bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization Trends of Nerve Autograft Alternatives for the Reconstruction of Peripheral Nerve Defects
Authors: Adidharma Widya , Wang Yichu , Kotsis Sandra V. , Wang Lu , Chung Kevin C. 
Published: October 2023

Background:
Autologous nerve grafting is the time-honored reconstruction method for peripheral nerve gaps. However, it is associated with donor site morbidities. A growing number of studies have demonstrated the effective use of decellularized nerve allograft and synthetic conduits, which are convenient options with no donor deficit. The specific aim of this study was to characterize changes in practice trends for peripheral nerve defect reconstruction.

Methods:
We queried the 2015-2020 Truven MarketScan database for patients who underwent nerve autograft, allograft, synthetic conduit, and/or vein graft reconstruction. Patient demographic data (i.e. location, indication) and hospital characteristics (i.e. facility, provider type) were recorded. Regression analysis identified changes in trends over the study period.

Results:
4331 patients underwent one or more nerve gap reconstructive procedures over the study period. Since the introduction of allograft CPT code in 2018, segmented mixed effect longitudinal modeling revealed allograft utilization significantly increased from 21.5% to 29.6% after 2018 (p<0.001), whereas nerve autograft utilization decreased from 18.6% to 15.8% and conduit utilization decreased from 60% to 54.7% (p=0.09 and p=0.03, respectively). When stratifying autograft by size, use of autograft ≥4cm significantly decreased from 10.6% to 7.7% after 2018 (p=0.03), and autograft >4cm did not. When stratifying by state, there is heterogeneity in utilizati

Conclusion:
After creation of a designated allograft CPT code in 2018, there was an increase in allograft use with concomitant decrease in conduit and short length autograft use, suggesting that allograft replaced a portion of procedures used in short nerve gap reconstruction.
A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis
Authors: Rabindranath Madhumitha , Zaya Rita , Prayitno Khairunnadiya , Orchanian-Cheff Ani , Patel Keyur , Jaeckel Elmar , Bhat Mamatha 
Published: October 2023

Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease. Recurrent hepatitis C virus infection was previously the most important cause of graft failure but is now curable in the majority of patients. However, with an increasing prevalence of obesity and diabetes and nonalcoholic fatty liver disease as the most rapidly increasing indication for liver transplantation, metabolic dysfunction-associated liver injury is anticipated to become an important cause of graft fibrosis alongside alloimmune hepatitis and alcoholic liver disease.
To better understand the landscape of the graft fibrosis literature, we summarize the associated epidemiology, cause, potential mechanisms, diagnosis, and complications. We additionally highlight the need for better noninvasive methods to ameliorate the management of graft fibrosis. Some examples include leveraging the microbiome, genetic, and machine learning methods to address these limitations. Overall, graft fibrosis is routinely seen by transplant clinicians, but it requires a better understanding of its underlying biology and contributors that can help inform diagnostic and therapeutic practices.
Indications for Magnetic Resonance Imaging in Patients With Behcet Uveitis
Authors: Borelli Anna , Behr Jordan , Ruggeri Maria , Han Mini , Zhou Yujia , Foster C. Stephen 
Published: October 2023

Background:
Behcet disease is a systemic vasculitis, which may involve the eyes and central nervous system. The true prevalence of neurological involvement is not precisely known but may be associated with ocular involvement. This study investigates the association between Behcet uveitis and neuro-Behcet disease.

Methods:
A retrospective single-center analysis was conducted for consecutive patients with Behcet uveitis at the Massachusetts Eye Research and Surgery Institution. Uveitis characteristics, neurological symptoms, fluorescein fundus angiography, and MRI results were recorded.

Results:
Our population included 108 patients with Behcet uveitis, and 26 (24.1%) were found to have neurological involvement associated with Behcet disease. Optic nerve leakage on fundus angiography and neurological symptoms were associated with an increased risk of neurological involvement. Three cases (11.5%) were nonparenchymal, while 23 (88.5%) were parenchymal with lesions in the cortex, subcortical white matter, thalamus, basal ganglia, and brainstem.

Conclusions:
There is a high comorbidity between ocular and neurological involvement in Behcet disease. Careful assessment of neurological symptoms and baseline fluorescein fundus angiography are recommended for patients with Behcet disease. MRI has a high diagnostic yield and should be pursued if there is concern for progressive or pre-existing neurological involvement.
PhysioFit: a software to quantify cell growth parameters and extracellular fluxes
Authors: Le Grégam Loïc , Guitton Yann , Bellvert Floriant , Heux Stéphanie , Jourdan Fabien , Portais Jean-Charles , Millard Pierre 
Published: October 2023

AbstractSummaryQuantification of growth parameters and extracellular uptake and production fluxes is central in systems and synthetic biology. Fluxes can be estimated using various mathematical models by fitting time-course measurements of the concentration of cells and extracellular substrates and products. A single tool is available to non-computational biologists to calculate extracellular fluxes, but it is hardly interoperable and is limited to a single hard-coded growth model. We present our open-source flux calculation software, PhysioFit, which can be used with any growth model and is interoperable by design. PhysioFit includes some of the most common growth models, and advanced users can implement additional models to calculate extracellular fluxes and other growth parameters for metabolic systems or experimental setups that follow alternative kinetics. PhysioFit can be used as a Python library and offers a graphical user interface for intuitive use by end-users and a command-line interface to streamline integration into existing pipelines.Availability and ImplementationPhysioFit is implemented in Python 3 and was tested on Windows, Unix and MacOS platforms. PhysioFit is also freely available online athttps://workflow4metabolomics.org. The source code, the data and the documentation are freely distributed under GPL3 license athttps://github.com/MetaSys-LISBP/PhysioFit/andhttps://physiofit.readthedocs.io/.
Scaling the fitness effects of mutations with respect to differentially adaptedArabidopsis thalianaaccessions under natural conditions
Authors: Stearns Frank W. , Zhou Juannan , Fenster Charles B. 
Published: October 2023

ABSTRACTMutations are the ultimate source of genetic variation for natural selection to act upon. A major question in evolutionary biology is the extent to which new mutations can generate genetic variation under natural conditions to permit adaptive evolution over ecological time scales. Here we collected fitness data for chemically induced (ethylmethane sulfonate, EMS) mutant lines descended from twoArabidopsis thalianaecotypes that show differential adaptation to the local environment of our common garden plot. Using a novel nonparametric Bayesian statistical approach, we found that both ecotypes accumulated substantial proportions of beneficial mutations. The poorly adapted ecotype showed higher variance in the fitness effect of mutations than the well-adapted ecotype. Furthermore, we predict that it takes less than 4000 generations for the fitness space of the two ecotypes to overlap through mutation accumulation, and that a single founder, through mutation accumulation, is able to achieve the species-wide genetic variation in less than 10,000 generations. Our results provide evidence for relatively rapid local adaptation ofArabidopsis thalianain natural conditions through new mutations, as well as the utility of nonparametric Bayesian method for modeling the distribution of fitness effects for field-collected data.
Understanding structural and functional diversity of ATP-PPases using protein domains and functional families in CATH database
Authors: Waman Vaishali P. , Yin Jialin , Sen Neeladri , Firdaus-Raih Mohd , Lam Su Datt , Orengo Christine 
Published: October 2023

SummaryATP-Pyrophosphatases (ATP-PPases) are the most primordial lineage of the large and diverse HUP (HIGH-motif proteins,Universal Stress Proteins, ATP-Pyrophosphatase) superfamily. There are four different ATP-PPase substrate-specificity groups, and members of each group show considerable sequence variation across the domains of life despite sharing the same catalytic function. Over the past decade, there has been a >20-fold expansion in the number of ATP-PPase domain structures most recently from advances in protein structure prediction (e.g. Alphafold2). Using the enriched structural information, we have characterised the two most populated ATP-PPase substrate-specificity groups, the NAD-synthases (NAD) and GMP synthases (GMPS). We performed local structural and sequence comparisons between the NADS and GMPS from different domains of life and identified taxonomic-group specific structural functional motifs. As GMPS and NADS are potential drug targets of pathogenic microorganisms includingMycobacterium tuberculosis, structural motifs specific to bacterial GMPS and NADS provide new insights that may aid antibacterial-drug design.
Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting
Authors: Radley Arthur , Smith Austin 
Published: October 2023

ABSTRACTSingle cell transcriptomics (scRNA-seq) transforms our capacity to define cell states and reveal developmental trajectories. Resolution is challenged, however, by high dimensionality and noisy data. Analysis is therefore typically performed after sub-setting to highly variable genes (HVGs). However, existing HVG selection techniques have been found to have poor agreement with one another, and tend to be biased towards highly expressed genes. Entropy sorting provides an alternative mathematical framework for feature subset selection. Here we implement continuous entropy sort feature weighting (cESFW). On synthetic datasets, cESFW outperforms HVG selection in distinguishing cell state specific genes. We apply cESFW to six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, cESFW generates a high-resolution embedding displaying coherent developmental progression from 8-cell to post-implantation stages, delineating 15 distinct cell states. The embedding highlights sequential lineage decisions during blastocyst development while unsupervised clustering identifies branch point populations. Cells previously claimed to lack a developmental trajectory reside in the first branching region where morula differentiates into Inner Cell Mass (ICM) or Trophectoderm (TE). We quantify the relatedness of pluripotent stem cell cultures to embryo cell types and identify naïve and primed marker genes conserved across culture conditions and the human embryo. Finally, by identifying genes with specifically enriched and dynamic expression during blastocyst formation, we provide markers for staging lineage progression from morula to blastocyst. Together these analyses indicate that cESFW provides the ability to reveal gene expression dynamics in scRNA-seq data that HVG selection can fail to elucidate.
New Interactive Machine Learning Tool for Marine Image Analysis
Authors: Clark H. Poppy , Smith Abraham George , Fletcher Daniel Mckay , Larsson Ann I. , Jaspars Marcel , De Clippele Laurence H. 
Published: October 2023

ABSTRACTDue to advances in imaging technologies, the rate of marine video and image data collection is drastically increasing. Often these datasets are not analysed to their full potential as extracting information for multiple species, such as their presence and surface area, is incredibly time-consuming. This study demonstrates the potential of a new open-source interactive machine learning tool, RootPainter, to analyse large marine image datasets quickly and accurately. The tool was initially developed to measure plant roots, but here was tested on its ability to measure the presence and surface area of the cold-water coral reef associate sponge species,Mycale lingua, in two types of underwater image data: 18,346 time-lapse images and 1,420 remotely operated vehicle video frames. New corrective annotation metrics integrated with RootPainter, such as dice score and species area error, allow for the objective assessment of when to stop model training and reduce the need for manual model validation. Three highly accurateMycale linguamodels were created using RootPainter, as indicated by their average dice score of 0.94 ± 0.06. Model transfer and optimisation aided in the production of two of these models, increasing analysis efficiency from 6 to 16 times faster than manual annotation in Photoshop, for underwater observatory images. Sponge and surface area measurements were extracted from both datasets allowing future investigation of sponge behaviours and distributions. This study demonstrates that interactive machine learning tools and model sharing have the potential to dramatically increase image analysis speeds, collaborative research, and our collective knowledge on spatiotemporal patterns in biodiversity.
Engineering Regionally-Activated Drugs for Neuroscience
Authors: Huang Zhimin , Mitrofan Andrei , Nouraein Shirin , Horak Clark , Seo Joon Pyung , Harb Manwal , Jin Rongshu , Szablowski Jerzy O. 
Published: October 2023

ABSTRACTThe brain is comprised of multiple regions performing distinct functions. Within each of these regions, there are multiple cell types that can affect brain physiology. Finally, within each cell there are multiple signaling pathways, that, when activated or inhibited, control the cell’s activity, and consequently the brain function. For these reasons, methods that can control the brain with regional, cell-type, and molecular precision have been widely used in neuroscience. However, so far, achieving sustained control over a brain region with that level of specificity relied either on gene delivery or placement of invasive devices. While gene therapy holds great promise, the risks of genomic integration, vector toxicity, vector-directed immune response, high cost, and gene delivery to the brain pose significant challenges. On the other hand, invasive devices enable site-specific delivery of drugs but can also surgically damage the modulated brain region, carrying risks of infection and hemorrhage. Here, we present a new approach that can provide multi-day, noninvasive, site-specific control over specific cell types in the brain without the need to use invasive devices or gene delivery. To achieve this, we introduce a new paradigm called Regionally Activated Interstitial Drugs, orRAID, which delivers a protein-based catalytic centers, or RAID enzymes, to the brain using focused ultrasound blood-brain barrier opening. This catalytic center is designed to attach to the interstitial space in the brain where it remains for days after initial delivery. While the catalytic center is present in the brain, it can locally process an inert BBB permeable prodrug into an active drug, resulting in localized therapy. Our proof-of concept studies demonstrated that the engineered RAID enzymes can retain activity in the brain parenchyma for several days, allowing for noninvasive site-specific induction of neuronal activity that was sufficiently potent to elicit behavioral effects. Overall, the RAID paradigm enabled noninvasive, tunable, temporally-re-solved, site-specific, non-genetic, neuromodulation over multiple days. The RAID paradigm is versatile and can be applied to any enzyme and prodrug pair to control various aspects of central nervous system physiology.
Low exposure to lithium does not induce nephrogenic diabetes insipidus but microcystic dilations of collecting ducts in a long-term rat model
Authors: Tabibzadeh Nahid , Klein Mathieu , Try Mélanie , Poupon Joël , Houillier Pascal , Klein Christophe , Cheval Lydie , Crambert Gilles , Lasaad Samia , Chevillard Lucie , Megarbane Bruno 
Published: October 2023

AbstractLithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As clinical studies suggested that NDI is dose-dependent and CKD time-dependent, we investigated the effects of low exposure to lithium in a long-term rat model. Sprague-Dawley rats were randomly fed during six months with normal diet (controls), addition of lithium to diet, or addition of lithium and amiloride to diet, allowing reaching low steady-state plasma lithium concentrations (0.25±0.06 and 0.43±0.16 mmol/L, respectively). Exposure to low plasma lithium concentrations did not induce NDI but microcystic dilations of kidney tubules, identified as collecting ducts (CDs) using immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. Principal cell-to-intercalated cell ratio was higher in dilated than in hypertrophied tubules. There was no correlation between aquaporin-2 mRNA levels and cellular remodelling of CDs. Amiloride/lithium co-administration did not allow significant consistent morphometric and cellular composition changes compared to lithium administration. To conclude, rat low exposure to lithium did not induce overt NDI but microcystic dilations of CDs, which include a marked alteration in cell composition of hypertrophied and dilated CDs, suggesting two distinct underlying pathophysiological mechanisms.
The transcription factor SpiB regulates Fibroblastic Reticular Cell network and CD8+T cell responses in lymph nodes
Authors: Horsnell Harry L , Cao Wang HJ , Belz Gabrielle T , Mueller Scott N , Alexandre Yannick O 
Published: October 2023

AbstractFibroblastic Reticular Cells (FRCs) construct microanatomical niches that support lymph node homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here we investigate the role of the transcription factor SpiB that is expressed in lymph node FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T cell zone of lymph nodes, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression. The size and cellularity of lymph nodes remained intact in the absence of SpiB but the space between the reticular network increased, indicating that although FRCs were reduced in number they stretched to maintain network integrity. Following virus infection, antiviral CD8+T cell responses were impaired, suggesting a role for SpiB expression in FRCs in orchestrating immune responses. Together, our findings reveal a new role for SpiB as a critical regulator of FRC functions and immunity in lymph nodes.
Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training
Authors: Viggars Mark R , Berko Hannah E , Hesketh Stuart J , Wolff Christopher A , Gutierrez-Monreal Miguel A , Martin Ryan A , Jennings Isabel G , Huo Zhiguang , Esser Karyn A 
Published: October 2023

AbstractObjectivesIn this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodelling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice.MethodsCombining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise.ResultsMuscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors includingNr4a3andPpargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of ‘exercise-training’ responsive genes shared for each tissue between genotypes.ConclusionOur investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle plays in the peripheral tissue adaptation to exercise training. We also note that the transcriptome adaptations to steady state training suggest that without BMAL1, skeletal muscle does not achieve the expected homeostatic program. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.