bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of clinical indicators for differentiating stages of chronic HBV infection based on pathological changes in liver tissue
Authors: Li Wentao , Zhang Binhao , Zhu Jiansheng , Liu Junyan , Wang Qiupeng , Feng Jiang , Xing Tongjing 
Published: March 2023

AbstractObjectiveTo screen and modify more accurate clinical and viral indicators for differentiating the different stages of chronic hepatitis B virus (HBV) infection based on liver histopathological changes.MethodsThe clinical and liver pathology data of chronic hepatitis B (CHB) patients undergoing liver biopsy were collected for retrospective analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the diagnostic value for differentiating the different stages of chronic HBV infection.ResultsA total of 118 patients who met the diagnostic and exclusion criteria were selected. There were significant differences among HBV DNA, hepatitis B surface antigen (HBsAg), HBeAg, HBcAb, and platelets (PLT) between the IT and IC stages. Platelets were significantly higher in patients with the IT stage of CHB than in patients with the IC stage, whereas HBcAb levels were directly reversed. Multivariate analysis showed that HBeAg independently correlated with the IT and IC stages. Univariate analysis showed that HBV DNA and HBsAg were quantified between the ICO and IR stages except for ALT. The cutoff value of HBeAg used to quantitatively differentiate between IT and IC was 1335 and the AUC was 0.921 (95% confidence interval (CI): 0.836 to 0.971).ConclusionsThe high levels of HBeAg rather than HBeAg positive might help to identify patients with the “true” IT stage. PLT and HBcAb are effective indicators for differentiating patients between the IT and IC stages of chronic HBV infection. HBV DNA of <20 IU/mL may be a more rational cutoff value for ICO patients.
Impact of Diabetes Mellitus on Myocardial Fibrosis in Patients with Hypertension: the REMODEL Study
Authors: Pua Chee Jian , Loo Germaine , Kui Michelle , Moy Wai Lun , Hii An-An , Lee Vivian , Chin Chee-Tang , Bryant Jennifer A , Toh Desiree-Faye , Lee Chi-Hang , Cook Stuart A , Richards A Mark , Le Thu-Thao , Chin Calvin WL 
Published: March 2023

ABSTRACTBACKGROUNDCompared to patients with hypertension only (HTN), those with hypertension and diabetes (HTN/DM) have worse prognosis. We aimed to characterize morphological differences between HTN and HTN/DM using cardiovascular magnetic resonance (CMR); and compare differentially expressed proteins associated with myocardial fibrosis using high throughput multiplex assays.METHODSAsymptomatic patients underwent CMR: 438 patients with HTN (60±8 years; 59% males) and 167 age- and sex-matched patients with HTN/DM (60±10 years; 64% males). Replacement myocardial fibrosis was defined as non-ischemic late gadolinium enhancement on CMR. Extracellular volume (ECV) fraction was used as a marker of diffuse myocardial fibrosis. A total of 184 serum proteins (Olink Target CVD II and III panels) were measured to identify unique signatures associated with myocardial fibrosis in all patients.RESULTSDespite similar left ventricular (LV) mass (P=0.344) and systolic blood pressure (P=0.086), patients with HTN/DM had increased concentricity and worse multi-directional strain (P<0.001 for comparison of all strain measures) compared to HTN only. Replacement myocardial fibrosis was present in 28% of patients with HTN/DM compared 16% of those with HTN (P<0.001). NT-proBNP was the only protein differentially upregulated in HTN patients with replacement myocardial fibrosis and independently associated with ECV. In patients with HTN/DM, GDF-15 was independently associated with replacement myocardial fibrosis and ECV. Ingenuity Pathway Analysis demonstrated a strong association between increased inflammatory response/immune cell trafficking and myocardial fibrosis in patients with HTN/DM.CONCLUSIONSAdverse cardiac remodeling was observed in patients with HTN/DM. The novel proteomic signatures and associated biological activities of increased immune and inflammatory response may partly explain these observations.CLINICAL PERSPECTIVESMyocardial fibrosis is a hallmark of heart failure and predicts worse cardiovascular outcomes in patients with hypertension. There is increasing interest to target the myocardial interstitium to improve diagnosis, risk stratification and to discover novel therapies. Our study demonstrates that myocardial fibrosis is a heterogeneous pathology resulting from cardiac disease-specific biology. In hypertensive patients, concomitant diabetes mellitus accelerates adverse cardiac remodeling. This observation endorses the importance to consider early risk stratification by imaging and/or biomarker profiling in these patients. Whether patients with hypertension and diabetes would derive incremental anti-fibrotic benefits from therapies targeting inflammation/immune activate require further investigations.
Ipsilateral restriction of chromosome movement along a centrosome, and apical-basal axis during the cell cycle
Authors: Cai Pingping , Casas Christian J. , Plancarte Gabriel Quintero , Hua Lisa L. , Mikawa Takashi 
Published: March 2023

AbstractLittle is known about how distance between homologous chromosomes are controlled during the cell cycle. Here, we show that the distribution of centromere components display two discrete clusters placed to either side of the centrosome and apical/basal axis from prophase to G1interphase. 4-Dimensional live cell imaging analysis of centromere and centrosome tracking reveals that centromeres oscillate largely within one cluster, but do not cross over to the other cluster. We propose a model of an axis-dependent ipsilateral restriction of chromosome oscillations throughout mitosis.
Single-cell transcriptome dataset of human and mousein vitroadipogenesis models
Authors: Li Jiehan , Jin Christopher , Gustafsson Stefan , Rao Abhiram , Wabitsch Martin , Park Chong Y. , Quertermous Thomas , Bielczyk-Maczynska Ewa , Knowles Joshua W. 
Published: March 2023

AbstractAdipogenesis is a process in which fat-specific progenitor cells (preadipocytes) differentiate into adipocytes that carry out the key metabolic functions of the adipose tissue, including glucose uptake, energy storage, and adipokine secretion. Several cell lines are routinely used to study the molecular regulation of adipogenesis, in particular the immortalized mouse 3T3-L1 line and the primary human Simpson-Golabi-Behmel syndrome (SGBS) line. However, the cell-to-cell variability of transcriptional changes prior to and during adipogenesis in these models is not well understood. Here, we present a single-cell RNA-Sequencing (scRNA-Seq) dataset collected before and during adipogenic differentiation of 3T3-L1 and SGBS cells. To minimize the effects of experimental variation, we mixed 3T3-L1 and SGBS cells and used computational analysis to demultiplex transcriptomes of mouse and human cells. In both models, adipogenesis results in the appearance of three cell clusters, corresponding to preadipocytes, early and mature adipocytes. These data provide a groundwork for comparative studies on human and mouse adipogenesis, as well as on cell-to-cell variability in gene expression during this process.
Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases
Authors: Boodaghidizaji Miad , Jungles Thaisa , Chen Tingting , Zhang Bin , Landay Alan , Keshavarzian Ali , Hamaker Bruce , Ardekani Arezoo 
Published: March 2023

AbstractGut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data has a potential to be a great source of information for the diagnosis and disease characteristics (phenotypes, disease course, therapeutic response) of diseases with dysbiotic microbiota community. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach is now feasible by availability of machine learning that is able to identify hidden patterns in the human microbiome and predict diseases. Accordingly, the aim of our study was to test the hypothesis that application of machine learning algorithms can distinguish stool microbiota pattern and microbiota response to fiber between diseases where overlapping dysbiotic microbiota have been previously reported. Here, we have applied machine learning algorithms to distinguish between Parkinson’s disease, Crohn’s disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We have shown that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, machine learning methods applied to the microbiome data to predict UC vs CD led to prediction accuracy as high as 90%.
Distinct mesoscale cortical dynamics encode search strategies during spatial navigation
Authors: Surinach Daniel , Rynes Mathew L , Saxena Kapil , Ko Eunsong , Redish A David , Kodandaramaiah Suhasa B 
Published: March 2023

ABSTRACTSpatial navigation is a complex cognitive process that involves neural computations in distributed regions of the brain. Little is known about how cortical regions are coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium (Ca2+) dynamics across large swathes of the dorsal cortex in mice solving the Barnes maze, a 2D spatial navigation task where mice used random, serial, and spatial search strategies to navigate to the goal. Cortical dynamics exhibited patterns of repeated calcium activity with rapid and abrupt shifts between cortical activation patterns at sub-second time scales. We used a clustering algorithm to decompose the spatial patterns of cortical calcium activity in a low dimensional state space, identifying 7 states, each corresponding to a distinct spatial pattern of cortical activation, sufficient to describe the cortical dynamics across all the mice. When mice used serial or spatial search strategies to navigate to the goal, the frontal regions of the cortex were reliably activated for prolonged durations of time (> 1s) shortly after trial initiation. These frontal cortex activation events coincided with mice approaching the edge of the maze from the center and were preceded by temporal sequences of cortical activation patterns that were distinct for serial and spatial search strategies. In serial search trials, frontal cortex activation events were preceded by activation of the posterior regions of the cortex followed by lateral activation of one hemisphere. In spatial search trials, frontal cortical events were preceded by activation of posterior regions of the cortex followed by broad activation of the lateral regions of the cortex. Our results delineated cortical components that differentiate goal- and non-goal oriented spatial navigation strategies.
A Pvr–AP-1–Mmp1 signaling pathway is activated in astrocytes upon traumatic brain injury
Authors: Li Tingting , Shi Wenwen , Ho Margaret S. , Zhang Yong Q. 
Published: March 2023

AbstractTraumatic brain injury (TBI) caused by external mechanical forces is a major health burden worldwide, but the underlying mechanism in glia remains largely unclear. We report herein thatDrosophilaadults exhibit a defective blood-brain-barrier (BBB), elevated innate immune responses, and astrocyte swelling upon consecutive strikes with a high-impact trauma device. RNA sequencing (RNA-seq) analysis of these astrocytes revealed upregulated expression of genes encoding PDGF and VEGF receptor-related (Pvr, a receptor tyrosine kinase (RTK)), adaptor protein complex 1 (AP-1, a transcription factor complex of the c-Jun N-terminal Kinase (JNK) pathway) composed of Jun-related antigen (Jra) and kayak (kay), and matrix metalloproteinase 1 (Mmp1) following TBI. Interestingly, Pvr is both required and sufficient for AP-1 and Mmp1 upregulation, while knockdown of AP-1 expression in the background of Pvr overexpression in astrocytes rescued Mmp1 upregulation upon TBI, indicating that Pvr acts as the upstream receptor for the downstream AP-1–Mmp1 transduction. Moreover, dynamin-associated endocytosis was found to be an important regulatory step in downregulating Pvr signaling. Our results identify a new Pvr–AP-1–Mmp1 signaling pathway in astrocytes in response to TBI, providing potential targets for developing new therapeutic strategies of TBI.Main PointsThe study provided RNA-seq data of astrocytes following traumatic brain injury (TBI)Genes involved in endocytic trafficking are upregulated in astrocytes after TBIA new Pvr–AP-1–Mmp1 pathway is activated in astrocytes following TBI.Inhibition of endocytosis in astrocytes upregulates the Pvr–AP-1–Mmp1 signaling.
Hip geometric parameters are associated with radiographic and clinical hip osteoarthritis: findings from a cross-sectional study in UK Biobank
Authors: Heppenstall SV , Ebsim R , Saunders FR , Lindner C , Gregory JS , Aspden RM , Harvey NC , Cootes T , Tobias JH , Frysz M , Faber BG 
Published: March 2023

AbstractObjectivesTo examine the extent to which geometric parameters derived from dual-energy x-ray absorptiometry (DXA) scans in the UK Biobank (UKB) study are related to hip osteoarthritis (HOA) independently of sex, age and body size.MethodsFemoral neck width (FNW), diameter of the femoral head (DFH) and hip axis length (HAL) were derived automatically from left hip DXA scans in UKB using outline points placed around the hip by a machine-learning program. Correlations were calculated between geometric parameters, age, height, and weight. Logistic regression was used to examine the relationship of geometric parameters with radiographic hip osteoarthritis (rHOA), and hospital diagnosed HOA (HESOA), and Cox proportional hazards model to evaluate the relationship with total hip replacement (THR). Analyses were adjusted for sex, age, height, weight, and geometric parameters.ResultsComplete data were available for 40,312 participants. In age and sex-adjusted analyses, FNW, HAL and DFH were all related to increased risk of rHOA. Despite strong relationships between geometric parameters and body size, relationships between geometric parameters and HOA showed little attenuation after adjustment for height and weight. Following mutual adjustment, both HAL and FNW retained independent relationships with rHOA, while DFH was now protective. Only FNW was independently related to HESOA and THR.ConclusionGreater FNW and HAL were independently related to an increased risk of rHOA, whereas greater DFH appeared to be protective. Greater FNW was independently predictive of HESOA and THR. These results suggest DXA-derived geometric parameters, particularly FNW, could help to predict HOA and THR risk.
Efficacy and feasibility of Pharmacoscopy-guided treatment for acute myeloid leukemia patients that exhausted all registered therapeutic options
Authors: Schmid Jonas Andreas , Festl Yasmin , Severin Yannik , Bacher Ulrike , Kronig Marie-Noëlle , Snijder Berend , Pabst Thomas 
Published: March 2023

AbstractElderly or unfit patients with relapsed acute myeloid leukemia (AML) face a poor prognosis and are likely to rapidly exhaust all registered treatment options. Pharmacoscopy, an image-basedex vivodrug screening platform, has previously been suggested as a tool for treatment selection in AML. We used pharmacoscopy to generate personalized treatment recommendations for 30 relapse settings of 24 AML patients which exhausted all standard therapeutic options. We evaluated whether pharmacoscopy can be employed within the narrow timeframe available under an AML relapse setting, how often recommended regimens could be started and whether they provided durable clinical benefits. 17 of 30 screens (56.7%) resulted in patients receiving a recommended therapy, leading to promising trends in clinical response and survival. A drug regimen’s integrated pharmacoscopy score proved to be an excellent predictor of clinical response: Patients receiving a regimen with above-median scores showed significantly higher rates of complete remission (OR 3.01, p < 0.0005) and significantly longer overall survival (ratio 3.39, p < 0.006). We conclude that pharmacoscopy is an efficient and valuable tool for therapy selection in AML at relapse and propose concrete measures to further improve clinical implementation.
Hippocampal and amygdala subfield volumes in obsessive-compulsive disorder differ according to medication status
Authors: Ntwatwa Ziphozihle , Lochner Christine , Roos Annerine , Sevenoaks Tatum , van Honk Jack , Alonso Pino , Batistuzzo Marcelo C. , Choi Sunah , Hoexter Marcelo Q. , Kim Minah , Kwon Jun S. , Mataix-Cols David , Menchón José M. , Miguel Euripides C. , Nakamae Takashi , Phillips Mary L. , Soriano-Mas Carles , Veltman Dick J. , Groenewold Nynke A. , van den Heuvel Odile A. , Stein Dan J. , Ipser Jonathan 
Published: March 2023

AbstractIntroAlthough it has been suggested that the hippocampus and amygdala (HA) are involved in the neurobiology of obsessive-compulsive disorder (OCD), volumetric findings have been inconsistent. Furthermore, the HA consist of heterogenous anatomic units with specific functions and cytoarchitecture, and little work has been undertaken on the volumetry of these subfields in OCD.MethodsT1-weighted images from 381 patients with OCD and 338 healthy controls (HCs) from the OCD Brain Imaging Consortium were segmented to produce twelve hippocampal subfields and nine amygdala subfields using FreeSurfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age, quadratic effects of age, sex, site, and whole HA volume. Given evidence of confounding effects of clinical characteristics on brain volumes in OCD, we also performed subgroup analyses to examine subfield volume in relation to comorbid anxiety and depression, medication status, and symptom severity.ResultsPatients with OCD and HCs did not significantly differ in HA subfield volume. However, medicated patients with OCD had significantly smaller hippocampal dentate gyrus (pFDR=0.042,d=-0.26) and molecular layer (pFDR=0.042, d=-0.29) and larger lateral (pFDR=0.049,d=0.23) and basal (pFDR=0.049,d=0.25) amygdala subfields than HCs. Unmedicated patients had significantly smaller hippocampal CA1 (pFDR=0.016, d=-0.28) than HCs. No association was detected between any subfield volume and OCD severity.ConclusionDifferences in HA subfields between OCD and HCs are dependent on medication status, in line with previous work on other brain volumetric alterations in OCD. This emphasizes the importance of considering psychotropic medication in neuroimaging studies of OCD.
The Intra-Host Evolutionary Landscape And Pathoadaptation Of PersistentStaphylococcus aureusIn Chronic Rhinosinusitis
Authors: Houtak Ghais , Bouras George , Nepal Roshan , Shaghayegh Gohar , Cooksley Clare , Psaltis Alkis James , Wormald Peter-John , Vreugde Sarah 
Published: March 2023

AbstractChronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated withStaphylococcus aureusbiofilm and relapsing infections. This study aimed to determine rates ofS. aureuspersistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic resistance/tolerance in longitudinally collectedS. aureusclinical isolates.A total of 68S. aureusisolates were sourced from 34 CRS patients at least six months apart. Isolates were grown into 48-hour biofilms and tested for tolerance to antibiotics. A hybrid sequencing strategy was used to obtain high-quality reference-grade assemblies of all isolates. Single nucleotide variants (SNV) divergence in the core genome and sequence type clustering were used to analyse the relatedness of the isolate pairs. Single nucleotide and structural genome variations, plasmid similarity, and plasmid copy numbers between pairs were examined.Our analysis revealed that 41% (14/34 pairs) ofS. aureusisolates were persisters, while 59% (20/34 pairs) were non-persisters. Persister isolates showed episode-specific mutational changes over time with a bias towards events in genes involved in adhesion to the host and mobile genetic elements such as plasmids, prophages, and insertion sequences. A significant increase in the copy number of conserved plasmids of persister strains (p<0.05) was seen, indicating a role of the “mobilome” in promoting persistence. This was accompanied by a significant increase in biofilm tolerance against all tested antibiotics (p<0.001), which was linked to a significant increase in biofilm biomass (p<0.05) over time, indicating a biofilm central pathoadaptive process in persisters. In conclusion, our study provides important insights into the mutational changes underlyingS. aureuspersistence in CRS patients highlighting pathoadaptive mechanisms inS. aureuspersisters culminating in increased biofilm biomass linked to an increase in plasmid copy number over time.
CA3 hippocampal synaptic plasticity supports ripple physiology during memory consolidation
Authors: Oussini Hajer El , Zhang Chun-Lei , François Urielle , Castelli Cecilia , Lampin-Saint-Amaux Aurélie , Lepleux Marilyn , Molle Pablo , Velez Legeolas , Dejean Cyril , Lanore Frédéric , Herry Cyril , Choquet Daniel , Humeau Yann 
Published: March 2023

AbstractConsolidation of recent memory depends on hippocampal activities during resting periods that immediately follows the memory encoding. There, Slow Save Sleep phases appear as privileged periods for memory consolidation as hosting the ripple activities, which are fast oscillations generated within the hippocampus whose inactivation leads to memory impairment. If a strong correlation exists between these replays of recent experience and the persistence of behavioural adaptations, the mobilisation, the localization and the importance of synaptic plasticity events in this process is largely unknown. To question this issue, we used cell-surface AMPAR immobilisation to block post-synaptic LTP within the hippocampal region at various steps of the memory process. 1- Our results show that hippocampal synaptic plasticity is engaged during the consolidation but is dispensable during the encoding or recall of a working memory based spatial memory task. 2- Blockade of plasticity during sleep leads to apparent forgetting of the encoded rule. 3-In vivorecordings of ripple activities during resting periods show a strong impact of AMPAR immobilization solely, prominent when a rule has been recently encoded. 4-In situexamination of the interplay between AMPAR mobility, hippocampal plasticity and spontaneous ripple activities pointed that post-synaptic plasticity at CA3-CA3 recurrent synapses support ripple generation. As crucial results were reproduced using another AMPARM blockade strategy, we propose that after rule encoding, post-synaptic AMPAR mobility at CA3 recurrent synapses support the generation of ripples necessary for rule consolidation.