bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome-Based Regimen Rescues Endometrial Fibrosis in Intrauterine Adhesions Via Targeting Clinical Fibrosis Biomarkers
Authors: Lin Yifeng , Li Yaoshen , Chen Panpan , Zhang Yanye , Sun Jiwei , Sun Xiao , Li Jiaqun , Jin Jiani , Xue Jinglei , Zheng Junyan , Jiang Xin-Chi , Chen Chuan , Li Xiaoqing , Wu Yiqing , Zhao Wei , Liu Juan , Ye Xiaohang , Zhang Runju , Gao Jianqing , Zhang Dan 
Published: March 2023

AbstractIntrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell–derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome–based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients.
A Method for Quantifying Phytophthora Oospore Viability Using Fluorescent Dyes and Automated Image Analysis
Authors: Fairhurst Michael J. , Vink Jochem N. A. , Deslippe Julie R. , Gerth Monica L. 
Published: March 2023

Phytophthora are eukaryotic microbes that cause disease in a wide range of agriculturally and ecologically important plants. During the Phytophthora disease cycle, thick-walled oospores can be produced via homothallic or heterothallic reproduction. These resting spores can survive in the soil for several years in the absence of a host plant, thus providing a long-term inoculum for disease. The ability to quantitatively evaluate oospore viability is an important part of many phytopathology studies. Here, we tested six fluorescent viability dyes for their ability to differentially stain Phytophthora agathidicida oospores: SYTO 9, FUN-1, fluorescein diacetate (FDA), 5-carboxyfluorescein diacetate (CFDA), propidium iodide, and TOTO-3 iodide. Each dye was first tested individually with untreated or heat-treated oospores as proxies for viable and nonviable oospores, respectively. SYTO9, FUN-1, CFDA and propidium iodide stained untreated and heat-treated oospores indiscriminately. In contrast, FDA (a green-fluorescent viable cell stain) and TOTO-3 (a red-fluorescent nonviable cell stain) differentially stained untreated or heat-treated oospores with no cross-fluorescence. We then tested the efficacy of dual-viability staining in conjunction with a pipeline for automated image analysis. To validate the method, untreated and heat-treated oospores were mixed at specific ratios, dual-stained, and analyzed using the pipeline. Linear regression of the resulting data showed a clear correlation between the expected and measured oospore ratios ( dy/dx = 0.95, R2 = 0.88). Overall, the combination of dual-fluorescence staining and automated image analysis provides a high-throughput method for quantitatively assessing oospore viability and therefore can facilitate further studies on this key part of the Phytophthora disease cycle. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Neuroanesthesiology Quality Improvement Reporting Patterns: A Tertiary Medical Center Experience
Authors: Slade Ian R. , Yang Jen-Ting , Wright David R. , James Adrienne , Sharma Deepak 
Published: March 2023

Background:
Understanding quality improvement (QI) reporting patterns is important for practice-based improvement and for prioritizing QI initiatives. The aim of this project was to identify major domains of neuroanesthesiology QI reports at a single academic institution with 2 hospital-based practice sites.

Methods:
We retrospectively reviewed institutional QI databases to identify reports from neuroanesthesia cases between 2013 and 2021. Each report was categorized into one of the 16 primary predefined QI domains; the QI report domains were ranked by frequency. Descriptive statistics are used to present the analysis.

Results:
Seven hundred three QI reports (3.2% of all cases) were submitted for the 22,248 neurosurgical and neuroradiology procedures during the study period. Most of the QI reports across the institution were in the domain of communication/documentation (28.4%). Both hospitals shared the same 6 top QI report domains, although the relative frequency of each domain differed between the 2 hospitals. Drug error was the top QI report domain at one hospital, representing 19.3% of that site’s neuroanesthesia QI reports. Communication/documentation was the top domain at the other hospital, representing 34.7% of that site’s reports. The other 4 shared top domains were equipment/device failure, oropharyngeal injury, skin injury, and vascular catheter dislodgement.

Conclusions:
The majority of neuroanesthesiology QI reports fell into 6 domains: drug error, communication/documentation, equipment/device failure, oropharyngeal injury, skin injury, and vascular catheter dislodgement. Similar analyses from other centers can guide generalizability and potential utility of using QI reporting domains to inform the development of neuroanesthesiology quality measures and reporting frameworks.
Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions
Authors: Lyu Mengyuan , Lai Hongli , Wang Yili , Zhou Yanbing , Chen Yi , Wu Dongsheng , Chen Jie , Ying Binwu 
Published: March 2023

Abstract
Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis-splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans-splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host–pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.
ALTERNATIVE INTRAVITREAL ANTIBIOTICS
Authors: Velez-Montoya Raul , Monroy-Esquivel Luz , Ortiz-Guevara Rocío , Quiroz-Mercado Hugo , Fromow-Guerra Jans ,   For the Mexican Endophthalmitis Study Group (Mex-ESG)
Published: March 2023

Purpose:To organize, categorize, and create a quick reference guide for the use of intravitreal antibiotic alternatives to the standard combination of vancomycin and ceftazidime for the treatment of endophthalmitis.Methods:A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The authors searched for all available information regarding intravitreal antibiotics in the last 21 years. Manuscripts were selected according to relevance, level of information, and the available data regarding intravitreal dose, potential adverse effects, bacterial coverage, and relevant pharmacokinetic information.Results:The authors included 164 of 1810 manuscripts. The antibiotics were classified according to their class into fluoroquinolones, cephalosporins, glycopeptide and lipopeptide, penicillins and beta-lactams, tetracyclines, and miscellaneous. The authors also included information regarding intravitreal adjuvants for the treatment of endophthalmitis and one ocular antiseptic.Conclusion:The treatment of infectious endophthalmitis is a therapeutic challenge. The current review summarizes the properties of possible intravitreal antibiotic alternatives that should be considered in cases of suboptimal response to initial treatment.
Impact of Season on Incidence of Sinusitis-related Orbital Cellulitis
Authors: Wladis Edward J. , Narravula Raghav , Foyt Alexander K. , Pauze Denis R. 
Published: March 2023

Purpose:
To explore the impact of season on the incidence of presentation to emergency departments with sinusitis-related orbital cellulitis in the United States.

Methods:
The National Emergency Department Sample was queried to identify cases of patients with sinusitis-related orbital cellulitis. Patient's age, location, and the month of presentation were recorded. Statistical correlations were analyzed via a dedicated software package.

Results:
A total of 439 patients with sinusitis-related orbital cellulitis were identified. The overall incidence was higher during the winter months (p < 0.05); while children were more likely to develop this disease during the winter (p < 0.05), season was not statistically correlated with its incidence among adults (p = 0.16). The incidence of orbital cellulitis was higher during the winter in the midwest and south regions of the United States (p < 0.05 for each region), although this correlation did not apply in the northeast and west (p = 0.60 and 0.99, respectively).

Conclusions:
While sinusitis incidence increases during the winter, the relationship between season and orbital cellulitis is complex and varies by age and geographic location. These findings may help to facilitate screening protocols for this disease and to define staffing issues for emergent ophthalmic care.
Alemtuzumab-Induced Thyroid Eye Disease: A Comprehensive Case Series and Review of the Literature
Authors: Nirmalan Aravindh , Blecher Nathanael , Hyder Sayyada , Couch Steven M. , Godfrey Kyle J. , Stan Marius N. , Bradley Elizabeth A. , Wagner Lilly H. , Tooley Andrea A. 
Published: March 2023

Purpose:
To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED).

Methods:
A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED.

Results:
Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1–4) and reached an average peak of 5.0 during the active phase of the disease (4–7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease.

Conclusions:
Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves’ disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.
Daily pain and opioid administration in hospitalized patients with cancer: the importance of psychological factors, recent surgery, and current opioid use
Authors: Azizoddin Desiree R. , Wilson Jenna M. , Flowers Kelsey Mikayla , Beck Meghan , Chai Peter , Enzinger Andrea C. , Edwards Robert , Miaskowski Christine , Tulsky James A. , Schreiber Kristin L. 
Published: March 2023

AbstractPain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing (B= 0.1,P≤ 0.001), more recent surgery (B= −0.2,P≤ 0.05), outpatient opioid use (B= 1.4,P≤ 0.001), and history of chronic pain before cancer diagnosis (B= 0.8,P≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing (B= 1.6,P≤ 0.05), higher anxiety (B= 3.7,P≤ 0.05), lower depression (B= −4.9,P≤ 0.05), metastatic disease (B= 16.2,P≤ 0.05), and outpatient opioid use (B= 32.8,P≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions.
Metabolomics signatures of plant protein intake: effects of amino acids and compounds associated with plant protein on cardiometabolic health
Authors: Gueugneau Marine , Capel Frederic , Monfoulet Laurent-Emmanuel , Polakof Sergio 
Published: March 2023

Purpose of review
An increase in the plant-based characteristics of the diet is now recommended for human and planetary health. There is growing evidence that plant protein (PP) intake has beneficial effects on cardiometabolic risk. However, proteins are not consumed isolated and the protein package (lipid species, fiber, vitamins, phytochemicals, etc) may contribute, besides the protein effects per se, to explain the beneficial effects associated with PP-rich diets.

Recent findings
Recent studies have shown the potential of nutrimetabolomics to apprehend the complexity of both the human metabolism and the dietary habits, by providing signatures associated to the consumption of PP-rich diets. Those signatures comprised an important proportion of metabolites that were representative of the protein package, including specific amino acids (branched-chain amino acids and their derivates, glycine, lysine), but also lipid species (lysophosphatidylcholine, phosphatidylcholine, plasmalogens) and polyphenol metabolites (catechin sulfate, conjugated valerolactones and phenolic acids).

Summary
Further studies are needed to go deeper in the identification of all metabolites making part of the specific metabolomic signatures, associated to the large range of protein package constituents and their effects on the endogenous metabolism, rather than to the protein fraction itself. The objective is to determine the bioactive metabolites, as well as the modulated metabolic pathways and the mechanisms responsible for the observed effects on cardiometabolic health.
Dynamics of Pre-Exposure (PrEP) Eligibility Because of Waxing and Waning of HIV Risk in Rakai, Uganda
Authors: Ssempijja Victor , Ssekubugu Robert , Kigozi Godfrey , Nakigozi Gertrude , Kagaayi Joseph , Ekstrom Anna Mia , Nalugoda Fred , Nantume Betty , Batte James , Kigozi Grace , Yeh Ping Teresa , Nakawooya Hadijja , Serwadda David , Quinn Thomas C. , Gray Ronald H. , Wawer Maria J. , Grabowski Kate M. , Chang Larry W. , Hoog Anja van't , Cobelens Frank , Reynolds Steven J. 
Published: March 2023

Background:
We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for pre-exposure prophylaxis (PrEP) eligibility.

Methods:
The study was conducted among HIV-negative study participants aged 15–49 years who participated in survey rounds of the Rakai Community Cohort Study between August 2011 and June 2018. Substantial HIV risk was defined based on the Uganda national PrEP eligibility as reporting sexual intercourse with >1 partner of unknown HIV status, nonmarital sex without a condom, having genital ulcers, or having transactional sex. Resumption of SHR meant resuming of SHR after stopping SHR, whereas persistence of SHR meant SHR on >1 consecutive visit. We used generalized estimation equations with log-binomial regression models and robust variance to estimate survey-specific prevalence ratios; Generalized estimation equations with modified Poisson regression models and robust variance to estimate incidence ratios for incidence, discontinuation, and resumption of PrEP eligibility.

Findings:
Incidence of PrEP eligibility increased from 11.4/100 person-years (pys) in the first intersurvey period to 13.9/100 pys (adjusted incidence rate ratios = 1.28; 95%CI = 1.10–1.30) and declined to 12.6/100 pys (adjusted incidence rate ratios = 1.06; 95%CI = 0.98–1.15) in the second and third intersurvey periods, respectively. Discontinuation rates of SHR for PrEP eligibility were stable (ranging 34.9/100 pys–37.3/100 pys; P = 0.207), whereas resumption reduced from 25.0/100 pys to 14.5/100 pys (P < 0.001). PrEP eligibility episodes lasted a median time of 20 months (IQR = 10–51).

Interpretation:
Pre-exposure prophylaxis use should be tailored to the dynamic nature of PrEP eligibility. Preventive-effective adherence should be adopted for assessment of attrition in PrEP programs.
Traumatic brain injury modifies adult hippocampal neural stem cell fate to promote neurogenesis at the cost of astrogliogenesis
Authors: Bielefeld P , Martirosyan A , Apresyan A , Meerhoff G , Pestana F , Poovathingal S , Reijners N , Koning W , Clement RA , Van de Veen I , Toledo E , Durá I , Hovhannisyan S. , Nilges B. , Bogdoll A. , Kashikar N. , Lucassen PJ , Belgard TG , Encinas JM , Holt MG , Fitzsimons CP 
Published: March 2023

AbstractModerate Traumatic brain injury (TBI) can result in long-lasting changes in brain function. Although frequently spared from the acute primary injury, the hippocampus becomes affected during a secondary phase that takes place hours, or even days, after TBI, contributing to cognitive deficits. The hippocampus is one of the few brain areas in the adult brain harboring native neural stem cells (NSCs) that continue to generate new neurons (neurogenesis), and to a lesser extent new astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, very little is known about how TBI may affect hippocampal astrogliogenesis.Here, we aimed to assess how TBI affects hippocampal NSCs and their subsequent commitment to the neuronal or astroglial lineages. Using a controlled cortical impact model of TBI, single cell RNA sequencing and spatial transcriptomics, we observed a cell population-specific increase in NSC-derived neuronal cells and a decrease in NSC-derived astrocytic cells. These cellular changes were associated with cell-population specific changes in gene expression and dysplasia within the dentate gyrus.Overall, our findings support the conclusion that TBI modifies adult hippocampal NSC fate to promote neurogenesis at the cost of astrogliogenesis, and highlights specific cell populations as possible targets to counteract the changes induced by TBI in the hippocampus.
Antigen-presenting type-I conventional dendritic cells facilitate curative checkpoint blockade immunotherapy in pancreatic cancer
Authors: Mahadevan Krishnan K. , Dyevoich Allison M. , Chen Yang , Li Bingrui , Sugimoto Hikaru , Sockwell Amari M. , McAndrews Kathleen M. , Wang Huamin , Shalapour Shabnam , Watowich Stephanie S. , Kalluri Raghu 
Published: March 2023

AbstractInflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type-I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8+T cell activation and eradication of ptPDAC with restoration of lifespan even upon PDAC re-challenge. Such eradication of ptPDAC was reversed following specific depletion of dendritic cells. Employing PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with a curative outcome. Analysis of the T-cell receptor (TCR) sequences in the tumor infiltrating CD8+T cells following cDC1 vaccination coupled with iCBT identified unique CDR3 sequences with potential therapeutic significance. Our findings identify a fundamental difference in the immune microenvironment and adaptive immune response in PDAC concurrent with, or without pancreatitis, and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.
Trophic interactions in microbiomes influence plant host population size and ecosystem function
Authors: Tan Jiaqi , Wei Na , Turcotte Martin M. 
Published: March 2023

AbstractPlant microbiomes that comprise diverse microorganisms, including prokaryotes, eukaryotes, and viruses are the key determinant of plant population dynamics and ecosystem function. Despite their importance, little is known about how interactions, especially trophic interactions, between microbes from different domains modify the importance of microbiomes for plant hosts and ecosystems. Using the common duckweedLemna minor, we experimentally examined the effects of predation (by bacterivorous protozoa) and parasitism (by bacteriophage) within microbiomes on plant population size and ecosystem phosphorus removal. Our results revealed that predation increased plant population size and phosphorus removal whereas parasitism showed the opposite pattern. The structural equation modeling further pointed out that predation and parasitism affected plant population size and ecosystem function via distinct mechanisms that were both mediated by microbiomes. Our results highlight the importance of understanding microbial trophic interactions for predicting the outcomes and ecosystem impacts of plant-microbiome symbiosis.