bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Omics Tools for Understanding the Fish Immune Response Due to Microbial Challenge
Authors: Natnan Maya E. , Low Chen-Fei , Chong Chou-Min , Bunawan Hamidun , Baharum Syarul N.
Published: June 2021

Nowadays, fish production through aquaculture and wild capture is escalating due to the higher fish protein demand for human consumption. Thus, the needs for fish products to be improved in scale and quality are becoming increasingly important to meet the nutrition requirements. The negative impacts caused by pathogens infection both in hatchery and grow-out ponds, have resulted in low aquaculture productivity and economic losses for the farmers. Therefore, a systematic study exploring relevant omics datasets through a systems biology approach will enable scientist to describe the complexity and characteristics of interactions in the host-pathogen network, leading to identifying new targets or biomarkers for diseases infection caused by bacteria, viruses, and parasites. The use of different approaches and emerging technologies as a powerful tool in obtaining a new knowledge for sustainable aquaculture production has been increasingly applied by many researchers over the years. In this paper, several omics approaches used to assess the fish immune response were reviewed. A brief description is provided for the omics approaches applicable to aquacultures, such as genomics, transcriptomics, proteomics, and metabolomics. Each tool used are contributes to develop better treatment and prevention strategies to overcome aquaculture disease due to the microbial infections. In genomics and transcriptomics analysis, their parallel approach involving gene expression studies play important role in identifying immune-related genes of the host, response to infectious diseases. While for proteomics and metabolomics approaches, these omics will provide information on the biomarker discovery and understanding the immune-related biosynthetic pathway during pathogen infection. Additionally, examples of the integrative analysis of multi-omics tools required for researchers to better understand the biological systems of aquatic animals especially fish, will also be provided.
Projected Responses of Tidal Dynamics in the North Sea to Sea-Level Rise and Morphological Changes in the Wadden Sea
Authors: Jordan Christian , Visscher Jan , Schlurmann Torsten
Published: June 2021

This study explores the projected responses of tidal dynamics in the North Sea induced by the interplay between plausible projections of sea-level rise (SLR) and morphological changes in the Wadden Sea. This is done in order to gain insight into the casual relationships between physical drivers and hydro-morphodynamic processes. To achieve this goal, a hydronumerical model of the northwest European shelf seas (NWES) was set-up and validated. By implementing a plausible set of projections for global SLR (SLRRCP8.5of 0.8 m and SLRhigh−endof 2.0 m) by the end of this century and beyond, the model was run to assess the responses of the regional tidal dynamics. In addition, for each considered SLR, various projections for cumulative rates of vertical accretion were applied to the intertidal flats in the Wadden Sea (ranging from 0 to 100% of projected SLR). Independent of the rate of vertical accretion, the spatial pattern of M2 amplitude changes remains relatively stable throughout most of the model domain for a SLR of 0.8 m. However, the model shows a substantial sensitivity toward the different rates of vertical accretion along the coasts of the Wadden Sea, but also in remote regions like the Skagerrak. If no vertical accretion is assumed in the intertidal flats of the Wadden Sea, the German Bight and the Danish west coast are subject to decreases in M2 amplitudes. In contrast, those regions experience increases in M2 amplitudes if the local intertidal flats are able to keep up with the projected SLR of 0.8 m. Between the different scenarios, the North Frisian Wadden Sea shows the largest differences in M2 amplitudes, locally varying by up to 14 cm. For a SLR of 2.0 m, the M2 amplitude changes are even more amplified. Again, the differences between the various rates of vertical accretion are largest in the North Frisian Wadden Sea (> 20 cm). The local distortion of the tidal wave is also significantly different between the scenarios. In the case of no vertical accretion, tidal asymmetry in the German estuaries increases, leading to a potentially enhanced sediment import. The presented results have strong implications for local coastal protection strategies and navigation in adjacent estuaries.
SdiA, a Quorum-Sensing Regulator, Suppresses Fimbriae Expression, Biofilm Formation, and Quorum-Sensing Signaling Molecules Production in Klebsiella pneumoniae
Authors: Pacheco Thaisy , Gomes Ana Érika Inácio , Siqueira Nathália Maria Gonçalves , Assoni Lucas , Darrieux Michelle , Venter Henrietta , Ferraz Lúcio Fábio Caldas
Published: June 2021

Klebsiella pneumoniae is a Gram-negative pathogen that has become a worldwide concern due to the emergence of multidrug-resistant isolates responsible for various invasive infectious diseases. Biofilm formation constitutes a major virulence factor for K. pneumoniae and relies on the expression of fimbrial adhesins and aggregation of bacterial cells on biotic or abiotic surfaces in a coordinated manner. During biofilm aggregation, bacterial cells communicate with each other through inter- or intra-species interactions mediated by signallng molecules, called autoinducers, in a mechanism known as quorum sensing (QS). In most Gram-negative bacteria, intra-species communication typically involves the LuxI/LuxR system: LuxI synthase produces N-acyl homoserine lactones (AHLs) as autoinducers and the LuxR transcription factor is their cognate receptor. However, K. pneumoniae does not produce AHL but encodes SdiA, an orphan LuxR-type receptor that responds to exogenous AHL molecules produced by other bacterial species. While SdiA regulates several cellular processes and the expression of virulence factors in many pathogens, the role of this regulator in K. pneumoniae remains unknown. In this study, we describe the characterization of sdiA mutant strain of K. pneumoniae. The sdiA mutant strain has increased biofilm formation, which correlates with the increased expression of type 1 fimbriae, thus revealing a repressive role of SdiA in fimbriae expression and bacterial cell adherence and aggregation. On the other hand, SdiA acts as a transcriptional activator of cell division machinery assembly in the septum, since cells lacking SdiA regulator exhibited a filamentary shape rather than the typical rod shape. We also show that K. pneumoniae cells lacking SdiA regulator present constant production of QS autoinducers at maximum levels, suggesting a putative role for SdiA in the regulation of AI-2 production. Taken together, our results demonstrate that SdiA regulates cell division and the expression of virulence factors such as fimbriae expression, biofilm formation, and production of QS autoinducers in K. pneumoniae.
Sphingosine-1-Phosphate Catabolizing Enzymes Predict Better Prognosis in Triple-Negative Breast Cancer Patients and Correlates With Tumor-Infiltrating Immune Cells
Authors: Nema Rajeev , Kumar Ashok
Published: June 2021

Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis. Sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes that are important for breast cancer (BC). S1P signaling regulates tumorigenesis, and response to chemotherapy and immunotherapy by affecting the trafficking, differentiation or effector function of tumor-infiltrating immune cells (TIICs).

Objective: In this study, using bioinformatics tools and publicly available databases, we have analyzed the prognostic value of S1P metabolizing genes and their correlation with TIICs in BC patients.

Methods: The expression of S1P metabolizing genes and receptors was evaluated by the UALCAN cancer database. The correlation between mRNA expression of S1P metabolizing genes and receptors and survival outcome of breast cancer patients was analyzed by the Kaplan-Meier plotter database. The association between the gene expression and infiltration of immune cells in the tumors was analyzed by “Tumor-Infiltrating Immune Estimation Resource (TIMER). In silico protein expression analysis was done using the Human Protein Atlas” database.

Results: TNBC patients with lower expression of S1P phosphatase 1 (SGPP1) or lipid phosphate phosphatase 3 (PLPP3) have much shorter relapse-free survival than the patients with a higher expression of these genes. SGPP1 and PLPP3 expression show a strong positive correlation with tumor-infiltrating dendritic cells (DCs), CD4+ and CD8+ T cells, neutrophils, and macrophages in the TNBC subtypes. In addition, S1P receptor 4 (S1PR4), an S1P receptor exhibit a strong positive correlation with DCs, CD4+ and CD8+ T cells and neutrophils in TNBC. We, therefore, conclude that low expression of SGPP1 and PLPP3 may hinder the recruitment of immune cells to the tumor environment, resulting in the blockage of cancer cell clearance and a subsequent poor prognosis.
Endoscopic Surgery for Supratentorial Deep Cavernous Malformation Adjacent to Cortical Spinal Tract: Preliminary Experience and Technical Note
Authors: Lin Fuxin , Li Chunwang , Yan Xiaorong , Wang Dengliang , Lin Yuanxiang , Kang Dezhi , Jiang Changzhen
Published: June 2021

In this study, we aimed to introduce a technical note and to explore the efficacy of endoscopic surgery combined with diffusion tensor imaging (DTI) navigation for supratentorial deep cerebral cavernous malformations (CCM). A prospectively maintained database of CCM patients was reviewed to identify all CCM patients treated by endoscopic surgery. The sagittal T1-weighted anatomical magnetic resonance imaging (MRI) and DTI were acquired before surgery. Endoscopic surgery was planned and performed based on preoperative DTI images and intraoperative DTI navigation. All patients were followed up more than 6 months. Motor function deficit and modified Rankin scale (mRS) scores were documented on follow-up. A final mRS score of 0–2 was considered a good outcome, and a final mRS score >2 was considered a poor outcome. Second DTI and 3DT1 were performed at 3 months after surgery. We tracked the ipsilateral corticospinal tract (CST) on pre- and postoperative DTI images. The overall mean FA values and the number of fibers of tracked CST were compared on pre- and postoperative DTI images. Risk factors associated with motor deficits and poor outcomes were analyzed. Seven patients with deep CCM and treated by endoscopic surgery were enrolled in this study. The mean value of preoperative mRS was 1.5 ± 0.98, but that score recovered to 0.86 ± 1.22 3 months later. The mRS scores were improved significantly according to statistical analysis (p = 0.012). According to the Spearman non-parametric test, only the fiber number of ipsilateral CST on postoperative DTI was significantly associated with muscle strength 6 months after surgery (p = 0.032). Compared with preoperative CST characteristics on DTI, the change of FA value (p = 0.289) and fiber number (p = 0.289) of ipsilateral CST on postoperative DTI was not significant It meant that the CST was protected during endoscopic surgery. Endoscopic surgery based on DTI navigation might be an effective method to protect fiber tracts in supratentorial deep CCM patients and improve long-term outcomes. However, more studies and cases are needed to confirm our findings.
Ki67 Index Changes and Tumor-Infiltrating Lymphocyte Levels Impact the Prognosis of Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy
Authors: Wang Yihua , Zong Beige , Yu Yu , Wang Yu , Tang Zhenrong , Chen Rui , Huang Man , Liu Shengchun
Published: June 2021

Purpose

The aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group.

Materials and Methods

Data from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan–Meier and Cox analyses.

Results

Ki67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135–3.658, P = 0.017; HR: 2.493, 95% CI: 1.335–4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173–4.077, P = 0.014; HR: 2.499, 95% CI: 1.285–4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475–8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512–9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively.

Conclusion

Ki67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.
Extrauterine Growth Restriction in Very Low Birth Weight Infants: Concordance Between Fenton 2013 and INTERGROWTH-21st Growth Charts
Authors: González-García Lara , García-López Enrique , Fernández-Colomer Belén , Mantecón-Fernández Laura , Lareu-Vidal Sonia , Suárez-Rodríguez Marta , Arias-Llorente Rosa Patricia , Solís-Sánchez Gonzalo
Published: June 2021

Postnatal growth restriction has high prevalence in very low birth weight (VLBW) preterm neonates, and this could affect their long-term prognosis. Nowadays, there is no consensus on how to monitor growth in these neonates.

Objective:This study aimed to compare prevalence of intra- and extrauterine growth restriction (IUGR and EUGR) in a sample of VLBW infants according to the Fenton 2013 charts and INTERGROWTH-21st (IW-21) standards and to analyze concordance between both in the different EUGR definitions criteria (cross-sectional, dynamic, and true).

Patients and Methods:An observational retrospective study of 635 VLBW preterm was performed. The study was carried out in Central University Hospital of Asturias. Body measurements (weight, length, and head circumference) were collected at birth and at hospital discharge and expressed in z-scores for the two references (Fenton 2010 and IW-21). Kappa concordance was calculated.

Results:Kappa concordance between Fenton and IW-21 was 0.887 for IUGR and 0.580 for static EUGR. Prevalence was higher according to Fenton in IUGR (36.5 vs. 35.1%), in static EUGR (73.8 vs. 59.3%), and in dynamic EUGR (44.3 vs. 29.3%). Despite observing low prevalence of EUGR when IW-21 was used to define EUGR, a statistical association between neonatal morbidity and diagnosis of EUGR was observed.

Conclusion:The Fenton and IW-21 concordance for IUGR is good. IW-21 is more restrictive than Fenton in EUGR. Patients diagnosed by IW-21 as EUGR are more likely to have neonatal morbidity, especially if we use EUGR dynamic definition. In our study, we cannot conclude that one graph is better than the other.
Dynamic Systems Approach in Sensorimotor Synchronization: Adaptation to Tempo Step-Change
Authors: Darabi Nima , Svensson U. Peter
Published: June 2021

This paper presents a dynamic systems model of a sensorimotor synchronization (SMS) task. An SMS task typically gives temporally discrete human responses to some temporally discrete stimuli. Here, a dynamic systems modeling approach is applied after converting the discrete events to regularly sampled time signals. To collect data for model parameter fitting, a previously published pilot study was expanded. Three human participants took part in an experiment: to tap a finger on a keyboard, following a metronome which changed tempo in steps. System identification was used to estimate the transfer function that represented the relationship between the stimulus and the step response signals, assuming a separate linear, time-invariant system for each tempo step. Different versions of model complexity were investigated. As a minimum, a second-order linear system with delay, two poles, and one zero was needed to model the most important features of the tempo step response by humans, while an additional third pole could give a somewhat better fit to the response data. The modeling results revealed the behavior of the system in two distinct regimes: tempo steps below and above the conscious awareness of tempo change, i.e., around 12% of the base tempo. For the tempo steps above this value, model parameters were derived as linear functions of step size for the group of three participants. The results were interpreted in the light of known facts from other fields like SMS, psychoacoustics and behavioral neuroscience.
Two Dyscalculia Subtypes With Similar, Low Comorbidity Profiles: A Mixture Model Analysis
Authors: Kißler Christian , Schwenk Christin , Kuhn Jörg-Tobias
Published: June 2021

Several studies have aimed to identify subtypes of dyscalculia. In many of these studies, either pre-defined groups (e.g., children with reading and mathematical difficulties vs. children with isolated mathematical difficulties) were analyzed regarding their cognitive profiles (top-down approach), or clusters of children with dyscalculia (CwD) were identified based on a narrow range of cognitive and mathematical skills (data-driven or bottom-up approach). However, it has remained difficult to establish robust subtypes of dyscalculia across studies. Against this background, we conducted a mixture model analysis in order to explore and identify subtypes of dyscalculia based on a broad range of variables (intelligence, reading fluency, working memory, attention, and various mathematical skills). The total sample comprised 174 elementary school CwD (IQ > 70; mathematical abilities: percentile rank <10), which consisted of two subsamples. The first subsample was based on a diagnostic test focusing on calculation (HRT 1–4; n = 71; 46 girls, 25 boys; age: M = 9.28 years, SD = 0.94) whereas the second subsample was based on a diagnostic test with a strong focus on basic numerical capacities (ZAREKI-R; n = 103; 78 girls, 25 boys; age: M = 8.94 years, SD = 1.05). Results provided convincing evidence for the existence of two subtypes in CwD: A slightly impaired subtype and a strongly impaired subtype. Subtypes differed most strongly regarding mathematical abilities, but the analyses suggest that differences in attention could also be a key factor. Therefore, comorbid attention difficulties seem to be a relevant factor that needs to be considered when establishing subtypes. Substantial intelligence differences between dyscalculia subtypes could not be found. Differences in working memory and reading fluency were negligible. Overall, the results seemed to be robust regardless of the diagnostic test used for assessing dyscalculia. When planning interventions for CwD, the existence of a subtype with substantial attention problems should be kept in mind.
Participant Experiences of Transcranial Direct Current Stimulation (tDCS) as a Treatment for Antipsychotic Medication Induced Weight Gain
Authors: Grycuk Luiza , Moruzzi Francesca , Bardjesteh Elena , Gaughran Fiona , Campbell Iain C. , Schmidt Ulrike
Published: June 2021

Background: Despite the growing number of studies on the use of non-invasive brain stimulation in people with schizophrenia, there is limited research on participant views of such treatment methods.

Aim: Explore participant experiences and perceptions of transcranial direct current stimulation (tDCS).

Methods: Twelve people with schizophrenia took part in semi-structured interviews after having completed 5 sessions of tDCS. Thematic analysis was used to identify codes and themes.

Results: Five themes were identified: (1) motivation for study enrolment; (2) concerns about tDCS; (3) factors reducing the fear of tDCS; (4) experience of tDCS; (5) perceived effects of tDCS.

Conclusions: The study provides insight into the perceptions and experiences of each individual. Participants were concerned about the safety of tDCS and associated it with invasive procedures such as electroconvulsive therapy and lobotomy. Educational materials and a good relationship with the researcher played an important role in reducing the fear of brain stimulation. All participants described tDCS as uncomfortable, however, agreed that unpleasant sensations only lasted for a short while (20 s−5 min). After the first session, participants no longer felt anxious about the remaining ones. Strategies to improve treatment experience and study recruitment have been identified.
Pills, PrEP, and Pals: Adherence, Stigma, Resilience, Faith and the Need to Connect Among Minority Women With HIV/AIDS in a US HIV Epicenter
Authors: Duthely Lunthita M. , Sanchez-Covarrubias Alex P. , Brown Megan R. , Thomas Tanya E. , Montgomerie Emily K. , Dale Sannisha , Safren Steven A. , Potter JoNell E.
Published: June 2021

Background: Ending HIV/AIDS in the United States requires tailored interventions. This study is part of a larger investigation to design mCARES, a mobile technology-based, adherence intervention for ethnic minority women with HIV (MWH).

Objective: To understand barriers and facilitators of care adherence (treatment and appointment) for ethnic MWH; examine the relationship between these factors across three ethnic groups; and, explore the role of mobile technologies in care adherence.

Methods: Cross-sectional, mixed-methods data were collected from a cohort of African-American, Hispanic-American and Haitian-American participants. Qualitative data were collected through a focus group (n = 8) to assess barriers and facilitators to care adherence. Quantitative data (n = 48) surveyed women on depressive symptomology (PHQ-9), HIV-related stigma (HSS) and resiliency (CD-RISC25). We examined the relationships between these factors and adherence to treatment and care and across groups.

Findings: Qualitative analyses revealed that barriers to treatment and appointment adherence were caregiver-related stressors (25%) and structural issues (25%); routinization (30%) and religion/spirituality (30%) promoted adherence to treatment and care. Caregiver role was both a hindrance (25%) and promoter (20%) of adherence to treatment and appointments. Quantitatively, HIV-related stigma differed by ethnic group; Haitian-Americans endorsed the highest levels while African-Americans endorsed the lowest. Depression correlated to stigma (R = 0.534; p < 0.001) and resiliency (R = −0.486; p < 0.001). Across ethnic groups, higher depressive symptomology and stigma were related to viral non-suppression (p < 0.05)—a treatment adherence marker; higher resiliency was related to viral suppression. Among Hispanic-Americans, viral non-suppression was related to depression (p < 0.05), and among African-Americans, viral suppression was related to increased resiliency (p < 0.04).

Conclusion: Multiple interrelated barriers to adherence were identified. These findings on ethnic group-specific differences underscore the importance of implementing culturally-competent interventions. While privacy and confidentiality were of concern, participants suggested additional intervention features and endorsed the use of mCARES as a strategy to improve adherence to treatment and appointments.
Logically Inferred Tuberculosis Transmission (LITT): A Data Integration Algorithm to Rank Potential Source Cases
Authors: Winglee Kathryn , McDaniel Clinton J. , Linde Lauren , Kammerer Steve , Cilnis Martin , Raz Kala M. , Noboa Wendy , Knorr Jillian , Cowan Lauren , Reynolds Sue , Posey James , Sullivan Meissner Jeanne , Poonja Shameer , Shaw Tambi , Talarico Sarah , Silk Benjamin J.
Published: June 2021

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2–69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation.

Code available at:https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171.
Identification of Variable Importance for Predictions of Mortality From COVID-19 Using AI Models for Ontario, Canada
Authors: Snider Brett , McBean Edward A. , Yawney John , Gadsden S. Andrew , Patel Bhumi
Published: June 2021

The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has challenged medical systems to the brink of collapse around the globe. In this paper, logistic regression and three other artificial intelligence models (XGBoost, Artificial Neural Network and Random Forest) are described and used to predict mortality risk of individual patients. The database is based on census data for the designated area and co-morbidities obtained using data from the Ontario Health Data Platform. The dataset consisted of more than 280,000 COVID-19 cases in Ontario for a wide-range of age groups; 0–9, 10–19, 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, and 90+. Findings resulting from using logistic regression, XGBoost, Artificial Neural Network and Random Forest, all demonstrate excellent discrimination (area under the curve for all models exceeded 0.948 with the best performance being 0.956 for an XGBoost model). Based on SHapley Additive exPlanations values, the importance of 24 variables are identified, and the findings indicated the highest importance variables are, in order of importance, age, date of test, sex, and presence/absence of chronic dementia. The findings from this study allow the identification of out-patients who are likely to deteriorate into severe cases, allowing medical professionals to make decisions on timely treatments. Furthermore, the methodology and results may be extended to other public health regions.
Evaluation of Medetomidine-Ketamine for Immobilization of Feral Horses in Romania
Authors: Roşu Ovidiu , Melega Iulia , Evans Alina L. , Arnemo Jon M. , Küker Susanne
Published: June 2021

Feral horses are immobilized for a variety of reasons including population control via contraceptives. Although opioid combinations have been successfully used for immobilization of feral horses, there is a need for combinations using drugs that are more readily available and present less of a human health hazard. We evaluated the chemical immobilization with physiological measurements and blood gas analyses of 91 free-ranging feral horses (Equus ferus caballus) remotely immobilized with a combination of 30 mg medetomidine and 775 mg ketamine in a single disposable 6 ml dart. During immobilization, heart rate, respiratory rate, rectal temperature, capillary refill time and peripheral oxygen hemoglobin saturation (SpO2) were evaluated. In eight horses, arterial blood samples were analyzed to evaluate the blood gases, acid-base status and hematologic variables. Targeted horses presented a wide range of age, size and body condition. Eighty-one horses had an uneventful mean induction of 7.2 min. Eighty-nine horses were immobilized in lateral recumbency with good muscle relaxation and a median recumbency time of 67 min. Ten horses required supplemental ketamine intravenously (x̄ = 434 mg) due to incomplete immobilization. In 58 horses the effects of medetomidine were antagonized with atipamezole intravenously. Increased respiratory rate (>20 breaths/min), increased heart rate (>45 beats/min) and decreased SpO2< 90% were noted in more than half of the individuals, while increased rectal temperature (>39.0°C) was recorded in six animals. Blood parameters showed hypoxemia (<90 mmHg,n= 8), hypercapnia (>45 mmHg,n= 5), high glucose levels (>134 mmol/L,n= 3), increased blood lactate (>1.5 mmol/L), total carbon dioxide, bicarbonate and base excess which further increased in the second sample, whereas SpO2and calcium values decreased. Recoveries were smooth, with one (n= 86) or more (n= 5) attempts of standing. Eighty-nine recoveries were uneventful, besides one male that showed signs of monoparesis of the left front leg and one mare with signs consistent with exertional myopathy. In conclusion, medetomidine-ketamine provided a reliable immobilization in feral horses over a wide range of body mass and age. However, based on the observed hypoxemia during immobilization, oxygen supplementation is strongly recommended for this protocol.
Lipopolysaccharide-Activated Canine Platelets Upregulate High Mobility Group Box-1 via Toll-Like Receptor 4
Authors: Li Ronald H. L. , Hommel Caelin , Nguyen Nghi
Published: June 2021

High mobility group box-1 (HMGB1) and the toll-like receptor 4 (TLR4) axis is a key mediator of inflammation. Platelet-derived high mobility group box-1 (HMGB1) may also play a critical role in sepsis-mediated thrombosis resulting in complications like disseminated intravascular coagulation and multiple organ failure. While elevated levels of HMGB1 have been documented in humans and dogs with systemic inflammatory response syndrome and sepsis, a better understanding of how platelet agonists and lipopolysaccharide (LPS) mediate platelet HMGB1 expression would open doors to novel therapies for sepsis-mediated thrombosis. Herein, we sought to determine if canine platelets express HMGB1 in the presence or absence of LPS and agonists (ADP or thrombin) and if surface expression of HMGB1 is dependent on platelet TLR4. Canine platelets were unstimulated (resting) or activated with thrombin or adenosine diphosphate (ADP) in the presence or absence of Escherichia coli LPS prior to flow cytometric and western blot analyses for HMGB1 expression. We also treated canine platelets with or without TLR4 function blocking antibody or its isotype control. We discovered that while thrombin upregulated both surface and cellular HMGB1 expression, LPS-mediated activation in the presence of ADP priming led to upregulation of surface HMGB1 expression. This expression was found to be most prominent in platelets that had undergone alpha-granule secretion. Inhibition of TLR4 attenuated LPS-induced HMGB1 expression indicating that exteriorization of HMGB1 may be dependent on the non-genomic pathway of platelet TLR4. Our findings indicate that upregulation of platelet-derived HMGB1 occurs as a result of thrombin or TLR4-mediated activation in dogs. Future studies should explore the translational implication of platelet-derived HMGB1 as novel therapeutic targets in humans and dogs with sepsis.
Adrenal Gland Ultrasonographic Measurements and Plasma Hormone Concentrations in Clinically Healthy Newborn Thoroughbred and Standardbred Foals
Authors: Lauteri Eleonora , Mariella Jole , Beccati Francesca , Roelfsema Ellen , Castagnetti Carolina , Pepe Marco , Peric Tanja , Barbato Olimpia , Montillo Marta , Rouge Stefanie , Freccero Francesca
Published: June 2021

Adrenal hormones, ACTH plasma concentrations and the ultrasonographic evaluation of the adrenal glands are considered complementary in clinical evaluations of the hypothalamic–pituitary–adrenal (HPA) axis function in several species. In dogs, age, size and weight have a significant effect on the ultrasonographic size of the adrenal glands. In neonatal foals, ultrasonographic evaluation and measurements of the adrenal glands have been demonstrated to be reliable; however, the effect of individual variables on ultrasonographic features has not been investigated, and the clinical usefulness of adrenal gland ultrasonography is still not known. The aims of this study were: (i) to provide and compare adrenal glands ultrasound measurements in healthy newborn Thoroughbred and Standardbred foals, and assess any effect of age, weight and sex on them; (ii) to assess and compare ACTH and steroid hormone concentrations in healthy neonatal foals of the two breeds. Venous blood samples and ultrasonographic images of the adrenal glands were collected from 10 healthy neonatal Thoroughbred and 10 healthy neonatal Standardbred foals. Ultrasonographic measurements of the adrenal glands were obtained and adrenocorticotropin (ACTH), cortisol, dehydroepiandrosterone (DHEA), progesterone (P4) and aldosterone plasma concentrations were assessed. The ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, ACTH/DHEA and cortisol/DHEA ratios were calculated. A significant positive correlation was found between the height of the right adrenal gland and the foal’s weight; the width of the right and left adrenal gland and the medulla was significantly lower in Thoroughbreds than in Standardbreds. Cortisol and ACTH plasma concentrations were significantly higher and lower, respectively, in Thoroughbreds compared with Standardbreds. The cortisol/DHEA ratio was significantly higher in Thoroughbreds. This study provides reference ranges for neonatal Thoroughbred and Standardbred foals, and suggests the presence of breed-related differences in ultrasonographic adrenal gland measurements, plasmatic cortisol and ACTH concentrations. The higher cortisol/DHEA ratio detected in Thoroughbred foals could suggest a different response to environmental stimulation in the two breeds.
Usefulness of Imaging Techniques in the Diagnosis of Selected Injuries and Lesions of the Canine Tarsus. A Review
Authors: Abako Justyna , Holak Piotr , Głodek Joanna , Zhalniarovich Yauheni
Published: June 2021

Tarsus lesions are not common in dogs, but they can cause serious health problem. They can lead to permanent changes in the joint and, in dogs involved in canine sports, to exclusion from training. The most common diseases and injuries involving the tarsal joint are osteochondrosis, fractures and ruptures of the Achilles tendon. These conditions can be diagnosed primarily through accurate orthopedic examination, but even this may be insufficient for performing a proper diagnosis. Imaging modalities such as radiography, ultrasonography, magnetic resonance imaging or computed tomography can facilitate the detection and assessment of lesions in the canine tarsal joint. This review paper briefly presents some characteristics of the above-mentioned imaging techniques, offering a comparison of their utility in the diagnosis of lesions and injuries involving the canine tarsus.
Genome-Wide Associations for Microscopic Differential Somatic Cell Count and Specific Mastitis Pathogens in Holstein Cows in Compost-Bedded Pack and Cubicle Farming Systems
Authors: Wagner Patricia , Yin Tong , Brügemann Kerstin , Engel Petra , Weimann Christina , Schlez Karen , König Sven
Published: June 2021

The aim of the present study was to detect significant SNP (single-nucleotide polymorphism) effects and to annotate potential candidate genes for novel udder health traits in two different farming systems. We focused on specific mastitis pathogens and differential somatic cell fractions from 2198 udder quarters of 537 genotyped Holstein Friesian cows. The farming systems comprised compost-bedded pack and conventional cubicle barns. We developed a computer algorithm for genome-wide association studies allowing the estimation of main SNP effects plus consideration of SNPs by farming system interactions. With regard to the main effect, 35 significant SNPs were detected on 14 different chromosomes for the cell fractions and the pathogens. Six SNPs were significant for the interaction effect with the farming system for most of the udder health traits. We inferred two possible candidate genes based on significant SNP interactions. HEMK1 plays a role in the development of the immune system, depending on environmental stressors. CHL1 is regulated in relation to stress level and influences immune system mechanisms. The significant interactions indicate that gene activity can fluctuate depending on environmental stressors. Phenotypically, the prevalence of mastitis indicators differed between systems, with a notably lower prevalence of minor bacterial indicators in compost systems.
Building Information Modeling Methods for Post-Earthquake Retrofitting Visualization of Buildings Using Augmented Reality
Authors: Liu Zhansheng , Bai Wenyan
Published: June 2021

The post-earthquake retrofitting and repair process of a building is a key factor in improving its seismic capability. A thorough understanding of retrofitting methods and processes will aid in repairing post-earthquake buildings and improving seismic resilience. This study aims to develop a visualization framework for the post-earthquake retrofitting of buildings which builds models based on building information modeling (BIM) and realizes visualization using augmented reality (AR). First, multi-level representation methods and coding criteria are used to process the models for a damaged member. Then, an information collection template is designed for integrating multi-dimensional information, such as damage information, retrofitting methods, technical solutions, and construction measures. Subsequently, a BIM model is presented in three dimensions (3D) using AR. Finally, the visualization process is tested through experiments, which demonstrate the feasibility of using the framework to visualize the post-earthquake retrofitting of a building.
Long-Range Atom–Ion Rydberg Molecule: A Novel Molecular Binding Mechanism
Authors: Deiß Markus , Haze Shinsuke , Hecker Denschlag Johannes
Published: June 2021

We present a novel binding mechanism where a neutral Rydberg atom and an atomic ion form a molecular bound state at a large internuclear distance. The binding mechanism is based on Stark shifts and level crossings that are induced in the Rydberg atom due to the electric field of the ion. At particular internuclear distances between the Rydberg atom and the ion, potential wells occur that can hold atom–ion molecular bound states. Apart from the binding mechanism, we describe important properties of the long-range atom–ion Rydberg molecule, such as its lifetime and decay paths, its vibrational and rotational structure, and its large dipole moment. Furthermore, we discuss methods of how to produce and detect it. The unusual properties of the long-range atom–ion Rydberg molecule give rise to interesting prospects for studies of wave packet dynamics in engineered potential energy landscapes.
The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Combination Mediated by the F3 Peptide/Nucleolin System Is Supported by the Downregulation of the PI3K/Akt Pathway
Authors: Cruz Ana F. , Caleiras Mariana B. , Fonseca Nuno A. , Gonçalves Nélio , Mendes Vera M. , Sampaio Susana F. , Moura Vera , Melo Joana B. , Almeida Ramiro D. , Manadas Bruno , Simões Sérgio , Moreira João N.
Published: June 2021

Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying molecular mechanism of action of the nucleolin-mediated intracellular delivery of C6-ceramide to cancer cells was also explored. The assessment of overexpression of surface nucleolin expression by flow cytometry was critical to dissipate differences identified by Western blot in membrane/cytoplasm of SKOV-3, OVCAR-3 and TOV-112D ovarian cancer cell lines. The former was in line with the significant extent of uptake into (bulk) ovarian cancer cells, relative to non-targeted and non-specific counterparts. This pattern of uptake was recapitulated with putative CSC-enriched ovarian SKOV-3 and OVCAR-3 sub-population (EpCAMhigh/CD44high). Co-encapsulation of DXR:C6-ceramide into F3 peptide-targeted liposomes improved cytotoxic activity relative to liposomes containing DXR alone, in an extent that depended on the intrinsic resistance to DXR and on the incubation time. The enhanced cytotoxicity of the targeted combination was mechanistically supported by the downregulation of PI3K/Akt pathway by C6-ceramide, only among the nucleolin-overexpressing cancer cells presenting a basal p-Akt/total Akt ratio lower than 1.
Myeloid-Specific Acly Deletion Alters Macrophage Phenotype In Vitro and In Vivo without Affecting Tumor Growth
Authors: de Goede Kyra E. , Verberk Sanne G. S. , Baardman Jeroen , Harber Karl J. , van Kooyk Yvette , de Winther Menno P. J. , Schetters Sjoerd T. T. , Van den Bossche Jan
Published: June 2021

Cancer cells rely on ATP-citrate lyase (Acly)-derived acetyl-CoA for lipid biogenesis and proliferation, marking Acly as a promising therapeutic target. However, inhibitors may have side effects on tumor-associated macrophages (TAMs). TAMs are innate immune cells abundant in the tumor microenvironment (TME) and play central roles in tumorigenesis, progression and therapy response. Since macrophage Acly deletion was previously shown to elicit macrophages with increased pro- and decreased anti-inflammatory responses in vitro, we hypothesized that Acly targeting may elicit anti-tumor responses in macrophages, whilst inhibiting cancer cell proliferation. Here, we used a myeloid-specific knockout model to validate that absence of Acly decreases IL-4-induced macrophage activation. Using two distinct tumor models, we demonstrate that Acly deletion slightly alters tumor immune composition and TAM phenotype in a tumor type-dependent manner without affecting tumor growth. Together, our results indicate that targeting Acly in macrophages does not have detrimental effects on myeloid cells.
Microsatellite Instability in Colorectal Cancers: Carcinogenesis, Neo-Antigens, Immuno-Resistance and Emerging Therapies
Authors: Randrian Violaine , Evrard Camille , Tougeron David
Published: June 2021

A defect in the DNA repair system through a deficient mismatch repair system (dMMR) leads to microsatellite instability (MSI). Microsatellites are located in both coding and non-coding sequences and dMMR/MSI tumors are associated with a high mutation burden. Some of these mutations occur in coding sequences and lead to the production of neo-antigens able to trigger an anti-tumoral immune response. This explains why non-metastatic MSI tumors are associated with high immune infiltrates and good prognosis. Metastatic MSI tumors result from tumor escape to the immune system and are associated with poor prognosis and chemoresistance. Consequently, immune checkpoint inhibitors (ICI) are highly effective and have recently been approved in dMMR/MSI metastatic colorectal cancers (mCRC). Nevertheless, some patients with dMMR/MSI mCRC have primary or secondary resistance to ICI. This review details carcinogenesis and the mechanisms through which MSI can activate the immune system. After which, we discuss mechanistic hypotheses in an attempt to explain primary and secondary resistances to ICI and emerging strategies being developed to overcome this phenomenon by targeting other immune checkpoints or through vaccination and modification of microbiota.
Development and Validation of an Interpretable Artificial Intelligence Model to Predict 10-Year Prostate Cancer Mortality
Authors: Bibault Jean-Emmanuel , Hancock Steven , Buyyounouski Mark K. , Bagshaw Hilary , Leppert John T. , Liao Joseph C. , Xing Lei
Published: June 2021

Prostate cancer treatment strategies are guided by risk-stratification. This stratification can be difficult in some patients with known comorbidities. New models are needed to guide strategies and determine which patients are at risk of prostate cancer mortality. This article presents a gradient-boosting model to predict the risk of prostate cancer mortality within 10 years after a cancer diagnosis, and to provide an interpretable prediction. This work uses prospective data from the PLCO Cancer Screening and selected patients who were diagnosed with prostate cancer. During follow-up, 8776 patients were diagnosed with prostate cancer. The dataset was randomly split into a training (n = 7021) and testing (n = 1755) dataset. Accuracy was 0.98 (±0.01), and the area under the receiver operating characteristic was 0.80 (±0.04). This model can be used to support informed decision-making in prostate cancer treatment. AI interpretability provides a novel understanding of the predictions to the users.
FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer
Authors: Liu Cassie , Barger Carter J. , Karpf Adam R.
Published: June 2021

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. In this review article, we address the current knowledge regarding the mechanisms of regulation and oncogenic functions of FOXM1, particularly in the context of ovarian cancer. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell (CSC) properties, (5) genomic instability, and (6) altered cellular metabolism. We additionally discuss the evidence for FOXM1 as a cancer biomarker, describe the rationale for FOXM1 as a cancer therapeutic target, and provide an overview of therapeutic strategies used to target FOXM1 for cancer treatment.
One-Carbon Metabolism Associated Vulnerabilities in Glioblastoma: A Review
Authors: Ghannad-Zadeh Kimia , Das Sunit
Published: June 2021

Altered cell metabolism is a hallmark of cancer cell biology, and the adaptive metabolic strategies of cancer cells have been of recent interest to many groups. Metabolic reprogramming has been identified as a critical step in glial cell transformation, and the use of antimetabolites against glioblastoma has been investigated. One-carbon (1-C) metabolism and its associated biosynthetic pathways, particularly purine nucleotide synthesis, are critical for rapid proliferation and are altered in many cancers. Purine metabolism has also been identified as essential for glioma tumourigenesis. Additionally, alterations of 1-C-mediated purine synthesis have been identified as commonly present in brain tumour initiating cells (BTICs) and could serve as a phenotypic marker of cells responsible for tumour recurrence. Further research is required to elucidate mechanisms through which metabolic vulnerabilities may arise in BTICs and potential ways to therapeutically target these metabolic processes. This review aims to summarize the role of 1-C metabolism-associated vulnerabilities in glioblastoma tumourigenesis and progression and investigate the therapeutic potential of targeting this pathway in conjunction with other treatment strategies.