bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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

AbstractIntroductionCommunity 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.MethodsWe 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.FindingsAcross 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.ConclusionImprovements 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

AbstractWe 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.StatementsThere 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

AbstractMicrobes 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

ABSTRACTBackgroundIntroduced 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.MethodsFrom 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.ResultsMean 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%.ConclusionThe 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

AbstractIn 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

AbstractSingle-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

AbstractIn 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.