bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy and Cannabis: A Harmful Drug Interaction or Reefer Madness?
Authors: Piper Brian J. , Tian Maria , Saini Pragosh , Higazy Ahmad , Graham Jason , Carbe Christian J. , Bordonaro Michael 
Published: January 2024

AbstractA retrospective (N=140) and a prospective (N=102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 191 times including by clinical practice guidelines. There have also been reports on PubPeer outlining unverifiable information in their statistics and numerous discrepancies calculating percentages. This report attempted to replicate the data-analysis including non-parametric statistics. Table 1 of the corrected prospective report contained 22 p-values but only one (4.5%) could be verified, despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < .0025) younger than non-users but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g. 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e. significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immuno-therapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g. greater nicotine smoking among cannabis users) may be warranted. 198 / 200 wordsSimple SummaryTwo Israeli studies about medical marijuana potentially interfering with immunotherapies like nivolumab for cancer treatment have received substantial attention. However, there have been anonymous but detailed concerns about these reports on PubPeer. This team attempted to verify the data-analysis and statistics of these two reports and the published correction. Many findings including some that could impact the statistical conclusions could not be verified. Of the 22 statistical tests on Table 1 of the prospective report, six could not be repeated using the same statistics and with the provided N. The p-value on 15 corresponded with that of a different statistical test than was listed in the methods. Re-analysis also identified some previously unreported significant differences (e.g. age) between cannabis users and non-users at baseline. Further study of the safety of immunotherapy and cannabis combination may be warranted using patient groups that have been matched on key demographic and medical variables. 150 / 150 wordsGraphical abstract
A Systematic Review and Meta-analysis for Association of Celiac Disease and Thyroid Disorders
Authors: Norouzi Zahra , Hasani Fatemeh , Besharat Sima , Shirzad-Aski Hesamaddin , Ghorbani Somayeh , Mohammadi Masoud , Yadegari Anahita , Kalhori Ali 
Published: January 2024

AbstractIt is probable that people who have celiac disease (CD) are more likely to have thyroid disorders. A comprehensive systematic review and meta-analysis were conducted to assess the link between thyroid disorders and CD. Articles were selected from PubMed, Web of Science, Scopus, Ovid, Embase, Cochrane, ProQuest, and Wiley from February 2022 and earlier. A meta-analysis was conducted to evaluate the outcomes, using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The meta-analysis comprised 31 articles with 3310256 participants including 101253 individuals with thyroid disorders. Overall, the frequency of thyroid disease was notably higher in patients with CD compared to the control groups (OR: 3.06, 95% CI: 2.51 – 3.72, P<0.001). The findings of our meta-analysis support the notion that patients with CD are more likely to have autoimmune thyroid disease (ATD) and other thyroid disorders than the control group, thus indicating that regular screening for thyroid disease is necessary for CD patients. Further cohort research is required to investigate the relationship between thyroid disorders and CD.
Data Driven Approach to Characterize Rapid Decline in Autosomal Dominant Polycystic Kidney Disease
Authors: Sim John J. , Shu Yu-Hsiang , Bhandari Simran K. , Chen Qiaoling , Harrison Teresa N. , Lee Min Young , Munis Mercedes A. , Morrissette Kerresa , Sundar Shirin , Pareja Kristin , Nourbakhsh Ali , Willey Cynthia J. 
Published: January 2024

AbstractBackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Insights into ADPKD progression could lead to earlier detection and management prior to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach.MethodsA retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using rapidly declining eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates.ResultsAmong 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively.ConclusionUsing real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.
Analysis of Repeated Measurements of HIV Viral Load as a Continuous Variable while Accounting for Missing Values
Authors: Sendege Susan Habert , Omala Saint Kizito , Wandiembe Symon Peter , Dumba Isaac 
Published: January 2024

AbstractRecent HIV research predominantly uses Single Measure Frameworks (SMF), focusing solely on the latest viral load data and overlooking missing values. This study explored repeated measures frameworks to assess factors affecting viral load copies while accounting for missing data. The analysis involved 1670 records of HIV patients,using the generalized linear mixed models (GLMM). All variables, except for treatment regimen changes and adherence rating, were recorded at patients’ treatment enrollment. A GLMM was applied to data before and after imputation accounting for the repeated nature of the HIV viral load copies over time. The best-fitting model, selected for discussion, was the GLMM fitted to multiply imputed data. Gender and adherence rating did not significantly affect viral load copies. The analysis included other variables such as patient age, marital status, treatment duration, WHO clinical stages, and facility ownership. Results show that viral load copies were higher among currently or formerly married individuals (β= 0.49, 0.30;SE= 0.042, 0.052;p= 0.0000). In contrast, viral load copies were lower for patients with longer treatment durations (β= −0.01;SE= 0.001;p= 0.0000) and those receiving treatment at a private facility (β= −0.196;SE= 0.077;p= 0.0000). The study highlights the significance of recognizing repeated data patterns in longitudinal settings and addressing missing values in health research. It proposes a similar investigation in controlled environments to evaluate SMF and RMF in presence of missing values.Author summaryThis work was conceptualized by, Susan Habert Sendege. The author was responsible for the initial drafting of the paper, including the analysis, discussion, conclusions, and recommendations. Saint Kizito and Symon Peter played a pivotal role in shaping the study and all provided numerous hours of time for proofreading and editing.
Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects ofSF3B1mutations
Authors: Pacholewska Alicja , Lienhard Matthias , Brüggemann Mirko , Hänel Heike , Bilalli Lorina , Königs Anja , Becker Kerstin , Köhrer Karl , Kaiser Jesko , Gohlke Holger , Gattermann Norbert , Hallek Michael , Herling Carmen D. , König Julian , Grimm Christina , Herwig Ralf , Zarnack Kathi , Schweiger Michal R. 
Published: January 2024

AbstractBackgroundMutations in splicing factor 3B subunit 1 (SF3B1) frequently occur in patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS). These mutations have a different effect on the disease prognosis with beneficial effect in MDS and worse prognosis in CLL patients. A full-length transcriptome approach can expand our knowledge onSF3B1mutation effects on RNA splicing and its contribution to patient survival and treatment options.ResultsWe applied long-read transcriptome sequencing to 44 MDS and CLL patients with and withoutSF3B1mutations and found > 60% of novel isoforms. Splicing alterations were largely shared between cancer types and specifically affected the usage of introns and 3’ splice sites. Our data highlighted a constrained window at canonical 3’ splice sites in which dynamic splice site switches occurred inSF3B1-mutated patients. Using transcriptome-wide RNA binding maps and molecular dynamics simulations, we showed multimodal SF3B1 binding at 3’ splice sites and predicted reduced RNA binding at the second binding pocket of SF3B1K700E.ConclusionsOur work presents the hitherto most complete long-read transcriptome sequencing study in CLL and MDS and provides a resource to study aberrant splicing in cancer. Moreover, we showed that different disease prognosis results most likely from the different cell types expanded during cancerogenesis rather than different mechanism of action of the mutatedSF3B1. These results have important implications for understanding the role ofSF3B1mutations in hematological malignancies and other related diseases.HighlightsLong-read transcriptome sequencing data enables the identification of > 60% of novel isoforms in the transcriptomes of CLL and MDS patients and isogenic cell lines.SF3B1mutations trigger common splicing alterations uponSF3B1mutations across patient cohorts, most frequently decreased intron retention and increased alternative 3’ splice site usage.Mutation effect depends on alternative 3’ splice site and branch point positioning that coincide with bimodal SF3B1 binding at these sitesMolecular dynamics simulations predict reduced binding of SF3B1K700Eto mRNA at the second binding pocket harboring the polypyrimidine tract.
The nunatak andtabula rasahypotheses may be compatible: the European phylogeography of a riparian earthworm
Authors: de Sosa Irene , Marchán Daniel F , Erséus Christer , Lapied Emmanuel , Jelic Misel , Jabłońska Aleksandra , Szederjesi Timea , Almodóvar Ana , Novo Marta , Cosín Darío Díaz 
Published: January 2024

ABSTRACTThetabula rasahypothesis of postglacial immigration supports the notion that species now found in northern European areas must have been recently recolonized from historical refugia. Until the 1960s, however, there was almost complete consensus that disjunctions and endemism in the North Atlantic region of Europe could not be explained without in situ survival during glacial periods (the nunatak hypothesis). Although some earthworms can survive in permafrost and tolerate cold conditions, it is generally believed that most earthworms were eradicated from northern latitudes during the Last Glacial Maximum. To test which hypothesis explains the phylogeography of the riparian and parthenogenetic earthwormEiseniella tetraedra, we collected 1,640 specimens from 19 different countries in Europe. We examined three molecular markers (COI, 16S and 28S) and their morphology. Eleven lineages were found, nested in five clades. Clade I was more prevalent in cold biogeographical regions such as the continental, the Atlantic or even the Arctic, while clade II was prevalent in Mediterranean regions. We investigated their potential niches through Species Distribution Models, which agreed with the distribution trends. The presence of restricted clades in the Iberian and Scandinavian peninsulas, as well as in Eastern Europe, suggests that these three regions served as refugia during the Last Glacial Maximum. Thus, both hypotheses were necessary to explain the actual distribution of this shore-dwelling earthworm.
PTBP2 promotes cell survival and autophagy in Chronic Myeloid Leukemia by stabilizing BNIP3
Authors: Barik Bibhudev , Lama Shristi , Sajitha IS , Chanda Sayantan , Mohapatra Sonali , Biswas Sutapa , Biswas Ghanashyam , Chakraborty Soumen 
Published: January 2024

AbstractPolypyrimidine tract binding protein 2 (PTBP2) regulates alternative splicing in neuronal, muscle, and Sertoli cells. PTBP2 and its paralog, PTBP1, which plays a role in B-cell development, was found to be expressed aberrantly in myeloid leukemia. Genetic ablation of Ptbp2 in the cells resulted in decreased cellular proliferation and repopulating ability, decreased reactive oxygen species (ROS), and altered mitochondrial morphology. The sensitivity of CML cells to imatinib increased after the knockout of Ptbp2. RNA immunoprecipitation followed by sequencing (RIP-seq) and functional assays confirmed that PTBP2 binds to Bcl-2 Interacting Protein 3 (Bnip3)-3’UTR and stabilizes its expression. Our study also suggests that PTBP2 promotes autophagy, as evidenced by the low levels of LC3-II expression in Ptbp2-knockout cells treated with Bafilomycin A1. This effect was restored upon overexpression of Bnip3 in the knockout cells. Notably, when KCL22-NTC cells were subcutaneously injected into the flanks of mice, they gave rise to malignant tumors, unlike Ptbp2-KO-KCL22 cells. This underscores the role of PTBP2 in promoting cell proliferation and tumor formation while enhancing autophagy through Bnip3, thereby supporting the role of PTBP2 as an oncogene in CML.
The integrated stress response/eIF2a pathway controls cytokine production in tissue-resident memory CD4+T cells
Authors: Asada Nariaki , Ginsberg Pauline , Paust Hans-Joachim , Song Ning , Riedel Jan-Hendrik , Turner Jan-Eric , Peters Anett , Kaffke Anna , Engeßer Jonas , Wang Huiying , Zhao Yu , Gild Philipp , Dahlem Roland , Das Sarada , Ignatova Zoya , Huber Tobias B. , Prinz Immo , Gagliani Nicola , Mittrücker Hans-Willi , Krebs Christian F. , Panzer Ulf 
Published: January 2024

SUMMARYTissue-resident memory T (Trm) cells are a specialized T cell population that resides in tissues and can play both a protective and pathogenic role. The mechanism that enables Trm cells to provide a rapid protective response while restricting their function in homeostasis remains unclear. Here, we show that human and mouse CD4+Trm cells exist in apoisedstate, characterized by storage of proinflammatory type-1 and type-3 cytokine mRNAs without protein production. In steady-state conditions, cytokine mRNA translation in Trm cells is suppressed by the integrated stress response (ISR)/eIF2α pathway, whereas Trm-cell activation under inflammatory conditions results in eIF2α dephosphorylation, leading to derepression and rapid translation of the cytokine mRNAs stored in stress granules. Pharmacological inhibition of eIF2α dephosphorylation resulted in reduced cytokine production from Trm cells, and ameliorated autoimmune kidney disease in mice. Consistent with these results, the ISR pathway in Trm cells was downregulated in patients with immune-mediated diseases of the kidney and the intestine. Our results identify ISR/eIF2α-mediated control of cytokine mRNA translation as an underlying mechanism that restricts Trm cell activity in homeostasis but also promotes rapid response upon local infection or autoimmune reaction.
Super-resolved protein imaging using bifunctional light-up aptamers
Authors: Grün Franziska , van den Bergh Niklas , Klevanski Maja , Verma Mrigank S. , Bühler Bastian , Nienhaus G. Ulrich , Kuner Thomas , Jäschke Andres , Sunbul Murat 
Published: January 2024

ABSTRACTEfficient labeling methods for protein visualization with minimal tag size and appropriate photophysical properties are required for single-molecule localization microscopy (SMLM), providing insights into the organization and interactions of biomolecules in cells at the molecular level. Among the fluorescent light-up aptamers (FLAPs) originally developed for RNA imaging, RhoBAST stands out due to its remarkable brightness, photostability, fluorogenicity, and rapid exchange kinetics, enabling super-resolved imaging with high localization precision. Here, we expand the applicability of RhoBAST to protein imaging by fusing it to protein-binding aptamers. The versatility of such bifunctional aptamers is demonstrated by employing a variety of protein-binding DNA or RNA aptamers and different FLAPs. Moreover, fusing RhoBAST with the GFP-binding aptamer AP3 facilitates high- and super-resolution imaging of GFP-tagged proteins, which is particularly valuable in view of the widespread availability of plasmids and stable cell lines expressing proteins fused to GFP. The bifunctional aptamers compare favorably with standard antibody-based immunofluorescence protocols, as they are 7-fold smaller than antibody conjugates and exhibit higher bleaching-resistance. We demonstrate the effectiveness of our approach in super-resolution microscopy in secondary mammalian cell lines and primary neurons by RhoBAST-PAINT, an SMLM protein imaging technique that leverages the transient binding of the fluorogenic rhodamine dye SpyRho to RhoBAST.
Uncovering functional lncRNAs by scRNA-seq with ELATUS
Authors: Goñi Enrique , Mas Aina Maria , Abad Amaya , Santisteban Marta , Fortes Puri , Huarte Maite , Hernaez Mikel 
Published: January 2024

AbstractLong non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level has been challenging due to their less accurate annotation and low expression compared to protein-coding genes. To identify the important, albeit widely overlooked, specific lncRNAs from scRNA-seq data, here, we develop a computational framework, ELATUS, based on the pseudoaligner Kallisto that enhances the detection of functional lncRNAs previously undetected and exhibits higher concordance with the ATAC-seq profiles in single-cell multiome data. Importantly, we then independently confirmed the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveiled biologically important lncRNAs, such asAL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression was unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs.
Planar, Spiral, and Concentric Traveling Waves Distinguish Cognitive States in Human Memory
Authors: Das Anup , Zabeh Erfan , Ermentrout Bard , Jacobs Joshua 
Published: January 2024

AbstractA fundamental challenge in neuroscience is explaining how widespread brain regions flexibly interact to support behaviors. We hypothesize that traveling waves of oscillations are a key mechanism of neural coordination, such that they propagate across the cortex in distinctive patterns that control how different regions interact. To test this hypothesis, we used direct brain recordings from humans performing multiple memory experiments and an analytical framework that flexibly measures the propagation patterns of traveling waves. We found that traveling waves propagated along the cortex in not only plane waves, but also spirals, sources and sinks, and more complex patterns. The propagation patterns of traveling waves correlated with novel aspects of behavior, with specific wave shapes reflecting particular cognitive processes and even individual remembered items. Our findings suggest that large-scale cortical patterns of traveling waves reveal the spatial organization of cognitive processes in the brain and may be relevant for neural decoding.
Highly specific intracellular ubiquitination of a small molecule
Authors: Li Weicheng , Garcia-Rivera Enrique M. , Mitchell Dylan C. , Chick Joel M. , Maetani Micah , Knapp John M. , Matthews Geoffrey M. , Shirasaki Ryosuke , de Matos Simoes Ricardo , Viswanathan Vasanthi , Pulice John L. , Rees Matthew G. , Roth Jennifer A. , Gygi Steven P. , Mitsiades Constantine S. , Kadoch Cigall , Schreiber Stuart L. , Ostrem Jonathan M.L. 
Published: January 2024

AbstractUbiquitin is a small, highly conserved protein that acts as a posttranslational modification in eukaryotes. Ubiquitination of proteins frequently serves as a degradation signal, marking them for disposal by the proteasome. Here, we report a novel small molecule from a diversity-oriented synthesis library, BRD1732, that is directly ubiquitinated in cells, resulting in dramatic accumulation of inactive ubiquitin monomers and polyubiquitin chains causing broad inhibition of the ubiquitin-proteasome system. Ubiquitination of BRD1732 and its associated cytotoxicity are stereospecific and dependent upon two homologous E3 ubiquitin ligases, RNF19A and RNF19B. Our finding opens the possibility for indirect ubiquitination of a target through a ubiquitinated bifunctional small molecule, and more broadly raises the potential for posttranslational modificationin trans.
Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction
Authors: Demopoulos Carly , Jesson Xuan , Gerdes Molly Rae , Jurigova Barbora G. , Hinkley Leighton B. , Ranasinghe Kamalini G. , Desai Shivani , Honma Susanne , Mizuiri Danielle , Findlay Anne , Nagarajan Srikantan S. , Marco Elysa J. 
Published: January 2024

AbstractSensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.