bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse effects of hypertension, supine hypertension, and perivascular space on cognition and motor function in PD
Authors: Shin Na-Young , Park Yae Won , Yoo Sang-Won , Yoo Ji-Yeon , Choi Yangsean , Jang Jinhee , Ahn Kook-Jin , Kim Bum-soo , Kim Joong-Seok 
Published: August 2021

AbstractDilated perivascular space (dPVS) has recently been reported as a biomarker for cognitive impairment in Parkinson’s disease (PD). However, comprehensive interrelationships between various clinical risk factors, dPVS, white-matter hyperintensities (WMH), cognition, and motor function in PD have not been studied yet. The purpose of this study was to test whether dPVS might mediate the effect of clinical risk factors on WMH, cognition, and motor symptoms in PD patients. A total of 154 PD patients were assessed for vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), autonomic dysfunction (orthostatic hypotension and supine hypertension [SH]), APOE ε4 genotype, rapid eye movement sleep-behavior disorder, motor symptoms, and cognition status. The degree of dPVS was evaluated in the basal ganglia (BG) and white matter using a 5-point visual scale. Periventricular, deep, and total WMH severity was also assessed. Path analysis was performed to evaluate the associations of these clinical factors and imaging markers with cognitive status and motor symptoms. Hypertension and SH were significantly associated with more severe BGdPVS, which was further associated with higher total WMH, consequently leading to lower cognitive status. More severe BGdPVS was also associated with worse motor symptoms, but without mediation of total WMH. Similar associations were seen when using periventricular WMH as a variable, but not when using deep WMH as a variable. In conclusion, BGdPVS mediates the effect of hypertension and SH on cognitive impairment via total and periventricular WMH, while being directly associated with more severe motor symptoms.
Dynamic face processing impairments are associated with cognitive and positive psychotic symptoms across psychiatric disorders
Authors: Darke Hayley , Sundram Suresh , Cropper Simon J. , Carter Olivia 
Published: August 2021

AbstractImpairments in social cognition—including recognition of facial expressions—are increasingly recognised as a core deficit in schizophrenia. It remains unclear whether other aspects of face processing (such as identity recognition) are also impaired, and whether such deficits can be attributed to more general cognitive difficulties. Moreover, while the majority of past studies have used picture-based tasks to assess face recognition, literature suggests that video-based tasks elicit different neural activations and have greater ecological validity. This study aimed to characterise face processing using video-based stimuli in psychiatric inpatients with and without psychosis. Symptom correlates of face processing impairments were also examined. Eighty-six psychiatric inpatients and twenty healthy controls completed a series of tasks using video-based stimuli. These included two emotion recognition tasks, two non-emotional facial identity recognition tasks, and a non-face control task. Symptoms were assessed using the Positive and Negative Syndrome Scale. Schizophrenia and bipolar disorder groups were significantly impaired on the emotion-processing tasks and the non-face task compared to healthy controls and patients without psychosis. Patients with other forms of psychosis performed intermediately. Groups did not differ in non-emotional face processing. Positive symptoms of psychosis correlated directly with both emotion-processing performance and non-face discrimination across patients. We found that identity processing performance was inversely associated with cognition-related symptoms only. Findings suggest that deficits in emotion-processing reflect symptom pathology independent of diagnosis. Emotion-processing deficits in schizophrenia may be better accounted for by task-relevant factors—such as attention—that are not specific to emotion processing.
Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection
Authors: Sahu Tejram , Gehrke Ella J. , Flores-Garcia Yevel , Mlambo Godfree , Romano Julia D. , Coppens Isabelle 
Published: August 2021

AbstractGenetically attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Here, we demonstrate that a liver stage-specific autophagy mutant ofPlasmodium berghei(ATG8 overexpressor), when used as a live vaccine under a CVac regimen, provides superior long-lasting protection, in both inbred and outbred mice, as compared to WT-CVac. Uniquely, the protection elicited by this mutant is predominantly dependent on a CD8+T-cell response through an IFN-γ-independent mechanism and is associated with a stable population of antigen-experienced CD8+T cells. Jointly, our findings support the exploitation of liver-stage mutants as vaccines under a CVac protocol. This vaccination strategy is also a powerful model to study the mechanisms of protective immunity and discover new protective antigens.
Rare variant contribution to human disease in 281,104 UK Biobank exomes
Authors: Wang Quanli , Dhindsa Ryan S. , Carss Keren , Harper Andrew R. , Nag Abhishek , Tachmazidou Ioanna , Vitsios Dimitrios , Deevi Sri V. V. , Mackay Alex , Muthas Daniel , Hühn Michael , Monkley Susan , Olsson Henric ,   AstraZeneca Genomics Initiative, Angermann Bastian R. , Artzi Ronen , Barrett Carl , Belvisi Maria , Bohlooly-Y Mohammad , Burren Oliver , Buvall Lisa , Challis Benjamin , Cameron-Christie Sophia , Cohen Suzanne , Davis Andrew , Danielson Regina F. , Dougherty Brian , Georgi Benjamin , Ghazoui Zara , Hansen Pernille B. L. , Hu Fengyuan , Jeznach Magda , Jiang Xiao , Kumar Chanchal , Lai Zhongwu , Lassi Glenda , Lewis Samuel H. , Linghu Bolan , Lythgow Kieren , Maccallum Peter , Martins Carla , Matakidou Athena , Michaëlsson Erik , Moosmang Sven , O’Dell Sean , Ohne Yoichiro , Okae Joel , O’Neill Amanda , Paul Dirk S. , Reznichenko Anna , Snowden Michael A , Walentinsson Anna , Zeron Jorge , Pangalos Menelas N. , Wasilewski Sebastian , Smith Katherine R. , March Ruth , Platt Adam , Haefliger Carolina , Petrovski Slavé 
Published: August 2021

AbstractGenome-wide association studies have uncovered thousands of common variants associated with human disease, but the contribution of rare variants to common disease remains relatively unexplored. The UK Biobank contains detailed phenotypic data linked to medical records for approximately 500,000 participants, offering an unprecedented opportunity to evaluate the effect of rare variation on a broad collection of traits1,2. Here we study the relationships between rare protein-coding variants and 17,361 binary and 1,419 quantitative phenotypes using exome sequencing data from 269,171 UK Biobank participants of European ancestry. Gene-based collapsing analyses revealed 1,703 statistically significant gene–phenotype associations for binary traits, with a median odds ratio of 12.4. Furthermore, 83% of these associations were undetectable via single-variant association tests, emphasizing the power of gene-based collapsing analysis in the setting of high allelic heterogeneity. Gene–phenotype associations were also significantly enriched for loss-of-function-mediated traits and approved drug targets. Finally, we performed ancestry-specific and pan-ancestry collapsing analyses using exome sequencing data from 11,933 UK Biobank participants of African, East Asian or South Asian ancestry. Our results highlight a significant contribution of rare variants to common disease. Summary statistics are publicly available through an interactive portal (http://azphewas.com/).
Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
Authors: Elahi Fanny M. , Harvey Danielle , Altendahl Marie , Brathaban Nivetha , Fernandes Nicole , Casaletto Kaitlin B. , Staffaroni Adam M. , Maillard Pauline , Hinman Jason D. , Miller Bruce L. , DeCarli Charles , Kramer Joel H. , Goetzl Edward J. 
Published: August 2021

AbstractWe test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regulatory proteins were quantified in extracts of plasma endothelial-derived exosomes (EDE) of 11 subjects (age 70–82) with and 15 without evidence of WMH on MRI. Group differences and associations with plasma markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling. EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of some complement components demonstrated significant associations with cognitive slowing and elevated systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Plasma inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several complement components. These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter disease, age-associated cognitive changes, and brain degeneration in functionally normal older individuals. Future endothelial biomarker development may permit recognition of early or preclinical stages of vascular contributions to cognitive impairment and dementia.
An experimental method for estimating the tearing energy in rubber-like materials using the true stored energy
Authors: Elmukashfi Elsiddig 
Published: August 2021

AbstractA method for determining the critical tearing energy in rubber-like materials is proposed. In this method, the energy required for crack propagation in a rubber-like material is determined by the change of recovered elastic energy which is obtained by deducting the dissipated energy due to different inelastic processes from the total strain energy applied to the system. Hence, the classical method proposed by Rivlin and Thomas using the pure shear tear test is modified using the actual stored elastic energy. The total dissipated energy is evaluated using cyclic pure shear and simple shear dynamic experiments at the critical stretch level. To accurately estimate the total dissipated energy, the unloading rate is determined from the time the crack takes to grow an increment. A carbon-black-filled natural rubber is examined in this study. In cyclic pure shear experiment, the specimens were cyclically loaded under quasi-static loading rate of $$0.01~{\rm {s}}^{-1}$$

0.01

s

-
1

and for different unloading rates, i.e. $$0.01$$

0.01

, $$0.1$$

0.1

and $$1.0~{\rm {s}}^{-1}$$

1.0

s

-
1

. The simple shear dynamic experiment is used to obtain the total dissipated energy at higher frequencies, i.e. $$0.5$$

0.5

-$$18~{\rm {Hz}}$$

18

Hz

which corresponds to unloading rates $$0.46$$

0.46

-$$16.41~{\rm {s}}^{-1}$$

16.41

s

-
1

, using the similarities between simple and pure shear deformation. The relationship between dissipated energy and unloading stretch rate is found to follow a power-law such that cyclic pure shear and simple shear dynamic experiments yield similar result. At lower unloading rates (i.e. $${\dot{\lambda }}_{\rm {U}} < 1.0~{\rm {s}}^{-1}$$

λ
˙

U

<
1.0

s

-
1

), Mullins effect dominates and the viscous dissipation is minor, whereas at higher unloading rates, viscous dissipation becomes significant. At the crack propagation unloading rate $$125.2~{\rm {s}}^{-1}$$

125.2

s

-
1

, the viscous dissipation is significant such that the amount of dissipated energy increases approximately by $$125.4\%$$

125.4
%

from the lowest unloading rate. The critical tearing energy is obtained to be $$7.04~{\rm {kJ}}/{\rm {m}}^{2}$$

7.04

kJ
/

m

2

using classical method and $$5.12~{\rm {kJ}}/{\rm {m}}^{2}$$

5.12

kJ
/

m

2

using the proposed method. Hence, the classical method overestimates the critical tearing energy by approximately $$37.5\%$$

37.5
%

.
In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations
Authors: Ajibola O. , Diop M. F. , Ghansah A. , Amenga-Etego L. , Golassa L. , Apinjoh T. , Randrianarivelojosia M. , Maiga-Ascofare O. , Yavo W. , Bouyou-Akotet M. , Oyebola K. M. , Andagalu B. , D’Alessandro U. , Ishengoma D. , Djimde A. A. , Kamau E. , Amambua-Ngwa A. 
Published: August 2021

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.
The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis
Authors: Balta Igori , Marcu Adela , Linton Mark , Kelly Carmel , Stef Lavinia , Pet Ioan , Ward Patrick , Pircalabioru Gratiela Gradisteanu , Chifiriuc Carmen , Gundogdu Ozan , Callaway Todd , Corcionivoschi Nicolae 
Published: August 2021

AbstractEimeria tenella and Eimeria bovis are complex parasites responsible for the condition of coccidiosis, that invade the animal gastrointestinal intestinal mucosa causing severe diarrhoea, loss of appetite or abortions, with devastating impacts on the farming industry. The negative impacts of these parasitic infections are enhanced by their role in promoting the colonisation of the gut by common foodborne pathogens. The aim of this study was to test the anti-Eimeria efficacy of maltodextrin, sodium chloride, citric acid, sodium citrate, silica, malic acid, citrus extract, and olive extract individually, in vitro and in combination, in vivo. Firstly, in vitro infection models demonstrated that antimicrobials reduced (p < 0.05), both singly and in combination (AG), the ability of E. tenella and E. bovis to infect MDBK and CLEC-213 epithelial cells, and the virulence reduction was similar to that of the anti-coccidial drug Robenidine. Secondly, using an in vivo broiler infection model, we demonstrated that AG reduced (p = 0.001) E. tenella levels in the caeca and excreted faeces, reduced inflammatory oxidative stress, improved the immune response through reduced ROS, increased Mn-SOD and SCFA levels. Levels of IgA and IgM were significantly increased in caecal tissues of broilers that received 0.5% AG and were associated with improved (p < 0.0001) tissue lesion scores. A prophylactic approach increased the anti-parasitic effect in vivo, and results indicated that administration from day 0, 5 and 10 post-hatch reduced tissue lesion scores (p < 0.0001) and parasite excretion levels (p = 0.002). Conclusively, our in vitro and in vivo results demonstrate that the natural antimicrobial mixture (AG) reduced parasitic infections through mechanisms that reduced pathogen virulence and attenuated host inflammatory events.
Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
Authors: Jain Swati , Plenter Robert , Nydam Trevor , Gill Ronald G. , Jani Alkesh 
Published: August 2021

AbstractAcute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by kidney transplant (CI + Txp) would be protected from AKI. C57Bl/6J wild type or TLR4KO kidneys were subjected to CI + Txp into wild type recipients. Tubular cell apoptosis, tubular injury and cast formation were significantly improved in recipients of TLR4KO kidneys. TLR4KO kidneys also demonstrated significantly decreased expression of the effector caspase 8. Brush border injury scores and serum creatinine were not different in recipients of TLR4KO versus wild type kidneys. Phosphorylated RIP3 and MLKL through which TLR4 signals programmed necrosis were expressed in both recipient groups. In addition, TNF-α and TNFR1 expression were significantly increased in recipient serum and TLR4KO kidneys respectively after CI + Txp, suggesting continued activation of programmed necrosis despite TLR4 deletion. Our results suggest that TLR4 deletion decreases apoptosis via inhibition of the death receptor pathway and decreases tubular injury and cast formation.
Exploring the selectivity of guanine scaffold in anticancer drug development by computational repurposing approach
Authors: Sherin D. R. , Manojkumar T. K. 
Published: August 2021

AbstractDrug repurposing is one of the modern techniques used in the drug discovery to find out the new targets for existing drugs. Insilico methods have a major role in this approach. We used 60 FDA approved antiviral drugs reported in the last 50 years to screen against different cancer cell receptors. The thirteen compounds selected after virtual screening are analyzed for their druggability based on ADMET parameters and found the selectivity of guanine derivatives—didanosine, entecavir, acyclovir, valganciclovir, penciclovir, ganciclovir and valacyclovir as suitable candidates. The pharmacophore model, AARR, suggested based on the common feature alignment, shows that the two fused rings as in guanine and two acceptors-one from keto-oxygen (A5) and other from the substituent attached to nitrogen of imidazole ring (A4) give the druggability to the guanine derivatives. The NBO analysis on N9 is indicative of charge distribution from the ring to substituents, which results in delocalization of negative character in most of the ligands. The molecular dynamics simulations also pointed out the importance of guanine scaffold, which stabilizes the ligands inside the binding pocket of the receptor. All these results are indicative of the selectivity of guanine scaffold in anticancer drug development, especially as PARP1 inhibitors in breast, ovarian and prostate cancer. As these seven molecules are already approved by FDA, we can safely go for further preclinical trials.
Agency rescues competition for credit assignment among predictive cues from adverse learning conditions
Authors: Kang Mihwa , Reverte Ingrid , Volz Stephen , Kaufman Keith , Fevola Salvatore , Matarazzo Anna , Alhazmi Fahd H. , Marquez Inmaculada , Iordanova Mihaela D. , Esber Guillem R. 
Published: August 2021

AbstractA fundamental assumption of learning theories is that the credit assigned to predictive cues is not simply determined by their probability of reinforcement, but by their ability to compete with other cues present during learning. This assumption has guided behavioral and neural science research for decades, and tremendous empirical and theoretical advances have been made identifying the mechanisms of cue competition. However, when learning conditions are not optimal (e.g., when training is massed), cue competition is attenuated. This failure of the learning system exposes the individual’s vulnerability to form spurious associations in the real world. Here, we uncover that cue competition in rats can be rescued when conditions are suboptimal provided that the individual has agency over the learning experience. Our findings reveal a new effect of agency over learning on credit assignment among predictive cues, and open new avenues of investigation into the underlying mechanisms.
Artificial intelligence-assisted fast screening cervical high grade squamous intraepithelial lesion and squamous cell carcinoma diagnosis and treatment planning
Authors: Wang Ching-Wei , Liou Yi-An , Lin Yi-Jia , Chang Cheng-Chang , Chu Pei-Hsuan , Lee Yu-Ching , Wang Chih-Hung , Chao Tai-Kuang 
Published: August 2021

AbstractEvery year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors’ best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher’s Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.