bluuebunny/crossref_metadata_2025_split huggingface dataset:
No difference in hepatocellular carcinoma risk between chronic hepatitis B patients treated with entecavir versus tenofovir
Authors: Su Feng , Berry Kristin , Ioannou George N 
Published: March 2020

ObjectiveEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line agents for the treatment of chronic hepatitis B (CHB). Recent studies have challenged the assumption that these agents are equally effective at preventing hepatocellular carcinoma (HCC). We aimed to determine whether the risk of HCC and mortality differ in patients with CHB treated with ETV and TDF.DesignWe performed a retrospective cohort study of Veterans Affairs patients with CHB in the USA who initiated treatment with ETV or TDF between the dates of Food and Drug Administration approval of these medications and 1 January 2017. Multivariable Cox proportional hazards regression was used to determine the association between antiviral therapy and HCC risk as well as the risk of death or liver transplantation. Propensity score adjustment and competing risks analysis were performed.ResultsWe identified 2193 ETV-treated and 1094 TDF-treated patients who were followed for a mean of 5.4 years. We found no difference in the risk of HCC in ETV-treated versus TDF-treated patients (adjusted HR (aHR) 1.00, 95% CI 0.76 to 1.32). Results were similar in propensity score adjusted and competing risks analysis, and in multiple sensitivity analyses. We also found no difference in the risk of death or liver transplantation (aHR 1.16, 95% CI 0.98 to 1.39).ConclusionsWe found no difference in the risk of HCC between patients with CHB treated with ETV versus TDF. Our results support current guideline recommendations that both agents are appropriate first-line options for the treatment of CHB.
Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)
Authors: Harris Kate L , Kuan Wei-Li , Mason Sarah L , Barker Roger A 
Published: March 2020

ObjectivesAlterations in dopamine neurotransmission underlie some of the clinical features of Huntington’s disease (HD) and as such are a target for therapeutic intervention, especially for the treatment of chorea and some behavioural problems. However, justification for such an intervention is mainly based on case reports and small open label studies and the effects these drugs have on cognition in HD remain unclear.MethodsIn this study, we used the Enroll-HD observational database to assess the effects of antidopaminergic medication on motor, psychiatric and cognitive decline, over a 3-year period. We first looked at the annual rate of decline of a group of HD patients taking antidopaminergic medication (n=466) compared with an untreated matched group (n=466). The groups were matched on specified clinical variables using propensity score matching. Next, we studied a separate group of HD patients who were prescribed such medications part way through the study (n=90) and compared their rate of change before and after the drugs were introduced and compared this to a matched control group.ResultsWe found that HD patients taking antidopaminergic medication had a slower progression in chorea and irritability compared with those not taking such medications. However, this same group of patients also displayed significantly greater rate of decline in a range of cognitive tasks.ConclusionIn conclusion we found that antidopaminergic treatment is associated with improvements in the choreic movements and irritability of HD but worsens cognition. However, further research is required to prospectively investigate this and whether these are causally linked, ideally in a double-blind placebo-controlled trial.
Depression, suicidal ideation and suicide risk in German veterinarians compared with the general German population
Authors: Schwerdtfeger Kathrin Angelika , Bahramsoltani Mahtab , Spangenberg Lena , Hallensleben Nina , Glaesmer Heide 
Published: March 2020

BackgroundHigher rates of depression, suicidal ideation and suicide risk have been reported for veterinarians in various studies worldwide. This study investigates whether this is also true for German veterinarians.MethodsA total of 3.118 veterinarians (78.8 per cent female, mean age 41.3 years) between 22 and 69 years were included and compared with two general population samples of the same age range using the Suicide Behaviours Questionnaire‐Revised and Patient Health Questionnaire.ResultsCurrent suicidal ideation was found in 19.2 per cent of veterinarians, compared with only 5.7 per cent in the general population. 32.11 per cent of veterinarians were classified with increased suicide risk, compared with 6.62 per cent in the general population. 27.78 per cent of veterinarians screened positive for depression, compared with 3.99 per cent of the general population.ConclusionThe study shows that veterinarians have an increased risk of depression and suicidal ideation and suicide risk compared with the general population in Germany. Similar to previous findings, the level of depression was higher among veterinarians than in the general population. However, this study does not explore causes for higher rates in depression, suicide risk and suicidal ideation. Since other studies strongly suggest specific risk factors lead to higher suicide risk and consequently elevated numbers of completed suicides, future research should focus on identifying and preventing causes.
Limits on non-minimal Lorentz violating parameters through FCNC and LFV processes
Authors: Gomes Y. M. P. , Helayel-Neto J. A. 
Published: March 2020

AbstractIn this work we analyze a non-minimal Lorentz-violating extension of the electroweak theory in the fermionic sector. Firstly we analyze the relation between the CKM rotation in the quark sector and possible contributions of this new coupling to flavor changing neutral currents processes. In sequel we look for non-diagonal terms through possible lepton flavor violation decays. Strong bounds are presented to the Lorentz violating parameters of both the quark and the lepton sectors.
Extreme and critical transition events in the memristor based Liénard system
Authors: Kingston S. Leo , Suresh K. , Thamilmaran K. , Kapitaniak T. 
Published: March 2020

AbstractWe study extreme and critical events in the forced Liénard systems with charge control memristor. It has been found that the system exhibits hidden attractors either in the absence or presence of an external sinusoidal force. We give evidence that these attractors play a crucial role in the appearance of critical events. We attempt to explain the mechanism leading to the emergence of catastrophic transitions. Finally, we present that the observed critical transitions are typical for memristor based models and understanding of them gives some insight on how to avoid these types of devastating events at the time of the device fabrication process.
Improving Youngsters’ Resilience Through Video Game-Based Interventions
Authors: Menendez-Ferreira R. , Torregrosa J. , Panizo-Lledot A. , Gonzalez-Pardo A. , Camacho David 
Published: March 2020

Radicalization, as a violent form of extremism, is a growing problem for Europe. Currently, it is possible to find extreme ideologies regarding almost every topic such as religion, politics or sports. This problem, which ranges from personal identity conflicts to complex societal issues, has an impact on several people everyday, especially on youngsters. To confront this situation, the European Union found several initiatives, as a way to face this problem from a scientific perspective. Some of these initiatives face the problem trying to reduce radicalization by working on personal and social skills through education, in such a way the youngster’s resilience is improved. This paper aims to present YoungRes, a European project whose goal is to improve the resilience of youngsters. To do so, it unifies an already created intervention — named Fortius — through the inclusion of video games in the learning process. This paper describes both: (1) how the Fortius program is modified to allow video games sessions and (2) the software architecture designed to allow students and educators to participate in YoungRes project. Finally, different suggestions to include in future versions of the game are discussed.
Dose-Dependent Chlormadinone Acetate Can Suppress Premature LH Surge in Parallel with LH Value Reduction
Authors: Takeshige Yuya , Hashimoto Tomoko , Kyono Koichi 
Published: March 2020

Background: Progestin-primed ovarian stimulation (PPOS) protocol is reported as an alternative method of premature luteinizing hormone (LH) surge suppression. How much dosage of chlormadinone acetate (CMA), a synthetic progestin, is appropriate treatment for this phenomenon? Methods: Retrospective case control study was performed at private assisted reproductive technology (ART) clinic in Japan. Collected data was 231 cycles in patients who underwent either PPOS protocol using 12, 6, 4, or 2 mg of CMA, groups 6C, 3C, 2C, and 1C, respectively (total, 113 cycles), or gonadotropin-releasing hormone (GnRH) antagonist protocol, groups 6A, 3A, 2A, and 1A, respectively (total, 118 cycles). In the CMA group, CMA and human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) were administered simultaneously beginning on menstrual cycle day 3. Serum P, E2, and LH were determined on the day of human chorionic gonadotropin (hCG) administration. Occurrence of premature LH surge was compared between two groups. Pregnancy outcomes were also calculated. Results: Premature LH surge was completely suppressed in CMA groups 6C, 3C, and 2C. On the other hand, this phenomenon was detected in antagonist method groups (5.9%, 7/118). But spontaneous ovulation was not observed in any group, and clinical outcomes are equal to those of GnRH antagonist treatment. Conclusions: Controlled ovarian stimulation (COS) using CMA can be an appropriate alternative progestin for PPOS protocol. Since CMA is an oral medication, this method can be easy to conduct and cost-effective compared with the antagonist method. From our observation, we suggest 4 mg/day of CMA can control the egg retrieval cycle without LH surge occurrence as in other PPOS methods.
Human intestinal enteroids as a model ofClostridioides difficile-induced enteritis
Authors: Engevik Melinda A. , Danhof Heather A. , Chang-Graham Alexandra L. , Spinler Jennifer K. , Engevik Kristen A. , Herrmann Beatrice , Endres Bradley T. , Garey Kevin W. , Hyser Joseph M. , Britton Robert A. , Versalovic James 
Published: March 2020

Clostridioides difficile is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. C. difficile toxin activity is commonly studied in cancer-derived and immortalized cell lines. However, the biological relevance of these models is limited. Moreover, no model is available for examining C. difficile-induced enteritis, an understudied health problem. We hypothesized that human intestinal enteroids (HIEs) express toxin receptors and provide a new model to dissect C. difficile cytotoxicity in the small intestine. We generated biopsy-derived jejunal HIE and Vero cells, which stably express LifeAct-Ruby, a fluorescent label of F-actin, to monitor actin cytoskeleton rearrangement by live-cell microscopy. Imaging analysis revealed that toxins from pathogenic C. difficile strains elicited cell rounding in a strain-dependent manner, and HIEs were tenfold more sensitive to toxin A (TcdA) than toxin B (TcdB). By quantitative PCR, we paradoxically found that HIEs expressed greater quantities of toxin receptor mRNA and yet exhibited decreased sensitivity to toxins when compared with traditionally used cell lines. We reasoned that these differences may be explained by components, such as mucins, that are present in HIEs cultures, that are absent in immortalized cell lines. Addition of human-derived mucin 2 (MUC2) to Vero cells delayed cell rounding, indicating that mucus serves as a barrier to toxin-receptor binding. This work highlights that investigation of C. difficile infection in that HIEs can provide important insights into the intricate interactions between toxins and the human intestinal epithelium.NEW & NOTEWORTHY In this article, we developed a novel model of Clostridioides difficile-induced enteritis using jejunal-derived human intestinal enteroids (HIEs) transduced with fluorescently tagged F-actin. Using live-imaging, we identified that jejunal HIEs express high levels of TcdA and CDT receptors, are more sensitive to TcdA than TcdB, and secrete mucus, which delays toxin-epithelial interactions. This work also optimizes optically clear C. difficile-conditioned media suitable for live-cell imaging.
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab
Authors: Hutchins Beth , Starling Gary C. , McCoy Mark A. , Herzyk Danuta , Poulet Frederique M. , Dulos John , Liu Liming , Kang Soonmo Peter , Fayadat-Dilman Laurence , Hsieh Mark , Andrews Christine L. , Ayanoglu Gulesi , Cullen Constance , Malefyt Rene de Waal , Kastelein Robert A. , Saux Sabine Le , Lee Julie , Li Sophie , Malashock Dan , Sadekova Svetlana , Soder George , van Eenennaam Hans , Willingham Aarron , Yu Ying , Streuli Michel , Carven Gregory J. , van Elsas Andrea 
Published: March 2020

Abstract
The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection. Pembrolizumab binds to human and cynomolgus monkey PD-1 with picomolar affinity and blocks the binding of human and cynomolgus monkey PD-1 to PD-L1 and PD-L2 with comparable potency. Pembrolizumab binds both the C′D and FG loops of PD-1. Pembrolizumab overcomes human and cynomolgus monkey PD-L1–mediated immune suppression in T-cell cultures by enhancing IL2 production following staphylococcal enterotoxin B stimulation of healthy donor and cancer patient cells, and IFNγ production in human primary tumor histoculture. Ex vivo and in vitro studies with human and primate T cells show that pembrolizumab enhances antigen-specific T-cell IFNγ and IL2 production. Pembrolizumab does not mediate FcR or complement-driven effector function against PD-1–expressing cells. Pembrolizumab displays dose-dependent clearance and half-life in cynomolgus monkey pharmacokinetic and toxicokinetic studies typical for human IgG4 antibodies. In nonhuman primate toxicology studies, no findings of toxicologic significance were observed. The preclinical data for pembrolizumab are consistent with the clinical anticancer activity and safety that has been demonstrated in human clinical trials.
Cardiovascular Disease Burden in Rural Africa: Does HIV and Antiretroviral Treatment Play a Role?
Authors: Vos Alinda G. , Barth Roos E. , Klipstein‐Grobusch Kerstin , Tempelman Hugo A. , Devillé Walter L. J. , Dodd Caitlin , Coutinho Roel A. , Grobbee Diederick E. ,   Ndlovu Research Consortium*
Published: March 2020

Background

HIV
is associated with an increased risk of cardiovascular disease (
CVD
) in high‐income countries. Little is known about the
CVD
burden in sub‐Saharan Africa, where 70% of the world's
HIV
‐positive population lives. This study aims to provide insight into the burden of
CVD
risk in a rural setting in sub‐Saharan Africa considering
HIV
infection and antiretroviral therapy (
ART
).

Methods and Results

A cross‐sectional analysis was conducted of the baseline of the Ndlovu Cohort study including
HIV
‐negative and
HIV
‐positive participants in rural South Africa between 2014 and 2017. Information was collected on demographics, socioeconomic status, and
CVD
risk factors. Carotid intima‐media thickness measurement was performed. The influence of
HIV
and
ART
on the burden of
CVD
was determined by comparing
HIV
‐positive participants who were
ART
naive on first‐line or second‐line
ART
with
HIV
‐negative participants. In total, 1927 participants were included, of whom 887 (46%) were HIV positive and 54% women. The median age was 38 years. Overall, 690 participants (79%) were on
ART
, with 613 (89%) on first‐line and 77 (11%) on second‐line therapy. Participants with
HIV
had lower values for most of the
CVD
risk factors but higher C‐reactive protein levels than
HIV
‐negative participants.
ART
‐naive,
HIV
‐positive participants had similar carotid intima‐media thickness compared with
HIV
‐negative participants but carotid intima‐media thickness was increased for participants on
ART
aged 30 years and older compared with
HIV
‐negative participants.

Conclusions

HIV
‐positive participants presented with a favorable
CVD
risk profile compared with
HIV
‐negative participants. However, carotid intima‐media thickness was increased in
HIV
‐positive participants on
ART
, indicating a higher burden of subclinical
CVD
for the
HIV
‐positive population.
Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon‐Like Peptide‐1 Receptor Agonist and Sodium‐Glucose Cotransporter‐2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta‐Analysis
Authors: Hu Mengdie , Cai Xiaoling , Yang Wenjia , Zhang Simin , Nie Lin , Ji Linong 
Published: March 2020

Background

Glucagon‐like peptide‐1 receptor agonists (
GLP
‐1
RAs
) and sodium‐glucose cotransporter‐2 inhibitors (
SGLT
2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (
BP
)–lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with
GLP
‐1
RA
treatment and
SGLT
2i treatment on
BP
changes in patients with type 2 diabetes mellitus.

Methods and Results

Studies were identified by a search of
MEDLINE
,
EMBASE
, and the Cochrane Central Register until June 2019. Meta‐regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of
BP
. A total of 184 trials were included. Both
GLP
‐1
RA
and
SGLT
2i led to significant reductions in systolic
BP
(weighted mean difference, −2.856 and −4.331 mm Hg, respectively;
P
<0.001 for both) and diastolic
BP
(weighted mean difference, −0.898 and −2.279 mm Hg, respectively;
P
<0.001 for both). For both drug classes, hemoglobin A1c reduction was not independently associated with systolic
BP
reduction or diastolic
BP
reduction. In
GLP
‐1
RA
treatment, weight reduction was positively associated with systolic
BP
reduction and diastolic
BP
reduction (β=0.821 and β=0.287, respectively;
P
<0.001 for both). In
SGLT
2i treatment, weight loss was significantly associated with systolic
BP
reduction (β=0.820;
P
=0.001) but was not associated with diastolic
BP
reduction.

Conclusions

Treatment with
GLP
‐1
RA
and
SGLT
2i led to significant reductions in
BP
in patients with type 2 diabetes mellitus. Weight reduction was significantly and independently associated with
BP
reductions in
GLP
‐1
RA
treatment and
SGLT
2i treatment.
Between Polite Economy and the Gift: Nineteenth-Century British Travelers and Persian Excess
Authors: Sarlati Niloofar 
Published: March 2020

Abstract
Nineteenth-century travelogues by British travelers to Persia commonly include warnings against “excessive” Persian politeness, casting it as flattery or deceit. While this pejorative representation of Persian cordiality is a token of British Orientalism, it also highlights the incompatible measures for pleasantries in Persia and Britain. This essay traces the competing economies of social courtesy in these two contexts: a desire for utmost calculability in the British market entailed a new conception of politeness, one more moderate and commercial; by contrast, Persian politeness operated through gift-giving and “extravagant” greetings and complimenting. While the former hinges on a “modern” conception of commerce, the latter pivots around the bargain entailed in gift-giving. (Mis)recognition and (mis)translation of Persian “excess” as the hypocrisy of the ancien régime in the travelogues, however, signpost a teleological fabrication of the past which urges a global circulation of the British notion of polite character.
Post-THA gait training to improve pelvic obliquity and decrease leg length discrepancy in DDH patients: a retrospective study
Authors: Qi Xinyu , Jie Ke , Chen Jinlun , Cao Houran , Koch John A , Li Jie , Zeng Jianchun , Feng Wenjun , Zeng Yirong 
Published: March 2020

Objectives To investigate the value of a post-operative gait training program to improve pelvic obliquity (PO) and decrease leg length discrepancy (LLD) for patients with Crowe type I developmental dysplasia of the hip (DDH) undergoing unilateral total hip arthroplasty (THA). Methods The prospective group consisted of 35 patients who underwent one-stage unilateral THA. Pre- and post-training PO and LLD were measured for the radiological assessment and Harris Hip Score (HHS) was used for the functional assessment. Results The HHS improved from 55.54 ± 10.61 pre-operatively to 84.97 ± 7.63 after surgery. The mean post-training PO angle for grade 0, grade 1, and grade 2 were 2.66 ± 1.42, 2.94 ± 1.42, and 5.60 ± 1.90, respectively, compared with pre-training values of 1.42 ± 0.58, 4.17 ± 0.90, and 6.96 ± 0.46. The mean post-training LLD for grade 0, grade 1, and grade 2 were 0.83 ± 0.91, 0.56 ± 0.48, and 0.36 ± 0.30, respectively, compared with pre-training values of 0.70 ± 0.23, 1.25 ± 0.90, and 1.46 ± 1.60. Conclusion Gait training following unilateral THA can improve PO and decrease functional LLD in grade I DDH patients. This method may have moderate success for grade 0 DDH patients and provide limited benefit for grade II patients. Appropriate release of the soft tissues may be required for grade II DDH patients to obtain a better walking gait.
Correlations between microRNA-146a and immunoglobulin and inflammatory factors in Guillain–Barré syndrome
Authors: Huang Pan , Xu Min , He Xiao-ying 
Published: March 2020

Objective To study correlations between expression of microRNA-146a (miR-146a) and immunoglobulin and inflammatory cytokines in serum of patients with Guillain–Barré syndrome (GBS). Methods Eighty-four patients with GBS were selected as the experimental group and 50 healthy individuals as controls. Reverse transcription-PCR was used to detect expression of miR-146a in peripheral blood of all participants. Immunoturbidometric assay was used to detect immunoglobulins (Ig)G, IgA, and IgM in peripheral blood of all participants. The levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by ELISA in peripheral blood. The expression of miR-146a was compared between the two groups and Pearson correlation analysis was used to analyze correlations between miR-146a and immunoglobulin and inflammatory factors. Results Expression of miR-146a was higher in the GBS group than in controls. Expression of IL-6, CRP, TNF-α, and IgG was significantly higher in the GBS group than in controls. miR-146a was significantly and positively correlated with IL-6, CRP, TNF-α, and IgG but not with IgA and IgM. Conclusion The expression profile of miR-146a in patients with GBS differs from that in healthy individuals. Thus, miR-146a may participate in the pathogenesis of GBS by regulating immune and inflammatory responses.