bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Genome Sequence of Pantoea agglomerans CHTF15, a Walnut Pathogen
Authors: Xiao Jiawen , Liu Zhaosha , Sun Shangyi , Fan Chenxi , Wang Dongmei , Zhang Dongdong 
Published: January 2023

The phytopathogen Pantoea agglomerans belongs to the Bacteria, Proteobacteria, Gammaproteobacteria, Enterobacterales, Erwiniaceae in species classification. It causes disease symptoms in many plants such as corn, banana, and walnut. This study aimed to report the complete genome of P. agglomerans CHTF15, which represents the first whole-genome sequence of an isolate from diseased walnut leaves. The total length of the assembled genome was 4,820,607 bp, with an average GC content of 55.3%, including a circular chromosome and three circular plasmids, two of which were previously unreported sequences and one was announced previously. The CHTF15 genome helps understand the pathogenic mechanism of this important plant pathogen and provides an important theoretical basis for disease epidemic and field control. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
ADP‐ribose transferase PARP16 mediated‐unfolded protein response contributes to neuronal cell damage in cerebral ischemia/reperfusion
Authors: Wang Jinghuan , Xu Jie , Dong Yejun , Su Zhenghua , Su Haibi , Cheng Qianwen , Liu Xinhua 
Published: January 2023

AbstractIschemic stroke is known to cause the accumulation of misfolded proteins and loss of calcium homeostasis, leading to impairment of endoplasmic reticulum (ER) function and activating the unfolded protein response (UPR). PARP16 is an active (ADP‐ribosyl)transferase known tail‐anchored ER transmembrane protein with a cytosolic catalytic domain. Here, we find PARP16 is highly expressed in ischemic cerebral hemisphere and oxygen–glucose deprivation/reoxygenation (OGD/R)‐treated immortalized hippocampal neuronal cell HT22. Using an adeno‐associated virus‐mediated PARP16 knockdown approach in mice, we find PARP16 knockdown decreases infarct demarcations and has a better neurological outcome after ischemic stroke. Our data indicate PARP16 knockdown decreases ER stress and neuronal death caused by OGD/R, whereas PARP16 overexpression promotes ER stress‐mediated cell damage in primary cortical neurons. Furthermore, PARP16 functions mechanistically as ADP‐ribosyltransferase to modulate the level of ADP‐ribosylation of the corresponding PERK and IRE1α arm of the UPR, and such modifications mediate activation of PERK and IRE1α. Indeed, pharmacological stimulation of the UPR using Brefeldin A partly counteracts PARP16 knockdown‐mediated neuronal protection upon OGD/R treatment. In conclusion, PARP16 plays a crucial role in post‐ischemic UPR and PARP16 knockdown alleviates brain injury after ischemic stroke. This study demonstrates the potential of the PARP16‐PERK/IRE1α axis as a target for neuronal survival in ischemic stroke.
Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury
Authors: Shearn Colin T. , Anderson Aimee L. , Miller Colin G. , Noyd Reed C. , Devereaux Michael W. , Balasubramaniyan Nata , Orlicky David J. , Schmidt Edward E. , Sokol Ronald J. 
Published: January 2023

Background and Aims:
Cholestatic liver diseases, including primary sclerosing cholangitis, are characterized by periportal inflammation with progression to hepatic fibrosis and ultimately cirrhosis. We recently reported that the thioredoxin antioxidant response is dysregulated during primary sclerosing cholangitis. The objective of this study was to examine the impact of genetic and pharmacological targeting of thioredoxin reductase 1 (TrxR1) on hepatic inflammation and liver injury during acute cholestatic injury.

Approach and Results:
Primary mouse hepatocytes and intrahepatic macrophages were isolated from 3-day bile duct ligated (BDL) mice and controls. Using wildtype and mice with a liver-specific deletion of TrxR1 (TrxR1LKO), we analyzed the effect of inhibition or ablation of TrxR1 signaling on liver injury and inflammation. Immunohistochemical analysis of livers from BDL mice and human cholestatic patients revealed increased TrxR1 staining in periportal macrophages and hepatocytes surrounding fibrosis. qPCR analysis of primary hepatocytes and intrahepatic macrophages revealed increased TrxR1 mRNA expression following BDL. Compared with sham controls, BDL mice exhibited increased inflammation, necrosis, and increased mRNA expression of pro-inflammatory cytokines, fibrogenesis, the NLRP3 inflammatory complex, and increased activation of NFkB, all of which were ameliorated in TrxR1LKO mice. Importantly, following BDL, TrxR1LKO induced periportal hepatocyte expression of Nrf2-dependent antioxidant proteins and increased mRNA expression of basolateral bile acid transporters with reduced expression of bile acid synthesis genes. In the acute BDL model, the TrxR1 inhibitor auranofin (10 mg/kg/1 d preincubation, 3 d BDL) ameliorated BDL-dependent increases in Nlrp3, GsdmD, Il1β, and TNFα mRNA expression despite increasing serum alanine aminotransferase, aspartate aminotransferase, bile acids, and bilirubin.

Conclusions:
These data implicate TrxR1-signaling as an important regulator of inflammation and bile acid homeostasis in cholestatic liver injury.
Human VH-based chimeric antigen receptor T cells targeting glypican 3 eliminate tumors in preclinical models of HCC
Authors: Kolluri Aarti , Li Dan , Li Nan , Duan Zhijian , Roberts Lewis R. , Ho Mitchell 
Published: January 2023

Background and Aims:
Efficacy of chimeric antigen receptor (CAR) T cells for treating solid tumors, including HCC, remains a challenge. Nanobodies are emerging building blocks of CAR T cells due to their small size and high expression. Membrane proximal sites have been shown as attractive epitopes of CAR T cells. However, current CAR formats are not tailored toward nanobodies or targeting membrane distal epitopes.

Approach and Results:
Using hYP7 Fv (membrane proximal) and HN3 VH nanobody (membrane distal) as GPC3 targeting elements, we sought to determine how hinges and transmembrane portions of varying structures and sizes affect CAR T-cell function. We generated multiple permutations of CAR T cells containing CD8, CD28, IgG4, and Fc domains. We show that engineered HN3 CAR T cells can be improved by 2 independent, synergistic changes in the hinge and transmembrane domains. The T cells expressing the HN3 CAR which contains the hinge region of IgG4 and the CD28 transmembrane domain (HN3-IgG4H-CD28TM) exhibited high cytotoxic activity and caused complete HCC tumor eradication in immunodeficient mice. HN3-IgG4H-CD28TM CAR T cells were enriched for cytotoxic-memory CD8+ T cells and NFAT signals, and reduced β catenin levels in HCC cells.

Conclusion:
Our findings indicate that altering the hinge and transmembrane domains of a nanobody-based CAR targeting a distal GPC3 epitope, in contrast to a membrane proximal epitope, lead to robust T-cell signaling and induce swift and durable eradication of HCC tumors.
Staffing transformation following Patient-Centered Medical Home recognition among Health Resources & Services Administration-funded health centers
Authors: Pourat Nadereh , Lu Connie , Chen Xiao , Zhou Weihao , Hair Brionna , Bolton Joshua , Hoang Hank , Sripipatana Alek 
Published: January 2023

Introduction
Patient-Centered Medical Home (PCMH) recognition is designed to promote whole-person team-based and integrated care.

Purpose
Our goal was to assess changes in staffing infrastructure that promoted team-based and integrated care delivery before and after PCMH recognition in Health Resources & Services Administration (HRSA)-funded health centers (HCs).

Methodology/Approach
We identified changes in staffing 2 years before and 3 years after PCMH recognition using 2010–2019 Uniform Data System data among three cohorts of HCs that received PCMH recognition in 2013 (n = 346), 2014 (n = 207), and 2015 (n = 115). Our outcomes were team-based ratio (full-time equivalent medical and nonmedical providers and staff to one primary care physician) and a multidisciplinary staff ratio (allied medical and nonmedical staff to 1,000 patients). We used mixed-effects Poisson regression models.

Results
The earlier cohorts served fewer complex patients and were larger before PCMH recognition. Three years following recognition, the 2013 and 2014 cohorts had significantly larger team-based ratios, and all three cohorts had significantly larger multidisciplinary staff ratios. Cohorts varied, however, in the type of staff that drove this change. Both ratios increased in the longer term.

Conclusion
Our study suggests that growth in team-based and multidisciplinary staff ratios in each cohort may have been due to a combination of HCs’ perceptions of need for specific services, HRSA funding, and technical assistance opportunities.

Policy Implications
Further research is needed to understand barriers such as costs of employing a multidisciplinary staff, particularly those that cannot directly bill for services as well as whether such changes lead to practice transformation and improved quality of care.
Gender Disparities in Physician Assistant Educator Promotion and Compensation: A Mixed Methods Approach
Authors: Loder Rayne , Coombs Jennifer , Najmabadi Shahpar , Henry Trenton , Ryujin Darin , Valentin Virginia 
Published: January 2023

Introduction
The gender wage gap is well documented in many industries. A disparity in salary between female and male physician assistant (PA) educators has been demonstrated, but disparities in academic rank have not been shown. The purpose of this study was to re-examine gender disparities in compensation to PA educators and to explore whether gender-based disparities exist in promotion to higher academic rank in this field.

Methods
An explanatory sequential mixed-methods design was used to determine differences in salary and rank by gender. PA Education Association Faculty and Directors Survey data from 2014, 2017, and 2019 were analyzed. A focus group was conducted to explain the findings and understand the barriers to promotion for female faculty.

Results
Female PA faculty members earn $7573 less than their male colleagues when controlling for all other variables. Female faculty members have an increased likelihood (RR 1.150) for being in early career stage versus late career stage. Obtaining a doctoral degree decreased the risk for being in an early career stage (RR 0.567) with men twice as likely to have a doctoral degree as women.

Discussion
Rank and salary disparities exist in PA faculty by gender. Female faculty are less likely to hold doctoral degrees or to be promoted to higher academic ranks, and they earn less than men. Degree level and career track are themes unique to the PA education profession, and further research is needed to understand their impact. With more women entering PA education, pay equity and promotion need to be addressed.
Patient Experience Coordinator
Authors: Oehlert Julie Kennedy , Montana-Rhodes Lou , Hill Kevin N. , Maldonado Julio , Bishop Brandon , Wei Holly 
Published: January 2023

OBJECTIVE
The aim of this study was to test the impact of an innovative nonclinical support role to improve patient experiences while supporting nurse work on inpatient units.

BACKGROUND
On the basis of the Hospital Consumer Assessment of Health Care Providers and Systems (HCAHPS) survey, patients' experience declined nationally during the COVID-19 pandemic. A nonclinical support role, titled an Experience Coordinator, was created as a test of change to collaborate with care teams and respond to patients' and families' nonclinical needs.

METHODS
This is a quality improvement (QI) project for a supportive role development and implementation. The health system's HCAHPS data were compared before and after the role was tested on 3 inpatient units.

RESULTS
The HCAHPS data indicated that 5 of the 10 domains' top box ratings increased during the QI project month compared with the previous month.

CONCLUSION
The study findings may support the implementation of new innovative nonclinical positions to alleviate nurses' workload and promote patients' hospital experience.
CHALLENGES IN THE DIAGNOSIS AND MANAGEMENT OF ATYPICAL FUNGAL KERATITIS DURING COVID-19 PANDEMIC: A CASE SERIES
Authors: Ali Dideeya , Vijayan Ajith , Shenoy Kashinatha , Antony Ann Tresa , Ramachandran Reshmi 
Published: January 2023

Fungal keratitis is a time-sensitive ocular infection that often requires a high index of suspicion followed by intensive medical/surgical interventions to achieve a successful clinical outcome. The COVID-19 pandemic-related restrictions necessitated modification of conventional protocols and guidelines related to the plan of care of keratomycosis. We report four cases of atypical fungal keratitis presenting with poorly differentiated clinical characteristics. The challenges faced during their management were: 1) dilemma to clinically differentiate fungal (Scedosporium and Purpureocillium lilacinum) from bacterial keratitis; 2) treatment of Scedosporium and Trichosporon keratitis with natamycin monotherapy; 3) mixed infection of Candida albicans and Aureobasidium pullulans and continuing medications before rescraping the corneal ulcer against the recommended treatment guidelines; 4) phenotypic identification and differentiation among morphologically resembling fungi; and 5) decision making related to disparities between KOH and fungal culture results. Three patients responded well to conservative treatments. However, the fourth patient needed therapeutic keratoplasty, and was lost to follow-up due to travel related pandemic restrictions. This case series seeks to broaden the clinician's knowledge of rare but emerging moulds as presumptive aetiologies of keratomycosis. It also intends to reinforce the significance of early microbiological investigations, (direct microscopy and culture) in resource limited settings, for initiating empirical treatment towards a better visual prognosis.
High quality genome and transcriptome data for two new species ofMantamonas, a deep-branching eukaryote clade
Authors: Blaz Jazmin , Galindo Luis Javier , Heiss Aaron A. , Kaur Harpreet , Torruella Guifré , Yang Ashley , Thompson L. Alexa , Filbert Alexander , Warring Sally , Narechania Apurva , Shiratori Takashi , Ishida Ken-ichiro , Dacks Joel B. , López-García Purificación , Moreira David , Kim Eunsoo , Eme Laura 
Published: January 2023

AbstractMantamonads were long considered to represent an “orphan” lineage in the tree of eukaryotes, likely branching near the most frequently assumed position for the root of eukaryotes. Recent phylogenomic analyses have placed them as part of the “CRuMs” supergroup, along with collodictyonids and rigifilids. This supergroup appears to branch at the base of Amorphea, making it of special importance for understanding the deep evolutionary history of eukaryotes. However, the lack of representative species and complete genomic data associated with them has hampered the investigation of their biology and evolution. Here, we isolated and described two new species of mantamonads,Mantamonas vickermanisp. nov. andMantamonas sphyraenaesp. nov., for each of which we generated transcriptomic sequence data, as well as a high-quality genome for the latter. The estimated size of theM. sphyraenaegenome is 25 Mb; our de novo assembly appears to be highly contiguous and complete with 9,416 predicted protein-coding genes. This near-chromosome-scale genome assembly is the first described for the CRuMs supergroup.
COVision: Convolutional Neural Network for the Differentiation of COVID-19 from Common Pulmonary Conditions Using CT Scans
Authors: Parikh Kush V. , Mathew Timothy J. 
Published: January 2023

AbstractWith the growing amount of COVID-19 cases, especially in developing countries with limited medical resources, it is essential to accurately and efficiently diagnose COVID-19. Due to characteristic ground-glass opacities (GGOs) and other types of lesions being present in both COVID-19 and other acute lung diseases, misdiagnosis occurs often — 26.6% of the time in manual interpretations of CT scans. Current deep-learning models can identify COVID-19 but cannot distinguish it from other common lung diseases like bacterial pneumonia. Concretely, COVision is a deep-learning model that can differentiate COVID-19 from other common lung diseases, with high specificity using CT scans and other clinical factors. COVision was designed to minimize overfitting and complexity by decreasing the number of hidden layers and trainable parameters while still achieving superior performance. Our model consists of two parts: the CNN which analyzes CT scans and the CFNN (clinical factors neural network) which analyzes clinical factors such as age, gender, etc. Using federated averaging, we ensembled our CNN with the CFNN to create a comprehensive diagnostic tool. After training, our CNN achieved an accuracy of 95.8% and our CFNN achieved an accuracy of 88.75% on a validation set. We found a statistical significance that COVision performs better than three independent radiologists with at least 10 years of experience, especially in differentiating COVID-19 from pneumonia. We analyzed our CNN’s activation maps through Grad-CAMs and found that lesions in COVID-19 presented peripherally, closer to the pleura, whereas pneumonia lesions presented centrally.
Genome expansion by a CRISPR trimmer-integrase
Authors: Wang Joy Y. , Tuck Owen T. , Skopintsev Petr , Soczek Katarzyna M. , Li Gary , Al-Shayeb Basem , Zhou Julia , Doudna Jennifer A. 
Published: January 2023

AbstractCRISPR-Cas adaptive immune systems capture DNA fragments from invading mobile genetic elements and integrate them into the host genome to provide a template for RNA-guided immunity. CRISPR systems maintain genome integrity and avoid autoimmunity by distinguishing between self and non-self, a process for which the CRISPR-Cas1:Cas2 integrase is necessary but not sufficient. In some microbes, the Cas4 endonuclease assists CRISPR adaptation, but many CRISPR-Cas systems lack Cas4. We show here that an elegant alternative pathway employs an internal exonuclease to select and process DNA for integration using the protospacer adjacent motif (PAM). A natural Cas1:Cas2-exonuclease fusion (trimmer-integrase) catalyzes coordinated DNA capture, trimming and integration. Five cryo-EM structures of the CRISPR trimmer-integrase, visualized both before and during DNA integration, show how asymmetric processing generates size-defined, PAM-containing substrates. Before genome integration, the PAM sequence is released by Cas1 and cleaved by the exonuclease, marking inserted DNA as self and preventing aberrant CRISPR targeting of the host. Together, these data support a model in which CRISPR systems lacking Cas4 use fused or recruited exonucleases for faithful acquisition of new CRISPR immune sequences.
The pGinger family of expression plasmids
Authors: Pearson Allison N. , Thompson Mitchell G. , Kirkpatrick Liam D. , Ho Cindy , Vuu Khanh M. , Waldburger Lucas M. , Keasling Jay D. , Shih Patrick M. 
Published: January 2023

AbstractThe pGinger suite of expression plasmids comprises 43 plasmids that will enable precise constitutive and inducible gene expression in a wide range of gram-negative bacterial species. Constitutive vectors are composed of 16 synthetic constitutive promoters upstream of RFP, with a broad host range BBR1 origin and a kanamycin resistance marker. The family also has seven inducible systems (Jungle Express, Psal/NahR, Pm/XylS, Prha/RhaS, LacO1/LacI, LacUV5/LacI, and Ptet/TetR) controlling RFP expression on BBR1/kanamycin plasmid backbones. For four of these inducible systems (Jungle Express, Psal/NahR, LacO1/LacI, and Ptet/TetR), we created variants that utilize the RK2 origin and spectinomycin or gentamicin selection. Relevant RFP expression and growth data have been collected in the model bacteriumEscherichia colias well asPseudomonas putida. All pGinger vectors are available via the Joint BioEnergy Institute (JBEI) Public Registry.
Rhythmically bursting songbird vocomotor neurons are organized into multiple sequences, suggesting a network/intrinsic properties model encoding song and error, not time
Authors: Fetterman Graham C. , Margoliash Daniel 
Published: January 2023

AbstractIn zebra finch, basal ganglia projecting “HVCX” neurons emit one or more spike bursts during each song motif (canonical sequence of syllables), which are thought to be driven in part by a process of spike rebound excitation. Zebra finch songs are highly stereotyped and recent results indicate that the intrinsic properties of HVCXneurons are similar within each bird, vary among birds depending on similarity of the songs, and vary with song errors. We tested the hypothesis that the timing of spike bursts during singing also evince individual-specific distributions. Examining previously published data, we demonstrated that the intervals between bursts of multibursting HVCXare similar for neurons within each bird, in many cases highly clustered at distinct peaks, with the patterns varying among birds. The fixed delay between bursts and different times when neurons are first recruited in the song yields precisely timed multiple sequences of bursts throughout the song, not the previously envisioned single sequence of bursts treated as events having statistically independent timing. A given moment in time engages multiple sequences and both single bursting and multibursting HVCXsimultaneously. This suggests a model where a population of HVCXsharing common intrinsic properties driving spike rebound excitation influence the timing of a given HVCXburst through lateral inhibitory interactions. Perturbations in burst timing, representing error, could propagate in time. Our results extend the concept of central pattern generators to complex vertebrate vocal learning and suggest that network activity (timing of inhibition) and HVCXintrinsic properties become coordinated during developmental birdsong learning.