bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Phylogenetic Tree Completeness and Mis-specification of Sampling Fractions on Trait Dependent Diversification Models
Authors: Mynard Poppy , Algar Adam C , Lancaster Lesley T , Bocedi Greta , Fahri Fahri , Gubry-Rangin Cécile , Lupiyaningdyah Pungki , Nangoy Meis , Osborne Owen G , Papadopulos Alexander S T , Sudiana I Made , Juliandi Berry , Travis Justin M J , Herrera-Alsina Leonel 
Published: January 2023

Abstract
Understanding the origins of diversity and the factors that drive some clades to be more diverse than others are important issues in evolutionary biology. Sophisticated SSE (state-dependent speciation and extinction) models provide insights into the association between diversification rates and the evolution of a trait. The empirical data used in SSE models and other methods is normally imperfect, yet little is known about how this can affect these models. Here, we evaluate the impact of common phylogenetic issues on inferences drawn from SSE models. Using simulated phylogenetic trees and trait information, we fitted SSE models to determine the effects of sampling fraction (phylogenetic tree completeness) and sampling fraction mis-specification on model selection and parameter estimation (speciation, extinction, and transition rates) under two sampling regimes (random and taxonomically biased). As expected, we found that both model selection and parameter estimate accuracies are reduced at lower sampling fractions (i.e., low tree completeness). Furthermore, when sampling of the tree is imbalanced across sub-clades and tree completeness is ≤ 60%, rates of false positives increase and parameter estimates are less accurate, compared to when sampling is random. Thus, when applying SSE methods to empirical datasets, there are increased risks of false inferences of trait dependent diversification when some sub-clades are heavily under-sampled. Mis-specifying the sampling fraction severely affected the accuracy of parameter estimates: parameter values were over-estimated when the sampling fraction was specified as lower than its true value, and under-estimated when the sampling fraction was specified as higher than its true value. Our results suggest that it is better to cautiously under-estimate sampling efforts, as false positives increased when the sampling fraction was over-estimated. We encourage SSE studies where the sampling fraction can be reasonably estimated and provide recommended best practices for SSE modeling. [Trait dependent diversification; SSE models; phylogenetic tree completeness; sampling fraction.]
Population Pharmacokinetic Analysis of Drug–Drug Interactions Between Perampanel and Carbamazepine Using Enzyme Induction Model in Epileptic Patients
Authors: Fujita Yuito , Murai Mariko , Muraki Shota , Suetsugu Kimitaka , Tsuchiya Yuichi , Hirota Takeshi , Matsunaga Naoya , Ieiri Ichiro 
Published: January 2023

Background:
Perampanel (PER) is an oral antiepileptic drug and its concomitant use with carbamazepine (CBZ) leads to decreased PER concentrations. However, the magnitude of its influence may vary, depending on the dynamics of the enzyme induction properties of CBZ. This study aimed to develop a population pharmacokinetic (PPK) model considering the dynamics of enzyme induction and evaluate the effect of CBZ on PER pharmacokinetics.

Methods:
We retrospectively collected data on patient background, laboratory tests, and prescribed drugs from electronic medical records. We developed 2 PPK models incorporating the effect of CBZ-mediated enzyme induction to describe time–concentration profiles of PER using the following different approaches: (1) treating the concomitant use of CBZ as a categorical covariate (empirical PPK model) and (2) incorporating the time-course of changes in the amount of enzyme by CBZ-mediated induction (semimechanistic PPK model). The bias and precision of the predictions were investigated by calculating the mean error, mean absolute error, and root mean squared error.

Results:
A total of 133 PER concentrations from 64 patients were available for PPK modelling. PPK analyses showed that the co-administration of CBZ increased the clearance of PER. Goodness-of-fit plots indicated a favorable description of the observed data and low bias. The mean error, mean absolute error, and root mean square error values based on the semimechanistic model were smaller than those obtained using the empirical PPK model for predicting PER concentrations in patients with CBZ.

Conclusions:
We developed 2 PPK models to describe PER pharmacokinetics based on different approaches, using electronic medical record data. Our PPK models support the use of PER in clinical practice.
Hepatocyte-to-cholangiocyte conversion occurs through transdifferentiation independently of proliferation in zebrafish
Authors: Lee Seung-Hoon , So Juhoon , Shin Donghun 
Published: January 2023

Background and aims:
Injury to biliary epithelial cells (BECs) lining the hepatic bile ducts leads to cholestatic liver diseases. Upon severe biliary damage, hepatocytes can convert to BECs, thereby contributing to liver recovery. Given a potential of augmenting this hepatocyte-to-BEC conversion as a therapeutic option for cholestatic liver diseases, it will be important to thoroughly understand the cellular and molecular mechanisms of the conversion process.

Approach and results:
Towards this aim, we have established a zebrafish model for hepatocyte-to-BEC conversion by employing Tg(fabp10a:CFP-NTR) zebrafish with a temporal inhibition of Notch signaling during regeneration. Cre/loxP-mediated permanent and H2B-mCherry-mediated short-term lineage tracing revealed that in the model, all BECs originate from hepatocytes. During the conversion, BEC markers are sequentially induced in the order of Sox9b, Yap/Taz, Notch activity/epcam, and Alcama/krt18; the expression of the hepatocyte marker Bhmt disappears between the Sox9b and Yap/Taz induction. Importantly, live time-lapse imaging unambiguously revealed transdifferentiation of hepatocytes into BECs: hepatocytes convert to BECs without transitioning through a proliferative intermediate state. In addition, using compounds and transgenic and mutant lines that modulate Notch and Yap signaling, we found that both Notch and Yap signaling are required for the conversion even in Notch- and Yap-overactivating settings.

Conclusions:
Hepatocyte-to-BEC conversion occurs through transdifferentiation independently of proliferation, and Notch and Yap signaling control the process in parallel with a mutually positive interaction. The new zebrafish model will further contribute to a thorough understanding of the mechanisms of the conversion process.
Conventional type 1 dendritic cells protect against gut barrier disruption via maintaining Akkermansia muciniphila in alcoholic steatohepatitis
Authors: Hao Liuyi , Zhong Wei , Woo Jongmin , Wei Xiaoyuan , Ma Hao , Dong Haibo , Guo Wei , Sun Xinguo , Yue Ruichao , Zhao Jiangchao , Zhang Qibin , Zhou Zhanxiang 
Published: January 2023

Background and Aims:
Alcohol-perturbed gut immune homeostasis is associated with the development of alcoholic liver disease (ALD). However, the role of intestinal dendritic cells (DCs) in ALD progression is still unknown. This study aimed to investigate the cellular and molecular mechanisms through which intestinal DCs respond to alcohol exposure and contribute to the pathogenesis of ALD.

Approach and Results:
After 8 weeks of alcohol consumption, the number of basic leucine zipper transcription factor ATF-like 3 (Batf3)-dependent conventional type 1 DCs (cDC1s) was dramatically decreased in the intestine but not the liver. cDC1 deficient Batf3 knockout mice along with wild-type mice were subjected to chronic-binge ethanol feeding to determine the role of intestinal cDC1s reduction in ALD. cDC1s deficiency exacerbated alcohol-induced gut barrier disruption, bacterial endotoxin translocation into the circulation, and liver injury. Adoptive transfer of cDC1s to alcohol-fed mice ameliorated alcohol-mediated gut barrier dysfunction and liver injury. Further studies revealed that intestinal cDC1s serve as a positive regulator of Akkermansia muciniphila (A. muciniphila). Oral administration of A. muciniphila markedly reversed alcoholic steatohepatitis in mice. Mechanistic studies revealed that cDC1s depletion exacerbated alcohol-downregulated intestinal antimicrobial peptides which play a crucial role in maintaining A. muciniphila abundance, by disrupting the IL-12-interferon gamma signaling pathway. Lastly, we identified that intestinal cDC1s were required for the protective role of Lactobacillus reuteri in alcoholic steatohepatitis.

Conclusions:
This study demonstrated that cDC1s protect alcohol-induced liver injury by maintaining A. muciniphila abundance in mice. Targeting cDC1s may serve as a promising therapeutic approach for treating ALD.
Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration
Authors: Badal Bryan D. , Silvey Scott , Dragilev Lyuba , O’Leary Jacqueline G. , Morgan Timothy R. , Cheung Ramsey , Patel Arpan , Rogal Shari , Patton Heather , Nobbe Anna , Jakab Sofia S. , Liu Jinze , Patel Nilang , Bajaj Jasmohan S. 
Published: January 2023

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit.

Aim:
Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli, K. pneumoniae, and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p<0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p<0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay.E. coli ciprofloxacin sensitivity rates were 50%–87% and 43%–92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%–100% and 72%–100% for TMP-SMX.

Conclusion:
Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.
An American Board of Surgery Pilot of Video Assessment of Surgeon Technical Performance in Surgery
Authors: Pryor Aurora D. , Lendvay Thomas , Jones Andrew , Ibáñez Beatriz , Pugh Carla 
Published: January 2023

Objective:
The American Board of Surgery (ABS) sought to investigate the suitability of video-based assessment (VBA) as an adjunct to certification for assessing technical skills.

Background:
Board certification is based on the successful completion of a residency program coupled with knowledge and reasoning assessments. VBA is a new modality for evaluating operative skills that have been shown to correlate with patient outcomes after surgery.

Methods:
Diplomates of the ABS were initially assessed for background knowledge and interest in VBA. Surgeons were then solicited to participate in the pilot. Three commercially available VBA platforms were identified and used for the pilot assessment. All participants served as reviewers and reviewees for videos. After the interaction, participants were surveyed regarding their experiences and recommendations to the ABS.

Results:
To the initial survey, 4853/25,715 diplomates responded. The majority were neither familiar with VBA, nor the tools used for operative assessments. Two hundred seventy-four surgeons actively engaged in the subsequent pilot. One hundred sixty-nine surgeons completed the postpilot survey. Most participants found the process straightforward. Of the participants, 74% felt that the feedback would help their surgical practice. The majority (81%) remain interested in VBA for continuing medical education credits. Using VBA in continuous certification could improve surgeon skills felt by 70%. Two-thirds of participants felt VBA could help identify and remediate underperforming surgeons. Identified barriers to VBA included limitations for open surgery, privacy issues, and technical concerns.

Conclusions:
VBA is promising as an adjunct to the current board certification process and should be further considered by the ABS.
Obsessive-compulsive symptoms in the schizophrenia-spectrum: current developments in psychopathology research
Authors: Rasmussen Andreas Rosén , Raballo Andrea 
Published: January 2023

Purpose of review
Schizophrenia-spectrum disorders (SSD) frequently involve symptoms that usually are ascribed to nonpsychotic disorder spectra, such as obsessive-compulsive symptoms (OCS). These symptoms can cause differential diagnostic challenges, particularly in early illness stages, and must be considered in treatment planning. In this review, we provide an overview of recent literature within the field of OCS in SSD, with a focus on psychopathology research.

Recent findings
OCS are seen in approximately a quarter of patients with SSD or at-risk mental state of psychosis. They are associated with more severe clinical features and specific temporal patterns of OCS may be linked with different clinical trajectories. However, the current definitions of OCS have been criticized for their overinclusive nature, which is a limiting step for differential diagnosis and more precise prognostic stratification. Specific phenomenological features, including a link with experiential anomalies (disorders of basic self), have been suggested to provide clinically relevant distinctions.

Summary
The presence of OCS in SSD is associated with more severe clinical features and invites a higher clinical attention and perspectival monitoring. Some findings suggest that more fine-grained psychopathological distinctions might be a viable clinical and research strategy to advance the field in the direction of precision psychiatry.
Long term anthropic management and associated loss of plant diversity deeply impact virome richness and composition ofPoaceaecommunities
Authors: Maclot François , Debue Virginie , Malmstrom Carolyn , Filloux Denis , Roumagnac Philippe , Eck Mathilde , Tamisier Lucie , Blouin Arnaud G. , Candresse Thierry , Massart Sébastien 
Published: January 2023

AbstractModern agriculture has influenced plant virus emergence through ecosystem simplification, introduction of new host species, and reduction in crop genetic diversity. Therefore, it is crucial to better understand virus distributions across cultivated and uncultivated communities in agro-ecological interfaces, as well as virus exchange among them. Here we advance fundamental understanding in this area by characterizing the virome of three co-occurring replicatedPoaceaecommunity types that represent a gradient of grass species richness and management intensity, from highly managed crop monocultures to little-managed, species-rich grasslands. We performed a large-scale study on 950 wild and cultivatedPoaceaeover two years combining untargeted virome analysis down to virus species level with targeted detection of three plant viruses. Deep sequencing revealed i) a diversified and largely unknownPoaceaevirome (at least 51 virus species/taxa), with an abundance of so-called persistent viruses; ii) an increase of virome richness with grass species richness within the community; iii) a stable virome richness over time but a large viral intraspecific variability; and iv) contrasted patterns of virus prevalence, co-infections and geographical distribution among plant communities and species. Our findings highlight the complex structure of plant virus communities in nature and suggest the influence of anthropic management on viral distribution and prevalence.
Perfusable biohybrid designs for bioprinted skeletal muscle tissue
Authors: Filippi Miriam , Yasa Oncay , Giachino Jan , Graf Reto , Balciunaite Aiste , Katzschmann Robert K. 
Published: January 2023

ABSTRACTEngineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately co-printed with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that (i) co-printed synthetic structures display highly coherent interfaces with the living tissue; (ii) perfusable designs preserve cells from hypoxia all over the scaffold volume; and (iii) constructs can undergo passive mechanical tension during matrix remodeling. Extrusion-based multimaterial bioprinting with our inks and design realizesin vitromatured biohybrid SMT for biomedical, nutritional, and robotic applications.
Improving gene regulatory network inference and assessment: The importance of using network structure
Authors: Escorcia-Rodríguez Juan M. , Gaytan-Nuñez Estefani , Hernandez-Benitez Ericka M. , Zorro-Aranda Andrea , Tello-Palencia Marco A. , Freyre-González Julio A. 
Published: January 2023

AbstractGene regulatory networks are graph models representing cellular transcription events. Networks are far from complete due to time and resource consumption for experimental validation and curation of the interactions. Previous assessments have shown the modest performance of the available network inference methods based on gene expression data. Here, we study several caveats on the inference of regulatory networks and methods assessment through the quality of the input data and gold standard, and the assessment approach with a focus on the global structure of the network. We used synthetic and biological data for the predictions and experimentally-validated biological networks as the gold standard (ground truth). Standard performance metrics and graph structural properties suggest that methods inferring co-expression networks should no longer be assessed equally with those inferring regulatory interactions. While methods inferring regulatory interactions perform better in global regulatory network inference than co-expression-based methods, the latter is better suited to infer function-specific regulons and co-regulation networks. When merging expression data, the size increase should outweigh the noise inclusion and graph structure should be considered when integrating the inferences. We conclude with guidelines to take advantage of inference methods and their assessment based on the applications and available expression datasets.
Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early pre-neoplastic pancreatic lesions
Authors: Carpenter Eileen S. , Elhossiny Ahmed M. , Kadiyala Padma , Li Jay , McGue Jake , Griffith Brian , Zhang Yaqing , Edwards Jacob , Nelson Sarah , Lima Fatima , Donahue Katelyn L. , Du Wenting , Bischoff Allison C. , Alomari Danyah , Watkoske Hannah , Mattea Michael , The Stephanie , Espinoza Carlos , Barrett Meredith , Sonnenday Christopher J. , Olden Nicholas , Peterson Nicole , Gunchick Valerie , Sahai Vaibhav , Rao Arvind , Bednar Filip , Shi Jiaqi , Frankel Timothy L. , Di Magliano Marina Pasca 
Published: January 2023

AbstractThe adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathological analysis of the samples revealed PanIN lesions in most individuals irrespective of age. Using a combination of multiplex immunohistochemistry, single cell RNA sequencing, and spatial transcriptomics, we provide the first ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts, and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.Statement of significanceThe causes underlying the onset of pancreatic cancer remain largely unknown, hampering early detection and prevention strategies. Here, we show that PanIN are abundant in healthy individuals and present at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell intrinsic factors that restrain, or, conversely, promote, malignant progression.
Design of amyloidogenic peptide traps
Authors: Sahtoe Danny D. , Andrzejewska Ewa A. , Han Hannah L. , Rennella Enrico , Schneider Matthias M. , Meisl Georg , Ahlrichs Maggie , Decarreau Justin , Nguyen Hannah , Kang Alex , Levine Paul , Lamb Mila , Li Xinting , Bera Asim K. , Kay Lewis E. , Knowles Tuomas P.J. , Baker David 
Published: January 2023

AbstractSegments of proteins with β-strand propensity can self associate to form amyloid fibrils associated with many diseases. These regions often adopt alternative structures in their folded states, or are intrinsically disordered in solution, making it difficult to generate binders or inhibitors with existing strategies. Here we describe a general approach to bind such segments in β-strand and β-hairpin conformations usingde novodesigned scaffolds that contain deep peptide binding clefts flanked by β-strands that form hydrogen bonds to the peptide upon binding. The designs bind their cognate peptidesin vitrowith nanomolar affinities and in mammalian cells. The crystal structure of a designed protein-peptide complex is close to the design model, and NMR characterization reveals how the peptide binding cleft is protected in the apo state. We use the approach to design binders to segments of the amyloid forming proteins Transthyretin, Tau, Serum amyloid A1 and Aβ42. The Aβ binders block assembly of Aβ fibrils as effectively as the most potent of the clinically tested antibodies to date.