bluuebunny/crossref_metadata_2025 huggingface dataset:
CAGEE: Computational Analysis of Gene Expression Evolution
Authors: Bertram Jason , Fulton Ben , Tourigny Jason P , Peña-Garcia Yadira , Moyle Leonie C , Hahn Matthew W
Published: May 2023

Despite the increasing abundance of whole transcriptome data, few methods are available to analyze global gene expression across phylogenies. Here, we present a new software package (Computational Analysis of Gene Expression Evolution [CAGEE]) for inferring patterns of increases and decreases in gene expression across a phylogenetic tree, as well as the rate at which these changes occur. In contrast to previous methods that treat each gene independently, CAGEE can calculate genome-wide rates of gene expression, along with ancestral states for each gene. The statistical approach developed here makes it possible to infer lineage-specific shifts in rates of evolution across the genome, in addition to possible differences in rates among multiple tissues sampled from the same species. We demonstrate the accuracy and robustness of our method on simulated data and apply it to a data set of ovule gene expression collected from multiple self-compatible and self-incompatible species in the genus Solanum to test hypotheses about the evolutionary forces acting during mating system shifts. These comparisons allow us to highlight the power of CAGEE, demonstrating its utility for use in any empirical system and for the analysis of most morphological traits. Our software is available at https://github.com/hahnlab/CAGEE/.
OpenXGR: a web-server update for genomic summary data interpretation
Authors: Bao Chaohui , Wang Shan , Jiang Lulu , Fang Zhongcheng , Zou Kexin , Lin James , Chen Saijuan , Fang Hai
Published: May 2023

How to effectively convert genomic summary data into downstream knowledge discovery represents a major challenge in human genomics research. To address this challenge, we have developed efficient and effective approaches and tools. Extending our previously established software tools, we here introduce OpenXGR (http://www.openxgr.com), a newly designed web server that offers almost real-time enrichment and subnetwork analyses for a user-input list of genes, SNPs or genomic regions. It achieves so through leveraging ontologies, networks, and functional genomic datasets (such as promoter capture Hi-C, e/pQTL and enhancer-gene maps for linking SNPs or genomic regions to candidate genes). Six analysers are provided, each doing specific interpretations tailored to genomic summary data at various levels. Three enrichment analysers are designed to identify ontology terms enriched for input genes, as well as genes linked from input SNPs or genomic regions. Three subnetwork analysers allow users to identify gene subnetworks from input gene-, SNP- or genomic region-level summary data. With a step-by-step user manual, OpenXGR provides a user-friendly and all-in-one platform for interpreting summary data on the human genome, enabling more integrated and effective knowledge discovery.
Discovery and characterization of novel Cre-type tyrosine site-specific recombinases for advanced genome engineering
Authors: Jelicic Milica , Schmitt Lukas Theo , Paszkowski-Rogacz Maciej , Walder Angelika , Schubert Nadja , Hoersten Jenna , Sürün Duran , Buchholz Frank
Published: May 2023

Tyrosine-type site-specific recombinases (Y-SSRs) are versatile tools for genome engineering due to their ability to mediate excision, integration, inversion and exchange of genomic DNA with single nucleotide precision. The ever-increasing need for sophisticated genome engineering is driving efforts to identify novel SSR systems with intrinsic properties more suitable for particular applications. In this work, we develop a systematic computational workflow for annotation of putative Y-SSR systems and apply this pipeline to identify and characterize eight new naturally occurring Cre-type SSR systems. We test their activity in bacterial and mammalian cells and establish selectivity profiles for the new and already established Cre-type SSRs with regard to their ability to mutually recombine their target sites. These data form the basis for sophisticated genome engineering experiments using combinations of Y-SSRs in research fields including advanced genomics and synthetic biology. Finally, we identify putative pseudo-sites and potential off-targets for Y-SSRs in the human and mouse genome. Together with established methods for altering the DNA-binding specificity of this class of enzymes, this work should facilitate the use of Y-SSRs for future genome surgery applications.
Media use and vaccine resistance
Authors: Green Jon , Druckman James N , Baum Matthew A , Ognyanova Katherine , Simonson Matthew D , Perlis Roy H , Lazer David
Published: May 2023

Public health requires collective action—the public best addresses health crises when individuals engage in prosocial behaviors. Failure to do so can have dire societal and economic consequences. This was made clear by the disjointed, politicized response to COVID-19 in the United States. Perhaps no aspect of the pandemic exemplified this challenge more than the sizeable percentage of individuals who delayed or refused vaccination. While scholars, practitioners, and the government devised a range of communication strategies to persuade people to get vaccinated, much less attention has been paid to where the unvaccinated could be reached. We address this question using multiple waves of a large national survey as well as various secondary data sets. We find that the vaccine resistant seems to predictably obtain information from conservative media outlets (e.g. Fox News) while the vaccinated congregate around more liberal outlets (e.g. MSNBC). We also find consistent evidence that vaccine-resistant individuals often obtain COVID-19 information from various social media, most notably Facebook, rather than traditional media sources. Importantly, such individuals tend to exhibit low institutional trust. While our results do not suggest a failure of sites such as Facebook's institutional COVID-19 efforts, as the counterfactual of no efforts is unknown, they do highlight an opportunity to reach those who are less likely to take vital actions in the service of public health.
Dynamics of Puccinia striiformis f. sp. tritici Urediniospores in Longnan, a Critical Oversummering Region of China
Authors: Hu Xuemin , Fu Songping , Li Yuxiang , Xu Xiangming , Hu Xiaoping
Published: May 2023

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici Erikss. (Pst), is a devastating disease resulting in yield reduction. Because the temperature limits the overwintering and oversummering of Pst, it cannot complete the whole year cycle in most areas of China. Longnan, located in the southeast of Gansu Province, is one of the annual cycle areas of Pst, which can supply urediniospores in autumn to eastern wheat-growing areas in China. In this study, a TaqMan real-time quantitative PCR (TaqMan-qPCR) detection system for Pst urediniospores was established, and the detection limit was a single urediniospore. The dynamics of Pst urediniospores in Longnan were monitored by spore trapping and TaqMan-qPCR for 3 years. Meanwhile, the meteorological conditions including air temperature, relative humidity, and precipitation were recorded. Results showed that Pst urediniospores can be captured from March to December, and two peaks of urediniospore density appeared in May and June, respectively. The density of urediniospore is closely related to temperature and precipitation from March to June. In addition, we found that the density of Pst urediniospore had the peak value when the average air temperature was 10 to 21°C, and the relative humidity was 60 to 85% from May to June. The exponential model could describe the variation of Pst urediniospore density based on average temperature and precipitation from March to June. It is worth mentioning that the exponential model based on average temperature 7 days before spore capture has a great advantage in predicting the urediniospore density in the air. This study laid a foundation for establishment of a prediction model for wheat stripe rust based on the density of urediniospores and meteorological factors.
Crossing the Gateless Barriers: Factors Involved in the Movement of Circulative Bacteria Within Their Insect Vectors
Authors: Sarkar Poulami , Lin Chun-Yi , Buritica Jacobo Robledo , Killiny Nabil , Levy Amit
Published: May 2023

Plant bacterial pathogens transmitted by hemipteran vectors pose a large threat to the agricultural industry worldwide. Although virus-vector relationships have been widely investigated, a significant gap exists in our understanding of the molecular interactions between circulative bacteria and their insect vectors, mainly leafhoppers and psyllids. In this review, we will describe how these bacterial pathogens adhere, invade, and proliferate inside their insect vectors. We will also highlight the different transmission routes and molecular factors of phloem-limited bacteria that maintain an effective relationship with the insect host. Understanding the pathogen−vector relationship at the molecular level will help in the management of vector-borne bacterial diseases.
RNase D Is Involved in 5S rRNA Degradation and Exopolysaccharide Production in Xanthomonas campestris pv. campestris
Authors: Chen Xin-Yi , Hu Shan-Shan , Xu Xiao-Can , Tang Ji-Liang , Tang Dong-Jie
Published: May 2023

Ribonucleases (RNases) play critical roles in RNA metabolism and are collectively essential for cell viability. However, most knowledge about bacterial RNases comes from the studies on Escherichia coli; very little is known about the RNases in plant pathogens. The crucifer black rot pathogen Xanthomonas campestris pv. campestris ( Xcc) encodes 15 RNases, but none of them has been functionally characterized. Here, we report the physiological function of the exoribonuclease RNase D in Xcc and provide evidence demonstrating that the Xcc RNase D is involved in 5S rRNA degradation and exopolysaccharide (EPS) production. Our work shows that the growth and virulence of Xcc were not affected by deletion of RNase D but were severely attenuated by RNase D overexpression. However, deletion of RNase D in Xcc resulted in a significant reduction in EPS production. In addition, either deletion or overexpression of RNase D in Xcc did not influence the tRNAs tested, inconsistent with the finding in E. coli that the primary function of RNase D is to participate in tRNA maturation and its overexpression degrades tRNAs. More importantly, deletion, overexpression, and in vitro enzymatic analyses revealed that the Xcc RNase D degrades 5S rRNA but not 16S and 23S rRNAs that share an operon with 5S rRNA. Our results suggest that Xcc employs RNase D to realize specific modulation of the cellular 5S rRNA content after transcription and maturation whenever necessary. The finding expands our knowledge about the function of RNase D in bacteria.
Artesunate protects against ocular fibrosis by suppressing fibroblast activation and inducing mitochondria‐dependent ferroptosis
Authors: Liu Jingyuan , Pan Zheng , Tong Boding , Wang Cong , Yang Jia , Zou Jingling , Jiang Jikuan , Zhang Lusi , Jiang Bing
Published: May 2023

Artesunate, a derivative from extracts of Artemisia annua, has recently been reported to alleviate fibrosis recently. Here, in this study, we sought to determine the anti‐fibrosis effect of artesunate in rabbit glaucoma filtration surgery (GFS) model and illuminate underlying mechanisms. Our results showed that artesunate subconjunctival injection alleviated bleb fibrosis by inhibiting fibroblast activation and inducing ferroptosis. Further mechanistic investigation in primary human ocular fibroblasts (OFs) showed that artesunate abrogated fibroblast activation by inhibiting TGF‐β1/SMAD2/3 and PI3K/Akt pathways and scavenged OFs by inducing mitochondria‐dependent ferroptosis. Mitochondrial dysfunction, mitochondrial fission, and iron‐dependent mitochondrial lipid peroxidation were observed in artesunate‐treated OFs. Besides, mitochondria‐localized antioxidants inhibited artesunate‐induced cell death, suggesting a critical role of mitochondria in artesunate‐induced ferroptosis. Our study also found that expression of mitochondrial GPX4 but no other forms of GPX4 was decreased after artesunate treatment and that mitochondrial GPX4 overexpression rescued artesunate‐induced lipid peroxidation and ferroptosis. Other cellular ferroptosis defense mechanisms, including cellular FSP1 and Nrf2, were also inhibited by artesunate. In conclusion, our study demonstrated that artesunate protects against fibrosis through abrogation of fibroblast activation and induction of mitochondria‐dependent ferroptosis in OFs, which may offer a potential treatment for ocular fibrosis.
Socioeconomic and Racial/Ethnic Disparities in Perception of Health Status and Literacy in Spine Oncological Patients
Authors: Elsamadicy Aladine A. , Wang Chelsea , Reeves Benjamin C. , Sherman Josiah J.Z. , Craft Samuel , Rajjoub Rami , Koo Andrew , Hersh Andrew M. , Pennington Zach , Lo Sheng-Fu Larry , Shin John H. , Mendel Ehud , Sciubba Daniel M.
Published: May 2023

Study Design.

A cross-sectional study was performed using the National Institutes of Health All of Us survey database.

Objective.

The aim of this study was to assess socioeconomic and racial disparities in the perception of personal health, health literacy, and healthcare access among spine oncology patients.

Summary of Background Data.

Racial, ethnic, and socioeconomic disparities in health literacy and perception of health status have been described for many disease processes. However, few studies have assessed the prevalence of these disparities among spine oncology patients.

Methods.

Adult spine oncology patients, identified using ICD-9/10-CM codes, were categorized by race/ethnicity: White/Caucasian (WC), Black/African-American (BAA), and Non-White Hispanic (NWH). Demographics and socioeconomic status were assessed. Questionnaire responses regarding baseline health status, perception of health status, health literacy, and barriers to healthcare were compared.

Results.

Of the 1,175 patients identified, 207 (17.6%) were BAA, 267 (22.7%) were NWH, and 701 (59.7%) were WC. Socioeconomic status varied among cohorts, with WC patients reporting higher levels of education (P<0.001), annual income greater than $50K (P<0.001), and home ownership (P<0.001). BAA and NWH patients reported greater rates of 7-day “Severe fatigue” (P<0.001) and “10/10 pain” (P<0.001) and lower rates of “Completely” able to perform everyday activities (P<0.001). WC patients had a higher response rate for “Excellent/Very Good” regarding their own general health (P<0.001) and quality (P<0.001). The WC cohort had a significantly higher proportion of patients responding “Never” when assessing difficulty understanding (P<0.001) and needing assistance with health materials (P<0.001). BAA and NWH were significantly less likely to report feeling “Extremely” confident with medical forms (P<0.001). BAA and NWH had significantly higher response rates to feeling “Somewhat Worried” about healthcare costs (P<0.001) and with delaying medical care given “Can’t Afford Co-pay” (P<0.001).

Conclusion.

We identified disparities in perception of health status, literacy, and access among spine oncology patients.

Level of Evidence.

4
Novel Custom Maxillary Disimpaction Splint
Authors: Jolly Lisa , Sudduth Jack D. , Marquez Jessica L. , White Michelle , Collar-Yagas Lucia , Yamashiro Duane , Siddiqi Faizi , Gociman Barbu
Published: May 2023

LeFort I, II, and III osteotomies are commonly used in complex craniofacial reconstruction. Patients requiring these procedures typically have a craniofacial cleft, other congenital craniofacial deformities, or severe facial trauma. Both the cleft and traumatized palate have poor bony support, which leads to possible complications when the disimpaction forceps are used during the downfracture of the maxilla. Such potential complications include trauma or formation of a fistula of the palatal, oral, or nasal mucosa; trauma to adjacent teeth; and fracture of the palate and alveolar bone. To help prevent these complications, we developed a custom disimpaction splint. The splint is designed to cover the palate and occlusal surfaces to increase retention and minimize splint movement during the maxillary downfracture portion of the surgical procedure. The base of the splint is fabricated from a two-layered biocryl material, and the palatal area is built with soft-cushion rebase material. This allows for a stable grip of the disimpaction forceps blades and provides protective coverage of the cleft, traumatized palate, or alveolar bone graft site during the downfracture. The custom maxillary disimpaction splint has been routinely used in our clinic from September 2019 to the present for LeFort osteotomies in patients with a compromised primary palate. No surgical complications related to the maxillary downfracture have been noted during this period of time. We conclude that the routine use of a custom maxillary disimpaction splint can result in improved outcomes and decreased complications of LeFort osteotomy procedures in patients with cleft and traumatized palate.
High incidence of trigger finger after carpal tunnel release: a systematic review and meta-analysis
Authors: Lo Yu-Chieh , Lin Cheng-Han , Huang Shu-Wei , Chen Yu-Pin , Kuo Yi-Jie
Published: May 2023

Introduction:

Trigger finger (TF) often occurs after carpal tunnel release (CTR), but the mechanism and outcomes remain inconsistent. This study evaluated the incidence of TF after CTR and its related risk factors.

Materials and Methods:

​PubMed, Embase, and Scopus databases were searched up to 27 August 2022, with the following keywords: “carpal tunnel release” and “trigger finger”. Studies with complete data on the incidence of TF after CTR and published full text. The primary outcome was the association between CTR and the subsequent occurrence of the TF and to calculate the pooled incidence of post-CTR TF. The secondary outcomes included the potential risk factors among patients with and without post-CTR TF as well as the prevalence of the post-CTR TF on the affected digits.

Results:

Ten studies with total 10,399 participants in 9 studies and 875 operated hands in one article were included for meta-analysis. CTR significantly increases the risk of following TF occurrence (odds ratio=2.67; 95% CI 2.344–3.043; P<0.001). The pooled incidence of TF development after CTR was 7.7%. Women were more likely to develop a TF after CTR surgery (odds ratio=2.02; 95% CI 1.054–3.873; P=0.034). Finally, the thumb was the most susceptible fingers, followed by middle and ring fingers.

Conclusions:

High incidence of TF comes after CTR, and women were more susceptible than man. Clinicians were suggested to notice the potential risk of TF after CTR in clinical practice.

Level of evidence:

Level III, meta-analysis.
Validation of the Structured Assessment of Gastrointestinal Symptoms Scale to Support Standardized Evaluation and Follow-up
Authors: Hammer Johann , Holtmann Gerald , Hammer Karin
Published: May 2023

Objectives:

Patient-reported outcome measures facilitate evaluation of patients and allow to better assess treatment effects. Validated tools are lacking for pediatric gastroenterological patients. We thus aimed to adapt and validate for pediatric populations a self-administered Structured Assessment of Gastrointestinal Symptoms (SAGIS) tool that previously has been validated in adult cohorts.

Methods:

Each item of the original SAGIS instrument was thoroughly reviewed for its relevance in the pediatric population. The resulting pediatric (p)SAGIS was utilized over a 35 months’ period in consecutive patients in a pediatric outpatient GI clinic. Principal component analysis (PCA) followed by varimax rotation and confirmatory factor analysis (CFA) was performed in derivation and validation samples. Responsiveness to change was assessed in 32 children with inflammatory bowel disease (IBD) after 12 months of therapy.

Results:

The final pediatric SAGIS (pSAGIS) consisted of 21 GI-related Likert-type questions, 8 dichotomous questions assessing extra-intestinal symptoms, and 2 most bothersome symptoms; 1153 children/adolescents completed a total of 2647 questionnaires. Cronbach alpha was 0.89, indicating good internal consistency. PCA supported a 5-factor model (symptom groups: abdominal pain, dyspepsia, diarrhea, constipation, dysphagia/nausea) and CFA showed good model fit (comparative fit index: 0.96, root-mean-square error of approximation: 0.075). The initial mean total GI symptom score in IBD patients (8.7 ± 10.3) decreased to 3.6 ± 7.7 after 1 year of therapy (P < 0.01), and 4 of 5 symptom group scores decreased significantly upon treatment (P < 0.05).

Conclusions:

The pSAGIS is a novel, easy to use, self-administered instrument for GI-symptom assessment in children/adolescents with excellent psychometric properties. It may standardize GI-symptom assessment and may enable uniform clinical analysis of treatment outcomes.
Association Between Race and Usage of Pain Medications in Children With Long Bone Fractures in US Emergency Departments, 2011–2019
Authors: Pekas Devon , Telken Wyatt , Sahmoun Abe E. , Beal James R.
Published: May 2023

Objectives

The purpose of this study was to determine the association between race and analgesic administration for children with long bone fracture (LBF) in US emergency departments. Previous studies have shown conflicting results regarding association between race and analgesic administration for pediatric LBFs.

Methods

We conducted a retrospective analysis of pediatric emergency department visits for LBF using the 2011–2019 National Hospital Ambulatory Medical Care Survey-Emergency Department. We investigated the diagnostic workup and analgesic prescription rate among White, Black, and other pediatric emergency department visits for LBF.

Results

Of the estimated 292 million pediatric visits to US emergency departments from 2011 to 2019, 3.1% were LBFs. Black children were less likely to be seen for a LBF than White or other children (1.8% vs 3.6% and 3.1%, P < 0.001). There was no association between race and subjective pain scale (P = 0.998), triage severity (P = 0.980), imaging (x-ray, P = 0.612; computed tomography scan, P = 0.291), or analgesic administration (opioids, P = 0.068; nonsteroidal antiinflammatory drugs/acetaminophen, P = 0.750). Trend analysis showed a significant decrease in opioid administration for pediatric LBF from 2011 to 2019 (P < 0.001), with 33.0% receiving opioids.

Conclusions

There was no association between race and analgesic administration, including opioids, or diagnostic workup in pediatric LBF. In addition, there was a significant downtrend in opioid administration for pediatric LBF from 2011 to 2019.
Unmasking a New Type of Gastrointestinal Foreign Body in the COVID-19 Era
Authors: Little Rebecca , Shpoliansky Michael , Greer Mary-Louise , Avitzur Yaron , Au Hosanna , Hulst Jessie
Published: May 2023

The incidence of foreign body ingestion has increased during the coronavirus disease 2019 pandemic. As face masks became increasingly available, we report a case of accidental ingestion of the metal strip insert of a surgical mask. After initially progressing, its progress halted after 24 hours. This case highlights the challenges of timing the endoscopic removal of long objects, especially considering the reduced endoscopic availability during the pandemic. Despite only causing local trauma, the strip was impacted at the duodenojejunal flexure with the potential to cause obstruction. Limiting morbidity relies on urgent removal and prevention of similar ingestions by emphasizing the safe use and storage of masks.
Autologous Diabetic Adipose-derived Stem Cells are Comparable to Allogeneic Non-diabetic Counterparts in Improving Diabetic Wound Healing
Authors: Chen Bin , Wei Yating , Cai Junrong , Zitkovsky Helen S. , Guo Lifei
Published: May 2023

Background:

Adipose tissue-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. While the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds.

Methods:

Diabetic ASCs (DMA) and non-diabetic ASCs (WTA) were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10-12-week db/db mice. Wound size was measured semiweekly until day 28, while histological and molecular analyses were performed at day 14.

Results:

Both ASCs had fibroblast-like morphology and were CD44 +/CD90 +/CD34 -/CD45 - at passage 4. Compared with WTA in vitro, DMA proliferative capability was restored by passage 4 (p > 0.05). Although DMA osteogenesis was attenuated (p < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 (p > 0.05). In vivo experiments showed that, compared with PBS control, both ASCs are comparable in improving wound healing (p < 0.0001), angiogenesis (p < 0.05), epithelial cell proliferation (p < 0.05), and granulation tissue formation (p < 0.0001).

Conclusion:

In both in vitro and in vivo murine models, Diabetic ASCs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, re-epithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments.

Clinical Relevance Statement:

This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients’ own ASCs to treat their wounds; bypassing any concerns of cross-host sourcing issue in regenerative medicine.
Enhanced effect of secondary administrations of adipose-derived stromal cells concurrent with fat grafting
Authors: Huang Yan , Jin Xian , Hong Ki Yong , Chang Hak
Published: May 2023

Background:

Cell-assisted lipotransfer, a fat graft mixed with adipose-derived stromal cells, is known to enhance fat graft retention. Previously, we showed that intravenous injection of adipose-derived stromal cells can improve the survival of grafted fat. In the present study, we investigated the effects of a secondary intravenous injection of adipose-derived stromal cells on fat grafting.

Methods:

Wild-type C57BL/6J (B6) mice were used as donors for grafted fat and as recipients. Adipose-derived stromal cells were harvested from green fluorescent protein and DsRed B6 mice. The recipient mice were divided into three groups: SI (n = 10), RI1 (n = 10), and RI2 (n = 11). All groups received intravenous injections of green fluorescent protein adipose-derived stromal cells immediately after fat grafting. The RI1 and RI2 groups received repeated intravenous injections of DsRed adipose-derived stromal cells at 1 and 2 weeks, respectively, after fat grafting. The grafted fat volume was measured using micro-computed tomography.

Results:

Secondarily injected DsRed adipose-derived stromal cells were recruited to the grafted fat and resulted in a higher retention of graft volume and vascular density (p < 0.05). The stromal-derived factor-1 and C-X-C chemokine receptor type 4 genes related to stem cell homing were highly expressed in the grafted fat and adipose-derived stromal cells (p < 0.05). The RI2 group showed a higher graft volume and vascular density than the SI and RI1 groups (p < 0.05).

Conclusions:

A secondary intravenous injection of adipose-derived stromal cells at a 2-week interval enhances the effect of adipose-derived stromal cell enrichment in fat grafting. These findings refine clinical protocols and enhance the therapeutic value of cell-assisted lipotransfer.
Effects of catalpol from Rehmannia glutinosa extract on skin flaps
Authors: Ma Xinyi , Lin Yi , Fang Miaojie , Liu yingying , Li Wenjie , He Jibing , Lin Dingsheng
Published: May 2023

Background:

Flaps are commonly used for repairing tissues and wounds in surgery. However, various factors can cause postoperative necrosis in these flaps. Catalpol is a bioactive component in extracts from Rehmannia glutinosa, which has pharmacological characteristics that may improve flap survival.

Methods:

The experiments were performed in 36 male Sprague–Dawley rats divided into three groups: control, low-dose catalpol, and high-dose catalpol. The flap survival rate, neutrophil density, microvessel density (MVD), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured; histopathological analysis was performed 7 days after surgery. Blood flow was measured by laser Doppler flowmetry (LDF) and lead oxide-gelatin angiography. The levels of vascular endothelial growth factor (VEGF), Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, Nod-like receptor 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), IL-1β, and IL-18 were determined by immunohistochemistry.

Results:

Catalpol treatment increased flap survival, reduced neutrophil recruitment and release, decreased MDA levels, and increased SOD levels; thus, it effectively reduced oxidative stress, upregulated the expression of VEGF, and increased microvessel density. LDF and gelatin-lead oxide angiography showed that catalpol treatment improved angiogenesis. Immunohistochemical analyses showed that catalpol inhibited the production of inflammatory factors, such as TNF-α and IL-6, by downregulating TLR4 and NF-κB. Furthermore, catalpol reduced cell pyroptosis by inhibiting the production of NLRP3 inflammasomes, thereby downregulating the release of IL-1β and IL-18.

Conclusion:

Catalpol can improve the rate of flap survival.
Neuroscience-based nomenclature as a teaching tool, introduction and pilot study
Authors: Zemach Sasson , Minkin Levy Daniel , Zohar Joseph
Published: May 2023

Neuroscience-based nomenclature (NbN) is a pharmacologically-driven nomenclature aiming to replace the current disease-based nomenclature of psychotropics, focusing on pharmacology and mode-of-action to encourage scientifically-minded prescribing. NbN might also be used as a teaching tool as it presents the depth and richness of the neuroscience of psychotropics. This study examines the effect of using NbN in student curriculum. Fifty-six medical students during clerkship in psychiatry, divided into a control group (n = 20), taught standard psychopharmacology, and an intervention group (n = 36) introduced with NbN. Both groups filled out identical questionnaires at the beginning and end of the clerkship, including questions of knowledge on psychopharmacology, views on current terminology and interest in psychiatric residency. Comparing the average change in scorings (delta post-pre) for each item in intervention vs. control questionnaires, the intervention group showed a significantly larger positive delta in 6 out of 10 items than the control group. Mean scores did not differ significantly between the two groups in the pre-questionnaires, while significantly higher scores were shown for the intervention group in within- and between-group comparisons. Introduction of NbN was associated with a better educational experience, a deeper understanding of psychotropics and increased interest in psychiatric residency.
Success in vaccination programming through community health workers: A case study of Nepal, Senegal, and Zambia
Authors: Ogutu Emily , Ellis Anna S. , Hester Kyra A. , Rodriguez Katie , Sakas Zoe , Jaishwal Chandni , Yang Chenmua , Dixit Sameer , Bose Anindya S. , Sarr Moussa , Kilembe William , Bednarczyk Robert A. , Freeman Matthew C.
Published: May 2023

Introduction

Community health workers are essential to frontline health outreach throughout low- and middle-income countries, including programming for early childhood immunization. The World Health Organization estimates a projected shortage of 18 million health workers by 2030. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunization coverage would support evidence-based policy guidance across contexts. To that end, we identified factors of community health worker programs that contributed to improved vaccination coverage in Nepal, Senegal, and Zambia.

Methods

We conducted interviews and focus group discussions at the national, regional, district, health facility, and community levels of the health systems of Nepal, Senegal, and Zambia, and used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunization within each country and across contexts. We developed a model that could be used for assessment and adaptation based on lessons learned.

Findings

Across all countries, implementation of vaccination programming relied principally on the 1) organization, 2) motivation, and 3) trust of community health workers. Organization was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation of community health workers was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on work.

Conclusion

Improvements in immunization coverage followed successful community health worker programs, facilitated by diversification of cadres, roles and responsibilities, motivation, and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to minority populations and populations in hard-to-reach areas. Although improvements in vaccination programming were seen in all three countries - including government - commitment to addressing human resource deficits, training and renumeration; workload, low and inconsistent compensation, inconsistency in training duration and scope, and supervision are still major challenges to immunization programming. Vaccination and health decision-makers should consider organization, motivation, and trust of community health workers to improve the implementation of immunization programming.
Comparing Classifier Performance to Predict Infectious Diseases
Authors: Gonzalez Roger Geertz
Published: May 2023

We compared the accuracy of the machine learning classifier algorithms: Random Forest, Naïve Bayes, Decision Tree, and Artificial Neural Network to predict zoonoses using the Random Forest extracted features and the serology data for seven different zoonotic diseases as the targets. We identified Random Forest and Naïve Bayes as having the best performance overall. The Random Forest models above did well using Positive Predictive Value (PPV), Area Under the Curve (AOC) and Receiver Operating Characteristic (ROC) performance measures in identifying the positive cases for each of the diseases which is imperative when it comes to being able to identify the disease and then use this information to implement prevention and medical aid to specific areas and people where it is most needed. It also does well in predicting the negative values which is important to ensure the negatives are not false negatives.

Naïve Bayes was found to be the best choice for accuracy and performance. NB works well because it treats each feature as independent and thus, any change in one feature will not affect the other in the NB model. Decision Tree could not capture the data and thus, underfit during the first initial modeling and after hyper tuning. Artificial Neural Network overfit the model by capturing all the data including noise in the initial model, but underfit after hyper tuning. Both Decision Tree and Artificial Neural Network classifier algorithms are not recommended as classifiers for this dataset.

Statements

There are no conflicts of interest in this work.

All methods were carried out in accordance with relevant guidelines and regulations.

All experimental protocols were approved by the Forestry Administration of Cambodia.

Informed consent was obtained from all subjects and/or their legal guardian(s) at the beginning of the survey.
Microbial Interactions from a New Perspective: Reinforcement Learning Reveals New Insights into Microbiome Evolution
Authors: Ghadermazi Parsa , Chan Siu Hung Joshua
Published: May 2023

Microbes are essential part of all ecosystems, influencing material flow and shaping their surroundings. Metabolic modeling has been a useful tool and provided tremendous insights into microbial community metabolism. However, current methods based on flux balance analysis (FBA) usually fail to predict metabolic and regulatory strategies that lead to long-term survival and stability especially in heterogenous communities. Here we introduce a novel reinforcement learning algorithm, Self-Playing Microbes in Dynamic FBA, that treats microbial metabolism as a decision-making process, allowing individual microbial agents to evolve by learning and adapting metabolic strategies for enhanced long-term fitness. This algorithm predicts what microbial flux regulation policies will stabilize in the dynamic ecosystem of interest in presence of other microbes with minimal reliance on predefined strategies. Throughout this article, we present several scenarios wherein our algorithm outperforms existing methods in reproducing outcomes, and we explore the biological significance of these predictions.
Fifteen-year Outcomes of 1,196 Ozaki Procedures
Authors: Ozaki Shigeyuki , Hoshino Yasuhiro , Unai Shinya , Harb Serge C. , Frankel William C. , Hayama Hiromasa , Takatoo Mikio , Kiyohara Nagaki , Kataoka Hiroshi , Svensson Lars G. , Rajeswaran Jeevanantham , Blackstone Eugene H. , Pettersson Gösta B.
Published: May 2023

Background

Introduced in 2007, the Ozaki procedure has become an attractive option for aortic valve disease. Our objective was to investigate outcomes of the Ozaki procedure in the original Ozaki cohort.

Methods

From April 2007 to May 2021, 1,196 consecutive Ozaki procedures were performed at Toho University Ohashi Medical Center. Patient age ranged from 11 to over 90 years, 484 (60%) were male, 50 (4.2%) had previous cardiac surgery, and 155 (13%) were on dialysis. 322 (27%) had bicuspid valves and 28 (2.3%) had infective endocarditis. 651 (54%) had aortic stenosis, 289 (24%) aortic regurgitation, and 87 (7.2%) mixed. 546 (46%) underwent concomitant procedures. Clinical outcomes, echocardiograms, and follow-up data were collected and analyzed for valve performance, and time-to-event analyses were performed for reoperation and mortality. 5023 patient-years of follow-up were available for analysis, with 50% of patients followed >3.2 years and 10% >9 years.

Results

Mean cardiopulmonary bypass and aortic clamp times for isolated Ozaki procedures were 151 ± 37 and 105 ± 29 minutes, respectively. Thirty-day mortality was 1.7% (n=20), new stroke 14 (2.6%), new dialysis 41(4.0%), and permanent pacemaker implantation 18 (1.5%). At 6 months, 5 years, and 10 years, peak/mean aortic valve gradients were 14.0/7.4, 15.5/8.0 and 15.5/8.2 mmHg, respectively, and ≥moderate regurgitation was 0.30%/2.9%/6.6%. Left ventricular mass index decreased from 141 ± 52 g/m2preoperatively to 100 ± 1.1 g/m2at 6 months and 90 ± 1.8 g/m2at 10 years. At 10 years, freedom from reoperation was 91.2% and survival 75%.

Conclusion

The Ozaki procedure creates good aortic valves with stable low gradients. Regurgitation increased over time, but risk of reoperation was low, supporting continued use.
The evolution of RNA interference among Metazoa
Authors: Formaggioni Alessandro , Cavalli Gianmarco , Hamada Mayuko , Sakamoto Tatsuya , Plazzi Federico , Passamonti Marco
Published: May 2023

In animals, three main RNA interference mechanisms have been described so far, which respectively maturate three types of small noncoding RNAs (sncRNAs): miRNAs, piRNAs and endo-siRNAs. The diversification of these mechanisms is deeply linked with the evolution of the Argonaute gene superfamily since each type of sncRNA is loaded by a specific Argonaute homolog protein. Moreover, other protein families play pivotal roles in the maturation of sncRNAs, like the DICER ribonuclease family, whose DICER1 and DICER2 paralogs maturate respectively miRNAs and endo-siRNAs. Among Metazoa, the distribution of these families has been only studied in major groups, and there are very few data for clades like Lophotrochozoa. Thus, we here inferred the evolutionary history of the animal Argonaute and DICER families including 43 lophotrochozoan species. Phylogenetic analyses along with newly sequenced sncRNA libraries depicted a loss of the endo-siRNA pathway along the Lophotrochozoa evolution, with the absence of DICER2 in Nematoda and Polyzoa, and with the absence of DICER2 and the Argonaute homolog in the rest of Trochozoa phyla. On the contrary, early diverging phyla, Platyhelminthes and Syndermata, showed a complete endo-siRNA pathway. On the other hand, miRNAs were revealed the most conserved and ubiquitous mechanism of the metazoan RNA interference machinery, confirming their pivotal role in animal cell regulation.
Spatiotemporal Dynamics of Single-stranded DNA Intermediates inEscherichia coli
Authors: Cherry Megan E. , Dubiel Katarzyna , Henry Camille , Wood Elizabeth A. , Revitt-Mills Sarah A. , Keck James L. , Cox Michael M. , van Oijen Antoine M. , Ghodke Harshad , Robinson Andrew
Published: May 2023

Single-stranded DNA gaps form within theE. colichromosome during replication, repair and recombination. However, information about the extent of ssDNA creation in the genome is limited. To complement a recent whole-genome sequencing study revealing ssDNA gap genomic distribution, size, and frequency, we used fluorescence microscopy to monitor the spatiotemporal dynamics of single-stranded DNA within liveE. colicells. The ssDNA was marked by a functional fluorescent protein fusion of the SSB protein that replaces the wild type SSB. During log-phase growth the SSB fusion produces a mixture of punctate foci and diffuse fluorescence spread throughout the cytosol. Many foci are clustered. Fluorescent markers of DNA polymerase III frequently co-localize with SSB foci, often localizing to the outer edge of the large SSB features. Novel SSB-enriched features form and resolve regularly during normal growth. UV irradiation induces a rapid increase in SSB foci intensity and produces large features composed of multiple partially overlapping foci. The results provide a critical baseline for further exploration of ssDNA generation during DNA metabolism. Alterations in the patterns seen in a mutant lacking RecB function tentatively suggest associations of particular SSB features with the repair of double strand breaks and post-replication gaps.
A novel virus-induced cyclic dinucleotide, 2′3′-c-di-GMP, mediates STING-dependent antiviral immunity inDrosophila
Authors: Cai Hua , Li Lihua , Slavik Kailey , Huang Jingxian , Yin Ting , Hédelin Léna , Xiang Zhangmin , Yang Yunyun , Li Xiaoyan , Chen Yuqiang , Wei Ziming , Deng Huimin , Chen Di , Jiao Renjie , Martins Nelson , Meignin Carine , Kranzusch Philip , Imler Jean-Luc
Published: May 2023

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2′3′-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organismDrosophila melanogastertwo cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3′2′-cGAMP, in addition to 2′3′-cGAMP. Here we explore CDN-mediated immunity in 14 differentDrosophilaspecies covering 50 million years of evolution and report that 2′3′-cGAMP and 3′2′-cGAMP fail to control infection byDrosophilaC virus inD. serrata, D. sechelliaandD. mojavensis. Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection inD. melanogaster, including a novel CDN, 2′3′-c-di-GMP. We show that 2′3′-c-di-GMP is the most potent STING agonist identified so far inD. melanogasterand that this molecule also activates a strong antiviral transcriptional response inD. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.
Digital Manufacturing of Functional Ready-to-Use Microfluidic Systems
Authors: Karamzadeh Vahid , Sohrabi-Kashani Ahmad , Shen Molly , Juncker David
Published: May 2023

Digital manufacturing (DM) strives for the seamless manufacture of a functional device from a digital file. DM holds great potential for microfluidics, but requirements for embedded conduits and high resolution beyond the capability of common manufacturing equipment, and microfluidic systems’ dependence on peripherals (e.g. connections, power supply, computer), have limited its adoption. Microfluidic capillaric circuits (CCs) are structurally-encoded, self-contained microfluidic systems that operate and self-fill thanks to precisely tailored hydrophilicity. CCs were heretofore hydrophilized in a plasma chamber, but which only produces transient hydrophilicity, lacks reproducibility, and limits CC design to open surface channels sealed with a tape. Here we introduce the additive DM of monolithic, fully functional and intrinsically hydrophilic CCs. CCs were 3D printed with commonly available light engine-based 3D printers using polyethylene(glycol)diacrylate-based ink co-polymerized with hydrophilic acrylic acid crosslinkers and optimized for hydrophilicity and printability. A new, robust capillary valve design and embedded conduits with circular cross-sections that prevent bubble trapping are presented, and complex interwoven circuit architectures created, and their use illustrated with an immunoassay. Finally, the need for external paper capillary pumps is eliminated by directly embedding the capillary pump in the chip as a porous gyroid structure, realizing fully functional, monolithic CCs. Thence, a computer-aided design file can be made into a CC by commonly available 3D printers in less than 30 minutes enabling low-cost, distributed, DM of fully functional ready-to-use microfluidic systems.
Hybrid vesicle and reaction-diffusion modeling with STEPS
Authors: Hepburn Iain , Lallouette Jules , Chen Weiliang , Gallimore Andrew R. , Nagasawa Sarah Y. , De Schutter Erik
Published: May 2023

Vesicles carry out many essential functions within cells through the processes of endocytosis, exocytosis, and passive and active transport. This includes transporting and delivering molecules between different parts of the cell, and storing and releasing neurotransmitters in neurons. To date, computational simulation of these key biological players has been rather limited and has not advanced at the same pace as other aspects of cell modeling. As computational power advances and researchers want to add new realism to their models an important advance in the field of computational biology is to simulate vesicles in a realistic yet efficient manner. We describe a general vesicle modeling tool that has been designed for wide application to a variety of cell models, implemented within our voxel-based approach to modeling reaction-diffusion processes in realistic mesh reconstructions of cell tissue in our software STEPS. The implementation is validated in an extensive test suite, parallel performance demonstrated in a realistic synaptic bouton model, and example models are visualized in a Blender extension module.