bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine profile of human septic shock serum inducing cardiomyocyte contractile dysfunction
Authors: Joulin O , Petillot P , Labalette M , Lancel S , Neviere R
Published: August 2021

This study was designed to measure nitrite/nitrate and cytokine levels of serum obtained from septic shock patients and to describe potential depressant effects of human septic serum on rat cardiomyocytes. Serum was prepared from 10 non-septic patients and 10 patients with documented septic shock. Adult rat ventricular myocytes were exposed to 20 % serum in the medium. Cardiomyocyte contractility was assessed by measuring shortening fraction and shortening velocity. Serum levels of nitrite/nitrate, a marker of nitric oxide final metabolites, and cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL) 1beta, 6, 10, 8 and 12p70) were measured. Compared with serum from non-septic patients, serum of septic shock patients induced rapid reduction of the extent and velocity of shortening in isolated cardiomyocytes. Nitrite/nitrate, TNF-alpha, IL-1beta and IL-12p70 concentrations of tested serum for cardiomyocyte studies were not increased in septic serum compared with controls. In contrast, septic serum that induced a depression of in vitro contractility, had increased levels of IL-6, IL-8 and IL-10. We can conclude that the depression of in vitro contractility induced by septic serum is not directly dependent on elevated levels of nitric oxide metabolites, TNF-alpha or IL-1beta. Our results support the view that other cytokines, including IL-6, IL-8 and IL-10, are potent circulating mediators of myocardial depression in cardiomyocytes.
Influence of load changes on tricuspid inflow
Authors: Mandysová E , Niederle P
Published: August 2021

In healthy subjects, the right ventricular filling pattern estimated from tricuspid valve inflow is highly load-dependent. This can be clearly demonstrated by changes of Doppler inflow tracings recorded during tidal breathing at rest. The aim of our study was to test the magnitude of tricuspid inflow changes during more pronounced load changes induced by specific maneuvers. In 31 apparently healthy subjects (16 men and 15 women, mean age 36+/-16 years) we recorded pulsed Doppler tracings of tricuspid inflow during forced inspiration, elevation of lower extremities (increased preload) and handgrip exercise (increased afterload). The obtained values were compared with end-expiratory phase of tidal breathing at rest. We found a significantly larger increase in the early and late filling velocities (for E and A p<0.001) under the conditions of increasing preload (elevation of legs) and less pronounced, but still significant changes with isometric exercise (for E p<0.001 and for A p<0.01). We conclude that the right ventricular filling pattern in healthy humans is highly load-sensitive and for this reason the effect of any intervention (e.g. pharmacological) must be studied under strict and well-defined resting conditions.
Single-Cell RNA-Sequencing Portraying Functional Diversity and Clinical Implications of IFI6 in Ovarian Cancer
Authors: Zhao Hongyu , Li Zhefeng , Gao Yan , Li Jie , Zhao Xiaoting , Yue Wentao
Published: August 2021

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies. Most patients die of metastasis due to a lack of other treatments aimed at improving the prognosis of OC patients. In the present study, we use multiple methods to identify prognostic S1 as the dominant subtype in OC, possessing the most ligand–receptor pairs with other cell types. Based on markers of S1, the consensus clustering algorithm is used to explore the clinical treatment subtype in OC. As a result, we identify two clusters associated with distinct survival and drug response. Notably, IFI6 contributes to the cluster classification and seems to be a vital gene in OC carcinogenesis. Functional enrichment analysis demonstrates that its functions involve G2M and cisplatin resistance, and downregulation of IFI6 suppresses proliferation capabilities and significantly potentiates cisplatin-induced apoptosis of OC cells in vitro. To explore possible mechanisms of IFI6 influencing OC proliferation and cisplatin resistance, GSEA is conducted and shows that IFI6 is positively correlated with the NF-κB pathway, which is validated by RT-qPCR. Significantly, we develop a prognostic model including IFI6, RiskScore, which is an independent prognostic factor and presents encouraging prognostic values. Our findings provide novel insights into elucidating the biology of OC based on single-cell RNA-sequencing. Moreover, this approach is potentially helpful for personalized anti-cancer strategies and predicting outcomes in the setting of OC.
SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis With the Assistance of Nucleocapsid Protein N in Cells
Authors: Ren Yujie , Wang An , Fang Yuan , Shu Ting , Wu Di , Wang Chong , Huang Muhan , Min Juan , Jin Liang , Zhou Wei , Qiu Yang , Zhou Xi
Published: August 2021

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don’t know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.
Methylprednisolone Plasma Concentrations During Cardiac Surgery With Cardiopulmonary Bypass in Pediatric Patients
Authors: van Saet Annewil , Zeilmaker-Roest Gerdien A. , Veen Kevin M. , de Wildt Saskia N. , Sorgel Fritz , Stolker Robert J. , Bogers Ad J. J. C. , Tibboel Dick
Published: August 2021

Introduction:To our knowledge, methylprednisolone pharmacokinetics and plasma concentrations have not been comprehensively investigated in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. It is unknown whether there is a significant influence of cardiopulmonary bypass on the plasma concentrations of methylprednisolone and whether this may be an explanation for the limited reported efficacy of steroid administration in cardiac surgery with cardiopulmonary bypass.

Methods:The study was registered in the Dutch Trial Register (NTR3579;https://www.trialregister.nl/trial/3428). Methylprednisolone 30 mg/kg was administered as an intravenous bolus after induction of anesthesia. Methylprednisolone concentration was measured with liquid chromatography tandem mass spectrometry and analyzed using linear mixed-effects modeling.

Results:Thirty-nine patients were included in the study, of which three were excluded. There was an acute decrease in observed methylprednisolone plasma concentration on initiation of cardiopulmonary bypass (median = 26.8%, range = 13.9–48.14%,p< 0.001). We found a lower intercept (p= 0.02), as well as a less steep slope of the model predicted methylprednisolone concentration vs. time curve for neonates (p= 0.048). A lower intercept (p= 0.01) and a less steep slope (p = 0.0024) if the volume of cell saver blood processed was larger than 91 ml/kg were also found.

Discussion:We report similar methylprednisolone plasma concentrations as earlier studies performed in children undergoing cardiopulmonary bypass, and we confirmed the large interindividual variability in achieved methylprednisolone plasma concentrations with weight-based methylprednisolone administration. A larger volume of distribution and a lower clearance of methylprednisolone for neonates were suggested. The half-life of methylprednisolone in our study was calculated to be longer than 6 h for neonates, 4.7 h for infants, 3.6 h for preschool children and 4.7 h for school children. The possible influence of treatment of pulmonary hypertension with sildenafil and temperature needs to be investigated further.
Vacteens.org: A Mobile Web app to Improve HPV Vaccine Uptake
Authors: Woodall W. Gill , Zimet Gregory , Kong Alberta , Buller David , Reither Jeannyfer , Chilton Lance , Myers Valerie , Starling Randall
Published: August 2021

U.S. HPV vaccine uptake remains below the Healthy People 2030 goal of 80% series completion. Parental concerns and misinformation about the efficacy and safety of the Human Papillomavirus (HPV) vaccine remain, and may be addressed by digital interventions tailored to their concerns. Reported here are results from a small scale randomized trial testing a mobile web app for parents and their adolescent daughters (ages 11–14 years) encouraging HPV vaccination in New Mexico, an ethnically-diverse U.S. state.

Methods: A clinic-cluster randomized trial where pediatric clinics (n = 9) were recruited and randomized, and parent-adolescent pairs (n = 82) within clinics received either the Vacteens.org/Vacunadolescente.org mobile web app or Usual and Customary (UC) HPV Vaccination information. Parents completed online surveys at baseline and 3-months. Daughters' HPV vaccine data were collected from the New Mexico State Immunization Information System 1 year post baseline.

Results: Three month survey results found Vacteens.org/Vacunadolescente.org parents to have higher positive HPV vaccine beliefs, informed decision making, intent to vaccinate and vaccine confidence outcomes than UC parents. HPV vaccine data found higher first dose HPV vaccination (Pearson χ2 = 6.13, p = 0.013, Vacteens.org/Vacunadolescente.org group 59.4%, UC group 40.6%), and higher HPV vaccination series completion (Pearson χ2 = 6.49, p = 0.011, Vacteens.org/Vacunadolescente.org group 68.4%, UC group 31.6%).

Conclusions: The small trial results showed the Vacteens.org/Vacunadolescente.org web app prompted positive vaccine-related attitudes and beliefs, and more HPV vaccination initiation and series completion. Mobile web apps can make decision-making tools for HPV vaccination widely available on digital platforms, reducing vaccine hesitancy, and confusion and increase HPV vaccine uptake.
The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) in Socially Isolated Adults 75+ Years Old: Randomized Controlled Trial Protocol and COVID-19 Related Study Modifications
Authors: Yu Kexin , Wild Katherine , Potempa Kathleen , Hampstead Benjamin M. , Lichtenberg Peter A. , Struble Laura M. , Pruitt Patrick , Alfaro Elena L. , Lindsley Jacob , MacDonald Mattie , Kaye Jeffrey A. , Silbert Lisa C. , Dodge Hiroko H.
Published: August 2021

Background: Increasing social interactions through communication technologies could offer a cost-effective prevention approach that slows cognitive decline and delays the onset of Alzheimer's disease. This paper describes the protocol of an active project named “Internet-based conversational engagement clinical trial (I-CONECT)” (ClinicalTrials.gov: NCT02871921). The COVID-19 pandemic related protocol modifications are also addressed in the current paper.

Methods: I-CONECT is a multi-site, assessor-blind, randomized controlled behavioral intervention trial (RCT). We aim to randomize 320 socially isolated adults 75+ years old [160 Caucasian and 160 African American participants, 50:50 split between those with normal cognition and mild cognitive impairment (MCI)] recruited from the community to either the video chat intervention group or the control group (1:1 allocation). Those in the video chat group receive a computer and Internet service for the duration of the study, which they use to video chat with study staff for 30 min/day 4×/week for 6 months (high dose), and then 2×/week for an additional 6 months (maintenance dose). Both video chat and control groups have a brief (about 10 min) telephone check-in with study staff once per week. The primary outcome is the change in global cognitive function measured by Montreal Cognitive Assessment (MoCA) from baseline to 6 months. Secondary outcomes include changes in cognition in memory and executive function domains, emotional well-being measured by NIH Toolbox emotional battery, and daily functional abilities assessed with the Revised Observed Tasks of Daily Living (OTDL-R). Eligible participants have MRIs at baseline and 6 months. Participants contribute saliva for genetic testing (optional consent), and all video chats, weekly check-in calls and neuropsychological assessment sessions are recorded for speech and language analysis. The pandemic halted research activities and resulted in protocol modifications, including replacing in-person assessment with remote assessment, remote deployment of study equipment, and revised targeted sample size.

Discussion: This trial provides user-friendly hardware for the conversational-based intervention that can be easily provided at participants' homes. The trial aspires to use age and culture-specific conversational materials and a related platform developed in this trial for enhancing cognitive reserve and improving cognitive function.
Predicting Anxiety in Routine Palliative Care Using Bayesian-Inspired Association Rule Mining
Authors: Haas Oliver , Lopera Gonzalez Luis Ignacio , Hofmann Sonja , Ostgathe Christoph , Maier Andreas , Rothgang Eva , Amft Oliver , Steigleder Tobias
Published: August 2021

We propose a novel knowledge extraction method based on Bayesian-inspired association rule mining to classify anxiety in heterogeneous, routinely collected data from 9,924 palliative patients. The method extracts association rules mined using lift and local support as selection criteria. The extracted rules are used to assess the maximum evidence supporting and rejecting anxiety for each patient in the test set. We evaluated the predictive accuracy by calculating the area under the receiver operating characteristic curve (AUC). The evaluation produced an AUC of 0.89 and a set of 55 atomic rules with one item in the premise and the conclusion, respectively. The selected rules include variables like pain, nausea, and various medications. Our method outperforms the previous state of the art (AUC = 0.72). We analyzed the relevance and novelty of the mined rules. Palliative experts were asked about the correlation between variables in the data set and anxiety. By comparing expert answers with the retrieved rules, we grouped rules into expected and unexpected ones and found several rules for which experts' opinions and the data-backed rules differ, most notably with the patients' sex. The proposed method offers a novel way to predict anxiety in palliative settings using routinely collected data with an explainable and effective model based on Bayesian-inspired association rule mining. The extracted rules give further insight into potential knowledge gaps in the palliative care field.
Improving the Specular Point Positioning Accuracy of Ship-Borne GNSS-R Observations in China Seas Based on Comprehensive Geophysical Correction
Authors: Wu Fan , Zheng Wei , Liu Zongqiang , Sun Xuezhi
Published: August 2021

The accurate modeled GNSS-R reflection delay, which is indispensable for the quantification, modeling, and correction of the GNSS-R altimetry sea-state bias, can be obtained based on the accurate modeled position of the specular point. At present, the reflection surface model of the specular point positioning still has the mean dynamic topography (MDT) error and the deviation of the vertical (DOV) error relative to the instantaneous sea surface. In this study, the following studies have been carried out. Based on the ship-borne GNSS-R observations in China seas, we introduced various elevation parameters including the MDT to correct the elevation error of the reflection surface. We introduced the DOV based on the elevation correction, and the DOV correction positioning method was proposed to correct the slope error of the reflection surface. The specular point was positioned on the instantaneous sea reflection surface. We verified the instantaneous sea reflection surface model and the specular point positioning results, analyzed the relationship between the position correction distance and the reflection incident angle, and discussed the spatial distribution characteristics of the MDT correction distance. The results showed that the reflection surface modeling and the specular point positioning were accurate. The positioning error increased to varying degrees with the increase of the reflection incident angle. The MDT correction improved the positioning by 0.91 m, and the DOV correction further improved the positioning by 0.12 m. Based on the combined application of the two kinds of correction positioning, the positioning was comprehensively improved by 0.99 m. The MDT correction of China seas gradually increased from the north to south. While in the regional sea areas, it gradually decreased from the north to south and showed randomness. The relative position between the antennas and their random changes introduced uncertainty, which can be reduced by integration. The new instantaneous sea reflection surface model and the corresponding specular point positioning method can provide accurate modeled reflection delay for the sea-state bias correction of ship-borne GNSS-R observations, and they can be extended to satellite-borne global observations.
Rwandan Women in Higher Education: Progress, Successes, and Challenges
Authors: Reilly Elizabeth C.
Published: August 2021

In nearly three decades since Rwanda’s genocide and civil war, its education sector has undergone reconstruction to an unprecedented degree within higher education. While greater numbers of girls are attending university, and more women are becoming university faculty members, their status in educational leadership roles remains unclear. This qualitative investigation sought to present insight into four women who serve as professors and executive leaders within the higher education system by examining their progress, successes, and challenges. Four of the many insights that have emerged include women’s smaller acceptance rate into higher education as undergraduates; the country’s lack of Ph.D. programs, thereby requiring women to leave the country in order to obtain the terminal degree; disproportionate service expectations placed on women academics as compared to men that affect scholarly output; and society’s expectation for women’s responsibilities as wives and mothers regardless of career responsibilities or status. To remedy these findings, further investigation can shed light on the reasons for low acceptance of women into the university; may lead to development of a strategic plan to address the lack of opportunities for students to enter graduate level education leading to the Ph.D.; and may address broader national policies that support women academics such as attention to child care and mentoring for promotion.
Communication Among Harvesters Leads to Sustainable Fishing Behaviour in a Continuous Time Common Pool Resource Experiment
Authors: Owusu Kwabena A. , Kulesz Micaela M. , Merico Agostino
Published: August 2021

The sustainable use of common pool resources (CPRs) such as fisheries constitutes a major challenge for society. A large body of empirical studies conducted in discrete time indicates that resource users are able to prevent the ‘tragedy of the commons' under institutional arrangements that can promote cooperation. However, the variability exhibited by the human behaviour and the dynamic nature of renewable resources require continuous time experiments to fully explain the mechanisms underpinning the sustainable use of resources. We conducted CPR experiments in continuous time to investigate how the extraction behaviour of resource users changes in real-time in response to changes in resource availability under communication and no communication. We find that when communication is allowed, users adjust their extraction efforts based on knowledge of previous resource availability. In contrast, when communication is not allowed, users do not incorporate resource availability into their utility function. These results suggest that communication does not merely provide a forum for coordination but mediates a causal relationship between resource levels and extraction behaviour. Our findings may help the development of effective resource management policies.
Physical Disturbance by Bottom Trawling Suspends Particulate Matter and Alters Biogeochemical Processes on and Near the Seafloor
Authors: Bradshaw Clare , Jakobsson Martin , Brüchert Volker , Bonaglia Stefano , Mörth Carl-Magnus , Muchowski Julia , Stranne Christian , Sköld Mattias
Published: August 2021

Bottom trawling is known to affect benthic faunal communities but its effects on sediment suspension and seabed biogeochemistry are less well described. In addition, few studies have been carried out in the Baltic Sea, despite decades of trawling in this unique brackish environment and the frequent occurrence of trawling in areas where hypoxia and low and variable salinity already act as ecosystem stressors. We measured the physical and biogeochemical impacts of an otter trawl on a muddy Baltic seabed. Multibeam bathymetry revealed a 36 m-wide trawl track, comprising parallel furrows and sediment piles caused by the trawl doors and shallower grooves from the groundgear, that displaced 1,000 m3 (500 t) sediment and suspended 9.5 t sediment per km of track. The trawl doors had less effect than the rest of the gear in terms of total sediment mass but per m2 the doors had 5× the displacement and 2× the suspension effect, due to their greater penetration and hydrodynamic drag. The suspended sediment spread >1 km away over the following 3–4 days, creating a 5–10 m thick layer of turbid bottom water. Turbidity reached 4.3 NTU (7 mgDW L–1), 550 m from the track, 20 h post-trawling. Particulate Al, Ti, Fe, P, and Mn were correlated with the spatio-temporal pattern of suspension. There was a pulse of dissolved N, P, and Mn to a height of 10 m above the seabed within a few hundred meters of the track, 2 h post-trawling. Dissolved methane concentrations were elevated in the water for at least 20 h. Sediment biogeochemistry in the door track was still perturbed after 48 h, with a decreased oxygen penetration depth and nutrient and oxygen fluxes across the sediment-water interface. These results clearly show the physical effects of bottom trawling, both on seabed topography (on the scale of km and years) and on sediment and particle suspension (on the scale of km and days-weeks). Alterations to biogeochemical processes suggest that, where bottom trawling is frequent, sediment biogeochemistry may not have time to recover between disturbance events and elevated turbidity may persist, even outside the trawled area.
Micro- and Nanowear of Self-Mated Steel Generated and Studied With an AFM at the Single Asperity Level
Authors: Reichelt Manuel , Cappella Brunero
Published: August 2021

Single asperity nanowear phenomena are fundamental for understanding basic tribological mechanisms. Yet, they are studied mostly through theoretical and simulation works. Few experiments were conducted in the past decades, usually with materials which are commonly used in micro- and nanotechnology, but not for macroscopic components with relevance in tribology. In the present work, we show for the first time tribotests performed with self-mated 100Cr6 steel, a very widespread material at the macroscale, taking advantage of an AFM, employed as a tribometer for the tribotests as well as for the inspection of wear of both tribopartners. Emphasis is put on the morphology of the scars, on wear particles, and on wear of the “colloidal” particles glued on the AFM cantilever. Measurements demonstrate the possibility of characterizing single asperity events leading to very small wear (scars with isolated, down to 1-nm-deep scratches). We highlight several phenomena, for example, transfer of wear particles and their negative contribution to wear volume, which are elementary key constituents of tribological processes. Such phenomena, probably occurring also at the macroscale, can be detected, identified, and characterized with high spatial and time resolution only at the nanoscale, thus giving insight into conditions and causes of their emergence.
Case Report: Phototherapeutic Keratectomy for Band Keratopathy Secondary to Chemo-Laser-Cryotherapy for Retinoblastoma
Authors: Wei Ruoyan , Li Meiyan , Yang Weiming , Xu Haipeng , Choi Joanne , Zhou Xingtao
Published: August 2021

Purpose: To report the clinical outcomes of phototherapeutic keratectomy (PTK) for pediatric band keratopathy after treatment for retinoblastoma.

Methods: A 5-year-old boy presented with a 2-year history of poor visual acuity and a horizontal gray-white band across the central cornea in the right eye. He was diagnosed with band keratopathy after chemo-laser-cryotherapy for retinoblastoma. The band keratopathy was treated via PTK using the Mel-90 excimer laser with an optical treatment zone of 7.0 mm and ablation depth of 120 μm. The patient was followed at 1 week and 3 months postoperatively.

Results: Surgery and postoperative follow-up were uneventful. At the 3-month follow-up, the uncorrected distant visual acuity of the right eye improved to 20/125, and the corrected distance visual acuity improved to 20/70 with a refraction of +10.00 D/−2.50 DC × 15. The clarity of the ablated area was evidently improved. The central corneal thickness decreases from 612 to 584 μm. The optical coherence tomography showed the thin band of hyperreflectivity in the ablated area disappeared, corneal transparency improved and the corneal surface smoothened.

Conclusions: PTK is a safe and effective procedure to treat band keratopathy following treatment of retinoblastoma in children. Early intervention can reduce the risk of developing deprivation amblyopia.
Digging Up the Roots: Taxonomic and Phylogenetic Disentanglements in Corticiaceae s.s. (Corticiales, Basidiomycota) and Evolution of Nutritional Modes
Authors: Ghobad-Nejhad Masoomeh , Langer Ewald , Nakasone Karen , Diederich Paul , Nilsson R. Henrik , Rajchenberg Mario , Ginns James
Published: August 2021

Corticiaceae is one of the traditional families of the Agaricomycetes and served for a long time as a convenient placement for basidiomycetes with a resupinate, corticioid form of fruiting body. Molecular studies have helped to assign many corticioid fungi to diverse families and orders; however, Corticiaceae still lacks a phylogenetic characterization and modern circumscription. Here, we provide the first comprehensive phylogenetic and taxonomic revision of the family Corticiaceae based on extensive type studies and sequences of nLSU, ITS, IGS, nSSU, and mtSSU regions. Our analyses support the recognition of ten monophyletic genera in the Corticiaceae, and show that nutritional mode is not a robust basis for generic delimitations in the family. The genus Mycobernardia and the species Corticium thailandicum, Erythricium vernum, and Marchandiomyces allantosporus are described as new to science, and five new combinations are proposed. Moreover, ancestral character state reconstruction revealed that saprotrophy is the plesiomorphic nutritional mode in the Corticiaceae, while several transitions have occurred to diverse nutritional modes in this family. Identification keys are provided to the genera in Corticiaceae s.s. as well as to the species in Corticium, Erythricium, Laetisaria, and Marchandiomyces.
A Low-Prevalence Single-Nucleotide Polymorphism in the Sensor Kinase PhoR in Mycobacterium tuberculosis Suppresses Its Autophosphatase Activity and Reduces Pathogenic Fitness: Implications in Evolutionary Selection
Authors: Waturuocha Uchenna Watson , Krishna M. S. , Malhotra Vandana , Dixit Narendra M. , Saini Deepak Kumar
Published: August 2021

The genome sequencing of Mycobacterium tuberculosis, the causative organism of tuberculosis, has significantly improved our understanding of the mechanisms that drive the establishment of infection and disease progression. Several clinical strains of M. tuberculosis exhibit single-nucleotide polymorphisms (SNPs), the implications of which are only beginning to be understood. Here, we examined the impact of a specific polymorphism in PhoR, the sensor kinase of the PhoPR two-component system. Biochemical analysis revealed reduced autophosphatase/ATPase activity, which led to enhanced downstream gene expression. We complemented M. tuberculosis H37Ra with the wild-type and mutant phoPR genes and characterized the strains in a cell line infection model. We provide an explanation for the low prevalence of the SNP in clinical strains (∼1%), as the mutation causes a survival disadvantage in the host cells. The study provides a rare example of selection of a signaling node under competing evolutionary forces, wherein a biochemically superior mutation aids bacterial adaptation within-host but has low fitness for infection and hence is not selected. Our study highlights the importance of accounting for such SNPs to test therapeutic and co-therapeutic methods to combat TB.
Phenotypic Traits and Immunomodulatory Properties of Leuconostoc carnosum Isolated From Meat Products
Authors: Raimondi Stefano , Spampinato Gloria , Candeliere Francesco , Amaretti Alberto , Brun Paola , Castagliuolo Ignazio , Rossi Maddalena
Published: August 2021

Twelve strains of Leuconostoc carnosum from meat products were investigated in terms of biochemical, physiological, and functional properties. The spectrum of sugars fermented by L. carnosum strains was limited to few mono- and disaccharides, consistently with the natural habitats of the species, including meat and fermented vegetables. The strains were able to grow from 4 to 37°C with an optimum of approximately 32.5°C. The ability to grow at temperatures compatible with refrigeration and in presence of up to 60 g/L NaCl explains the high loads of L. carnosum frequently described in many meat-based products. Six strains produced exopolysaccharides, causing a ropy phenotype of colonies, according to the potential involvement on L. carnosum in the appearance of slime in packed meat products. On the other side, the study provides evidence of a potential protective role of L. carnosum WC0321 and L. carnosum WC0323 against Listeria monocytogenes, consistently with the presence in these strains of the genes encoding leucocin B. Some meat-based products intended to be consumed without cooking may harbor up to 108 CFU/g of L. carnosum; therefore, we investigated the potential impact of this load on health. No strains survived the treatment with simulated gastric juice. Three selected strains were challenged for the capability to colonize a mouse model and their immunomodulatory properties were investigated. The strains did not colonize the intestine of mice during 10 days of daily dietary administration. Intriguingly, despite the loss of viability during the gastrointestinal transit, the strains exhibited different immunomodulatory effect on the maturation of dendritic cells in vivo, the extent of which correlated to the production of exopolysaccharides. The ability to stimulate the mucosal associated immune system in such probiotic-like manner, the general absence of antibiotic resistance genes, and the lack of the biosynthetic pathways for biogenic amines should reassure on the safety of this species, with potential for exploitation of selected starters.
Amelioration of Hippocampal Insulin Resistance Reduces Tau Hyperphosphorylation and Cognitive Decline Induced by Isoflurane in Mice
Authors: Peng Liangyu , Fang Xin , Xu Fangxia , Liu Shuai , Qian Yue , Gong Xiangdan , Zhao Xin , Ma Zhengliang , Xia Tianjiao , Gu Xiaoping
Published: August 2021

General anesthetics can induce cognitive impairments and increase the risk of Alzheimer’s disease (AD). However, the underlying mechanisms are still unknown. Our previous studies shown that long-term isoflurane exposure induced peripheral and central insulin resistance (IR) in adult mice and aggravated IR in type 2 diabetes mellitus (T2DM) mice. Clinical and preclinical studies revealed an association between impaired insulin signaling and tau pathology in AD and other tauopathies. We investigated if alleviation of hippocampal IR by the antidiabetic agent metformin could reduce tau hyperphosphorylation and cognitive decline induced by isoflurane in mice. The effects of prolonged (6 h) isoflurane anesthesia on hippocampal IR, hippocampal tau hyperphosphorylation, and hippocampus-dependent cognitive function were evaluated in wild type (WT) adult mice and the high-fat diet plus streptozotocin (HFD/STZ) mouse model of T2DM. Here we shown that isoflurane and HFD/STZ dramatically and synergistically induced hippocampal IR and fear memory impairment. Metformin pretreatment strongly ameliorated hippocampal IR and cognitive dysfunction caused by isoflurane in WT mice, but was less effective in T2DM mice. Isoflurane also induced hippocampal tau hyperphosphorylation and metformin reversed this effect. In addition, isoflurane significantly increased blood glucose levels in both adult and T2DM mice, and metformin reversed this effect as well. Administration of 25% glucose to metformin-pretreated mice induced hyperglycemia, but surprisingly did not reverse the benefits of metformin on hippocampal insulin signaling and fear memory following isoflurane anesthesia. Our findings show hippocampal IR and tau hyperphosphorylation contribute to acute isoflurane-induced cognitive dysfunction. Brief metformin treatment can mitigate these effects through a mechanism independent of glycemic control. Future studies are needed to investigate whether long-term metformin treatment can also prevent T2DM-induced hippocampal IR and cognitive decline.
Graphene, Carbon Nanotube and Plasmonic Nanosensors for Detection of Viral Pathogens: Opportunities for Rapid Testing in Pandemics like COVID-19
Authors: Bardhan Neelkanth M. , Jansen Peter , Belcher Angela M.
Published: August 2021

With the emergence of global pandemics such as the Black Death (Plague), 1918 influenza, smallpox, tuberculosis, HIV/AIDS, and currently the COVID-19 outbreak caused by the SARS-CoV-2 virus, there is an urgent, pressing medical need to devise methods of rapid testing and diagnostics to screen a large population of the planet. The important considerations for any such diagnostic test include: 1) high sensitivity (to maximize true positive rate of detection); 2) high specificity (to minimize false positives); 3) low cost of testing (to enable widespread adoption, even in resource-constrained settings); 4) rapid turnaround time from sample collection to test result; and 5) test assay without the need for specialized equipment. While existing testing methods for COVID-19 such as RT-PCR (real-time reverse transcriptase polymerase chain reaction) offer high sensitivity and specificity, they are quite expensive – in terms of the reagents and equipment required, the laboratory expertise needed to run and interpret the test data, and the turnaround time. In this review, we summarize the recent advances made using carbon nanotubes for sensors; as a nanotechnology-based approach for diagnostic testing of viral pathogens; to improve the performance of the detection assays with respect to sensitivity, specificity and cost. Carbon nanomaterials are an attractive platform for designing biosensors due to their scalability, tunable functionality, photostability, and unique opto-electronic properties. Two possible approaches for pathogen detection using carbon nanomaterials are discussed here: 1) optical sensing, and 2) electrochemical sensing. We explore the chemical modifications performed to add functionality to the carbon nanotubes, and the physical, optical and/or electronic considerations used for testing devices or sensors fabricated using these carbon nanomaterials. Given this progress, it is reason to be cautiously optimistic that nanosensors based on carbon nanotubes, graphene technology and plasmonic resonance effects can play an important role towards the development of accurate, cost-effective, widespread testing capacity for the world’s population, to help detect, monitor and mitigate the spread of disease outbreaks.
Gait Speed Modulations Are Proportional to Grades of Virtual Visual Slopes—A Virtual Reality Study
Authors: Benady Amit , Zadik Sean , Zeilig Gabriel , Gilaie-Dotan Sharon , Plotnik Meir
Published: August 2021

Gait is a complex mechanism relying on integration of several sensory inputs such as vestibular, proprioceptive, and visual cues to maintain stability while walking. Often humans adapt their gait to changes in surface inclinations, and this is typically achieved by modulating walking speed according to the inclination in order to counteract the gravitational forces, either uphill (exertion effect) or downhill (braking effect). The contribution of vision to these speed modulations is not fully understood. Here we assessed gait speed effects by parametrically manipulating the discrepancy between virtual visual inclination and the actual surface inclination (aka visual incongruence). Fifteen healthy participants walked in a large-scale virtual reality (VR) system on a self-paced treadmill synchronized with projected visual scenes. During walking they were randomly exposed to varying degrees of physical-visual incongruence inclinations (e.g., treadmill leveled & visual scene uphill) in a wide range of inclinations (−15° to +15°). We observed an approximately linear relation between the relative change in gait speed and the anticipated gravitational forces associated with the virtual inclinations. Mean relative gait speed increase of ~7%, ~11%, and ~17% were measured for virtual inclinations of +5°, +10°, and +15°, respectively (anticipated decelerating forces were proportional to sin[5°], sin[10°], sin[15°]). The same pattern was seen for downhill virtual inclinations with relative gait speed modulations of ~-10%, ~-16%, and ~-24% for inclinations of −5°, −10°, and −15°, respectively (in anticipation of accelerating forces). Furthermore, we observed that the magnitude of speed modulation following virtual inclination at ±10° was associated with subjective visual verticality misperception. In conclusion, visual cues modulate gait speed when surface inclinations change proportional to the anticipated effect of the gravitational force associated the inclinations. Our results emphasize the contribution of vision to locomotion in a dynamic environment and may enhance personalized rehabilitation strategies for gait speed modulations in neurological patients with gait impairments.
Memory Clinics and Day Care Centers in Thessaloniki, Northern Greece: 30 Years of Clinical Practice and Experience
Authors: Tsolaki Magda , Tsatali Marianna , Gkioka Mara , Poptsi Eleni , Tsolaki Anthoula , Papaliagkas Vasileios , Tabakis Irene-Maria , Lazarou Ioulietta , Makri Marina , Kazis Dimitrios , Papagiannopoulos Sotirios , Kiryttopoulos Andreas , Koutsouraki Efrosyni , Tegos Thomas
Published: August 2021

Background: This review describes the diagnostic and interventional procedures conducted in two university memory clinics (established network of G. Papanikolaou Hospital: 1988–2017 and AHEPA hospital: 2017–today) and 2 day care centers (established network of DCCs: 2005–today) in North Greece and their contribution in the scientific field of dementia. The aims of this work are (1) to provide a diagnosis and treatment protocol established in the network of memory clinics and DCCs and (2) to present further research conducted in the aforementioned network during the last 30 years of clinical practice.

Methods: The guidelines to set a protocol demand a series of actions as follows: (1) set the diagnosis criteria, neuropsychological assessment, laboratory examinations, and examination of neurophysiological, neuroimaging, cerebrospinal fluid, blood, and genetic markers; and (2) apply non-pharmacological interventions according to the needs and specialized psychosocial interventions of the patient to the caregivers of the patient.

Results: In addition to the guidelines followed in memory clinics at the 1st and 3rd Department of Neurology and two DCCs, a database of patients, educational programs, and further participation in international research programs, including clinical trials, make our contribution in the dementia field strong.

Conclusion: In the current paper, we provide useful guidelines on how major and minor neurocognitive disorders are being treated in Thessaloniki, Greece, describing successful practices which have been adapted in the last 30 years.
Prediction, Suppression of Visual Response, and Modulation of Visual Perception: Insights From Visual Evoked Potentials and Representational Momentum
Authors: Kimura Motohiro
Published: August 2021

When a visual object changes its position along with certain sequential regularities, the visual system rapidly and automatically forms a prediction regarding the future position of the object based on the regularities. Such prediction can drastically alter visual perception. A phenomenon called representational momentum (RM: a predictive displacement of the perceived final position of a visual object along its recent regular pattern) has provided extensive evidence for the predictive modulation of visual perception. The purpose of the present study was to identify neural effects that could explain individual differences in the strength of the predictive modulation of visual perception as measured by RM. For this purpose, in two experiments with a conventional RM paradigm where a bar was discretely presented in a regular rotation manner (with a step of 18° in Experiment 1 and a step of 20° in Experiment 2), visual evoked potentials (VEPs) in response to the regularly rotated bar were measured, and correlations between the magnitudes of RM and VEPs were examined. The results showed that the magnitudes of RM and central P2 were negatively correlated, consistently in both experiments; participants who showed a smaller central P2 tended to exhibit greater RM. Together with a previous proposal that central P2 would represent delayed reactivation of lower visual areas around the striate and prestriate cortices via reentrant feedback projections from higher areas, the present results suggest that greater suppression of delayed reactivation of lower visual areas (as indicated by smaller central P2) may underlie stronger predictive modulation of visual perception (as indicated by greater RM).
Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models
Authors: Haase Florencia D. , Coorey Bronte , Riley Lisa , Cantrill Laurence C. , Tam Patrick P. L. , Gold Wendy A.
Published: August 2021

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in MECP2. The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets. Brain organoid models that recapitulate much of the tissue architecture and the complexity of cell types in the developing brain, offer further unprecedented opportunity for elucidating human neural development, without resorting to conventional animal models and the limited resource of human neural tissues. This review focuses on the new knowledge of RTT that has been gleaned from the iPSC-based models as well as limitations of the models and strategies to refine organoid technology in the quest for clinically relevant disease models for RTT and the broader spectrum of neurodevelopmental disorders.
In vitro Colon Fermentation of Soluble Arabinoxylan Is Modified Through Milling and Extrusion
Authors: Demuth Teresa , Edwards Veronica , Bircher Lea , Lacroix Christophe , Nyström Laura , Geirnaert Annelies
Published: August 2021

Dietary fibers such as arabinoxylan (AX) are promising food constituents to prevent particular diet-related chronic diseases because of their prebiotic properties. Arabinoxylan fermentation by the gut microbiota depends on the structural architecture of AX, which can be modified during food processing and consequently affect its prebiotic potential, but it is little investigated. Therefore, the aim of this study was to evaluate the effects of naturally occurring and processing-induced structural alterations of the soluble AX of wheat bran and rye flour on the in vitro human colon fermentation. It was found that fermentation behavior is strongly linked to the AX fine structure and their processing-induced modifications. The short-chain fatty acid (SCFA) metabolism, acidification kinetics, bacterial growth, and bacterial composition revealed that wheat bran AX (WBAX) was fermented faster than rye flour AX. Increased levels of bound phenolic acids resulting from processing were identified as the inhibiting factor for AX fermentation kinetics. Bacterial genera promoted by AX varied between AX source and processing type, but also between microbiota. Extruded WBAX promoted butyrate production and growth of butyrate-producing Faecalibacterium in the butyrogenic microbiota while it did not enhance fermentation and inhibited the growth of Prevotella in the propiogenic microbiota. We anticipate that the findings of this study are a starting point for further investigation on the impact of processing-induced changes on the prebiotic potential of dietary fibers prior to human studies.