothy J. , Houghton Audrey , Larsen Bart , Li Hongming , Miranda-Dominguez Oscar , Roalf David R. , Perrone Anders , Shetty Alisha , Shinohara Russell T. , Fan Yong , Fair Damien A. , Satterthwaite Theodore D. 
Published: December 2023

AbstractIndividual differences in cognition during childhood are associated with important social, physical, and mental health outcomes in adolescence and adulthood. Given that cortical surface arealization during development reflects the brain’s functional prioritization, quantifying variation in the topography of functional brain networks across the developing cortex may provide insight regarding individual differences in cognition. We test this idea by defining personalized functional networks (PFNs) that account for interindividual heterogeneity in functional brain network topography in 9–10 year olds from the Adolescent Brain Cognitive Development℠ Study. Across matched discovery (n = 3525) and replication (n = 3447) samples, the total cortical representation of fronto-parietal PFNs positively correlates with general cognition. Cross-validated ridge regressions trained on PFN topography predict cognition in unseen data across domains, with prediction accuracy increasing along the cortex’s sensorimotor-association organizational axis. These results establish that functional network topography heterogeneity is associated with individual differences in cognition before the critical transition into adolescence.
A DARPin promotes faster onset of botulinum neurotoxin A1 action
Authors: Leka Oneda , Wu Yufan , Zanetti Giulia , Furler Sven , Reinberg Thomas , Marinho Joana , Schaefer Jonas V. , Plückthun Andreas , Li Xiaodan , Pirazzini Marco , Kammerer Richard A. 
Published: December 2023

AbstractIn this study, we characterize Designed Ankyrin Repeat Proteins (DARPins) as investigative tools to probe botulinum neurotoxin A1 (BoNT/A1) structure and function. We identify DARPin-F5 that completely blocks SNAP25 substrate cleavage by BoNT/A1 in vitro. X-ray crystallography reveals that DARPin-F5 inhibits BoNT/A1 activity by interacting with a substrate-binding region between the α- and β-exosite. This DARPin does not block substrate cleavage of BoNT/A3, indicating that DARPin-F5 is a subtype-specific inhibitor. BoNT/A1 Glu-171 plays a critical role in the interaction with DARPin-F5 and its mutation to Asp, the residue found in BoNT/A3, results in a loss of inhibition of substrate cleavage. In contrast to the in vitro results, DARPin-F5 promotes faster substrate cleavage of BoNT/A1 in primary neurons and muscle tissue by increasing toxin translocation. Our findings could have important implications for the application of BoNT/A1 in therapeutic areas requiring faster onset of toxin action combined with long persistence.
Intranasal mask for protecting the respiratory tract against viral aerosols
Authors: Hu Xiaoming , Wang Shuang , Fu Shaotong , Qin Meng , Lyu Chengliang , Ding Zhaowen , Wang Yan , Wang Yishu , Wang Dongshu , Zhu Li , Jiang Tao , Sun Jing , Ding Hui , Wu Jie , Chang Lingqian , Cui Yimin , Pang Xiaocong , Wang Youchun , Huang Weijin , Yang Peidong , Wang Limin , Ma Guanghui , Wei Wei 
Published: December 2023

AbstractThe spread of many infectious diseases relies on aerosol transmission to the respiratory tract. Here we design an intranasal mask comprising a positively-charged thermosensitive hydrogel and cell-derived micro-sized vesicles with a specific viral receptor. We show that the positively charged hydrogel intercepts negatively charged viral aerosols, while the viral receptor on vesicles mediates the entrapment of viruses for inactivation. We demonstrate that when displaying matched viral receptors, the intranasal masks protect the nasal cavity and lung of mice from either severe acute respiratory syndrome coronavirus 2 or influenza A virus. With computerized tomography images of human nasal cavity, we further conduct computational fluid dynamics simulation and three-dimensional printing of an anatomically accurate human nasal cavity, which is connected to human lung organoids to generate a human respiratory tract model. Both simulative and experimental results support the suitability of intranasal masks in humans, as the likelihood of viral respiratory infections induced by different variant strains is dramatically reduced.
Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans
Authors: Pu Longjun , Wang Jing , Lu Qiongxuan , Nilsson Lars , Philbrook Alison , Pandey Anjali , Zhao Lina , Schendel Robin van , Koh Alan , Peres Tanara V. , Hashi Weheliye H. , Myint Si Lhyam , Williams Chloe , Gilthorpe Jonathan D. , Wai Sun Nyunt , Brown Andre , Tijsterman Marcel , Sengupta Piali , Henriksson Johan , Chen Changchun 
Published: December 2023

AbstractG protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts.
Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
Authors: Liang Qingnan , Huang Yuefan , He Shan , Chen Ken 
Published: December 2023

AbstractAdvances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are active at various stages of mouse brain development. Finally, GSDensity can identify spatially relevant pathways in mouse brains and human tumors including those following high-order organizational patterns in the ST data. Particularly, we create a pan-cancer ST map revealing spatially relevant and recurrently active pathways across six different tumor types.