bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Anxiety with Uncinate Fasciculus Lesion Burden in Multiple Sclerosis
Authors: Baller Erica B. , Luo Audrey C. , Schindler Matthew K. , Cooper Elena C. , Pecsok Margaret K. , Cieslak Matthew C. , Martin Melissa Lynne , Bar-Or Amit , Elahi Ameena , Perrone Christopher M. , Reid Donovan , Spangler Bailey C. , Satterthwaite Theodore D. , Shinohara Russell T. 
Published: October 2024

ABSTRACTImportanceMultiple sclerosis (MS) is an immune-mediated neurological disorder that affects 2.4 million people world-wide, and up to 60% experience anxiety.ObjectiveWe investigated how anxiety in MS is associated with white matter lesion burden in the uncinate fasciculus (UF).DesignRetrospective case-control study of participants who received research-quality 3-tesla (3T) neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from June 1stto September 30th, 2024.SettingSingle-center academic medical specialty MS clinic.ParticipantsParticipants were identified from the electronic medical record. All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 372 were stratified into three groups which were balanced for age and sex: 1) MS without anxiety (MS+noA, n=99); 2) MS with mild anxiety (MS+mildA, n=249); and 3) MS with severe anxiety (MS+severeA, n=24).ExposureAnxiety diagnosis and anxiolytic medication.Main Outcome and MeasureWe first evaluated whether MS+severeA patients had greater lesion burden in the UF than MS+noA. Next, we examined whether increasing anxiety severity was associated with greater UF lesion burden. Generalized additive models were employed, with the burden of lesions (e.g. proportion of fascicle impacted) within the UF as the outcome measure and sex and spline of age as covariates.ResultsUF burden was higher in MS+severeA as compared to MS+noA (T=2.02, P=0.045, Cohen’sf2=0.19). A dose-response effect was also found, where higher mean UF burden was associated with higher anxiety severity (T=2.08, P=0.038, Cohen’sf2=0.10).Conclusions and RelevanceWe demonstrate that overall lesion burden in UF was associated with the presence and severity of anxiety in patients with MS. Future studies linking white matter lesion burden in UF with treatment prognosis are warranted.KEY POINTSQuestionAre white matter lesions that impact the uncinate fasciculus (UF) associated with anxiety in patients with multiple sclerosis (MS)?FindingsThis retrospective, case-control study of 372 patients with MS included 3 anxiety severity groups: 1) MS without anxiety (MS+noA, n=99); 2) MS with mild anxiety (MS+mildA, n=249); and 3) MS with severe anxiety (MS+severeA, n=24). We identified associations between anxiety and UF lesion burden. Specifically, we showed that MS+severeA had higher UF lesion burden than MS+noA, and worsening anxiety severity increased with greater UF burden.MeaningLesion burden in the UF may contribute to anxiety comorbidity in MS.
The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in aDrosophilacarcinoma model
Authors: Mira-Osuna Marta , Plunder Steffen , Theveneau Eric , Le Borgne Roland 
Published: October 2024

AbstractCarcinomas originate in epithelia and are the most frequent type of cancers. Tumor progression starts with the collective delamination of live tumors out of the epithelium, and requires modulation of cell adhesion. Yet, it remains elusive exactly how remodeling of epithelial cell-cell and cell-extracellular matrix contacts contribute to metastasis onset and delamination directionality. We usedDrosophila melanogasterlarval eye disc to study cooperative oncogenesis and determine the contribution of bi- and tricellular septate junction (SJ) components to tumor progression in flat and pseudostratified epithelia. We reveal that loss-of-function of septate junction components alone can promote cell death whereas synergic interaction with oncogenic Ras triggers the collective delamination of living tumorigenic cells. Spatiotemporal analyses reveal apical and basal delamination processes differ in terms of cell identity, cell polarity and remodeling of cell-cell and cell-ECM contacts. Using a combination ofin vivoandin silicoapproaches, we report that SJ-depletedRasV12tumors in pseudostratified epithelia trigger tissue folding or basal collective delamination regardless of the order in which cell contacts are remodeled. In striking contrast, SJ-depletedRasV12tumors formed in flat, squamous epithelia, first undergo apical constriction and acquire a dome-like shape. Tumors are enriched in adhesion molecules and form an apical neck at the interface of contact between mutant cells and wild-type neighbors. Concomitant to cytoskeleton remodeling, tumors emit apical protrusions in the lumen and progressively delaminate through the apical neck while remaining cohesive. Our study reveals that tissue architecture and changes in cell adhesion drive the directionality of collective delamination of neoplastic tumors out of an epithelium.
EPHA2 Regulates SOX2 during Esophageal Development
Authors: Li Tianxia , Mitani Yosuke , Cruz-Acuña Ricardo , Karaksheva Tatiana A. , Sahu Varun , Martin Cecilia , Nakagawa Hiroshi , Gabre Joel 
Published: October 2024

AbstractThe human esophagus, derived from the anterior foregut endoderm, requires proper dorsal-ventral patterning for development. The transcription factor SOX2, crucial in this process, when dysregulated, leads to congenital esophageal abnormalities. EPHA2, a receptor tyrosine kinase, is vital in various developmental processes and cancer models, where it activates SOX2. This study demonstrates that EPHA2 regulates SOX2 expression during esophageal development using human iPSCs and iPSC-derived human esophageal organoids (HEO). Inhibition of EPHA2 decreased iPSC-derived HEO formation and SOX2 expression. These findings provide evidence of EPHA2 as being a key regulator of SOX2 signaling in early esophageal development.Graphical AbstractSFD: Serum-Free Differentiation media; EPC: esophageal progenitor cells; HEO: human esophageal organoidsCreated with BioRender.comHighlightsSOX2 is crucial for proper esophageal development.EPHA2 is a receptor tyrosine kinase involved in various developmental processes.EPHA2 activates SOX2.Inhibition of EPHA2 decreased SOX2 expression and human esophageal organoid formation.
Interstitial infusion of purified collagenase Clostridium histolyticum in the cirrhotic liver causes rapid reduction in fibrosis with minimal liver toxicity
Authors: Leaker Ben D. , Fuchs Christiane , Wise Emma , Tam Joshua , Anderson R. Rox 
Published: October 2024

AbstractCrude mixtures of matrix-degrading enzymes called collagenase Clostridium histolyticum (CCH) have been used to efficiently breakdown tissue for many years. Recently, direct injection of purified CCH has been successfully developed as a treatment for Dupuytren’s contracture (DC), a fibrotic disorder of the hand. Given similar histologic and mechanical features between the fibrous bands in DC and cirrhosis, a similar approach may be feasible for the treatment of cirrhosis. Crude and purified CCH were first compared through composition and substrate specificity. The biodistribution of a macromolecule delivered via interstitial infusion in the liver was mapped and quantified with a fluorescent dextran tracer to design a protocol for efficient delivery throughout the liver with minimal off-target exposure. Safety and efficacy of interstitial CCH infusion in the liver was investigated in cirrhotic mice using serum markers of injury and histological analysis of fibrosis. Purified CCH showed high purity and efficient degradation of type I collagen. Tracer experiments showed that interstitial infusion in one lobe of the liver will reach the entire organ in the mouse. A significant amount of the tracer was also found to enter the bloodstream where it is cleared by the kidneys, but was not found to significantly infiltrate other organs. Mild elevation in liver enzymes AST and ALT were observed 1d after infusion of purified CCH, but this was not significantly different than infusion with saline. No elevation in creatinine was observed. Cirrhotic mice infused with purified CCH showed 38% reduction in collagen proportionate area compared to mice infused with saline. These results show interstitial delivery of purified CCH in the cirrhotic liver rapidly decreases collagen content with minimal liver toxicity. This strategy merits further study as a potential treatment for cirrhosis.
Cultured Bacteria Isolated from Primary Sclerosing Cholangitis Patient Bile Induce Inflammation and Cell Death
Authors: Powell Chelsea E. , McCurry Megan D. , Quevedo Silvia Fernanda , Ventura Lindsay , Krishnan Kumar , Dave Malav , Mahmood Shaikh Danish , Specht Katherine , Bordia Raghav , Pratt Daniel S. , Korzenik Joshua R. , Devlin A. Sloan 
Published: October 2024

ABSTRACTBackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and progressive fibrosis of the biliary tree. The pathogenesis of PSC remains poorly understood, and there are no effective therapeutic options. Previous studies have observed associations between changes in the colonic and biliary microbiome and PSC. We aimed to determine whether bacterial isolates cultured from PSC patient bile induced disease-associated phenotypes in cells.MethodsBile was collected from PSC patients (n=10) by endoscopic retrograde cholangiography and from non-PSC controls (n=3) undergoing cholecystectomies. Biliary bacteria were cultured anaerobically, and 50 colonies per sample were identified by 16S rRNA sequencing. The effects of supernatants from seven PSC-associated bacterial strains on cellular phenotypes were characterized using human colonic (Caco-2), hepatic (HepG2), and biliary (EGI-1) cells.ResultsNo bacteria were isolated from non-PSC controls, while bacteria were cultured from most PSC patients. The PSC bile microbiomes exhibited reduced diversity compared to the gut or oral cavity, with one or two bacterial strains predominating. Overall, PSC-associated bacteria produced factors that were cytotoxic to hepatic and biliary cells.Enterococcus faecalis, and to a lesser extentVeillonella parvula, induced epithelial permeability, whileEscherichia coli, Fusobacterium necrophorum, andKlebsiella pneumoniaeinduced inflammatory cytokines in biliary cells.ConclusionsOur data suggest that bacteria cultured from PSC bile induce cellular changes that may contribute to PSC disease pathogenesis.Enterococcusmay promote intestinal permeability, facilitating bacterial migration to the biliary tree. Once there,Escherichia, FusobacteriumandKlebsiella, may cause inflammation and damage in biliary and liver cells.
A Benchmark of methods for SARS-CoV-2 whole genome sequencing and development of a more sensitive method
Authors: Bayega Anthony , Reiling Sarah J. , Dubuc Isabelle , Gravel Annie , Flamand Louis , Ragoussis Jiannis 
Published: October 2024

AbstractThe raging COVID-19 pandemic caused by SARS-CoV-2 has so far claimed the lives of 4.6 million people and continues to infect many more. Further, virus evolution has caused mutations that have compromised public health interventions like vaccination regimes and monoclonal antibody and convalescent sera treatments. In response, unprecedented large-scale whole genome viral surveillance approaches have been devised to keep track of the evolution and transmission patterns of the virus within and across populations. Here, we aimed to compare efficiencies of SARS-CoV-2 whole genome sequencing approaches using synthetic SARS-CoV-2 genome and six cell culture SARS-CoV-2 variants titrated to represent samples at high, medium, and low viral load. We found that the ARTIC protocols performed best in terms of PCR amplicon yield returning 67% more amplicons than Entebbe protocol which was the second highest PCR amplicon yielding protocol. ARTIC v4.1 protocol yields were only slightly better than ARTIC v3. Despite yielding the lowest PCR amplicons, the SNAP protocol showed the highest genome completeness using a synthetic genome at high viral titre followed by ARTIC protocols. However, the ARTIC protocols showed highest genome completeness with cell culture SARS-CoV-2 variants across high, medium and low viral titres. ARTIC protocol also performed best in calling the correct lineage among cell culture SARS-CoV-2 variants across different viral titres. We also designed a new method termed ARTIC-Amp which leverages ARTIC protocol and performs a rolling circle amplification to increase yield of amplicons. In a proof-of-principle experiment, this method showed 100% coverage in all four targeted genes across three replicates unlike the ARTIC protocol missed one gene in two of the three replicates. Our results demonstrate the robustness of the ARTIC protocol and propose an improved method that could be useful for samples that routinely have limited SARS-CoV-2 RNA such as wastewater samples.Contribution to the field
Type 1 Diabetes Mellitus in Tanzania: a systematic review of prevalence and incidence
Authors: Mrema Lucy Elauteri , Mapunda Anthony , Sylvester Pauline , Olomi Willyhelmina , Ntinginya Nyanda Elias , Mayige Mary 
Published: October 2024

AbstractObjectiveType 1 diabetes mellitus (T1DM) is a chronic disease that affects children and adolescents globally. However, there is a paucity of data on the incidence and prevalence T1DM in Tanzania. This systematic review aimed to determine the prevalence and incidence of type 1 diabetes mellitus Tanzania through a comprehensive review of available literature.MethodsA systematic literature search was conducted in six electronic databases (PubMed, Scopus, Web of Science, Embase, African Journals Online, and Tanzania Medical Journal) to identify studies reporting on the prevalence and incidence of T1DM in Tanzania. The search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsA total of 63 studies were identified through the initial search, of which two studies met the inclusion criteria. Both studies were conducted in Dar es Salaam, Mwanza, Zanzibar, Kilimanjaro Tanzania, and reported on the incidence and prevalence of T1DM in children and adolescents. The studies were published in 1993 and 2019, respectively. The first study reported an annual incidence of T1DM of 1.5 per 100,000 population aged 0-19 years, while the second study reported an annual incidence ranging from 1.8 to 1.9 per 100,000 children and a prevalence ranging from 10.1 to 11.9 per 100,000 children.ConclusionThe prevalence and incidence of T1DM in Tanzania are relatively low, based on the limited evidence available. More prevalence and incidence studies are needed to provide a better understanding of the burden of T1DM to inform diabetes management strategies in the country.EthicsSince this review has used previously published studies, consent of an ethics committee was not sought.PROSPERO registration numberCRD42022369954.
The Efficacy of transcranial Direct Current Stimulation (tDCS) on Emotional Processing
Authors: Akbari Fatemeh , Narmashiri Abdolvahed 
Published: October 2024

AbstractWhile some research has reported the positive impacts of transcranial direct current stimulation (tDCS) on emotional processing, the conflicting results and variations in study quality and design make it challenging to draw firm conclusions about its effects. To address this issue, we conducted a meta-analysis of the published literature on tDCS effects on emotional processing. We evaluated the effects of anodal and cathodal tDCS on emotional processing by analyzing a total of 32 articles and a combined sample of 2,107 participants. Our study illustrates the significant effects of both anodal and cathodal tDCS on emotional processing. The results highlight significant differences in how tDCS stimulation parameters influence emotional processing, demonstrating that frontal tDCS enhances emotional outcomes more effectively than stimulation of other brain regions. Key findings include that longer stimulation durations (over 20 minutes) and higher current intensities (2 mA) yield better results, with online tDCS being more effective than offline stimulation, particularly in younger participants and in non-clinical populations. Our results reveal that tDCS can effectively enhance emotional processing, offering valuable insights into the potential benefits of this method for emotion improvement.
A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer
Authors: Scales TashJaé Q. , Smith Bradley , Blanchard Lisa M. , Wixom Nellie , Tuttle Emily T. , Altman Brian J. , Peppone Luke J. , Munger Joshua , Campbell Thomas M. , Campbell Erin K. , Harris Isaac S. 
Published: October 2024

AbstractBackgroundAmino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. The extent to which a plant-based diet lowers the serum levels of amino acids in patients with cancer is unclear.MethodsPatients with metastatic breast cancer (n=17) were enrolled in a clinical trial with an ad libitum whole food, plant-based diet for 8 weeks without calorie or portion restriction. Dietary changes by participants were monitored using a three-day food record. Serum was collected from participants at baseline and 8 weeks. Food records and serum were analyzed for metabolic changes.ResultsWe found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF were reduced in participants. The diet contained lower levels of essential and non-essential amino acids, except for arginine (glutamine and asparagine were not measured). Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids).ConclusionsThese findings provide a tractable approach to limiting amino acid levels in persons with cancer. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.Trial RegistrationThe clinical trial was registered withClinicalTrials.govidentifierNCT03045289on 2017-02-07.
Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single particle cryo-EM
Authors: Cook Matthew , Freniere Christian , Wu Chunxiang , Lozano Faith , Xiong Yong 
Published: October 2024

SummaryOne of the most striking features of HIV is the capsid; a fullerene cone comprised of the pleomorphic capsid protein (CA) which shields the viral genome from cellular defense mechanisms and recruits cellular cofactors to the virus. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interaction, HIV-2 CA remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we were able to determine high resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and in complexes with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6. While the overall fold and mode of binding the FG-peptides are conserved with HIV-1, this study reveals distinctive structural features that define the HIV-2 CA lattice, potential differences in interactions with other host factors such as CypA, and divergence in the mechanism of formation of hexameric and pentameric CA assemblies. This study extends our understanding of HIV capsids and highlights an approach with significant potential to facilitate the study of lentiviral capsid biology.
Loss of 18q alters TGFβ signalling affecting anteroposterior neuroectodermal fate in human embryonic stem cells
Authors: Lei Yingnan , Duong Mai Chi , Krivec Nuša , Janssens Charlotte , Regin Marius , Huyghebaert Anfien , Couvreu de Deckersberg Edouard , Sermon Karen , Delbany Diana Al , Spits Claudia 
Published: October 2024

AbstractChromosomal abnormalities acquired during cell culture can compromise the differentiation potential of human pluripotent stem cells (hPSCs). In this work, we identified a diminished differentiation capacity to retinal progenitor cells in human embryonic stem cells (hESCs) with loss of chromosome 18q. Time-course gene-expression analysis during spontaneous differentiation and single-cell RNA sequencing found that these variant cell lines poorly specified into anterior neuroectoderm, and, when progressing through differentiation, they yielded poorly pigmented cells, with proliferating and pluripotent cell populations. The variant cell lines showed dysregulation of TGFβ signaling during differentiation, and chemical modulation of the TGFβ pathways showed that the basis of the improper specification was due to imbalances in the anteroposterior neuroectodermal fate commitment.
Neural processes linking joint hypermobility and anxiety: Key roles for the amygdala and insular cortex
Authors: Kampoureli Christina N , Rae Charlotte L , Gould Van Praag Cassandra , Harrison Neil A , Garfinkel Sarah N , Critchley Hugo D , Eccles Jessica A 
Published: October 2024

AbstractBackground and AimsAnxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.MethodsWe used functional magnetic resonance neuroimaging (fMRI) to quantify regional brain responses to emotional stimuli (facial expressions) in patients with generalised anxiety disorder (N=30) and a non-anxious comparison group (N=33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of Hypermobility Syndrome (HMS: now considered Hypermobility Spectrum Disorder).ResultsHMS participants showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices), and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in HMS patients with generalised anxiety disorder. Severity of hypermobility in anxious, compared to non-anxious, individuals correlated with activity within anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in HMS, compared to non-HMS, participants.ConclusionsThe predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate of amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.