bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Individuals With Hepatitis B Virus-Related Cirrhosis in a Large Integrated Health Care Organization, 2008-2019
Authors: Florea Ana , Pak Katherine J. , Gounder Prabhu , Malden Debbie E. , Im Theresa M. , Chitnis Amit S. , Wong Robert J. , Sahota Amandeep K. , Tartof Sara Y. 
Published: June 2024

Context:
Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected.

Objective:
Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring.

Design:
Retrospective cohort study.

Setting and Participants:
We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review.

Main Outcome Measures:
Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without.

Results:
Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging.

Conclusions:
Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.
Injury to Anatomic Structures Due to Fixation Device in Management of Mandibular Fracture
Authors: Sahoo Nanda Kishore , Vaswani Himani 
Published: June 2024

Introduction:
ORIF is the gold standard for the management of mandibular fractures. The chances of postoperative complications are due to infection, damage of the inferior alveolar nerve canal, or tooth root during the fixation of the fracture fragments. Fixation hardware placed in the vicinity of the vital structures may encroach on the anatomic structures, leading to postoperative complications.

Aim:
The aim of this study is to evaluate the injury to the anatomic structures in the proximity of the fracture line due to the fixation device.

Material and Methods:
This retrospective study was conducted in a tertiary care teaching hospital from July 2021 to June 2023. The cases of maxillofacial trauma reported and referred from peripheral centers were considered duly, applying the inclusion and exclusion criteria. Patients having mandibular fractures from one mandibular foramen to another with or without associated other facial fractures were treated by ORIF under general anesthesia. The patient was followed up at 1 week, 1 month, 3 months, and 6 months. The cases of postoperative complications were further investigated by CBCT.

Result:
There were 67 patients (56 males and 11 females) with 86 fracture lines in the age group of 18–55 years with an average age of 35.2 years. Postoperatively 7 patients presented with unilateral paresthesia of the lower lip and chin region. CBCT revealed that the mean distance of the screw from the inferior alveolar nerve canal was 3.02 mm. None of these cases had injury to the nerve canal or roots of teeth. All the patients recovered from paresthesia within 6 months.

Discussion:
Complications like injury to the inferior alveolar nerve (IAN) with sensory disturbances to the lower lip and chin, as well as tooth/tooth root fractures, may occur due to mandibular fracture, surgical manipulation, and fixation devices. The anatomic structures in the vicinity of the fracture line can be damaged during the fixation of the fracture fragments by the bone plates and screws. In the present study, it was found that 7 out of 67 patients presented with unilateral paresthesia of the lower lip and chin. CBCT analysis showed a considerable distance of 3.02 mm from the inferior alveolar nerve canal to the screws. There was no evidence of hardware encroachment on the IAN or tooth roots.

Conclusion:
Selection and placement of appropriate fixation devices, particularly the length of the bone screws, are crucial to avoid injury to the anatomic structures.
CHANGES OF HISTIDINE-RICH GLYCOPROTEIN LEVELS IN CRITICALLY ILL SEPTIC PATIENTS
Authors: Pradana Ayu Nabila Kusuma , Akahoshi Tomohiko , Guo Jie , Mizuta Yukie , Matsunaga Shuntaro , Narahara Sayoko , Murata Masaharu , Yamaura Ken 
Published: June 2024

ABSTRACT

Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 μg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management.
Interplay of Long- and Short-term Synaptic Plasticity in a Spiking Network Model of Rat’s Episodic Memory
Authors: Chrysanthidis N. , Fiebig F. , Lansner A. , Herman P. 
Published: June 2024

AbstractWe investigated the interaction of long-term episodic processes with effects of short-term dynamics of recency. This work takes inspiration from a seminal experimental work involving an odor-in-context association task conducted on rats (Panoz-Brown et al., 2016). In the experimental task, rats were presented with odor pairs in two arenas serving as old or new contexts for specific odors-items. Rats were rewarded for selecting the odor that was new to the current context. New odor items were deliberately presented with higher recency relative to old items, so that episodic memory was put in conflict with non-episodic recency effects. To study our hypothesis about the major role of synaptic interplay of long- and short-term plasticity phenomena in explaining rats’ performance in such episodic memory tasks, we built a computational spiking model consisting of two reciprocally connected networks that stored contextual and odor information as consolidated and distributed memory patterns (cell assemblies). We induced context-item coupling between the two networks using Bayesian-Hebbian plasticity with eligibility traces to account for reward based learning. We first reproduced quantitatively and explained mechanistically the findings of the experimental study, and further simulated alternative tasks, e.g. where old odor items were instead encoded with higher recency, thus synergistically confounding episodic memory with effects of recency. Our model predicted that higher recency of old items enhances item-in-context memory by boosting the activations of old items resulting in further enhancement of memory performance. We argue that the model offers a computational framework for studying behavioral implications of the synaptic underpinning of different memory effects in experimental episodic memory paradigms.Significance StatementAn important aspect of computational modeling is its ability to bridge spatial scales. Our cortical memory model represents a novel computational attempt to unravel neural and synaptic processes with mesoscopic manifestations underpinning the complex effects of short-term memory dynamics on episodic memory recall. We consider the quantitative match with Panoz-Brown et al.’s (2016) experimental findings, obtained in a detailed spiking network model constrained by available biological data, a significant step towards bridging the gap between behavioral correlates of episodic memory and synaptic mechanisms. Our findings and additional predictions on a suite of different episodic memory tasks invite further experimental examination.
Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner
Authors: Kane Alice E , Chellappa Karthikeyani , Schultz Michael B , Arnold Matthew , Li Jien , Amorim Joao , Diener Christian , Zhu Dantong , Mitchell Sarah J , Griffin Patrick , Tian Xiao , Petty Christopher , Conway Ryan , Walsh Katie , Shelerud Lukas , Duesing Charlotte , Mueller Amber , Li Karlin , McNamara Maeve , Shima Rafaella T. , Mitchell James , Bonkowski Michael S , de Cabo Rafael , Gibbons Sean M. , Wu Lindsay E , Ikeno Yuji , Baur Joseph A , Rajman Luis , Sinclair David A 
Published: June 2024

SUMMARYNicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD+can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD+precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels ofAnerotruncus colihominis,a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD+metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD+boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.
Quantification of transcript isoforms at the single-cell level using SCALPEL
Authors: Ake Franz , Fernández-Moya Sandra M. , Schilling Marcel , Ganesh Akshay Jaya , Gutiérrez-Franco Ana , Li Lei , Plass Mireya 
Published: June 2024

AbstractSingle-cell RNA sequencing (scRNA-seq) has facilitated the study of gene expression and the development of new tools to quantify transcript in individual cells. Yet, most of these methods have low sensitivity and accuracy. Here we present SCALPEL, a Nextflow-based tool to quantify and characterize transcript isoforms at the single-cell level using standard 3’ based scRNA-seq data. SCALPEL predictions have higher sensitivity than other tools and can be validated experimentally. We have used SCALPEL to study the changes in isoform usage during mouse spermatogenesis and in the differentiation of induced pluripotent stem cells (iPSCs) to neural progenitors. These analyses allow the identification of novel cell populations that cannot be defined using conventional gene expression profiles, confirm known changes in 3’ UTR length during cell differentiation, and identify cell-type specific miRNA signatures controlling isoform expression in individual cells. Together, our work highlights how SCALPEL expands the current scRNA-seq toolset to explore post-transcriptional gene regulation in individual cells from different species, tissues, and technologies to investigate the variability and the specificity of gene regulatory mechanisms at the single-cell level.
Dual DNA Replication Modes: Varying Fork Speeds and Initiation Rates within the spatial replication program inXenopus
Authors: Ciardo Diletta , Haccard Olivier , de Carli Francesco , Hyrien Olivier , Goldar Arach , Marheineke Kathrin 
Published: June 2024

AbstractLarge vertebrate genomes duplicate by activating tens of thousands of DNA replication origins, irregularly spaced along the genome. The spatial and temporal regulation of the replication process is not yet fully understood. To investigate the DNA replication dynamics, we developed a methodology called RepliCorr, which uses the spatial correlation between replication patterns observed on stretched single-molecule DNA obtained by either DNA combing or high-throughput optical mapping. The analysis revealed two independent spatiotemporal processes that regulate the replication dynamics in theXenopusmodel system. These mechanisms are referred to as a fast and a slow replication mode, differing by their opposite replication fork speed and rate of origin firing. We found that Polo-like kinase 1 (Plk1) depletion abolished the spatial separation of these two replication modes. In contrast, neither replication checkpoint inhibition nor Rif1 depletion affected the distribution of these replication patterns. These results suggest that Plk1 plays an essential role in the local coordination of the spatial replication program and the initiation-elongation coupling along the chromosomes inXenopus, ensuring the timely completion of the S phase.
Separating the genetic and environmental drivers of body temperature during the development of endothermy in an altricial bird
Authors: Winder Lucy A. , Hogger Gadsby Jacob , Wellman Eleanor , Pick Joel L. , Simons Mirre J.P. , Burke Terry 
Published: June 2024

AbstractWhen altricial birds hatch, they are unable to regulate their own temperature, but by the time they fledge they are thermally independent. Early-life conditions have been shown to be an important factor contributing to an individuals’ performance in adult life. However, it is currently unknown to what extent body temperature during endothermy development is driven by genetic variation or by the early environment. We use thermal images of cross-fostered house sparrows (Passer domesticus) throughout the nestling period to separate genetic and environmental drivers of body temperature. Our results show small heritability of body temperature. We further found that there are effects from the natal environment which carry over into the late nestling stage. A correlation between early to the mid-nestling period was explained by the natal environment and during this period body temperature and growth follow independent developmental trajectories. Furthermore, higher body temperature is under viability selection independent of body mass. We, therefore, demonstrate the natal environment influences future offspring phenotype in a novel measure; body temperature. Our study provides the first study into the environmental and genetic drivers of body temperature variation in a wild bird, furthering our understanding of how an individuals’ traits evolve.
Analysis of coding gene expression from small RNA sequencing
Authors: Azadova Aygun , Ekperuoh Anthonia , Brooke Greg N. , Marco Antonio 
Published: June 2024

ABSTRACTThe popularity of microRNA expression analyses is reflected by the existence of thousands of works in the literature in which sRNAseq has been performed in myriads of samples, but for which no matched total RNAseq exists. The lack of paired sequencing experiments severely restricts the analysis of microRNA-gene regulatory networks. We therefore explored whether protein-coding gene expression can be quantified from transcript fragments present in sRNAseq experiments. We first considered studies containing matched total RNA and small RNA from four human tissues and recovered transcript fragments from the small RNA experiments. We found that the expression levels of protein-coding gene transcripts from sRNAseq datasets was comparable to those from total RNAseq experiments (R2ranging 0.33-0.76). We then analysed the expression of both microRNAs and coding genes from the same sRNAseq experiments and demonstrated that known microRNA-target interactions are, as expected, inversely correlated with the expression profiles of these microRNA-mRNA pairs. To confirm the utility of this approach, we applied our method to investigate microRNAs and their targets in breast cancer patient samples for which only sRNAseq was performed and only microRNAs studied. We again identified a clear inverse correlation between the expression of microRNAs and mRNAs that they are predicted to regulate (i.e. presence of a target site). We also found that upregulation of mir-429 is associated with the downregulation of QKI, an RNA-binding protein, in breast cancer samples. In conclusion, although the analysis of mRNA fragments to study gene expression from sRNAseq experiments may have its limitations, it can be very informative in the study of microRNA-mRNA interactions.
TimiGP-Response: the pan-cancer immune landscape associated with response to immunotherapy
Authors: Li Chenyang , Hong Wei , Reuben Alexandre , Wang Linghua , Maitra Anirban , Zhang Jianjun , Cheng Chao 
Published: June 2024

AbstractAccumulating evidence suggests that the tumor immune microenvironment (TIME) significantly influences the response to immunotherapy, yet this complex relationship remains elusive. To address this issue, we developed TimiGP-Response (TIME Illustration based on Gene Pairing designed for immunotherapy Response), a computational framework leveraging single-cell and bulk transcriptomic data, along with response information, to construct cell-cell interaction networks associated with responders and estimate the role of immune cells in treatment response. This framework was showcased in triple-negative breast cancer treated with immune checkpoint inhibitors targeting the PD-1:PD-L1 interaction, and orthogonally validated with imaging mass cytometry. As a result, we identified CD8+ GZMB+ T cells associated with responders and its interaction with regulatory T cells emerged as a potential feature for selecting patients who may benefit from these therapies. Subsequently, we analyzed 3,410 patients with seven cancer types (melanoma, non-small cell lung cancer, renal cell carcinoma, metastatic urothelial carcinoma, hepatocellular carcinoma, breast cancer, and esophageal cancer) treated with various immunotherapies and combination therapies, as well as several chemo- and targeted therapies as controls. Using TimiGP-Response, we depicted the pan-cancer immune landscape associated with immunotherapy response at different resolutions. At the TIME level, CD8 T cells and CD4 memory T cells were associated with responders, while anti-inflammatory (M2) macrophages and mast cells were linked to non-responders across most cancer types and datasets. Given that T cells are the primary targets of these immunotherapies and our TIME analysis highlights their importance in response to treatment, we portrayed the pan-caner landscape on 40 T cell subtypes. Notably, CD8+ and CD4+ GZMK+ effector memory T cells emerged as crucial across all cancer types and treatments, while IL-17-producing CD8+ T cells were top candidates associated with immunotherapy non-responders. In summary, this study provides a computational method to study the association between TIME and response across the pan-cancer immune landscape, offering resources and insights into immune cell interactions and their impact on treatment efficacy.
TissueViewer: A Web-Based Multiplexed Image Viewer
Authors: van IJzendoorn D.G.P. , Matusiak M. , West R.B. , van de Rijn M. 
Published: June 2024

AbstractDatasets generated by spatial biology techniques such as multiplex immunofluorescence staining or spatial transcriptomics profiling of histologic sections carry a tremendous wealth of information. Several commercial platforms exist that can simultaneously acquire 1-1000 distinct marker signals (e.g., MIBI, CODEX, Orion, Nanostring CosMX SMI, Vizgen). However, due to the large size of these datasets, their viewing and sharing are slow, laborious, and require extensive computational resources. To overcome this, we developed TissueViewer, a web-based viewer designed to deliver high-resolution images over the internet with low bandwidth requirements and at high speed.
Weather and leaf age separately contribute to temporal shifts in phyllosphere community structure and composition
Authors: Heil Jacob A. , Simler-Williamson Allison , Striluk Miranda L. , Trawick Danielle , Capezza Rachel , DeFehr Chadwick , Osorio Aubrey , Finney Bruce , Turner Kathryn G. , Bittleston Leonora S. 
Published: June 2024

AbstractMicrobial communities living on plant leaves can positively or negatively influence plant health and, by extension, can impact whole ecosystems. Most research into the leaf microbiome consists of snapshots, and little is known about how microbial communities change over time. Weather and host physiological characteristics change over time and are often collinear with other time-varying factors, such as substrate availability, making it difficult to separate the factors driving microbial community change. We leveraged repeated measures over the course of an entire year to isolate the relative importance of environmental, host physiological, and substrate age-related factors on the assembly, structure, and composition of leaf-associated fungal communities. We applied both culturing and sequencing approaches to investigate these communities, focusing on a foundational, widely-distributed plant of conservation concern: basin big sagebrush (Artemisia tridentatasubsp.tridentata). We found that changes in alpha diversity were independently affected by the age of a community and the air temperature. Surprisingly, total fungal abundance and species richness were not positively correlated and responded differently, sometimes oppositely, to weather. With regard to beta diversity, communities were more similar to each other across similar leaf ages, air temperatures, leaf types, and δ13C stable isotope ratios. Nine different genera were differentially abundant with air temperature, δ13C, leaf type, and leaf age, and a set of 20 genera were continuously present across the year. Our findings highlight the necessity for longer-term, repeated sampling to parse drivers of temporal change in leaf microbial communities.Open Research StatementAll ITS DNA amplicon sequence raw data are deposited in the NCBI Sequence Read Archive (SRA), BioProject number PRJNA1107252, data will be released upon publication. All community data, metadata, taxonomic data, and R code necessary to reproduce these results are deposited in the GitHub repository archived on Zenodo: 10.5281/zenodo.11106439.