bluuebunny/crossref_metadata_2025_split huggingface dataset:
The atypical faces of optic neuritis: neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease
Authors: Poonja Sabrina , Rattanathamsakul Natthapon , Chen John J. 
Published: November 2024

Purpose of review
The purpose of this article is to provide a review of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), with a focus on what renders optic neuritis “atypical” in these two conditions. Clinical features, diagnostic criteria, and epidemiology are outlined. Acute treatments for optic neuritis, as well as immunotherapy for NMOSD and MOGAD are discussed.

Recent findings
Updates in NMOSD and MOGAD are highlighted, with an emphasis on novel work including the new 2023 MOGAD diagnostic criteria, our evolving understanding on the epidemiology of these conditions, and recently FDA-approved NMOSD treatments. Pipeline therapies are also discussed.

Summary
A thorough history and examination, supported by ancillary testing, continues to be the mainstay of optic neuritis diagnosis. Stratifying typical versus atypical optic neuritis is paramount. Within the atypical category, NMOSD and MOGAD are important considerations. Clues can point towards these diagnoses and guide steps for treatment, which is increasingly becoming targeted to individual diseases, as the pathophysiology is different for these disorders.
IGHG4Expression in C2 Human Dorsal Root Ganglion Potentially Links B Cells to Spreading Chronic Neck Pain
Authors: Mancilla Moreno Marisol , Payne Cathryn , Mazhar Khadijah , Arendt-Tranholm Asta , Yap Natalie , Chiu Abby P. , Wilde Michael A. , Patel Pooja J. , Yousuf Muhammad Saad , Tavares Ferreira Diana , Jarvik Jeffrey G. , Turner Judith A. , Grace Peter M. , Hofstetter Christoph P. , Price Theodore J. , Curatolo Michele 
Published: November 2024

ABSTRACTVery little is known about the molecular mechanisms underlying chronic neck pain, a highly prevalent and burdensome condition. We analyzed the C2 dorsal root ganglion (DRG) of patients with neck pain who underwent C1-2 arthrodesis surgery. Using spatial transcriptomics, we provide the first report ofIGHG4expression in a human DRG.IGHG4encodes immunoglobulin G4 (IgG4). Infiltration of IgG4-producing lymphocytes characterizes IgG4-related disease, an immune-mediated inflammatory condition, and IgG4 autoantibodies sensitize DRG sensory neurons. The expression was found only in one of the 8 patients analyzed, was very high, and co-localized with B cells, which have a crucial role in IgG4 production. The findings uncover a molecular mechanism potentially involved in chronic neck pain in patients susceptible to infiltration of IgG4-producing B cells.
Analysis of Curcumin and Piperine for Breast Cancer Prevention and Treatment via Simulation and Artificial Intelligence Methods
Authors: Sivakumar Ashwin , Kumar Rishi Senthil , Pravin Sheena Christabel , Monica P Reena 
Published: November 2024

AbstractFrom published literature, the combined properties of Curcumin and Piperine infers that the two molecules are potential preventative agents. The nutraceutical combination of Curcumin and Piperine may aid in breast cancer prevention by enhancing Curcumin’s anti-inflammatory and antioxidant effects. In this paper, we demonstrate the following analysis on these two nutraceutical drug molecules in the effort to replicate these inferences in-silico: Drug Synergy Analysis, Molecular Docking and Simulation of Dose-Response curves. We have predicted the synergy (i.e., the effect of two drug molecules when administered simultaneously) between the two molecules on the basis of the Bliss’ Additivity Score. These scores have been predicted by devising a deep learning model using neural networks to determine that the two molecules of interest are synergetic in nature (i.e., one molecule improves the effectiveness of the other). The data used for this model has been extracted from the DrugComb database and filtered to having drug combinations under the MCF7 cell line. The drug molecules are converted from its original SMILES representation to the ECFP6 molecular fingerprint format prior to training the data with the output feature as the Bliss’ score. In this work we also study the interactions between the molecules of interest and protein targets which are of interest (TRPV1 and STAT3) via Molecular Docking. From this, we have been able to determine the binding affinity of the two ligands of interest by docking simultaneously. We have also identified the coordinates of the binding sites of the respective ligands and other potential binding sites for effective binding. From the binding free energies simulated from molecular docking, we have derived the IC50 values using the Cheng-Prusoff Equation. From these IC50 values we have derived the monotherapy dose-response curves with respect to the activation of each the protein targets and the molecules of interest over a range of molar concentrations (0.01um to 100um) using the 4 – parameter logistic curve equation. Furthermore, we have devised a 3D heatmap indicating the combined effectiveness of Curcumin and Piperine from the 4 – parameter log – logistic curve of the Loewe’s Additivity Model over each of the protein targets in focus.
Reduced prevalence of phage defense systems inPseudomonas aeruginosastrains from Cystic Fibrosis Patients
Authors: van den Berg Daan F. , Brouns Stan J.J. 
Published: November 2024

AbstractCystic fibrosis is a genetic disorder that affects mucus clearance, particularly of the lungs. As a result, cystic fibrosis patients often experience infections from bacteria, which contribute to the disease progression.Pseudomonas aeruginosais one of the most common opportunistic pathogens associated with cystic fibrosis. The presence ofP. aeruginosacomplicates the treatment due to its high antibiotic resistance. Thus, research is ongoing to treat these infections with bacterial viruses instead, known as bacteriophages. Notably,P. aeruginosaclinical strains possess a variety of phage defense mechanisms that may limit the effectiveness of phage therapy. In this study, we compared the defense system repertoire ofP. aeruginosastrains isolated from cystic fibrosis patients with those from non-cystic fibrosis patients. Our findings reveal thatP. aeruginosastrains isolated from cystic fibrosis patients have fewer phage defense mechanisms per strain than from non-cystic fibrosis patients, suggesting altered phage selection pressures in strains colonizing CF patient lungs.ImportanceCystic fibrosis patients often experience chronicPseudomonas aeruginosalung infections, which are challenging to treat with antibiotics and contribute to disease progression and eventual respiratory failure. Phage therapy is being explored as an alternative treatment strategy for these infections. However, assessing strain susceptibility to phage treatment is essential for ensuring efficacy. To address this, we investigated whether CF-associated clinicalP. aeruginosastrains have a distinct phage defense repertoire compared to those isolated from other lung patients. We observedthat CF-associatedP. aeruginosastrains have significantly fewer phage defenses, possibly affecting the susceptibility of these strains to phage infection.
The use of X-ray Computed Tomography revolutionises soil pathogen detection
Authors: Pereira Eric C. , Bell Christopher , Urwin Peter E. , Tracy Saoirse 
Published: November 2024

AbstractPotato cyst nematodes (PCN), namelyGlobodera pallida, pose a significant threat to potato production worldwide. Accurately quantifying nematode population densities is crucial for effective management strategies. However, traditional detection methods are time-consuming and often imprecise. X-ray computed tomography (CT) offers high-resolution, non-destructive and three-dimensional (3D) imaging frequently used to visualise internal structures of objects, materials or biological tissues, allowing for detailed analysis of their composition, defects, and morphology. Here, we demonstrate the effectiveness of X-ray CT in detecting and quantifying PCN cysts in different soil types. The ability to achieve 3D imaging and volume quantification of PCN cysts from soils allows accurate enumeration of their egg content. To explore future potential, we propose that when integrated with AI-led quantification of X-ray CT-generated cyst counts, this method could evolve into a next-generation technology to accurately and rapidly quantify these damaging pests in agricultural soils. Combined with the potential to co-analyse other organisms within the same sample, we propose X-ray CT as a fundamental tool for comprehensive soil health assessments and sustainable pest management in agriculture.Author SummaryPotato cyst nematodes are a major threat causing significant crop losses worldwide. Traditionally, detecting this pathogen in soil is challenging, often requiring time-consuming and imprecise. Our study explores a new approach using X-ray computed tomography (CT), a powerful imaging tool that creates detailed 3D imagesin situ. We observed that X-ray CT can effectively detect and measure the cysts nematodes, even within different soil types. This detailed analysis allows us to determine the cyst structures and estimate the eggs contained. In the future, combining X-ray CT with artificial intelligence could make detecting and quantifying these nematodes even faster and more accurate. This method could also be expanded to study other soil organisms, making it a valuable tool for monitoring soil health and improving agricultural pest management.
Centromere-proximal crossovers disrupt proper homologous chromosome disjunction during meiosis
Authors: Sen Sucharita , Sarkar Sneha , Menon Gopika , Nambiar Mridula 
Published: November 2024

AbstractCentromere-proximal crossovers are repressed during meiosis across all species. However, there is a strong correlation between aberrant centromeric crossovers (C-COs) and the occurrence of meiotic aneuploidy and disorders such as Down syndrome. Despite decades of work in understanding repression of C-COs, the molecular basis of how they cause chromosomal mis-segregation is unknown. Here, we show that increased C-COs result in improper separation of homologs leading to increased meiosis I errors and aneuploidy inSchizosaccharomyces pombe. C-COs cause nondisjunction events that cannot be explained by random segregation of homologs and additionally, may also disrupt mono-orientation of sister chromatids in meiosis I leading to their premature separation. We provide evidence that the protected population of cohesins at centromeres during meiosis I may interfere with timely resolution of C-COs causing homolog nondisjunction. These molecular insights will improve our understanding of infertility and aneuploidy-associated developmental disorders in humans.
RNA editing is a molecular clock in unmodified human cells
Authors: Ghareeb Ali E. , Bayne James , Wagen Aaron Z. , Abdelhafid Alya Masoud , Miller David , Cubitt Laura , Meran Laween , Hill Ciaran , Cribbs Adam P. , Ryten Mina , Gandhi Sonia , Gaffney Eamonn , Coles Mark , Young George , Rodriques Samuel G. 
Published: November 2024

AbstractDespite major advances in spatial RNA sequencing, the ability to extract temporal information in RNA sequencing experiments is still limited. Here, we describe Transcriptome Timestamping (T2), a system which harnesses naturally occurring A-to-I editing of RNA transcripts in unmodified human cells to infer transcriptional history. T2 provides age estimates for individual RNA transcripts, and serves as an endogenous molecular recorder, differentiating between complex transcriptional programs. We show that T2 can identify transient and transitional transcriptional programs in primary differentiating monocytes that are not apparent from gene expression analysis alone, including a regulatory module in the monocyte-to-macrophage transition that, to our knowledge, has not yet been described in humans. Finally, we show that T2 can also be applied to single cell data, allowing us to identify transcriptional programs in heterogeneous populations, such as asynchronously dividing cells. T2 is a scalable approach to temporal transcriptomics that can be applied to track the activity of thousands of genes in unmodified, primary human cells and tissues, with no genetic engineering.
The Mechanism of Dynamic Steady States in Lamellipodia
Authors: Kim June Hyung , Kim Taeyoon 
Published: November 2024

ABSTRACTLamellipodia are quasi-two-dimensional actin projections formed on the leading edge of the cell, playing an important role in sensing surrounding environments by forming focal adhesions. A branched actin network in the lamellipodia exhibits a stable, dynamic steady state characterized by a retrograde flow, which is attributed to a balance between network assembly at the leading edge and disassembly at the rear. Although the molecular players and architecture of the lamellipodia have been investigated extensively during recent decades, it still remains elusive how the dynamic steady state with continuous retrograde flow is achieved and robustly maintained. In this study, using an agent-based computational model, we probed how physical interactions between subcellular components in the lamellipodia lead to the dynamic steady state. We reproduced a steady retrograde flow induced by myosin activity and balance between network assembly and disassembly but hindered by resistances from adhesions formed on the underlying substrate. We demonstrated that different modes of dynamic steady states are possible, and that a network which failed to show the retrograde flow due to perturbations can be rescued by altering other factors. Our study provides insights into understanding how cells maintain the dynamic steady state of the lamellipodia in highly varying microenvironments.
SuperWater: Predicting Water Molecule Positions on Protein Structures by Generative AI
Authors: Kuang Xiaohan , Su Zhaoqian , Liu Yunchao (Lance) , Lin Xiaobo , Spencer-Smith Jesse , Derr Tyler , Wu Yinghao , Meiler Jens 
Published: November 2024

AbstractWater molecules play a significant role in maintaining protein structural stability and facilitating molecular interactions. Accurate prediction of water molecule positions around protein structures is essential for understanding their biological roles and has significant implications for protein engineering and drug discovery. Here, we introduce SuperWater, a novel generative AI framework that integrates a score-based diffusion model with equivariant graph neural networks to predict water molecule placements around proteins with high accuracy. SuperWater surpasses existing methods, delivering state-of-the-art performance in both crystal water coverage and prediction precision, achieving water localization within 0.3 ± 0.06 °A of experimentally validated positions. We demonstrate the capabilities of SuperWater through case studies involving protein hydration, protein-ligand binding, and protein-protein binding sites. This framework can be adapted for various applications, including structural biology, binding site prediction, multi-body docking, and water-mediated drug design.
A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation
Authors: Wang Yu , Zhang Yunxiao , Leung Verina , Heydari Seradj Saba , Sonmez Utku , Servin-Vences Rocio , Lipomi Darren , Ye Li , Patapoutian Ardem 
Published: November 2024

SummaryCompared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. We found that selective PIEZO2 deletion in fat-innervating neurons phenocopied the molecular alternations in adipose tissue caused by DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.
Berberine: A dual anti-HIV and anti- cervical cancer compound
Authors: Naushad Wasifa , Okeoma Bryson C. , Islam Humayun K , Wang Zhen Zhen , Yang Nan , Li XiuMin , Okeoma Chioma M. 
Published: November 2024

AbstractWe report the effects of berberine (BBR), a benzylisoquinoline alkaloid small molecule on inhibition of HIV infection of cervical cancer cells. We used HeLa cell-derived TZM-bl cell line as a model of cervical cancer and HIV infection. BBR significantly inhibits viral and cancer processes, including expression of cell-associated HIV RNA, secretion of HIV reverse transcriptase, and HIV Tat-mediated LTR promoter transactivation. BBR significantly inhibits HIV-induced cancer cell viability and cell clustering. Besides its ability to inhibit HIV-induced cancer cell viability, BBR inhibits migration and matrix invasion of cervical cancer cells that are infected with HIV or treated with HIV Tat protein. The ability of BBR to inhibit cell clustering, collective cell migration, and cell invasion may have an effect in controlling progression of cervical cancer and HIV since collective migration and invasion are strategies for local tissue infiltration, as well as metastatic invasion in epithelial cancers. Interestingly, molecular docking and dynamic stimulation show that BBR binds HIVIIIBTat amino acid residues through non-covalent interactions that occurs at multiple sites including LYS71, providing mechanistic insights into BBR regulation HIV infection. The results of the present study suggest that BBR has the potential to inhibit HIV infection and comorbid cervical cancer progression.Graphical abstractBerberine (BBR), a benzylisoquinoline alkaloid small molecule, inhibits HIV infection of cervical cancer cells, suppresses HIV-induced migration and invasion of the cancer cells. Mechanistically, BBR interferes with Tat-mediated HIV LTR promoter transactivation and expression of different HIV RNA species, expression of early genes (multiply spliced Tat-Rev) and late genes (unspliced Gag-Pol).
A Realist Evaluation of a Fatigue Risk Management Plan (FRMP) Implementation in Obstetrics and Gynecology Residency: Calls for Systemic, Structural and Cultural Reform
Authors: Kassam Aliya , Antepim Benedicta , Thornton Kimberley , Kumagai Jason , Glaze Sarah 
Published: November 2024

AbstractBackgroundAccreditation standards in residency education are calling for initiatives to promote the wellness of resident physicians including the implementation of fatigue risk management plans (FRMPs). We sought to conduct a realist evaluation of a FRMP within a five-year Obstetrics and Gynecology (OBGYN) residency training program in labour and delivery units.MethodRealist inquiry askes what works, for whom, in what circumstances, and why? through examining contexts, mechanisms, and outcomes. Using a mixed method study design, we collected quantitative and qualitative data from OBGYN residents sequentially across three time points.ResultsThere were n=19 unique participants (60% response rate). Most of the participants identified as women (93.7%), single (56.2%) and without children (93.7%). Participants mean age was 28.5 years and ranged from junior to senior residents. We found no significant difference between median sleepiness scores across three timepoints (p=0.17) however 20% of residents reported starting and ending shifts with high sleepiness scores signaling impairment that is hazardous to both residents and patients. The n=6 resident interview participants, reported overlooking patient details (forgetting to order tests, and delaying care) as well as personal safety issues such as driving home whilst fatigued despite FRMP implementation.DiscussionSpecific aspects of the OBGYN FRMP such as the nap model and nutrition could help with decreasing perceptions of fatigue related to lack of sleep and lack of available food. While FRMPs might be helpful in de-stigmatizing fatigue in residency, FRMPs are unlikely to decrease levels of resident fatigue because of systemic, structural, and cultural barriers.
Gal-9 and DCN Serum Expression Reflect Accelerated Brain Aging and Are Attenuated by the Green-Mediterranean Diet: The 18-month DIRECT PLUS Proteomics-Brain MRI Trial
Authors: Pachter Dafna , Yaskolka Meir Anat , Kaplan Alon , Tsaban Gal , Zelicha Hila , Rinott Ehud , Levakov Gidon , Finkelstein Ofek , Shelef Ilan , Salti Moti , Beyer Frauke , Witte Veronica , Klöting Nora , Isermann Berend , Ceglarek Uta , Raviv Tammy Riklin , Blüher Matthias , Stumvoll Michael , Wang Dong D. , Hu Frank B , Stampfer Meir J , Avidan Galia , Shai Iris 
Published: November 2024

AbstractBackgroundWe recently reported that a green-Mediterranean (green-MED), high-polyphenol diet is potentially neuroprotective for age-related brain atrophy. Here, we explored the interplay between dietary intervention, proteomics profile, and accelerated brain age.MethodsIn the 18-month DIRECT PLUS trial, 294 participants (adherence rate=89%) were randomized to one of three arms: 1) Healthy dietary guidelines (HDG); 2) MED diet; or 3) green-MED diet. Both MED diets included 28g/day of walnuts. Additionally, the low red/processed meat green-MED group received daily supplements of polyphenol-rich green-tea and green Mankai aquatic plant. In this secondary analysis, we measured 87 serum proteins (Olink-CVDII) and conducted Magnetic Resonance Imaging (MRI) to obtain brain 3D-T1-weighted for brain age calculation based on brain convolutional neural network to identify protein markers reflecting the brain age gap (BAG: residual deviation of MRI-assessed brain age from chronological age).ResultsWe analyzed eligible brain MRIs (216 at baseline and 18-month) for BAG calculation. At baseline (age=51.3yrs, 90% men), lower weight, waist circumference, diastolic blood pressure, and HbA1c parameters were associated with younger brain age than expected (p<0.05 for all). At baseline, higher levels of two specific proteins: Galectin-9 (Gal-9) and Decorin (DCN), were associated with larger BAG (accelerated brain aging; FDR<0.05). A proteomics principal component analysis (PCA) revealed a significant difference between the 18-month time points among participants who completed the trial with accelerated brain aging (p=0.02). Between baseline and 18 months, Gal-9 significantly decreased (p<0.05) among individuals who completed the intervention with attenuated brain age, and DCN significantly increased (p<0.05) among those who completed the trial with accelerated brain age. A significant interaction was observed between the green-MED diet and proteomics PCA change compared to the HDG (β=-1.7; p-interaction=0.05). Participants in the green-MED diet significantly decreased Gal-9 compared to the HDG diet (p=0.015) and from baseline (p=0.003). DCN levels, however, marginally increased in the HDG diet from baseline (p=0.053).ConclusionHigher serum levels of Gal-9 and DCN may indicate an acceleration of brain aging and might be reduced by the green-MED/high-polyphenol diet rich in Mankai and green-tea and low in red/processed meat.Trial registration numberNCT03020186.