bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke
Authors: Arlt Friederike A. , Sperber Pia S. , von Rennenberg Regina , Gebert Pimrapat , Teegen Bianca , Georgakis Marios K. , Fang Rong , Dewenter Anna , Görtler Michael , Petzold Gabor C. , Wunderlich Silke , Zerr Inga , Dichgans Martin , Prüss Harald , Endres Matthias ,   On behalf of the DEMDAS Investigators, Endres Matthias , Liman Thomas , Nolte Christian , Kerti Lucia , Wittenberg Tatjana , Scheitz Jan F. , Sperber Pia S. , Nave Alexander H. , Kufner Anna Ibaroule , Bode Felix , Stösser Sebastian , Meißner Julius N. , Ebrahimi Taraneh , Nordsiek Julia , Beckonert Niklas , Hermann Peter , Schmitz Matthias , Goebel Stefan , Schütte-Schmidt Julia , Nuhn Sabine , Volpers Corinna , Dechent Peter , Bähr Matthias , Glanz Wenzel , Georgakis Marios , Tiedt Steffen , Waegemann Karin , Janowitz Daniel , Ikenberg Benno , Bermkopf Kathleen , Huber Christiane , Wagner Michael , Neumann Katja , Spottke Annika , Stöcker Tony , Dühring Marco , Speck Oliver , Duezel Emrah , Bartenstein Peter 
Published: October 2024

AbstractPatients suffering from strokes are at increased risk of developing post-stroke dementia. Serum anti-NMDA receptor autoantibodies (NMDAR1-abs) have been associated with unfavorable post-stroke outcomes. However, their effect on specific cognitive domains remains unclear. We used data from the prospective multicenter DZNE—mechanisms after stroke (DEMDAS) cohort, and measured NMDAR1-abs in serum at baseline. Cognitive function was assessed with a comprehensive neuropsychological test battery at 6- and 12-months follow-up. We employed crude and stepwise confounder adjusted linear and logistic regression models as well as generalized estimating equation models (GEE) to determine the relevance of NMDAR1-abs seropositivity on cognitive function after stroke. 10.2% (58/569) DEMDAS patients were NMDAR1-abs seropositive (IgM:n = 44/IgA:n = 21/IgG:n = 2). Seropositivity was not associated with global cognitive impairment after stroke. However, NMDAR1-abs seropositive patients performed lower in the memory domain (βadjusted = −0.11; 95%CI = −0.57 to −0.03) and were at increased risk for memory impairment (ORadjusted = 3.8; 95%CI = 1.33–10.82) compared to seronegative patients, 12 months after stroke. Further, NMDAR1-abs were linked to memory impairment over time in GEE from 6- to 12-months follow-up (ORadjusted = 2.41; 95%CI = 1.05–5.49). Our data suggests that NMDAR1-abs contribute to memory dysfunction 1 year after stroke while not affecting other cognitive subdomains. Hence, antineuronal autoimmunity may be involved in distinct mechanisms of post-stroke memory impairment. Clinical trial name and registration number: The Determinants of Dementia After Stroke (DEMDAS; study identifier on clinical trials.gov: NCT01334749)
Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma
Authors: Villa Matteo , Sharma Geeta G. , Malighetti Federica , Mauri Mario , Arosio Giulia , Cordani Nicoletta , Lobello Cosimo , Larose Hugo , Pirola Alessandra , D’Aliberti Deborah , Massimino Luca , Criscuolo Lucrezia , Pagani Lisa , Chinello Clizia , Mastini Cristina , Fontana Diletta , Bombelli Silvia , Meneveri Raffaella , Lovisa Federica , Mussolin Lara , Janikova Andrea , Pospíšilová Šárka , Turner Suzanne D. , Inghirami Giorgio , Magni Fulvio , Urso Mario , Pagni Fabio , Ramazzotti Daniele , Piazza Rocco , Chiarle Roberto , Gambacorti-Passerini Carlo , Mologni Luca 
Published: October 2024

Abstract
Background
Anaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory.

Methods
We investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models.

Results
Recurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients.

Conclusions
These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.
The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo
Authors: Memar Nadin , Sherrard Ryan , Sethi Aditya , Fernandez Carla Lloret , Schmidt Henning , Lambie Eric J. , Poole Richard J. , Schnabel Ralf , Conradt Barbara 
Published: October 2024

AbstractWe report that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for differential gene expression in cells produced by asymmetric cell divisions in C. elegans. We found that the C. elegans CMG component, PSF-2 GINS2, is necessary for transcriptional upregulation of the pro-apoptotic gene egl-1 BH3-only that occurs in cells programmed to die after they are produced through asymmetric cell divisions. We propose that CMG’s histone chaperone activity causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for egl-1 upregulation in cells programmed to die. We find that PSF-2 is also required for the divergence of other cell fates during C. elegans development, suggesting that this function is not unique to egl-1 expression. Our work uncovers an unexpected role of CMG in cell fate decisions and an intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.
High-parametric protein maps reveal the spatial organization in early-developing human lung
Authors: Sariyar Sanem , Sountoulidis Alexandros , Hansen Jan Niklas , Marco Salas Sergio , Mardamshina Mariya , Martinez Casals Anna , Ballllosera Navarro Frederic , Andrusivova Zaneta , Li Xiaofei , Czarnewski Paulo , Lundeberg Joakim , Linnarsson Sten , Nilsson Mats , Sundström Erik , Samakovlis Christos , Lundberg Emma , Ayoglu Burcu 
Published: October 2024

AbstractThe respiratory system, including the lungs, is essential for terrestrial life. While recent research has advanced our understanding of lung development, much still relies on animal models and transcriptome analyses. In this study conducted within the Human Developmental Cell Atlas (HDCA) initiative, we describe the protein-level spatiotemporal organization of the lung during the first trimester of human gestation. Using high-parametric tissue imaging with a 30-plex antibody panel, we analyzed human lung samples from 6 to 13 post-conception weeks, generating data from over 2 million cells across five developmental timepoints. We present a resource detailing spatially resolved cell type composition of the developing human lung, including proliferative states, immune cell patterns, spatial arrangement traits, and their temporal evolution. This represents an extensive single-cell resolved protein-level examination of the developing human lung and provides a valuable resource for further research into the developmental roots of human respiratory health and disease.
Encoding extracellular modification of artificial cell membranes using engineered self-translocating proteins
Authors: Harjung Alexander , Fracassi Alessandro , Devaraj Neal K. 
Published: October 2024

AbstractThe development of artificial cells has led to fundamental insights into the functional processes of living cells while simultaneously paving the way for transformative applications in biotechnology and medicine. A common method of generating artificial cells is to encapsulate protein expression systems within lipid vesicles. However, to communicate with the external environment, protein translocation across lipid membranes must take place. In living cells, protein transport across membranes is achieved with the aid of complex translocase systems which are difficult to reconstitute into artificial cells. Thus, there is need for simple mechanisms by which proteins can be encoded and expressed inside synthetic compartments yet still be externally displayed. Here we present a genetically encodable membrane functionalization system based on mutants of pore-forming proteins. We modify the membrane translocating loop of α-hemolysin to translocate functional peptides up to 52 amino acids across lipid membranes. Full membrane translocation occurs in the absence of any translocase machinery and the translocated peptides are recognized by specific peptide-binding ligands on the opposing membrane side. Engineered hemolysins can be used for genetically programming artificial cells to display interacting peptide pairs, enabling their assembly into artificial tissue-like structures.
α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice
Authors: Morais Livia H. , Boktor Joseph C. , MahmoudianDehkordi Siamak , Kaddurah-Daouk Rima , Mazmanian Sarkis K. 
Published: October 2024

AbstractPathological forms of α-synuclein contribute to synucleinopathies, including Parkinson’s disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.
Fibrolytic vaccination against ADAM12 reduces desmoplasia in preclinical pancreatic adenocarcinomas
Authors: Chen Jing , Sobecki Michal , Krzywinska Ewelina , Thierry Kevin , Masmoudi Mélissa , Nagarajan Shunmugam , Fan Zheng , He Jingyi , Ferapontova Irina , Nelius Eric , Seehusen Frauke , Gotthardt Dagmar , Takeda Norihiko , Sommer Lukas , Sexl Veronika , Münz Christian , DeNardo David , Hennino Ana , Stockmann Christian 
Published: October 2024

AbstractA hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12+ cells reduces fibrosis in various organs. In preclinical mouse models of PDAC, we observe ADAM12 expression in CAFs as well as in tumor cells but not in healthy mouse pancreas. Therefore, we tested prophylactic and therapeutic vaccination against ADAM12 in murine PDAC and observed delayed tumor growth along with a reduction in CAFs and tumor desmoplasia. This is furthermore associated with vascular normalization and alleviated tumor hypoxia. The ADAM12 vaccine induces a redistribution of CD8+ T cells within the tumor and cytotoxic responses against ADAM12+ cells. In summary, vaccination against the endogenous fibroblast target ADAM12 effectively depletes CAFs, reduces desmoplasia and delays the growth of murine PDACs. These results provide proof-of-principle for the development of vaccination-based immunotherapies to treat tumor desmoplasia.
Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple-negative breast cancer
Authors: Fournier Morgane , Javary Joaquim , Roh Vincent , Fournier Nadine , Radtke Freddy 
Published: October 2024

AbstractCancer cell plasticity contributes significantly to the failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a genome-wide CRISPR-Cas9 screen, we investigated escape mechanisms of NOTCH-driven TNBC treated with a gamma-secretase inhibitor (GSI) and identified SOX2 as a target of resistance to Notch inhibition. We describe a novel reciprocal inhibitory feedback mechanism between Notch signaling and SOX2. Specifically, Notch signaling inhibits SOX2 expression through its target genes of the HEY family, and SOX2 inhibits Notch signaling through direct interaction with RBPJ. This mechanism shapes divergent cell states with NOTCH positive TNBC being more epithelial-like, while SOX2 expression correlates with epithelial-mesenchymal transition, induces cancer stem cell features and GSI resistance. To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second-line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.
Right Information, Right Care, Right Patient, Right Time: Community Preferences to Inform a Self-Management Support Tool for Upper Respiratory Symptoms
Authors: Gutnick Damara , Lutz Carlo , Mani Kyle A. , Weldon Christine B. , Trosman Julia R. , Rapkin Bruce , Jinnett Kimberly , Fleurimont Judes , Kaur Savneet , Jariwala Sunit P. 
Published: October 2024

Abstract
Objectives During and since the coronavirus disease 2019 (COVID-19) pandemic, communities have needed to cope with several conditions that cause similar upper respiratory symptoms but are managed differently. We describe community reactions to a self-management toolkit for patients with upper respiratory symptoms to inform mobile e-health app development. The toolkit is based on the “4R” (Right Information, Right Care, Right Patient, Right Time) care planning and management model.
Methods The 4R Cold, Flu, and COVID-19 Information Tool (4R-Toolkit) along with a brief evaluation survey were distributed in three ways: through a Bronx NY Allergy/Asthma clinic, through the Bronx Borough President's Office listserv, and through peer recruitment. The survey assessed respondents' perceptions of the 4R-Toolkit's accessibility, preferences for sharing symptoms with clinicians, social media use, and e-health literacy.
Results We obtained a diverse sample of 106 Bronx residents, with 83% reporting personal or a social contact with symptoms suggestive of COVID-19. Respondents varied in the information sources they preferred: computer (39%), smartphone (28%), paper (11%), and no preference (22%). Most (67%) reported that social media had at least some impact on their health care decisions. Regardless of media preferences, respondents were positive about the 4R-Toolkit. Out of 106 respondents, 91% believed the 4R-Toolkit would help people self-manage upper respiratory symptoms and 85% found it easy to understand. Respondents strongly endorsed retention of all 4R-Toolkit content domains with 81% indicating that they would be willing to share symptoms with providers using a 4R-Toolkit smartphone app.
Conclusion The 4R-Toolkit can offer patients and community members accurate and up-to-date information on COVID-19, the common cold, and the flu. The user-friendly tool is accessible to diverse individuals, including those with limited e-health literacy. It has potential to support self-management of upper respiratory symptoms and promote patient engagement with providers.
Pharmacological Effects of Paeonia lactiflora Focusing on Painful Diabetic Neuropathy
Authors: Wiegand Vanessa , Gao Ying , Teusch Nicole 
Published: October 2024

AbstractPainful diabetic neuropathy (PDN) is a highly prevalent complication in patients suffering from diabetes mellitus. Given the inadequate pain-relieving effect of current therapies for PDN, there is a high unmet medical need for specialized therapeutic options. In traditional Chinese medicine (TCM), various herbal formulations have been implemented for centuries to relieve pain, and one commonly used plant in this context is Paeonia lactiflora (P. lactiflora). Here, we summarize the chemical constituents of P. lactiflora including their pharmacological mechanisms-of-action and discuss potential benefits for the treatment of PDN. For this, in silico data, as well as preclinical and clinical studies, were critically reviewed and comprehensively compiled. Our findings reveal that P. lactiflora and its individual constituents exhibit a variety of pharmacological properties relevant for PDN, including antinociceptive, anti-inflammatory,
antioxidant, and antiapoptotic activities. Through this multifaceted and complex combination of various pharmacological effects, relevant hallmarks of PDN are specifically addressed, suggesting that P. lactiflora may represent a promising source for novel therapeutic approaches for PDN.
Ear Correction of Newborn Ear Deformity
Authors: Zhorov Iris , Goldstein Melissa , Carniol Eric 
Published: October 2024

AbstractOtoplasty has been described for nearly 200 years for children and adults. Although auricular deformity has been recognized in newborns, treatment options were lacking. With the development of ear molding techniques, newborn ear deformities can now be corrected nonsurgically. However, these techniques have distinct limitations with much dependent on the age of initiation of treatment and deformities present. Awareness of these early interventions is therefore crucial to initiate treatment in the early developmental period when the ear is still malleable. During the first few weeks of life, the ears are malleable, and the ears are rapidly growing, relatively. Therefore, the neonatal period provides a unique opportunity to contour the ears properly. Different techniques have been developed. However, the premise is that the ears are stabilized in a favorable contour continuously for several weeks to hold into proper position. This procedure carries minimal risk and can be quite efficacious, preventing a child from needing surgery later in life.
Intensity and enjoyment of play-based HIIT in children and
adolescents with obesity
Authors: Simonsen MortenBilde , Eggertsen CharlotteNørkjær , Pedersen JeppeBech , Christiansen Stine , Vestergaard EsbenThyssen , Hagstrøm Søren , Larsen Ryan Godsk 
Published: October 2024

AbstractHigh-intensity interval training (HIIT) has been suggested as an effective
treatment approach of childhood obesity. The objective of the present study was
to examine intensity, enjoyment, and perceived exertion of a 4x4-minute
play-based HIIT program for children and adolescents with obesity. 83
participants (42.2% girls, 12.3±1.5 years, 57.8% boys, 12.0±1.6 years) completed
a 12-week intervention comprising three weekly sessions. After nine sessions
(weeks 2, 6, and 11), participants rated perceived exertion (RPE) with a Borg
scale and enjoyment of activities using the Physical Activity Enjoyment Scale
(PACES). Heart rate (HR) was recorded to assess time spent in high- and
moderate-intensity. Participants spent more time in high-intensity during
strength-based (P=0.004) and running-based (P=0.007) activities compared to ball
games, and more time was spent in moderate-intensity during ball games compared
to strength-based (P=0.033) and running-based (P=0.028) activities. Overall,
boys spent more time in moderate-intensity than girls (P=0.007). Participants
rated RPE lower for ball games than for strength-based (P<0.001) and
running-based (P<0.001) activities. Boys rated running-based activities more
enjoyable than girls (P=0.021). Exercise intensity and RPE vary by activity in
HIIT for children and adolescents with obesity. Ball games led to less
high-intensity time and were seen as less exhausting. No differences in RPE or
enjoyment were found over time.
Strong-lensing cosmography using third-generation gravitational-wave detectors
Authors: Jana Souvik , J Kapadia Shasvath , Venumadhav Tejaswi , More Surhud , Ajith Parameswaran 
Published: October 2024

AbstractWe present a detailed exposition of a statistical method for estimating cosmological parameters from the observation of a large number of strongly lensed binary-black-hole (BBH) mergers observable by next (third) generation (XG) gravitational-wave (GW) detectors. This method, first presented in Jana (2023Phys. Rev. Lett.130261401), compares the observed number of strongly lensed GW events and their time delay distribution (between lensed images) with observed events to infer cosmological parameters. We show that the precision of the estimation of the cosmological parameters does not have a strong dependance on the assumed BBH redshift distribution model. Using the large number of unlensed mergers, XG detectors are expected to measure the BBH redshift distribution with sufficient precision for the cosmological inference. However, a biased inference of the BBH redshift distribution will bias the estimation of cosmological parameters. An incorrect model for the distribution of lens properties can also lead to a biased cosmological inference. However, Bayesian model selection can assist in selecting the right model from a set of available parametric models for the lens distribution. We also present a way to incorporate the effect of contamination in the data due to the limited efficiency of lensing identification methods, so that it will not bias the cosmological inference.
Ab initio calculations of second-, third-, and fourth-order partial and inner elastic constants of diamond
Authors: Zhou Zhukun , Chen Tangyan , Liu Yangzhou , Wang Hao , Li Mo 
Published: October 2024

Abstract
By means of ab initio calculations, a unified framework is presented to investigate the effect of internal displacement on the linear and nonlinear elasticity of single diamond crystals. The calculated linear and nonlinear elastic constants, internal strain tensor and internal displacement in single diamond crystals are compatible with the available experimental data and other theoretical calculations. The complete set of second-, third- and fourth-order elastic constants and internal strain tensor not only offer a better insight into the nonlinear and anisotropic elasticity behaviors, but also shows us the basic internal mechanical response of diamond. This study provides a route to calculate the nonlinear internal and external elasticity response in a nonprimitive lattice.