bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm
Authors: Stijlemans Benoit , Schoovaerts Maxime , De Baetselier Patrick , Magez Stefan , De Trez Carl 
Published: April 2022

African trypanosomes are extracellular flagellated unicellular protozoan parasites transmitted by tsetse flies and causing Sleeping Sickness disease in humans andNaganadisease in cattle and other livestock. These diseases are usually characterized by the development of a fatal chronic inflammatory disease if left untreated. During African trypanosome infection and many other infectious diseases, the immune response is mediating a see-saw balance between effective/protective immunity and excessive infection-induced inflammation that can cause collateral tissue damage. African trypanosomes are known to trigger a strong type I pro-inflammatory response, which contributes to peak parasitaemia control, but this can culminate into the development of immunopathologies, such as anaemia and liver injury, if not tightly controlled. In this context, the macrophage migration inhibitory factor (MIF) and the interleukin-10 (IL-10) cytokines may operate as a molecular “Yin-Yang” in the modulation of the host immune microenvironment during African trypanosome infection, and possibly other infectious diseases. MIF is a pleiotropic pro-inflammatory cytokine and critical upstream mediator of immune and inflammatory responses, associated with exaggerated inflammation and immunopathology. For example, it plays a crucial role in the pro-inflammatory response against African trypanosomes and other pathogens, thereby promoting the development of immunopathologies. On the other hand, IL-10 is an anti-inflammatory cytokine, acting as a master regulator of inflammation during both African trypanosomiasis and other diseases. IL-10 is crucial to counteract the strong MIF-induced pro-inflammatory response, leading to pathology control. Hence, novel strategies capable of blocking MIF and/or promoting IL-10 receptor signaling pathways, could potentially be used as therapy to counteract immunopathology development during African trypanosome infection, as well as during other infectious conditions. Together, this review aims at summarizing the current knowledge on the opposite immunopathological molecular “Yin-Yang” switch roles of MIF and IL-10 in the modulation of the host immune microenvironment during infection, and more particularly during African trypanosomiasis as a paradigm.
The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Authors: Xue Jun-Shuai , Ding Zi-Niu , Meng Guang-Xiao , Yan Lun-Jie , Liu Hui , Li Hai-Chao , Yao Sheng-Yu , Tian Bao-Wen , Dong Zhao-Ru , Chen Zhi-Qiang , Hong Jian-Guo , Wang Dong-Xu , Li Tao 
Published: April 2022

BackgroundNatural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.MethodsSeveral electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).Results26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.ConclusionNK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.
Rise of the Machines: Best Practices and Experimental Evaluation of Computer-Assisted Dorsal Fin Image Matching Systems for Bottlenose Dolphins
Authors: Tyson Moore Reny B. , Urian Kim W. , Allen Jason B. , Cush Carolyn , Parham Jason R. , Blount Drew , Holmberg Jason , Thompson Jamie W. , Wells Randall S. 
Published: April 2022

Photographic-identification (photo-ID) of bottlenose dolphins using individually distinctive features on the dorsal fin is a well-established and useful tool for tracking individuals; however, this method can be labor-intensive, especially when dealing with large catalogs and/or infrequently surveyed populations. Computer vision algorithms have been developed that can find a fin in an image, characterize the features of the fin, and compare the fin to a catalog of known individuals to generate a ranking of potential matches based on dorsal fin similarity. We examined if and how researchers use computer vision systems in their photo-ID process and developed an experiment to evaluate the performance of the most commonly used, recently developed, systems to date using a long-term photo-ID database of known individuals curated by the Chicago Zoological Society’s Sarasota Dolphin Research Program. Survey results obtained for the “Rise of the machines – Application of automated systems for matching dolphin dorsal fins: current status and future directions” workshop held at the 2019 World Marine Mammal Conference indicated that most researchers still rely on manual methods for comparing unknown dorsal fin images to reference catalogs of known individuals. Experimental evaluation of the finFindR R application, as well as the CurvRank, CurvRank v2, and finFindR implementations in Flukebook suggest that high match rates can be achieved with these systems, with the highest match rates found when only good to excellent quality images of fins with average to high distinctiveness are included in the matching process: for the finFindR R application and the CurvRank and CurvRank v2 algorithms within Flukebook more than 98.92% of correct matches were in the top 50-ranked positions, and more than 91.94% of correct matches were returned in the first ranked position. Our results offer the first comprehensive examination into the performance and accuracy of computer vision algorithms designed to assist with the photo-ID process of bottlenose dolphins and can be used to build trust by researchers hesitant to use these systems. Based on our findings and discussions from the “Rise of the Machines” workshop we provide recommendations for best practices for using computer vision systems for dorsal fin photo-ID.
Theoretical Analysis on the Stability of Single Bulk Nanobubble
Authors: Wang Yao , Zhou Limin , Hu Jun , Zhang Lijuan 
Published: April 2022

As predicted by classical macroscopic theory, the lifetime for nanoscale gas bubbles is extremely short, which causes conflict when detecting stable bulk nanobubbles experimentally in recent years. In fact, the stability of bulk nanobubbles depends on the surrounding liquid environment. Also, the dynamic process of gas in water involves the dissolution, diffusion, release, and transportation of gas as well as the properties of nanobubbles inside. Here, based on previous reports, we introduce the gas transport parameter ℓ in the classical diffusion equation by considering the gas diffusion near the bulk nanobubble at different locations in a container and consider the MacLeod-Sugden relationship between the surface tension and densities of liquid and gas for computing the lifetime of single bulk nanobubbles in an open system. The results show that the single nanobubble lifetime depends on the inner density and gas transport length. It could reach the order of 10–100 s for a single nanobubble with an initial radius of 200 nm, and provides a new idea to prolong the lifetime of the single bulk nanobubble. Meanwhile, compared with the continuous influence of the inner density on the gas diffusion flux near the nanobubble, the range of the gas transport near the nanobubble on the gas diffusion flux is limited, which is affected by the dissolution time of the nanobubble. Our findings would be helpful to explore the storage conditions of nanobubbles and the mechanism of mass transfer at the gas-liquid interface at the micro-scale.
Oxybutynin-Nanoemulgel Formulation as a Successful Skin Permeation Strategy: In-vitro and ex-vivo Evaluation
Authors: Mohammadi-Samani Soliman , Masoumzadeh Pedram , Ghasemiyeh Parisa , Alipour Shohreh 
Published: April 2022

Among different topical drug delivery systems, nanoemulsions (NEs) are attractive due to enhanced skin permeation potential and minimum toxicity. Topical nanoemulgels (NEMGELs) contain both gelling agents and NEs and thus can enhance skin permeation with sustained effects at the site of application. Oxybutynin (OXB) is an anti-muscarinic agent that is administered orally to treat hyperhidrosis but its systemic side effects may decrease patient compliance. Therefore, it assumes that oxybutynin-nanoemulgel (OXB-NEMGEL) with sustained release properties and skin permeation ability may be a suitable alternative. Using Design Expert software®, 17 OXB-NE formulations were prepared and optimized based on particle size, zeta potential and physical stability. Three polymers were used to prepare and optimized OXB-NEMGEL based on spreadability and viscosity. In-vitro drug release and ex-vivo skin permeation were investigated for optimized formulation. The model suggested by Design-Expert was quadratic and there was significant association between response variables including particle size and zeta potential and independent variables (Oil:Surfactant ratio, Oil:Water ratio, and surfactants HLB) with P-values of 0.0334 and 0.0173, respectively. Also, the lack of fit was not significant (P-values 0.057 and 0.569, respectively) which confirms the fitness of this model. Average size and zeta potential of optimized nanoemulsions were 99 ± 0.1 nm and -57.3 ± 0.5 mv, respectively. Carboxymethyl cellulose-based nanoemulgels (CMC-NEMGEL) showed acceptable viscosity with a shear thinning rheological pattern and good spreadability which released OXB within 8 h. Ex-vivo OXB skin permeation revealed OXB flux of 1.5 ± 0.3 and 3.6 ± 0.2 μg/cm2/h after 12 and 24 h, respectively, which was equal to 5.3 ± 1.1% and 11.9 ± 0.7% of drug, while simple OXB gel did not permeate through skin layers. Thus, OXB-NEMGEL with effective skin permeation potential would be a novel promising drug delivery system for hyperhidrosis management which may lower systemic side effects.
Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study
Authors: Li Yang , Kong Yanlei , Ebell Mark H. , Martinez Leonardo , Cai Xinyan , Lennon Robert P. , Tarn Derjung M. , Mainous Arch G. , Zgierska Aleksandra E. , Barrett Bruce , Tuan Wen-Jan , Maloy Kevin , Goyal Munish , Krist Alex H. , Gal Tamas S. , Sung Meng-Hsuan , Li Changwei , Jin Yier , Shen Ye 
Published: April 2022

ObjectivesAn accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information.DesignMulticenter retrospective observational cohort study.SettingFour health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles.PatientsCoronavirus Disease 2019-confirmed and hospitalized adult patients.Measurements and Main ResultsWe included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate &gt;100 beats/min, respiratory rate ≥30 breaths/min, and SpO2 &lt;93% into the predictive model. Besides age and SpO2, the second step used blood urea nitrogen, absolute neutrophil count, C-reactive protein, platelet count, and neutrophil-to-lymphocyte ratio as predictors. C-statistics reflected very good discrimination with internal validation at VCU (0.83, 95% CI 0.79–0.88) and external validation at the other three health systems (range, 0.79–0.85). A one-step model was also derived for comparison. Overall, the two-step risk score had better performance than the one-step score.ConclusionsThe two-step scoring system used widely available, point-of-care data for triage of COVID-19 patients and is a potentially time- and cost-saving tool in practice.
Strongyloidiasis in a Patient Diagnosed by Metagenomic Next-Generation Sequencing: A Case Report
Authors: Qu Junyan , Zong Zhiyong 
Published: April 2022

BackgroundStrongylodiasis may be asymptomatic or cause mild gastrointestinal symptoms, and may be a fatal disseminated disease or Strongyloides hyperinfection syndrome. Non-specific clinical manifestations, such as pneumonia and gastroenteritis, pose a diagnostic dilemma.Case PresentationWe report a case of a 67-year-old Chinese male who presented with abdominal pain, fever, headache, vomiting, constipation, and slight cough with sputum for nearly 2 months. He had been in good health and had no history of glucocorticoid use. He was diagnosed with enterococcal meningitis and intestinal obstruction at a local hospital and improved after treatment with vancomycin, but symptoms of headache and abdominal pain soon recurred. The metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid using Illumina X10 sequencer revealed seven sequence reads matching Strongyloides stercoralis. Strongyloidiasis was suspected. Microscopic examination of gastric fluid revealed the presence of S. stercoralis larvae, which was confirmed by PCR to amplify both S. stercoralis ribosomal DNA gene and mitochondrial cytochrome c oxidase subunit 1 gene and sequencing amplicons. Strongyloidiasis was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient recovered gradually.ConclusionmNGS may be a useful tool for detecting uncommon infectious disease. The case would help clinicians to raise awareness of strongyloidiasis in non-endemic areas and reduce fatality.
Late-Onset Bartter Syndrome Type II Due to a Novel Compound Heterozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review
Authors: Tian Mi , Peng Hui , Bi Xin , Wang Yan-Qiu , Zhang Yong-Zhe , Wu Yan , Zhang Bei-Ru 
Published: April 2022

BackgroundBartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle’s loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults.Case PresentationA 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation.ConclusionWe report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.
Treatment of Placenta Increta With High-Intensity Focused Ultrasound Ablation and Leaving the Placenta in situ: A Multicenter Comparative Study
Authors: Guan Xiaoping , Huang Xiaoqin , Ye Min , Huang Guohua , Xiao Xiao , Chen Jinyun 
Published: April 2022

ObjectiveTo explore the feasibility of simple high-intensity focused ultrasound (HIFU) ablation for placenta increta.MethodsNinety-five patients after a vaginal delivery were enrolled in this retrospective cohort study, 53 patients were treated with simple HIFU ablation, and 42 patients were treated with HIFU followed by uterine curettage.ResultsAll 95 patients were successfully treated with a single-session HIFU procedure, and in the control group, the necrotic placental tissue was removed with curettage. Vaginal hemorrhage did not occur in either group. The duration of bloody lochia was 25.9 ± 8.6 days in the sHIFU group and 24.2 ± 8.8 days in the control group (P &gt; 0.05). The median serum human chorionic gonadotropin (HCG) level was 3,222 mIU/mL and 2,838 mIU/mL in the sHIFU and control groups, respectively, which decreased and returned to normal within 30 days, and the differences were not significantly on comparing the blood HCG level in the two groups at 7, 15, and 30 days after HIFU (all P &gt; 0.05). Decreased menstrual volume occurred in 85.71% of patients in the control group, which was higher than that in the sHIFU group (23.08%) (χ2 = 6.839, P &lt; 0.001). During 2–8 years of follow-up, six pregnancies occurred in the sHIFU group without any recurrence of placenta increta, three pregnancies occurred in the control group, and one patient developed a repeat placenta increta.ConclusionSimple HIFU treatment is safe and effective for postpartum placenta increta and leaving the placenta in situ. It is a promising option for patients who wish to preserve their fertility and conceive.
Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma
Authors: Xiao Yiwei , Cao Junning , Zhang Ze , Zeng Chaoting , Ou Guomin , Shi Jihang , Liu Zhixiu , Li Yi , Deng Juan , Xu Yinzhe , Zhang Wenwen , Li Jie , Li Tong , Zhuang Hui , Lu Shichun , Xiang Kuanhui 
Published: April 2022

BackgroundThe existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients.MethodsWe collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis.ResultsWe found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44.ConclusionHBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.
Interactive Training of the Emergency Medical Services Improved Prehospital Stroke Recognition and Transport Time
Authors: Sveikata Lukas , Melaika Kazimieras , Wiśniewski Adam , Vilionskis Aleksandras , Petrikonis Kȩstutis , Stankevičius Edgaras , Jurjans Kristaps , Ekkert Aleksandra , Jatužis Dalius , Masiliūnas Rytis 
Published: April 2022

Background and PurposeAcute stroke treatment outcomes are predicated on reperfusion timeliness which can be improved by better prehospital stroke identification. We aimed to assess the effect of interactive emergency medical services (EMS) training on stroke recognition and prehospital care performance in a very high-risk cardiovascular risk population in Lithuania.MethodsWe conducted a single-center interrupted time-series study between March 1, 2019 and March 15, 2020. Two-hour small-group interactive stroke training sessions were organized for 166 paramedics serving our stroke network. We evaluated positive predictive value (PPV) and sensitivity for stroke including transient ischemic attack identification, onset-to-door time, and hospital-based outcomes during 6-months prior and 3.5 months after the training. The study outcomes were compared between EMS providers in urban and suburban areas.ResultsIn total, 677 suspected stroke cases and 239 stroke chameleons (median age 75 years, 54.8% women) were transported by EMS. After the training, we observed improved PPV for stroke recognition (79.8% vs. 71.8%, p = 0.017) and a trend of decreased in-hospital mortality (7.8% vs. 12.3, p = 0.070). Multivariable logistic regression models adjusted for age, gender, EMS location, and stroke subtype showed an association between EMS stroke training and improved odds of stroke identification (adjusted odds ratio [aOR] 1.6 [1.1–2.3]) and onset-to-door ≤ 90 min (aOR 1.6 [1.1–2.5]). The improvement of PPV was observed in urban EMS (84.9% vs. 71.2%, p = 0.003), but not in the suburban group (75.0% vs. 72.6%, p = 0.621).ConclusionsThe interactive EMS training was associated with a robust improvement of stroke recognition, onset to hospital transport time, and a trend of decreased in-hospital mortality. Adapted training strategies may be needed for EMS providers in suburban areas. Future studies should evaluate the long-term effects of the EMS training and identify optimal retraining intervals.