bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Drug Treatment Strategies for Atrial Fibrillation and TASK-1 Inhibition as an Emerging Novel Therapy Option
Authors: Kraft Manuel , Büscher Antonius , Wiedmann Felix , L’hoste Yannick , Haefeli Walter E. , Frey Norbert , Katus Hugo A. , Schmidt Constanze
Published: March 2021

Atrial fibrillation (AF) is the most common sustained arrhythmia with a prevalence of up to 4% and an upwards trend due to demographic changes. It is associated with an increase in mortality and stroke incidences. While stroke risk can be significantly reduced through anticoagulant therapy, adequate treatment of other AF related symptoms remains an unmet medical need in many cases. Two main treatment strategies are available: rate control that modulates ventricular heart rate and prevents tachymyopathy as well as rhythm control that aims to restore and sustain sinus rhythm. Rate control can be achieved through drugs or ablation of the atrioventricular node, rendering the patient pacemaker-dependent. For rhythm control electrical cardioversion and pharmacological cardioversion can be used. While electrical cardioversion requires fasting and sedation of the patient, antiarrhythmic drugs have other limitations. Most antiarrhythmic drugs carry a risk for pro-arrhythmic effects and are contraindicated in patients with structural heart diseases. Furthermore, catheter ablation of pulmonary veins can be performed with its risk of intraprocedural complications and varying success. In recent years TASK-1 has been introduced as a new target for AF therapy. Upregulation of TASK-1 in AF patients contributes to prolongation of the action potential duration. In a porcine model of AF, TASK-1 inhibition by gene therapy or pharmacological compounds induced cardioversion to sinus rhythm. The DOxapram Conversion TO Sinus rhythm (DOCTOS)-Trial will reveal whether doxapram, a potent TASK-1 inhibitor, can be used for acute cardioversion of persistent and paroxysmal AF in patients, potentially leading to a new treatment option for AF.
Pb Toxicity on Gut Physiology and Microbiota
Authors: Liu Wenya , Feng Hai , Zheng Shuilin , Xu Shuaishuai , Massey Isaac Yaw , Zhang Chengcheng , Wang Xiaoyan , Yang Fei
Published: March 2021

Lead (Pb) is a toxic heavy metal, having profound threats to the global population. Multiple organs such as kidney, and liver, as well as nervous, hematologic, and reproductive systems, are commonly considered the targets of Pb toxicity. Increasing researches reported that the effects of Pb on gastrointestinal tracts are equally intensive, especially on intestinal microbiota. This review summarized Pb toxicity on gut physiology and microbiota in different animal models and in humans, of which the alterations may further have effects on other organs in host. To be more specific, Pb can impair gut barrier and increase gut permeability, which make inflammatory cytokines, immunologic factors, as well as microbial metabolites such as bile acids (BA) and short-chain fatty acids (SCFAs) enter the enterohepatic circulation easily, and finally induce multiple systematic lesion. In addition, we emphasized that probiotic treatment may be one of the feasible and effective strategies for preventing Pb toxicity.
New Advances in Monitoring Cardiac Output in Circulatory Mechanical Assistance Devices. A Validation Study in a Porcine Model
Authors: Quintana-Villamandos Begoña , Barranco Mónica , Fernández Ignacio , Ruiz Manuel , del Cañizo Juan Francisco
Published: March 2021

Cardiac output (CO) measurement by continuous pulmonary artery thermodilution (COCTD) has been studied in patients with pulsatile-flow LVADs (left ventricular assist devices), confirming the clinical utility. However, it has not been validated in patients with continuous-flow LVADs. Therefore, the aim of this study was to assess the validity of COCTD in continuous-flow LVADs. Continuous-flow LVADs were implanted in six miniature pigs for partial assistance of the left ventricle. Both methods of measuring CO—measurement by COCTD and intermittent pulmonary artery thermodilution, standard technique (COITD)—were used in four consecutive moments of the study: before starting the LVAD (basal moment), and with the LVAD started in normovolemia, hypervolemia (fluid overloading), and hypovolemia (shock hemorrhage). At the basal moment, COCTD and COITD were closely correlated (r2 = 0.97), with a mean bias of −0.13 ± 0.16 L/min and percentage error of 11%. After 15 min of partial support LVAD, COCTD and COITD were closely correlated (r2 = 0.91), with a mean bias of 0.31 ± 0.35 L/min and percentage error of 20%. After inducing hypervolemia, COCTD and COITD were closely correlated (r2 = 0.99), with a mean bias of 0.04 ± 0.07 L/min and percentage error of 5%. After inducing hypovolemia, COCTD and COITD were closely correlated (r2 = 0.74), with a mean bias of 0.08 ± 0.22 L/min and percentage error of 19%. This study shows that continuous pulmonary thermodilution could be an alternative method of monitoring CO in a porcine model with a continuous-flow LVAD.
Abscisic Acid Regulates the Root Growth Trajectory by Reducing Auxin Transporter PIN2 Protein Levels in Arabidopsis thaliana
Authors: Xie Qijun , Essemine Jemaa , Pang Xiaochen , Chen Haiying , Jin Jing , Cai Weiming
Published: March 2021

The root is in direct contact with soil. Modulation of root growth in response to alterations in soil conditions is pivotal for plant adaptation. Extensive research has been conducted concerning the adjustment of root elongation and architecture in response to environmental factors. However, little is known about the modulation of the root growth trajectory, as well as its hormonal mechanism. Here we report that abscisic acid (ABA) participated in controlling root growth trajectory. The roots upon ABA treatment or from ABA-accumulation double mutantcyp707a1,3exhibit agravitropism-like growth pattern (wavy growth trajectory). The agravitropism-like phenotype is mainly ascribed to the compromised shootward transportation of auxin since we detected a reduced fluorescence intensity of auxin reporter DR5:VENUS in the root epidermis upon exogenous ABA application or in the endogenous ABA-accumulation double mutantcyp707a1,3. We then tried to decipher the mechanism by which ABA suppressed shootward auxin transport. The membrane abundance of PIN2, a facilitator of shootward auxin transport, was significantly reduced following ABA treatment and incyp707a1,3. Finally, we revealed that ABA reduced the membrane PIN2 intensity through suppressing thePIN2expression rather than accelerating PIN2 degradation. Ultimately, our results suggest a pivotal role for ABA in the root growth trajectory and the hormonal interactions orchestrating this process.
Genomic Selection for F1 Hybrid Breeding in Strawberry (Fragaria × ananassa)
Authors: Yamamoto Eiji , Kataoka Sono , Shirasawa Kenta , Noguchi Yuji , Isobe Sachiko
Published: March 2021

Cultivated strawberry is the most widely consumed fruit crop in the world, and therefore, many breeding programs are underway to improve its agronomic traits such as fruit quality. Strawberry cultivars were vegetatively propagated through runners and carried a high risk of infection with viruses and insects. To solve this problem, the development of F1hybrid seeds has been proposed as an alternative breeding strategy in strawberry. In this study, we conducted a potential assessment of genomic selection (GS) in strawberry F1hybrid breeding. A total of 105 inbred lines were developed as candidate parents of strawberry F1hybrids. In addition, 275 parental combinations were randomly selected from the 105 inbred lines and crossed to develop test F1hybrids for GS model training. These populations were phenotyped for petiole length, leaf area, Brix, fruit hardness, and pericarp color. Whole-genome shotgun sequencing of the 105 inbred lines detected 20,811 single nucleotide polymorphism sites that were provided for subsequent GS analyses. In a GS model construction, inclusion of dominant effects showed a slight advantage in GS accuracy. In the across population prediction analysis, GS models using the inbred lines showed predictability for the test F1hybrids and vice versa, except for Brix. Finally, the GS models were used for phenotype prediction of 5,460 possible F1hybrids from 105 inbred lines to select F1hybrids with high fruit hardness or high pericarp color. These F1hybrids were developed and phenotyped to evaluate the efficacy of the GS. As expected, F1hybrids that were predicted to have high fruit hardness or high pericarp color expressed higher observed phenotypic values than the F1hybrids that were selected for other objectives. Through the analyses in this study, we demonstrated that GS can be applied for strawberry F1hybrid breeding.
The Q-Matrix Anchored Mixture Rasch Model
Authors: Tseng Ming-Chi , Wang Wen-Chung
Published: March 2021

Mixture item response theory (IRT) models include a mixture of latent subpopulations such that there are qualitative differences between subgroups but within each subpopulation the measure model based on a continuous latent variable holds. Under this modeling framework, students can be characterized by both their location on a continuous latent variable and by their latent class membership according to Students’ responses. It is important to identify anchor items for constructing a common scale between latent classes beforehand under the mixture IRT framework. Then, all model parameters across latent classes can be estimated on the common scale. In the study, we proposed Q-matrix anchored mixture Rasch model (QAMRM), including a Q-matrix and the traditional mixture Rasch model. The Q-matrix in QAMRM can use class invariant items to place all model parameter estimates from different latent classes on a common scale regardless of the ability distribution. A simulation study was conducted, and it was found that the estimated parameters of the QAMRM recovered fairly well. A real dataset from the Certificate of Proficiency in English was analyzed with the QAMRM, LCDM. It was found the QAMRM outperformed the LCDM in terms of model fit indices.
Electrophysiological Evidence of Dissociation Between Explicit Encoding and Fast Mapping of Novel Spoken Words
Authors: Shtyrov Yury , Filippova Margarita , Blagovechtchenski Evgeni , Kirsanov Alexander , Nikiforova Elizaveta , Shcherbakova Olga
Published: March 2021

Existing behavioral, neuropsychological and functional neuroimaging data suggest that at least two major cognitive strategies are used for new word learning: fast mapping (FM) via context-dependent inference and explicit encoding (EE) via direct instruction. However, these distinctions remain debated at both behavioral and neurophysiological levels, not least due to confounds related to diverging experimental settings. Furthermore, the neural dynamics underpinning these two putative processes remain poorly understood. To tackle this, we designed a paradigm presenting 20 new spoken words in association with pictures in either FM or EE settings, closely matched for auditory and visual features and overall task demands. We tested word acquisition using a range of behavioral measures as well as passive event-related potential (ERP) responses, an established measure of word memory trace activation, and compared brain activity elicited by novel FM and EE words before and after the learning session. Behavioral data obtained in free recall, recognition and semantic word-picture matching tasks indicated successful acquisition of new words after just 10 exposures. Crucially, we found no behavioral evidence of different acquisition outcomes between FM and EE learning. ERP data, which exhibited the main response peaks at ~170, 250, and 520 ms, also indicated successful learning, with statistically different responses between novel and familiar words present only before, but not after the training, suggesting rapid formation of new neural memory circuits matching in activation those for previously known words. Furthermore, already at the earliest peak, we found different topographic distributions for the two learning types, with left-lateralized FM dynamics, suggestive of core language system involvement, and more diffuse activity for EE items, possibly suggesting the role of attention/executive control network. A similar effect also manifested later, at ~520 ms. Our data suggest that while both EE and FM learning can be successful for rapid word acquisition at the behavioral level, the diverging electrophysiological patterns suggest a dissociation between the neural systems underpinning these learning strategies.
Study of the Influencing Factors of Cyberbullying Among Chinese College Students Incorporated With Digital Citizenship: From the Perspective of Individual Students
Authors: Zhong Jinping , Zheng Yunxiang , Huang Xingyun , Mo Dengxian , Gong Jiaxin , Li Mingyi , Huang Jingxiu
Published: March 2021

Understanding the influencing factors of cyberbullying is key to effectively curbing cyberbullying. Among the various factors, this study focused on the personal level of individual students and categorized the influencing factors of cyberbullying among college students into five sublevels, i.e., background, Internet use and social network habits, personality, emotion, and literacy related to digital citizenship. Then a questionnaire survey was applied to 947 Chinese college students. The results show that cyberbullying among Chinese college students are generally at a low level. There are many factors influence cyberbullying. Specifically, at the personal background level, gender has a significant impact on cyberbullying and being cyberbullied. In terms of personal Internet use and social network habits, students’ average daily online time has no significant correlation with cyberbullying and being cyberbullied; however, the proportion of online non-learning time has a significantly positive correlation with cyberbullying, and the proportion of online learning/work time has a significant impact on being cyberbullied. At the personality level, the Big Five personality traits have varying degrees of correlation with and influence on cyberbullying and being cyberbullied. At the personal emotions level, students’ life satisfaction has a significantly negative correlation with cyberbullying and being cyberbullied while it only has a significant impact on being cyberbullied; the personal stress and empathetic concern aspects of empathy have a significantly positive correlation with cyberbullying and being cyberbullied among female students. At the literacy related to digital citizenship level, students’ understanding of and compliance with Internet etiquette have significantly negative impacts on cyberbullying; the ability to communicate and collaborate online and Internet addiction have significantly positive impacts on cyberbullying and being cyberbullied; the understanding of and compliance with relevant digital laws and regulations have significantly negative correlations with cyberbullying and being cyberbullied. Overall, college students’ digital citizenship level has a significantly negative correlation with cyberbullying but no significant correlation with being cyberbullied. Finally, analysis and suggestions were provided according to these statistical results and the effects of these factors on cyberbullying and being cyberbullied among college students, so as to help solve this problem and provide a new perspective for research in this field.
A Serious Game to Improve Emotion Regulation in Treatment-Seeking Individuals With Gambling Disorder: A Usability Study
Authors: Mena-Moreno Teresa , Fernández-Aranda Fernando , Granero Roser , Munguía Lucero , Steward Trevor , López-González Hibai , del Pino-Gutiérrez Amparo , Lozano-Madrid María , Gómez-Peña Mónica , Moragas Laura , Giroux Isabelle , Grall-Bronnec Marie , Sauvaget Anne , Mora-Maltas Bernat , Valenciano-Mendoza Eduardo , Menchón José M. , Jiménez-Murcia Susana
Published: March 2021

Background: Serious games have shown positive results in increasing motivation, adherence to treatment and strengthening the therapeutic alliance in multiple psychiatric disorders. In particular, patients with impulse control disorders and other disorders in which the patient suffers from inhibitory control deficits (e.g., behavioral addictions) have been shown to benefit from serious games.

Aim: The aim of this study was to describe the characteristics and to evaluate the usability of a new serious videogame, e-Estesia. This serious videogame was designed to improve emotion regulation in patients with gambling disorder (GD). Preliminary results from a pilot sample are also reported.

Method: A pilot sample of 26 patients undergoing treatment for GD was recruited (ranging from 22 to 74 years, mean = 41.2 and SD = 12.9; 80.8% men). Participants used e-Estesia on a tablet, which was connected to a thoracic band that sent heart rate (HR) and heart rate variability (HRV) data to the videogame platform in order to provide biofeedback. The System Usability Scale was completed by patients to determine the usability of e-Estesia.

Results and Discussion: e-Estesia performed comparatively well for all the explored groups (i.e., sex, age, and online vs. offline gambling: mean usability score = 83.8, SD = 13.1). Around 84.6% of the patients endorsed that it was easy to use. Female patients with GD presented higher HRV during the use of the serious videogame compared to men.
A Systematic Review Examining the Relationship Between Habit and Physical Activity Behavior in Longitudinal Studies
Authors: Feil Katharina , Allion Sarah , Weyland Susanne , Jekauc Darko
Published: March 2021

Purpose: To explain physical activity behavior, social-cognitive theories were most commonly used in the past. Besides conscious processes, the approach of dual processes additionally incorporates non-conscious regulatory processes into physical activity behavior theories. Habits are one of various non-conscious variables that can influence behavior and thus play an important role in terms of behavior change. The aim of this review was to examine the relationship between habit strength and physical activity behavior in longitudinal studies.

Methods: According to the PRISMA guidelines, a systematic search was conducted in three databases. Only peer-reviewed articles using a longitudinal study design were included. Both, habit and physical activity were measured at least once, and habit was related to physical activity behavior. Study quality was evaluated by assessment tools of the NHLBI.

Results: Of 3.382 identified publications between 2016 and 2019, fifteen studies with different study designs were included. Most studies supported that positive correlations between habit and physical activity exist. Some positive direct and indirect effects of habit on physical activity were detected and only a minority of studies showed the influence of physical activity on habit strength. Studies differentiating between instigation and execution habit found positive correlations and revealed instigation habit as a stronger predictor of physical activity. The quality of studies was rated as reasonable using assessment tools of the NHLBI.

Conclusion: This review revealed a bidirectional relationship between habit and physical activity. Whether habit predicts physical activity or vice versa is still unclear. The observation of habit influencing physical activity may be most appropriate in studies fostering physical activity maintenance while the influence of physical activity on habit may be reasonable in experimental studies with physical activity as intervention content to form a habit. Future investigations should differentiate between habit formation and physical activity maintenance studies depending on the research objective. Long-term study designs addressing the complexity of habitual behavior would be beneficial for establishing cue-behavior associations for the formation of habits. Furthermore, studies should differentiate between instigation and execution habit in order to investigate the influence of both variables on physical activity behavior independently.
Probing the Hypersalience Hypothesis—An Adapted Judge-Advisor System Tested in Individuals With Psychotic-Like Experiences
Authors: Scheunemann Jakob , Fischer Rabea , Moritz Steffen
Published: March 2021

Individuals with psychotic-like experiences and psychosis gather and use information differently than controls; in particular they seek and rely on less information or over-weight currently available information. A new paradigm, the judge-advisor system, has previously been used to investigate these processes. Results showed that psychosis-prone individuals tend to seek less advice but at the same time use the available advice more. Some theoretical models, like the hypersalience of evidence-matching hypothesis, predict that psychosis-prone individuals weight recently available information to a greater extent and thus provide an explanation for increased advice-weighting scores in psychosis-prone individuals. To test this model, we adapted the previously used judge-advisor system by letting participants receive consecutively multiple pieces of advice. To meet this aim, we recruited a large MTurk community sample (N = 1,396), which we split in a group with high levels of psychotic-like experiences (at least 2 SD above the mean, n = 80) and a group with low levels of psychotic-like experiences (maximum 0.5 SD above the mean, n = 1,107), using the Community Assessment of Psychic Experiences' positive subscale. First, participants estimated five people's age based on photographs. Then, they received consecutive advice in the form of manipulated age estimates by allegedly previous participants, with outliers in some trials. After each advice, participants could adjust their estimate. This procedure allowed us to investigate how participants weighted each currently presented advice. In addition to being more confident in their final estimates and in line with our preregistered hypothesis, participants with more frequent psychotic-like experiences did weight currently available advice more than participants with less frequent psychotic-like experiences. This effect was especially pronounced in response to outliers, as fine-grained post-hoc analysis suggested. Result thus support models predicting an overcorrection in response to new incoming information and challenges an assumed general belief inflexibility in people with psychotic experiences.
Super Placebos: A Feasibility Study Combining Contextual Factors to Promote Placebo Effects
Authors: Olson Jay A. , Lifshitz Michael , Raz Amir , Veissière Samuel P. L.
Published: March 2021

Background: Ample evidence demonstrates that placebo effects are modulated by contextual factors. Few interventions, however, attempt to combine a broad range of these factors. Here, we explore the therapeutic power of placebos by leveraging factors including social proof, positive suggestion, and social learning. This study aimed to test the feasibility of an elaborate “super placebo” intervention to reduce symptoms of various disorders in a pediatric population.

Methods: In a single-arm qualitative study, participants entered an inactive MRI scanner which they were told could help their brain heal itself through the power of suggestion. The sample included 11 children (6–13 years old) diagnosed with disorders known to be receptive to placebos and suggestion (Attention Deficit Hyperactivity Disorder, Tourette Syndrome, chronic skin picking, and migraines). The children were given positive suggestions during 2–4 placebo machine sessions over the span of approximately 1 month. We assessed open-ended treatment outcomes via recorded interviews and home visits.

Results: The procedure was feasible and no adverse events occurred. Ten of the 11 parents reported improvements in their children after the intervention, ranging from minor transient changes to long-term reductions in subjective and objective symptoms (e.g., migraines and skin lesions).

Discussion: These preliminary findings demonstrate the feasibility and promise of combining a broad range of contextual factors in placebo studies. Future research is needed to assess the causal effects of such interventions.
Behavioral Inhibition/Activation Systems and Depression Among Females With Substance Use Disorder: The Mediating Role of Intolerance of Uncertainty and Anhedonia
Authors: Xie Jinlan , Fang Ping , Zhang Zhihao , Luo Ronglei , Dai Bibing
Published: March 2021

Previous studies have shown that the behavioral inhibition/activation systems (BIS/BAS) have substantial effects on substance use disorder and emotional disorders, and substance use disorder and emotional disorders often occur; in particular, females with substance use disorder are more likely to also have serious emotional disorders including depression than their male counterparts. However, the associations between the BIS/BAS and depression in females with substance use disorder have received little attention. Furthermore, the underlying mechanisms of these relations are largely unknown. The present study examines the mediating roles of intolerance of uncertainty and anhedonia in the associations between the BIS/BAS and depression among females with substance use disorder from the Research Domain Criteria (RDoC) framework. A total of 303 females with substance use disorder from a compulsory substance abuse detention center were tested using a cross-sectional survey involving BIS/BAS Scales, Intolerance of Uncertainty Scale, Snaith-Hamilton Pleasure Scale, and Center for Epidemiologic Studies Depression Scale. The path analysis model revealed that both the BIS and BAS had a direct effect on depression, that the BIS had an indirect effect on depression through intolerance of uncertainty, and that the BAS had an indirect effect on depression via anhedonia. These findings contribute to a more thorough understanding of how the BIS/BAS influence depression among females with substance use disorder and suggest that the utility of targeting these associations in treatments would help reduce depression in females with substance use disorder.
Do You Like to Breathe? Diatoms Can Help You With That!
Authors: Virta Leena , Norkko Alf
Published: March 2021

Have you ever thought about why we never run out of oxygen even though there are so many of us breathing constantly? The answer is that there are plants and algae that produce new oxygen at the same rate as we use it. Surprisingly, the most important oxygen producers are not large trees but tiny algae that live in the water, and one of the most important groups among them are the diatoms. Because the diversity of life is now decreasing all over the world, we wanted to find out whether having many different species of diatoms is important for oxygen production, or if just a few species would be enough. Our results showed that species-rich communities of diatoms were more effective in providing oxygen. This means that we should work to avoid destroying our oceans, lakes, and rivers to make sure that we have healthy diatom communities also in the future.
Current Management of Membranous Urethral Strictures Due to Radiation
Authors: Waterloos Marjan , Martins Francisco , Verla Wesley , Kluth Luis Alex , Lumen Nicolaas
Published: March 2021

Radiotherapy is a frequently used treatment for prostate cancer. It does not only causes the intended damage to cancer cells, but also affects healthy surrounding tissue. As a result radiation-induced urethral strictures occur in 2.2% of prostate cancer patients. Management of urethral strictures is challenging due to the presence of poor vascularized tissue for reconstruction and the proximity of the sphincter, which can impair the functional outcome. This review provides a literature overview of risk factors, diagnostics and management of radiation-induced urethral strictures.
Real-Time Quaking-Induced Conversion Detection of PrPSc in Fecal Samples From Chronic Wasting Disease Infected White-Tailed Deer Using Bank Vole Substrate
Authors: Hwang Soyoun , Greenlee Justin J. , Nicholson Eric M.
Published: March 2021

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that is fatal to free-range and captive cervids. CWD has been reported in the United States, Canada, South Korea, Norway, Finland, and Sweden, and the case numbers in both wild and farmed cervids are increasing rapidly. Studies indicate that lateral transmission of cervids likely occurs through the shedding of infectious prions in saliva, feces, urine, and blood into the environment. Therefore, the detection of CWD early in the incubation time is advantageous for disease management. In this study, we adapt real-time quacking-induced conversion (RT-QuIC) assays to detect the seeding activity of CWD prions in feces samples from clinical and preclinical white-tailed deer. By optimizing reaction conditions for temperature as well as the salt and salt concentration, prion seeding activity from both clinical and preclinical animals were detected by RT-QuIC. More specifically, all fecal samples collected from 6 to 30 months post inoculation showed seeding activity under the conditions of study. The combination of a highly sensitive detection tool paired with a sample type that may be collected non-invasively allows a useful tool to support CWD surveillance in wild and captive cervids.
Serological Evidence of Exposure to Peste des Petits Ruminants in Small Ruminants in Rwanda
Authors: Shyaka Anselme , Ugirabe Marie Aurore , Wensman Jonas Johansson
Published: March 2021

The status of Peste des Petits Ruminants (PPR) in Rwanda is unknown, despite its prevalence in neighboring countries. A cross-sectional sampling of goats and sheep was carried out in five districts of Rwanda located closer to neighboring countries endemic to PPR. Serum samples were analyzed using a commercial ELISA, to detect antibodies to PPR virus (PPRV). Sixty-eight samples [14.8, 95% Confidence Interval (CI): 11.7–18.4] were seropositive for PPR, of which 17.4% (95% CI: 11.6–24.6; 25/144) were from sheep, whereas 13.6% (95% CI: 10.0–17.9; 43/316) were from goats. Seropositivity ranged from 8.9 to 17.3% (goats) and from 10.5 to 25.8% (sheep) in sampled districts. Seropositivity was slightly higher in males than females in both goats (15.7 vs. 12.4%) and sheep (17.7 vs. 17.1%), and were significantly marked in goats and sheep aged more than 15 months (goats: 17.9, 95% CI: 12.9–24.0; sheep: 22.2, 95% CI: 14.1–32.2) than those between 6 and 15 months (goats: 6.1, 95% CI: 2.5–12.1; sheep: 9.3, 95% CI: 3.1–20.3). Sampling was non-randomized and results are not representative of the true prevalence of PPR antibody in small ruminants. Thus, data does not allow to fully discuss the findings beyond the presence/absence certitude and the comparisons made must be interpreted with caution. The presence of specific antibodies to PPRV may, however, be linked to one or a combination of following scenarios: (1) prevalence and persistence of PPRV in sampled regions which would cause low level of clinical cases and/or mortalities that go unnoticed; (2) introduction of PPRV to herds through movements of livestock from neighboring infected countries, and/or (3) events of disease outbreaks that are underreported by farmers and veterinarians. In addition to strengthen veterinary surveillance mechanisms, further studies using robust sampling methods and integrating livestock and wildlife, should be carried out to fully elucidate PPR epidemiology in Rwanda.
Controlling the Colonization of Clostridium perfringens in Broiler Chickens by an Electron-Beam-Killed Vaccine
Authors: Jesudhasan Palmy R. , Bhatia Sohini S. , Sivakumar Kirthiram K. , Praveen Chandni , Genovese Kenneth J. , He Haiqi L. , Droleskey Robert , McReynolds Jack L. , Byrd James A. , Swaggerty Christina L. , Kogut Michael H. , Nisbet David J. , Pillai Suresh D.
Published: March 2021

Clostridium perfringens (Cp) is a Gram-positive anaerobe that is one of the causative agents of necrotic enteritis (NE) in chickens, which leads to high mortality. Owing to the ban of administering antibiotics in feed to chickens, there has been an increase in the number of NE outbreaks all over the world, and the estimated loss is approximately 6 billion U.S. dollars. The best alternative method to control NE without antibiotics could be vaccination. In this study, we exposed three different strains of Cp to electron beam (eBeam) irradiation to inactivate them and then used them as a killed vaccine to control the colonization of Cp in broiler chickens. The vaccine was delivered to 18-day old embryos in ovo and the chickens were challenged with the respective vaccine strain at two different time points (early and late) to test the protective efficacy of the vaccine. The results indicate that an effective eBeam dose of 10 kGy inactivated all three strains of Cp, did not affect the cell membrane or epitopes, induced significant levels of IgY in the vaccinated birds, and further reduced the colonization of Cp strains significantly (p < 0.0001) in late challenge (JGS4064: 4 out of 10; JGS1473: 0 out of 10; JGS4104: 3 out of 10). Further studies are necessary to enhance the efficacy of the vaccine and to understand the mechanism of vaccine protection.
Mucosa-Associated Lymphoid Tissue 1 Is an Oncogene Inducing Cell Proliferation, Invasion, and Tumor Growth via the Upregulation of NF-κB Activity in Human Prostate Carcinoma Cells
Authors: Tsui Ke-Hung , Chang Kang-Shuo , Sung Hsin-Ching , Hsu Shu-Yuan , Lin Yu-Hsiang , Hou Chen-Pang , Yang Pei-Shan , Chen Chien-Lun , Feng Tsui-Hsia , Juang Horng-Heng
Published: March 2021

Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue 1 (MALT1) is a novel gene involved in nuclear factor κB (NF-κB) signal transduction by acting as an adaptor protein and paracaspase, with an essential role in inflammation and tumorigenesis in many cancers. This study investigated the functions and the potential regulatory mechanisms of MALT1 in the human prostate cancer cells. We found that MALT1 is abundant in prostate cancer tissues. MALT1 facilitated NF-κB subunits (p50 and p65) nuclear translocation to induce gene expression of interleukin 6 (IL-6) and C-X-C motif chemokine 5 (CXCL5) in prostate carcinoma cells. MALT1 promoted cell proliferation, invasion, and tumor growth in vitro and in vivo. MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells.
Histopathological and Immune Prognostic Factors in Colo-Rectal Liver Metastases
Authors: Rigamonti Alessandra , Feuerhake Friedrich , Donadon Matteo , Locati Massimo , Marchesi Federica
Published: March 2021

Prognostic studies are increasingly providing new tools to stratify colo-rectal liver metastasis patients into clinical subgroups, with remarkable implications in terms of clinical management and therapeutic choice. Here, the strengths and hurdles of current prognostic tools in colo-rectal liver metastasis are discussed. Alongside more classic histopathological parameters, which capture features related to the tumor component, such as tumor invasion, tumor growth pattern and regression score, we will discuss immune mediators, which are starting to be considered important features. Their objective quantification has shown significant results in prognostication studies, with most of the work focused on adaptive immune cells, namely T cells. As for macrophages, they are only starting to be appreciated and we will present recent advances in evaluation of macrophage morphological features. Deeper knowledge acquired by multiparametric analyses is rapidly uncovering the variety of immune players that should be assessed. The future projection is to implement deep-learning histopathological tools and to integrate histopathological and immune metrics in multiparametric scores, with the ultimate objective to achieve a deeper resolution of the tumor features and their relevance for colo-rectal liver metastasis.
Adrenocortical Carcinoma
Authors: Berruti Alfredo , Tiberio Guido Alberto Massimo , Sigala Sandra
Published: March 2021

Adrenocortical carcinoma (ACC) is an extremely rare disease, the incidence of which is 0 [...]
Influence of Antihypertensive Treatment on RAAS Peptides in Newly Diagnosed Hypertensive Patients
Authors: Vischer Annina S. , Kuster Gabriela M. , Twerenbold Raphael , Pfister Otmar , Zhou Qian , Villiger Andrea , Poglitsch Marko , Krähenbühl Stephan , Mayr Michael , Osswald Stefan , Haschke Manuel , Burkard Thilo
Published: March 2021

(1) Background: Recently, influences of antihypertensive treatment on the renin–angiotensin–aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1–7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1–7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II (p < 0.0005 for 8 a.m., 12 a.m.) and Ang (1–7) (p = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p < 0.0005), amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001). Ang (1–7) was increased by perindopril and olmesartan (p = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.
Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8+ T Cell Response during Chronic Hepatitis C
Authors: Peña-Asensio Julia , Calvo Henar , Torralba Miguel , Miquel Joaquín , Sanz-de-Villalobos Eduardo , Larrubia Juan-Ramón
Published: March 2021

Hepatitis C virus (HCV)-specific CD8+ T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8+ T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.
KLF4, Slug and EMT in Head and Neck Squamous Cell Carcinoma
Authors: Ingruber Julia , Savic Dragana , Steinbichler Teresa Bernadette , Sprung Susanne , Fleischer Felix , Glueckert Rudolf , Schweigl Gabriele , Skvortsova Ira-Ida , Riechelmann Herbert , Dudás József
Published: March 2021

Epithelial to mesenchymal transition (EMT) is clinically relevant in head and neck squamous cell carcinoma (HNSCC). We hypothesized that EMT-transcription factors (EMT-TFs) and an anti-EMT factor, Krüppel-like-factor-4 (KLF4) regulate EMT in HNSCC. Ten control mucosa and 37 HNSCC tissue samples and three HNSCC cell lines were included for investigation of EMT-TFs, KLF4 and vimentin at mRNA and protein levels. Slug gene expression was significantly higher, whereas, KLF4 gene expression was significantly lower in HNSCC than in normal mucosa. In the majority of HNSCC samples, there was a significant negative correlation between KLF4 and Slug gene expression. Slug gene expression was significantly higher in human papilloma virus (HPV) negative HNSCC, and in tumor samples with irregular p53 gene sequence. Transforming-growth-factor-beta-1 (TGF- β1) contributed to downregulation of KLF4 and upregulation of Slug. Two possible regulatory pathways could be suggested: (1) EMT-factors induced pathway, where TGF-β1 induced Slug together with vimentin, and KLF4 was down regulated at the same time; (2) p53 mutations contributed to upregulation and stabilization of Slug, where also KLF4 could co-exist with EMT-TFs.
Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides
Authors: Dharmaratne Nayanthara U. , Kaplan Alanna R. , Glazer Peter M.
Published: March 2021

The delivery of cancer therapeutics can be limited by pharmacological issues such as poor bioavailability and high toxicity to healthy tissue. pH-low insertion peptides (pHLIPs) represent a promising tool to overcome these limitations. pHLIPs allow for the selective delivery of agents to tumors on the basis of pH, taking advantage of the acidity of the hypoxic tumor microenvironment. This review article highlights the various applications in which pHLIPs have been utilized for targeting and treating diseases in hypoxic environments, including delivery of small molecule inhibitors, toxins, nucleic acid analogs, fluorescent dyes, and nanoparticles.
The Effect of Well Child Visit Location on Preventative Dental Visit
Authors: Tiwari Tamanna , Marinucci Jennie , Tranby Eric P. , Frantsve-Hawley Julie
Published: March 2021

Recent emphasis has been placed on the integration of dental and medical primary care in an effort to promote recommendations from both American Academy of Pediatrics (AAP) and American Academy of Pediatric Dentistry (AAPD) that highlight the importance of preventing, intervening, and managing oral disease in childhood. The study aims to provide a population level insight into the role of location of service of medical well-child visit (WCV) and its association to preventative dental visit (PDV) for children between the ages of 0–20 years. Administrative claims data for 3.17 million Medicaid-enrolled children aged 0 to 20 years of age in 13 states in 2016 and 2017 were identified from the IBM Watson MarketScan Medicaid Database. Descriptive and survival analysis reveals most Medicaid enrolled children receive their WCV at an office and hospital, as compared to federally qualified health center, or rural or public health clinic. Further, this study demonstrates increased utilization of dental preventive services for children who receive a WCV. Hispanic children, female children, and children 5–9 years of age had a higher rate of PDV after a WCV at all three locations. This study contributes to the understanding of medical-dental integration among Medicaid-enrolled children and offers insight into the promotion of oral health prevention within medical primary care.
Repeated Laser Shock-Wave Adhesion Test for Metallic Coatings: Adhesion Durability and Its Mechanism Studied by Molecular Dynamics Simulation
Authors: Kanamori Kohei , Toriumi Shuto , Kimoto Yoshikatsu , Yonezu Akio
Published: March 2021

We evaluated the adhesion of polycrystalline metallic coatings using the laser shock-wave adhesion test (LaSAT). This study used Cu plating on stainless steel as a coating model. The adhesion strength and toughness were successfully estimated using LaSAT and finite element method with cohesive zone model. Next, repeated LaSAT was conducted to apply cyclic loading to evaluate adhesion fatigue life, i.e., the number of loading cycles required for delamination. Furthermore, this study performed molecular dynamics (MD) simulations to elucidate the adhesion mechanism for the Cu/Fe interface. To verify our model, the interfacial fracture toughness was computed using the MD simulation and compared with the results of LaSAT. Next, cyclic loading was applied to the MD model to investigate crack initiation around the interface. We found that dislocations are generated from the internal grain and are accumulated at grain boundaries. This accumulation results in fatigue crack initiation due to stress concentration.
Entropy-Regularized Optimal Transport on Multivariate Normal and q-normal Distributions
Authors: Tong Qijun , Kobayashi Kei
Published: March 2021

The distance and divergence of the probability measures play a central role in statistics, machine learning, and many other related fields. The Wasserstein distance has received much attention in recent years because of its distinctions from other distances or divergences. Although computing the Wasserstein distance is costly, entropy-regularized optimal transport was proposed to computationally efficiently approximate the Wasserstein distance. The purpose of this study is to understand the theoretical aspect of entropy-regularized optimal transport. In this paper, we focus on entropy-regularized optimal transport on multivariate normal distributions and q-normal distributions. We obtain the explicit form of the entropy-regularized optimal transport cost on multivariate normal and q-normal distributions; this provides a perspective to understand the effect of entropy regularization, which was previously known only experimentally. Furthermore, we obtain the entropy-regularized Kantorovich estimator for the probability measure that satisfies certain conditions. We also demonstrate how the Wasserstein distance, optimal coupling, geometric structure, and statistical efficiency are affected by entropy regularization in some experiments. In particular, our results about the explicit form of the optimal coupling of the Tsallis entropy-regularized optimal transport on multivariate q-normal distributions and the entropy-regularized Kantorovich estimator are novel and will become the first step towards the understanding of a more general setting.