bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase
Authors: Carrer Andrea , Tommasin Ludovica , Šileikytė Justina , Ciscato Francesco , Filadi Riccardo , Urbani Andrea , Forte Michael , Rasola Andrea , Szabò Ildikò , Carraro Michela , Bernardi Paolo
Published: August 2021

F-ATP synthase is a leading candidate as the mitochondrial permeability transition pore (PTP) but the mechanism(s) leading to channel formation remain undefined. Here, to shed light on the structural requirements for PTP formation, we test cells ablated for g, OSCP and b subunits, and ρ0 cells lacking subunits a and A6L. Δg cells (that also lack subunit e) do not show PTP channel opening in intact cells or patch-clamped mitoplasts unless atractylate is added. Δb and ΔOSCP cells display currents insensitive to cyclosporin A but inhibited by bongkrekate, suggesting that the adenine nucleotide translocator (ANT) can contribute to channel formation in the absence of an assembled F-ATP synthase. Mitoplasts from ρ0 mitochondria display PTP currents indistinguishable from their wild-type counterparts. In this work, we show that peripheral stalk subunits are essential to turn the F-ATP synthase into the PTP and that the ANT provides mitochondria with a distinct permeability pathway.
The structural dynamics of macropinosome formation and PI3-kinase-mediated sealing revealed by lattice light sheet microscopy
Authors: Quinn Shayne E. , Huang Lu , Kerkvliet Jason G. , Swanson Joel A. , Smith Steve , Hoppe Adam D. , Anderson Robert B. , Thiex Natalie W. , Scott Brandon L.
Published: August 2021

Macropinosomes are formed by shaping actin-rich plasma membrane ruffles into large intracellular organelles in a phosphatidylinositol 3-kinase (PI3K)-coordinated manner. Here, we utilize lattice lightsheet microscopy and image visualization methods to map the three-dimensional structure and dynamics of macropinosome formation relative to PI3K activity. We show that multiple ruffling morphologies produce macropinosomes and that the majority form through collisions of adjacent PI3K-rich ruffles. By combining multiple volumetric representations of the plasma membrane structure and PI3K products, we show that PI3K activity begins early throughout the entire ruffle volume and continues to increase until peak activity concentrates at the base of the ruffle after the macropinosome closes. Additionally, areas of the plasma membrane rich in ruffling had increased PI3K activity and produced many macropinosomes of various sizes. Pharmacologic inhibition of PI3K activity had little effect on the rate and morphology of membrane ruffling, demonstrating that early production of 3′-phosphoinositides within ruffles plays a minor role in regulating their morphology. However, 3′-phosphoinositides are critical for the fusogenic activity that seals ruffles into macropinosomes. Taken together, these data indicate that local PI3K activity is amplified in ruffles and serves as a priming mechanism for closure and sealing of ruffles into macropinosomes.
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

Dilated 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

Impairments 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

Genetically 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

Genome-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

We 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

A 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

Genetic 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

Eimeria 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

Acute 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

Drug 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

A 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

Every 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.
Optimal flickering light stimulation for entraining gamma waves in the human brain
Authors: Lee Kanghee , Park Yeseung , Suh Seung Wan , Kim Sang-Su , Kim Do-Won , Lee Jaeho , Park Jaehyeok , Yoo Seunghyup , Kim Ki Woong
Published: August 2021

Although light flickering at 40 Hz reduced Alzheimer’s disease (AD) pathologies in mice by entraining gamma waves, it failed to reduce cerebral amyloid burden in a study on six patients with AD or mild cognitive impairment. We investigated the optimal color, intensity, and frequency of the flickering light stimulus for entraining gamma waves in young adults. We compared the event-related synchronization (ERS) values of entrained gamma waves between four different light colors (white, red, green, and blue) in the first experiment and four different luminance intensities in the second experiment. In both experiments, we compared the ERS values of entrained gamma waves between 10 different flickering frequencies from 32 to 50 Hz. We also examined the severity of six adverse effects in both experiments. We compared the propagation of gamma waves in the visual cortex to other brain regions between different luminance intensities and flickering frequencies. We found that red light entrained gamma waves most effectively, followed by white light. Lights of higher luminance intensities (700 and 400 cd/m2) entrained stronger gamma waves than those of lower luminance intensities (100 and 10 cd/m2). Lights flickering at 34–38 Hz entrained stronger and more widely spread beyond the visual cortex than those flickering at 40–50 Hz. Light of 700 cd/m2 resulted in more moderate-to-severe adverse effects than those of other luminance intensities. In humans, 400 cd/m2 white light flickering at 34–38 Hz was most optimal for gamma entrainment.
Depression, combined visual and hearing impairment (dual sensory impairment): a hidden multi-morbidity among the elderly in Residential Care in India
Authors: Marmamula Srinivas , Kumbham Thirupathi Reddy , Modepalli Satya Brahmanandam , Barrenkala Navya Rekha , Yellapragada Ratnakar , Shidhaye Rahul
Published: August 2021

To report the prevalence of depression and its association with combined visual (VI) and hearing impairment (HI) in the elderly in residential care in India. Participants aged ≥ 60 years were recruited from 41 homes. Data on personal and sociodemographic information were obtained. Visual acuity was measured using the logMAR chart. Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Hearing Handicap Inventory for the Elderly Screening (HHIE) was administered to assess hearing status. Data of all 867 eligible elderly participants were analysed. The mean age of the participants was 74.2 years (standard deviation: 8.2 years) and included 537 (61.9%) women and 117 (13.5%) participants who had no education. The prevalence of depression was 60.0% (95% CI: 45.2–73.4) in the elderly with combined VI and HI compared to 20.9% (95% CI:14.4–28.8) among those with VI only and 37.8% (95% CI: 26.6–46.5) among those with HI only. On multiple logistic regression analyses, depression was approximately 5 times higher among the participants with DSI after adjusting for other covariates. Six out of ten elderly with combined HI and VI had depression highlighting the need for screening and referral when elderly present with combined vision and hearing loss.
Increased mortality and altered local immune response in secondary peritonitis after previous visceral operations in mice
Authors: Menz Jonas , Hundt Laura , Schulze Tobias , Schmoeckel Katrin , Menges Pia , Domanska Grazyna
Published: August 2021

Postoperative peritonitis is characterized by a more severe clinical course than other forms of secondary peritonitis. The pathophysiological mechanisms behind this phenomenon are incompletely understood. This study used an innovative model to investigate these mechanisms, combining the models of murine Colon Ascendens Stent Peritonitis (CASP) and Surgically induced Immune Dysfunction (SID). Moreover, the influence of the previously described anti-inflammatory reflex transmitted by the vagal nerve was characterized. SID alone, or 3 days before CASP were performed in female C57BL/6 N mice. Subdiaphragmatic vagotomy was performed six days before SID with following CASP. The immune status was assessed by FACS analysis and measurement of cytokines. Local intestinal inflammatory changes were characterized by immunohistochemistry. Mortality was increased in CASP animals previously subjected to SID. Subclinical bacteremia occurred after SID, and an immunosuppressive milieu occurred secondary to SID just before the induction of CASP. Previous SID modified the pattern of intestinal inflammation induced by CASP. Subdiaphragmatic vagotomy had no influence on sepsis mortality in our model of postoperative peritonitis. Our results indicate a surgery-induced inflammation of the small intestine and the peritoneal cavity with bacterial translocation, which led to immune dysfunction and consequently to a more severe peritonitis.
Disentangling predictive processing in the brain: a meta-analytic study in favour of a predictive network
Authors: Ficco Linda , Mancuso Lorenzo , Manuello Jordi , Teneggi Alessia , Liloia Donato , Duca Sergio , Costa Tommaso , Kovacs Gyula Zoltán , Cauda Franco
Published: August 2021

According to the predictive coding (PC) theory, the brain is constantly engaged in predicting its upcoming states and refining these predictions through error signals. Despite extensive research investigating the neural bases of this theory, to date no previous study has systematically attempted to define the neural mechanisms of predictive coding across studies and sensory channels, focussing on functional connectivity. In this study, we employ a coordinate-based meta-analytical approach to address this issue. We first use the Activation Likelihood Estimation (ALE) algorithm to detect spatial convergence across studies, related to prediction error and encoding. Overall, our ALE results suggest the ultimate role of the left inferior frontal gyrus and left insula in both processes. Moreover, we employ a meta-analytic connectivity method (Seed-Voxel Correlations Consensus). This technique reveals a large, bilateral predictive network, which resembles large-scale networks involved in task-driven attention and execution. In sum, we find that: (i) predictive processing seems to occur more in certain brain regions than others, when considering different sensory modalities at a time; (ii) there is no evidence, at the network level, for a distinction between error and prediction processing.
Contactless and spatially structured cooling by directing thermal radiation
Authors: Kerschbaumer Nicola M. , Niedermaier Stefan , Lohmüller Theobald , Feldmann Jochen
Published: August 2021

In recent years, radiative cooling has become a topic of considerable interest for applications in the context of thermal building management and energy saving. The idea to direct thermal radiation in a controlled way to achieve contactless sample cooling for laboratory applications, however, is scarcely explored. Here, we present an approach to obtain spatially structured radiative cooling. By using an elliptical mirror, we are able to enhance the view factor of radiative heat transfer between a room temperature substrate and a cold temperature landscape by a factor of 92. A temperature pattern and confined thermal gradients with a slope of ~ 0.2 °C/mm are created. The experimental applicability of this spatially structured cooling approach is demonstrated by contactless supercooling of hexadecane in a home-built microfluidic sample. This novel concept for structured cooling yields numerous applications in science and engineering as it provides a means of controlled temperature manipulation with minimal physical disturbance.
Entanglement protection of classically driven qubits in a lossy cavity
Authors: Nourmandipour Alireza , Vafafard Azar , Mortezapour Ali , Franzosi Roberto
Published: August 2021

Quantum technologies able to manipulating single quantum systems, are presently developing. Among the dowries of the quantum realm, entanglement is one of the basic resources for the novel quantum revolution. Within this context, one is faced with the problem of protecting the entanglement when a system state is manipulated. In this paper, we investigate the effect of the classical driving field on the generation entanglement between two qubits interacting with a bosonic environment. We discuss the effect of the classical field on the generation of entanglement between two (different) qubits and the conditions under which it has a constructive role in protecting the initial-state entanglement from decay induced by its environment. In particular, in the case of similar qubits, we locate a stationary sub-space of the system Hilbert space, characterized by states non depending on the environment properties as well as on the classical driving-field. Thus, we are able to determine the conditions to achieve maximally entangled stationary states after a transient interaction with the environment. We show that, overall, the classical driving field has a constructive role for the entanglement protection in the strong coupling regime. Also, we illustrate that a factorable initial-state can be driven in an entangled state and, even, in an entangled steady-state after the interaction with the environment.
Synthesis and characterization of manganese ferrite from low grade manganese ore through solid state reaction route
Authors: Ahmad Salar , Ali Sajjad , Ullah Ikram , Zobaer M. S. , Albakri Ashwag , Muhammad Taseer
Published: August 2021

Manganese ferrite spinel has been synthesized by using low grade manganese ore and ferric oxide as sources of manganese oxide and iron oxide through solid state reaction route by taking manganese and iron mole ratio of 1:2 respectively. The impact of sintering temperature on phase composition and particle size is investigated. Similarly, the impact of frequency on dielectric constant, dielectric loss, AC (alternating current) conductivity and tangent losses is also investigated. The results shows the presence of spinel structure manganese ferrite (MnFe2O4) as the major phase for the sample sintered at 1200 °C. It has been established that the crystallite size increase with rise in sintering temperature. The surface morphology of the sample sintered at 1200 °C show pyramidal and triangular shape grains. The dielectric constant (εʹ) and dielectric losses (εʹʹ) were observed to decrease with increasing the sintering temperature and frequency. Furthermore, the AC (alternating current) conductivity was found to rise with rise in applied frequency. On the other hand, the tangent losses falls considerably with rise in applied frequency.
Prediction of radiation pneumonitis after definitive radiotherapy for locally advanced non-small cell lung cancer using multi-region radiomics analysis
Authors: Kawahara Daisuke , Imano Nobuki , Nishioka Riku , Ogawa Kouta , Kimura Tomoki , Nakashima Taku , Iwamoto Hiroshi , Fujitaka Kazunori , Hattori Noboru , Nagata Yasushi
Published: August 2021

To predict grade ≥ 2 radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (NSCLC) using multi-region radiomics analysis. Data from 77 patients with NSCLC who underwent definitive radiotherapy between 2008 and 2018 were analyzed. Radiomic feature extraction from the whole lung (whole-lung radiomics analysis) and imaging- and dosimetric-based segmentation (multi-region radiomics analysis) were performed. Patients with RP grade ≥ 2 or < 2 were classified. Predictors were selected with least absolute shrinkage and selection operator logistic regression and the model was built with neural network classifiers. A total of 49,383 radiomics features per patient image were extracted from the radiotherapy planning computed tomography. We identified 4 features and 13 radiomics features in the whole-lung and multi-region radiomics analysis for classification, respectively. The accuracy and area under the curve (AUC) without the synthetic minority over-sampling technique (SMOTE) were 60.8%, and 0.62 for whole-lung and 80.1%, and 0.84 for multi-region radiomics analysis. These were improved 1.7% for whole-lung and 2.1% for multi-region radiomics analysis with the SMOTE. The developed multi-region radiomics analysis can help predict grade ≥ 2 RP. The radiomics features in the median- and high-dose regions, and the local intensity roughness and variation were important factors in predicting grade ≥ 2 RP.
Lumbar spine abnormalities in patients with obstructive sleep apnoea
Authors: Tarnoki Adam Domonkos , Tarnoki David Laszlo , Oláh Csaba , Szily Marcell , Kovacs Daniel T. , Dienes András , Piroska Marton , Forgo Bianka , Pinheiro Marina , Ferreira Paulo , Kostyál László , Meszaros Martina , Pako Judit , Kunos Laszlo , Bikov Andras
Published: August 2021

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland‐Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0–3.5/ vs. 0/0–1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.
Dependency of hydration and growth conditions on the mechanical properties of oral biofilms
Authors: Pattem J. , Davrandi M. , Aguayo S. , Slak B. , Maev R. , Allan E. , Spratt D. , Bozec L.
Published: August 2021

Within the oral cavity, dental biofilms experience dynamic environments, in part due to changes in dietary content, frequency of intake and health conditions. This can impact bacterial diversity and morpho-mechanical properties. While phenotypic properties of oral biofilms are closely related to their composition, these can readily change according to dynamic variations in the growth environment and nutrient availability. Understanding the interlink between phenotypic properties, variable growth conditions, and community characterization is an essential requirement to develop structure–property relationships in oral-biofilms. In this study, the impact of two distinct growth media types with increasing richness on the properties of oral biofilms was assessed through a new combination of in-vitro time-lapse biophysical methods with microbiological assays. Oral biofilms grown in the enriched media composition presented a decrease in their pH, an increase in soluble EPS production, and a severe reduction in bacterial diversity. Additionally, enriched media conditions presented an increase in biofilm volumetric changes (upon hydration) as well as a reduction in elastic modulus upon indentation. With hydration time considered a major factor contributing to changes in biofilm mechanical properties, we have shown that it is less associated than media richness. Future investigations can now use this time-lapse approach, with a clearer focus on the extracellular matrix of oral biofilms dictating their morpho-mechanical properties.
Relationship between total cholesterol level and tuberculosis risk in a nationwide longitudinal cohort
Authors: Jo Yong Suk , Han Kyungdo , Kim Dahye , Yoo Jung Eun , Kim Yuji , Yang Bumhee , Choi Hayoung , Sohn Jang Won , Shin Dong Wook , Lee Hyun
Published: August 2021

The association between the total cholesterol level and tuberculosis (TB) risk has been controversial. Our study aimed to evaluate whether total cholesterol level can predict the risk of TB. Data from 5,000,566 subjects who participated in a health screening exam in 2009 were investigated using the Korean National Health Insurance Service database (2009–2018). Cox hazard regression analyses were used to evaluate TB risk according to the quartile of total cholesterol levels. During an average of 8.2 years of follow-up, 32,078 cases of TB occurred. There was a significant inverse association between the total cholesterol level and TB risk. Compared with subjects in the highest quartile, those in the lowest quartile had a 1.35-fold increased TB risk (95% confidence interval = 1.31–1.39). The association between total cholesterol level and TB risk was more apparent in young subjects (age < 65 years), those without diabetes mellitus (DM), and those without obesity (p for interaction < 0.001 for age group, DM, and body mass index). Although there was a significant inverse association between total cholesterol level and TB risk in subjects who did not use a statin, no significant association was observed between the total cholesterol level and TB risk in subjects who used a statin. A low total cholesterol level was significantly associated with an increased risk of TB, even after adjusting for confounders, especially in patients younger than 65 years, those without DM or obesity, and those who did not use a statin.
Developing a novel parameter-free optimization framework for flood routing
Authors: Bozorg-Haddad Omid , Sarzaeim Parisa , Loáiciga Hugo A.
Published: August 2021

The Muskingum model is a popular hydrologic flood routing technique; however, the accurate estimation of model parameters challenges the effective, precise, and rapid-response operation of flood routing. Evolutionary and metaheuristic optimization algorithms (EMOAs) are well suited for parameter estimation task associated with a wide range of complex models including the nonlinear Muskingum model. However, more proficient frameworks requiring less computational effort are substantially advantageous. Among the EMOAs teaching–learning-based optimization (TLBO) is a relatively new, parameter-free, and efficient metaheuristic optimization algorithm, inspired by the teacher-student interactions in a classroom to upgrade the overall knowledge of a topic through a teaching–learning procedure. The novelty of this study originates from (1) coupling TLBO and the nonlinear Muskingum routing model to estimate the Muskingum parameters by outflow predictability enhancement, and (2) evaluating a parameter-free algorithm’s functionality and accuracy involving complex Muskingum model’s parameter determination. TLBO, unlike previous EMOAs linked to the Muskingum model, is free of algorithmic parameters which makes it ideal for prediction without optimizing EMOAs parameters. The hypothesis herein entertained is that TLBO is effective in estimating the nonlinear Muskingum parameters efficiently and accurately. This hypothesis is evaluated with two popular benchmark examples, the Wilson and Wye River case studies. The results show the excellent performance of the “TLBO-Muskingum” for estimating accurately the Muskingum parameters based on the Nash–Sutcliffe Efficiency (NSE) to evaluate the TLBO’s predictive skill using benchmark problems. The NSE index is calculated 0.99 and 0.94 for the Wilson and Wye River benchmarks, respectively.
Horses with sustained attention follow the pointing of a human who knows where food is hidden
Authors: Ringhofer Monamie , Trösch Miléna , Lansade Léa , Yamamoto Shinya
Published: August 2021

When interacting with humans, domesticated species may respond to communicative gestures, such as pointing. However, it is currently unknown, except for in dogs, if species comprehend the communicative nature of such cues. Here, we investigated whether horses could follow the pointing of a human informant by evaluating the credibility of the information about the food-hiding place provided by the pointing of two informants. Using an object-choice task, we manipulated the attentional state of the two informants during food-hiding events and differentiated their knowledge about the location of the hidden food. Furthermore, we investigated the horses’ visual attention levels towards human behaviour to evaluate the relationship between their motivation and their performance of the task. The result showed that horses that sustained high attention levels could evaluate the credibility of the information and followed the pointing of an informant who knew where food was hidden (Z =  − 2.281, P = 0.002, n = 36). This suggests that horses are highly sensitive to the attentional state and pointing gestures of humans, and that they perceive pointing as a communicative cue. This study also indicates that the motivation for the task should be investigated to determine the socio-cognitive abilities of animals.