bluuebunny/crossref_metadata_2025 huggingface dataset:
ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway
Authors: Ji Liang , Wang Zhi-hong , Zhang Yu-hua , Zhou Yi , Tang De-sheng , Yan Chang-sheng , Ma Jia-min , Fang Kun , Gao Lei , Ren Nian-sheng , Cheng Long , Guo Xiao-yu , Sun Bei , Wang Gang
Published: March 2022

The present study was performed to explore whether and how impaired autophagy could modulate calcium/calmodulin-dependent protein kinase II (CAMKII)-regulated necrosis in the pathogenesis of acute pancreatitis (AP). Wistar rats and AR42J cells were used for AP modeling. When indicated, genetic regulation of CAMKII or ATG7 was performed prior to AP induction. AP-related necrotic injury was positively regulated by the incubation level of CAMKII. ATG7 positively modulated the level of CAMKII and necrosis following AP induction, indicating that there might be a connection between impaired autophagy and CAMKII-regulated necrosis in the pathogenesis of AP. microRNA (miR)-30b-5p was predicted and then verified as the upstream regulator of CAMKII mRNA in our setting of AP. Given that the level of miR-30b-5p was negatively correlated with the incubation levels of ATG7 after AP induction, a rescue experiment was performed and indicated that the miR-30b-5p mimic compromised ATG7 overexpression-induced upregulation of CAMKII-regulated necrosis after AP induction. In conclusion, our results indicate that ATG7-enhanced impaired autophagy exacerbates AP by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.
Plasma-activated medium induces ferroptosis by depleting FSP1 in human lung cancer cells
Authors: Jo Ara , Bae Jin Hee , Yoon Yu Jeong , Chung Tae Hun , Lee Eun-Woo , Kim Young-Ho , Joh Hea Min , Chung Jin Woong
Published: March 2022

Cold atmospheric plasma (CAP) that generates reactive oxygen species (ROS) has received considerable scientific attentions as a new type of anticancer. In particular, an indirect treatment method of inducing cancer cell death through plasma-activated medium (PAM), rather than direct plasma treatment has been well established. Although various cell death pathways such as apoptosis, necroptosis, and autophagy have been suggested to be involved in PAM-induced cell death, the involvement of ferroptosis, another type of cell death regulated by lipid ROS is largely unknown. This study reports, that PAM promotes cell death via ferroptosis in human lung cancer cells, and PAM increases intracellular and lipid ROS, thereby resulting in mitochondrial dysfunction. The treatment of cells with N-acetylcysteine, an ROS scavenging agent, or ferrostatin-1, a ferroptosis inhibitor, protects cells against PAM-induced cell death. Interestingly, ferroptosis suppressor protein 1 (FSP1) is downregulated upon PAM treatment. Furthermore, the treatment of cells with iFSP1, an inhibitor of FSP1, further enhances PAM-induced ferroptosis. Finally, this study demonstrates that PAM inhibits tumor growth in a xenograft model with an increase in 4-hydroxynoneal and PTGS2, a byproduct of lipid peroxidation, and a decrease in FSP1 expression. This study will provide new insights into the underlying mechanism and therapeutic strategies of PAM-mediated cancer treatment.
Exploring the ethics of genetic prioritisation for COVID-19 vaccines
Authors: Bruce Jago , Johnson Stephanie B.
Published: March 2022

There is evidence to suggest that host genomic factors may account for disease response variability in COVID-19 infection. In this paper, we consider if and how host genomics should influence decisions about vaccine allocation. Three potential host genetic factors are explored: vulnerability to infection, resistance to infection, and increased infectivity. We argue for the prioritisation of the genetically vulnerable in vaccination schemes, and evaluate the potential for ethical de-prioritisation of individuals with genetic markers for resistance. Lastly, we discuss ethical prioritisation of individuals with genetic markers for increased infectivity (those more likely to spread COVID-19).
Precursors of Majorana modes and their length-dependent energy oscillations probed at both ends of atomic Shiba chains
Authors: Schneider Lucas , Beck Philip , Neuhaus-Steinmetz Jannis , Rózsa Levente , Posske Thore , Wiebe Jens , Wiesendanger Roland
Published: March 2022

Isolated Majorana modes (MMs) are highly non-local quantum states with non-Abelian exchange statistics, which localize at the two ends of finite-size 1D topological superconductors of sufficient length. Experimental evidence for MMs is so far based on the detection of several key signatures: for example, a conductance peak pinned to the Fermi energy or an oscillatory peak splitting in short 1D systems when the MMs overlap. However, most of these key signatures were probed only on one of the ends of the 1D system, and firm evidence for an MM requires the simultaneous detection of all the key signatures on both ends. Here we construct short atomic spin chains on a superconductor—also known as Shiba chains—up to a chain length of 45 atoms using tip-assisted atom manipulation in scanning tunnelling microscopy experiments. We observe zero-energy conductance peaks localized at both ends of the chain that simultaneously split off from the Fermi energy in an oscillatory fashion after altering the chain length. By fitting the parameters of a low-energy model to the data, we find that the peaks are consistent with precursors of MMs that evolve into isolated MMs protected by an estimated topological gap of 50 μeV in chains of at least 35 nm length, corresponding to 70 atoms.
Nonlocal nonlinear phononics
Authors: Henstridge M. , Först M. , Rowe E. , Fechner M. , Cavalleri A.
Published: March 2022

Nonlinear phononics relies on the resonant optical excitation of infrared-active lattice vibrations to induce targeted structural deformations in solids. This form of dynamical crystal structure design has been applied to control the functional properties of many complex solids, including magnetic materials, superconductors and ferroelectrics. However, phononics has so far been restricted to protocols in which structural deformations occur within the optically excited volume, sometimes resulting in unwanted heating. Here, we extend nonlinear phononics to propagating polaritons, spatially separating the functional response from the optical drive. We use mid-infrared optical pulses to resonantly drive a phonon at the surface of ferroelectric LiNbO3. Time-resolved stimulated Raman scattering reveals that the ferroelectric polarization is reduced over the entire 50 µm depth of the sample, far beyond the micrometre depth of the evanescent phonon field. We attribute this effect to the anharmonic coupling between the driven mode and a polariton that propagates into the material. For high excitation amplitudes, we reach a regime in which the ferroelectric polarization is reversed, as revealed by a sign change in the Raman tensor coefficients of all the polar modes.
A method for direct estimation of left ventricular global longitudinal strain rate from echocardiograms
Authors: Meyers Brett A. , Brindise Melissa C. , Kutty Shelby , Vlachos Pavlos P.
Published: March 2022

We present a new method for measuring global longitudinal strain and global longitudinal strain rate from 2D echocardiograms using a logarithmic-transform correlation (LTC) method. Traditional echocardiography strain analysis depends on user inputs and chamber segmentation, which yield increased measurement variability. In contrast, our approach is automated and does not require cardiac chamber segmentation and regularization, thus eliminating these issues. The algorithm was benchmarked against two conventional strain analysis methods using synthetic left ventricle ultrasound images. Measurement error was assessed as a function of contrast-to-noise ratio (CNR) using mean absolute error and root-mean-square error. LTC showed better agreement to the ground truth strain $${({\varvec{R}}}^{2}=0.91)$$

(

R

2

=
0.91
)

and ground truth strain rate $${({\varvec{R}}}^{2}=0.85)$$

(

R

2

=
0.85
)

compared with agreement to ground truth for two block-matching speckle tracking algorithms (one based on sum of square difference and the other on Fourier transform correlation; strain $${({\varvec{R}}}^{2}=0.70)$$

(

R

2

=
0.70
)

, strain rate $${({\varvec{R}}}^{2}=0.70)$$

(

R

2

=
0.70
)

). A 200% increase in strain measurement accuracy was observed compared to the conventional algorithms. Subsequently, we tested the method using a 53-subject clinical cohort (20 subjects diseased with cardiomyopathy, 33 healthy controls). Our method distinguished between normal and abnormal left ventricular function with an AUC = 0.89, a 5% improvement over the conventional GLS algorithms.
Ultrasound stimulation improves inflammatory resolution, neuroprotection, and functional recovery after spinal cord injury
Authors: Hong Yu-ri , Lee Eun-hee , Park Ki-su , Han Mun , Kim Kyoung-Tae , Park Juyoung
Published: March 2022

Spinal cord injury (SCI) is associated with limited functional recovery. Despite advances in neuroscience, realistic therapeutic treatments for SCI remain unavailable. In this study, the effects of non-invasive ultrasound (US) treatment on behavior and inflammatory responses were evaluated in a rat model of SCI. Adult female Sprague–Dawley rats were subjected to spinal cord contusion injury. Two different US parameters (SCIU5: 5% and SCIU40: 40% duty cycle) were applied, and their effects on behavioral recovery after SCI were quantified. Tissue and neuronal responses were detected. Immunofluorescence was used to detect inflammatory markers. In the rat model of SCI, motor function was more effectively restored, and the lesion cavity area was smaller in the SCIU5 group. Furthermore, the SCIU5 protocol elicited an anti-inflammatory response at the injury site by reducing degenerative FJC-labeled neurons, macrophage/microglia activation, and infiltration. Thus, the lesion area decreased, and tissue density increased. Meanwhile, the SCIU40 protocol did not improve motor function or induce an anti-inflammatory response at the injury site. The SCIU5 protocol effectively accelerated the rate of improved exercise performance in the rat model while reducing inflammation. Accordingly, appropriate US stimulation may represent a promising treatment modality for SCI with beneficial anti-inflammatory effects.
Shared genetic loci for body fat storage and adipocyte lipolysis in humans
Authors: Kulyté Agné , Lundbäck Veroniqa , Arner Peter , Strawbridge Rona J. , Dahlman Ingrid
Published: March 2022

Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.
Seasonal variation in space use and territoriality in a large mammal (Sus scrofa)
Authors: Schlichting Peter E. , Boughton Raoul K. , Anderson Wes , Wight Bethany , VerCauteren Kurt C. , Miller Ryan S. , Lewis Jesse S.
Published: March 2022

An individual’s spatial behavior is shaped by social and environmental factors and provides critical information about population processes to inform conservation and management actions. Heterogeneity in spatial overlap among conspecifics can be evaluated using estimates of home ranges and core areas and used to understand factors influencing space use and territoriality. To understand and test predictions about spatial behavior in an invasive large mammal, the wild pig (Sus scrofa), we examined variation in space use between sexes and seasons. We predicted that if animals were territorial that there would be a reduction in space-use overlap when comparing overlap of home ranges (HR–HR), to home ranges and core areas (HR–CA), and in-turn between core areas (CA–CA). Home ranges and core areas were estimated for 54 wild pigs at Buck Island Ranch, FL from GPS telemetry data. Overlap indices were calculated to estimate the strength (space-use overlap) and number of potential interactions within three wet seasons (June–October) and two dry seasons (December–April). Among sexes, home range size did not vary seasonally, and males exhibited larger home ranges compared to females (M = 10.36 ± 0.79 km2 (± SE), F = 3.21 ± 0.16 km2). Strength of overlap varied by season with wild pig home ranges overlapping more during the dry season. Males interacted with a greater number of individuals of both sexes, compared to females, and exhibited greater strength of overlap during the dry season. Consistent with our predictions, wild pigs appeared to exhibit territorial behavior, where strength of overlap decreased when comparing HR–HR to HR–CA and HR–CA to CA–CA. Our framework can be used to understand patterns of space use and territoriality in populations, which has important implications in understanding intraspecific interactions and population processes, such as how pathogens and parasites might spread within and among populations.
A red fluorescent protein with improved monomericity enables ratiometric voltage imaging with ASAP3
Authors: Kim Benjamin B. , Wu Haodi , Hao Yukun A. , Pan Michael , Chavarha Mariya , Zhao Yufeng , Westberg Michael , St-Pierre François , Wu Joseph C. , Lin Michael Z.
Published: March 2022

A ratiometric genetically encoded voltage indicator (GEVI) would be desirable for tracking transmembrane voltage changes in the presence of sample motion. We performed combinatorial multi-site mutagenesis on a cyan-excitable red fluorescent protein to create the bright and monomeric mCyRFP3, which proved to be uniquely non-perturbing when fused to the GEVI ASAP3. The green/red ratio from ASAP3-mCyRFP3 (ASAP3-R3) reported voltage while correcting for motion artifacts, allowing the visualization of membrane voltage changes in contracting cardiomyocytes and throughout the cell cycle of motile cells.
Modeling solubility of CO2–N2 gas mixtures in aqueous electrolyte systems using artificial intelligence techniques and equations of state
Authors: Nakhaei-Kohani Reza , Taslimi-Renani Ehsan , Hadavimoghaddam Fahime , Mohammadi Mohammad-Reza , Hemmati-Sarapardeh Abdolhossein
Published: March 2022

Determining the solubility of non-hydrocarbon gases such as carbon dioxide (CO2) and nitrogen (N2) in water and brine is one of the most controversial challenges in the oil and chemical industries. Although many researches have been conducted on solubility of gases in brine and water, very few researches investigated the solubility of power plant flue gases (CO2–N2mixtures) in aqueous solutions. In this study, using six intelligent models, including Random Forest, Decision Tree (DT), Gradient Boosting-Decision Tree (GB-DT), Adaptive Boosting-Decision Tree (AdaBoost-DT), Adaptive Boosting-Support Vector Regression (AdaBoost-SVR), and Gradient Boosting-Support Vector Regression (GB-SVR), the solubility of CO2–N2mixtures in water and brine solutions was predicted, and the results were compared with four equations of state (EOSs), including Peng–Robinson (PR), Soave–Redlich–Kwong (SRK), Valderrama–Patel–Teja (VPT), and Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The results indicate that the Random Forest model with an average absolute percent relative error (AAPRE) value of 2.8% has the best predictions. The GB-SVR and DT models also have good precision with AAPRE values of 6.43% and 7.41%, respectively. For solubility of CO2present in gaseous mixtures in aqueous systems, the PC-SAFT model, and for solubility of N2, the VPT EOS had the best results among the EOSs. Also, the sensitivity analysis of input parameters showed that increasing the mole percent of CO2in gaseous phase, temperature, pressure, and decreasing the ionic strength increase the solubility of CO2–N2mixture in water and brine solutions. Another significant issue is that increasing the salinity of brine also has a subtractive effect on the solubility of CO2–N2mixture. Finally, the Leverage method proved that the actual data are of excellent quality and the Random Forest approach is quite reliable for determining the solubility of the CO2–N2gas mixtures in aqueous systems.
Deprogramming metabolism in pancreatic cancer with a bi-functional GPR55 inhibitor and biased β2 adrenergic agonist
Authors: Wnorowski Artur , Dudzik Danuta , Bernier Michel , Wójcik Jakub , Keijzers Guido , Diaz-Ruiz Alberto , Mazur Karolina , Zhang Yongqing , Han Haiyong , Scheibye-Knudsen Morten , Jozwiak Krzysztof , Barbas Coral , Wainer Irving W.
Published: March 2022

Metabolic reprogramming contributes to oncogenesis, tumor growth, and treatment resistance in pancreatic ductal adenocarcinoma (PDAC). Here we report the effects of (R,S′)-4′-methoxy-1-naphthylfenoterol (MNF), a GPR55 antagonist and biased β2-adrenergic receptor (β2-AR) agonist on cellular signaling implicated in proliferation and metabolism in PDAC cells. The relative contribution of GPR55 and β2-AR in (R,S′)-MNF signaling was explored further in PANC-1 cells. Moreover, the effect of (R,S′)-MNF on tumor growth was determined in a PANC-1 mouse xenograft model. PANC-1 cells treated with (R,S′)-MNF showed marked attenuation in GPR55 signal transduction and function combined with increased β2-AR/Gαs/adenylyl cyclase/PKA signaling, both of which contributing to lower MEK/ERK, PI3K/AKT and YAP/TAZ signaling. (R,S′)-MNF administration significantly reduced PANC-1 tumor growth and circulating l-lactate concentrations. Global metabolic profiling of (R,S′)-MNF-treated tumor tissues revealed decreased glycolytic metabolism, with a shift towards normoxic processes, attenuated glutamate metabolism, and increased levels of ophthalmic acid and its precursor, 2-aminobutyric acid, indicative of elevated oxidative stress. Transcriptomics and immunoblot analyses indicated the downregulation of gene and protein expression of HIF-1α and c-Myc, key initiators of metabolic reprogramming in PDAC. (R,S′)-MNF treatment decreased HIF-1α and c-Myc expression, attenuated glycolysis, shifted fatty acid metabolism towards β-oxidation, and suppressed de novo pyrimidine biosynthesis in PANC-1 tumors. The results indicate a potential benefit of combined GPR55 antagonism and biased β2-AR agonism in PDAC therapy associated with the deprogramming of altered cellular metabolism.
Evaluating COVID-19 control measures in mass gathering events with vaccine inequalities
Authors: Al-Shaery Ali M. , Hejase Bilal , Tridane Abdessamad , Farooqi Norah S. , Al Jassmi Hamad
Published: March 2022

With the increasing global adoption of COVID-19 vaccines, limitations on mass gathering events have started to gradually loosen. However, the large vaccine inequality recorded among different countries is an important aspect that policymakers must address when implementing control measures for such events. In this paper, we propose a model for the assessment of different control measures with the consideration of vaccine inequality in the population. Two control measures are considered: selecting participants based on vaccine efficacy and restricting the event capacity. We build the model using agent-based modeling to capture the spatiotemporal crowd dynamics and utilize a genetic algorithm to assess the control strategies. This assessment is based on factors that are important for policymakers such as disease prevalence, vaccine diversity, and event capacity. A quantitative evaluation of vaccine diversity using the Simpson’s Diversity Index is also provided. The Hajj ritual is used as a case study. We show that strategies that prioritized lowering the prevalence resulted in low event capacity but facilitated vaccine diversity. Moreover, strategies that prioritized diversity resulted in high infection rates. However, increasing the prioritization of participants with high vaccine efficacy significantly decreased the disease prevalence. Strategies that prioritized ritual capacity did not show clear trends.
Changes of the retinal and choroidal vasculature in cerebral small vessel disease
Authors: Geerling Clara F. , Terheyden Jan H. , Langner S. Magdalena , Kindler Christine , Keil Vera C. , Turski Christopher A. , Turski Gabrielle N. , Wintergerst Maximillian W. M. , Petzold Gabor C. , Finger Robert P.
Published: March 2022

Cerebral small vessel disease (CSVD) is associated with changes in the retinal vasculature which can be assessed non-invasively with much higher resolution than the cerebral vasculature. To detect changes at a microvascular level, we used optical coherence tomography angiography which resolves retinal and choroidal vasculature. Participants with CSVD and controls were included. White matter lesions were determined on magnetic resonance imaging (MRI). The retinal and choroidal vasculature were quantified using swept-source optical coherence tomography angiography. Data were analysed using linear regression. We included 30 participants (18 females; patients, n = 20; controls, n = 10) with a mean age of 61 ± 10 years. Patients had a higher mean white matter lesion index and number of lesions than controls (p ≤ 0.002). The intraindividual deviation of choriocapillaris reflectivity differed significantly between age-matched patients (0.234 ± 0.012) and controls (0.247 ± 0.011; p = 0.029). Skeleton density of the deep retinal capillaries was significantly associated with the number of lesions on MRI (β = − 5.3 × 108, 95%-confidence interval [− 10.3 × 108; − 0.2 × 108]) when controlling for age. The choroidal microvasculature and the deep retinal vascular plexus, as quantified by optical coherence tomography angiography, are significantly altered in CSVD. The value of these findings in diagnosing or monitoring CSVD need to be assessed in future studies.
Characterisation of the volatile profile of microalgae and cyanobacteria using solid-phase microextraction followed by gas chromatography coupled to mass spectrometry
Authors: Moran Lara , Bou Gemma , Aldai Noelia , Ciardi Martina , Morillas-España Ainoa , Sánchez-Zurano Ana , Barron Luis Javier R. , Lafarga Tomas
Published: March 2022

Microalgae and microalgae-derived ingredients are one of the top trends in the food industry. However, consumers’ acceptance and purchase intention of a product will be largely affected by odour and flavour. Surprisingly, the scientific literature present a very limited number of studies on the volatile composition of microalgae and cyanobacteria. In order to fill the gap, the main objective of the present study was to elucidate the volatile composition of seven microalgal and cyanobacterial strains from marine and freshwaters, with interest for the food industry while establishing its potential impact in odour. Among the seven selected strains, Arthrospira platensis showed the highest abundance and chemical diversity of volatile organic compounds (VOCs). Aldehydes, ketones, and alcohols were the families with the highest diversity of individual compounds, except in Arthrospira platensis and Scenedesmus almeriensis that showed a profile dominated by branched hydrocarbons. Marine strains presented a higher abundance of sulfur compounds than freshwater strains, while the ketones individual profile seemed to be more related to the taxonomical domain. The results of this study indicate that the VOCs composition is mainly driven by the individual strain although some volatile profile characteristics could be influenced by both environmental and taxonomical factors.
Link between the EZH2 noncanonical pathway and microtubule organization center polarization during early T lymphopoiesis
Authors: Deshayes Frederique , Fradet Magali , Kaminski Sandra , Viguier Mireille , Frippiat Jean-Pol , Ghislin Stephanie
Published: March 2022

EZH2 plays an essential role at the β-selection checkpoint of T lymphopoiesis by regulating histone H3 lysine 27 trimethylation (H3K27me3) via its canonical mode of action. Increasing data suggest that EZH2 could also regulate other cellular functions, such as cytoskeletal reorganization, via its noncanonical pathway. Consequently, we investigated whether the EZH2 noncanonical pathway could be involved in early T-cell maturation, which requires cell polarization. We observed that EZH2 localization is tightly regulated during the early stages of T-cell development and that EZH2 relocalizes in the nucleus of double-negative thymocytes enduring TCRβ recombination and β-selection processes. Furthermore, we observed that EZH2 and EED, but not Suz12, colocalize with the microtubule organization center (MTOC), which might prevent its inappropriate polarization in double negative cells. In accordance with these results, we evidenced the existence of direct or indirect interaction between EED and α-tubulin. Taken together, these results suggest that the EZH2 noncanonical pathway, in association with EED, is involved in the early stages of T-cell maturation.
Association of physical activity and positive thinking with global sleep quality
Authors: Chen Morgan , He Zhonghui , Zhang Zhanjia , Chen Weiyun
Published: March 2022

This study examined the association of different intensity levels of physical activity and positive thinking with a global sleep quality among college students. The research question was: to what degree were the different intensity levels of physical activity and positive thinking significantly associated with the global sleep quality among college students? We recruited students, who enrolled in regular physical education classes during a fall semester at a major public university. 553 students signed the consent form and indicated their voluntary participation in this study. The final data set for analysis consisted of 403 college students with the mean age of 19.01 years ± 1.559 years (217 males vs. 186 females) based on the results of data screening. They completed three questionnaires: International Physical Activity Questionnaire (IPAQ), Pittsburgh Sleep Quality Index (PSQI), and Positive Thinking Scale (PTS) during a regular physical education class. The multiple regression model revealed that vigorous-intensity physical activity, positive thinking, and negative thinking were collectively and individually associated with the Global PSQI sleep quality (F = 19.389, p = .000), explaining 12.8% of the total variance in the Global PSQI sleep quality for the total sample. College students’ engaging in vigorous intensity level of physical activity, and having a good level of positive thinking and a low level of negative thinking were both collectively and individually linked to the Global PSQI sleep quality.
The influence of the pH on the incorporation of caffeic acid into biomimetic membranes and cancer cells
Authors: Naumowicz Monika , Kusaczuk Magdalena , Zając Marcin , Jabłońska-Trypuć Agata , Mikłosz Agnieszka , Gál Miroslav , Worobiczuk Mateusz , Kotyńska Joanna
Published: March 2022

Caffeic acid (CA) is a phenolic compound synthesized by all plant species. It constitutes the main hydroxycinnamic acid found in human diet and presents a variety of beneficial effects including anticancer activity. Current data suggests essential role of the interplay between anticancer drugs and the cell membrane. Given this, biophysical interactions between CA and cancer cells or biomimetic membranes were investigated. Glioblastoma cell line U118MG and colorectal adenocarcinoma cell line DLD-1, as well as lipid bilayers and liposomes, were used as in vitro models. Electrophoretic light scattering was used to assess the effect of CA on the surface charge of cancer cells and liposomal membranes. Electrochemical impedance spectroscopy was chosen to evaluate CA-dependent modulatory effect on the electrical capacitance and electrical resistance of the bilayers. Our results suggest that CA fulfills physicochemical criteria determining drug-like properties of chemical compounds, and may serve as a potential cytostatic agent in cancer treatment.
Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE)
Authors: Sun Lijuan , Goh Hui Jen , Verma Sanjay , Govindharajulu Priya , Sadananthan Suresh Anand , Michael Navin , Henry Christiani Jeyakumar , Goh Julian Park-Nam , Velan S. Sendhil , Leow Melvin Khee-Shing
Published: March 2022

Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves’ disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12–24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.

Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.
Antimicrobial activity of supramolecular salts of gallium(III) and proflavine and the intriguing case of a trioxalate complex
Authors: Guerrini Marzia , d’Agostino Simone , Grepioni Fabrizia , Braga Dario , Lekhan Andrii , Turner Raymond J.
Published: March 2022

The use of the gallium oxalate complex [Ga(ox)3]3− as a building block in the formation of a drug-drug salt with the antimicrobial agent proflavine (PF) as its proflavinium cation (HPF+), namely [HPF]3[Ga(ox)3]·4H2O, is reported together with the preparation of the potassium salt K3[Ga(ox)3] and the novel dimeric gallium(III) salt K4[Ga2(ox)4(μ-OH)2]·2H2O. All compounds have been characterized by solid state methods, and their performance as antimicrobial agents has been evaluated by disk diffusion assay against the bacteria strains Pseudomonas aeruginosa ATCC27853, Staphylococcus aureus ATCC25923, and Escherichia coli ATCC25922. While the [HPF]3[Ga(ox)3]·4H2O drug-drug salt is effective against all three strains, the gallium oxalate salt K3[Ga(ox)3] showed impressive selectivity towards P. aeruginosa, with little to no antimicrobial activity against the other two organisms. This work presents novel breakthroughs towards Ga based antimicrobial agents.
White matter integrity changes and neurocognitive functioning in adult-late onset DM1: a follow-up DTI study
Authors: Labayru Garazi , Camino Borja , Jimenez-Marin Antonio , Garmendia Joana , Villanua Jorge , Zulaica Miren , Cortes Jesus M. , López de Munain Adolfo , Sistiaga Andone
Published: March 2022

Myotonic Dystrophy Type 1 (DM1) is a multisystemic disease that affects gray and white matter (WM) tissues. WM changes in DM1 include increased hyperintensities and altered tract integrity distributed in a widespread manner. However, the precise temporal and spatial progression of the changes are yet undetermined. MRI data were acquired from 8 adult- and late-onset DM1 patients and 10 healthy controls (HC) at two different timepoints over 9.06 years. Fractional anisotropy (FA) and mean diffusivity (MD) variations were assessed with Tract-Based Spatial Statistics. Transversal and longitudinal intra- and intergroup analyses were conducted, along with correlation analyses with clinical and neuropsychological data. At baseline, reduced FA and increased MD values were found in patients in the uncinate, anterior-thalamic, fronto-occipital, and longitudinal tracts. At follow-up, the WM disconnection was shown to have spread from the frontal part to the rest of the tracts in the brain. Furthermore, WM lesion burden was negatively correlated with FA values, while visuo-construction and intellectual functioning were positively correlated with global and regional FA values at follow-up. DM1 patients showed a pronounced WM integrity loss over time compared to HC, with a neurodegeneration pattern that suggests a progressive anterior–posterior disconnection. The visuo-construction domain stands out as the most sensitive neuropsychological measure for WM microstructural impairment.
The effect of oxygen concentration on the speciation of laser ablated uranium
Authors: Burton Mark A. , Auner Alex W. , Crowhurst Jonathan C. , Boone Peter S. , Finney Lauren A. , Weisz David G. , Koroglu Batikan , Jovanovic Igor , Radousky Harry B. , Knight Kim B.
Published: March 2022

In order to model the fate and transport of particles following a nuclear explosion, there must first be an understanding of individual physical and chemical processes that affect particle formation. One interaction pertinent to fireball chemistry and resultant debris formation is that between uranium and oxygen. In this study, we use laser ablation of uranium metal in different concentrations of oxygen gas, either 16O2 or 18O2, to determine the influence of oxygen on rapidly cooling uranium. Analysis of recovered particulates using infrared absorption and Raman spectroscopies indicate that the micrometer-sized particulates are predominantly amorphous UOx (am-UOx, where 3 ≤ x ≤ 4) and UO2 after ablation in 1 atm of pure O2 and a 1% O2/Ar mixture, respectively. Energy dispersive X-ray spectroscopy (EDS) of particulates formed in pure O2 suggest an O/U ratio of ~ 3.7, consistent with the vibrational spectroscopy analysis. Both am-UOx and UO2 particulates convert to α-U3O8 when heated. Lastly, experiments performed in 18O2 environments show the formation of 18O-substituted uranium oxides; vibrational frequencies for am-U18Ox are reported for the first time. When compared to literature, this work shows that cooling timescales can affect the structural composition of uranium oxides (i.e., crystalline vs. amorphous). This indicator can be used in current models of nuclear explosions to improve our predicative capabilities of chemical speciation.
High energy storage capabilities of CaCu3Ti4O12 for paper-based zinc–air battery
Authors: Bhardwaj Upasana , Sharma Aditi , Gupta Vinay , Batoo Khalid Mujasam , Hussain Sajjad , Kushwaha H. S.
Published: March 2022

Zinc–air batteries proffer high energy density and cyclic stability at low costs but lack disadvantages like sluggish reactions at the cathode and the formation of by-products at the cathode. To resolve these issues, a new perovskite material, CaCu3Ti4O12 (CCTO), is proposed as an efficacious electrocatalyst for oxygen evolution/reduction reactions to develop zinc–air batteries (ZAB). Synthesis of this material adopted an effective oxalate route, which led to the purity in the electrocatalyst composition. The CCTO material is a proven potential candidate for energy applications because of its high dielectric permittivity (ε) and occupies an improved ORR-OER activity with better onset potential, current density, and stability. The Tafel value for CCTO was obtained out to be 80 mV dec−1. The CCTO perovskite was also evaluated for the zinc–air battery as an air electrode, corresponding to the high specific capacitance of 801 mAh g−1 with the greater cyclic efficiency and minimum variations in both charge/discharge processes. The highest power density (Pmax) measured was 127 mW cm−2. Also, the CCTO based paper battery shows an excellent performance achieving a specific capacity of 614 mAh g−1. The obtained results promise CCTO as a potential and cheap electrocatalyst for energy applications.
Single 3′-exonuclease-based multifragment DNA assembly method (SENAX)
Authors: Dao Viet Linh , Chan Sheena , Zhang Jingyun , Ngo Russell Kai Jie , Poh Chueh Loo
Published: March 2022

DNA assembly is a vital process in biotechnology and synthetic biology research, during which DNA plasmids are designed and constructed using bioparts to engineer microorganisms for a wide range of applications. Here, we present an enzymatic homology-based DNA assembly method, SENAX (Stellar ExoNuclease Assembly miX), that can efficiently assemble multiple DNA fragments at ambient temperature from 30 to 37 °C and requires homology overlap as short as 12–18 base pairs. SENAX relies only on a 3′–5′ exonuclease, XthA (ExoIII), followed by Escherichia coli transformation, enabling easy scaling up and optimization. Importantly, SENAX can efficiently assemble short fragments down to 70 bp into a vector, overcoming a key shortcoming of existing commonly used homology-based technologies. To the best of our knowledge, this has not been reported elsewhere using homology-based methods. This advantage leads us to develop a framework to perform DNA assembly in a more modular manner using reusable promoter-RBS short fragments, simplifying the construction process and reducing the cost of DNA synthesis. This approach enables commonly used short bioparts (e.g., promoter, RBS, insulator, terminator) to be reused by the direct assembly of these parts into intermediate constructs. SENAX represents a novel accurate, highly efficient, and automation-friendly DNA assembly method.
Guiding of keV ions between two insulating parallel plates
Authors: DuBois R. D. , Tőkési K. , Giglio E.
Published: March 2022

Experimental data are presented for low-energy singly charged ion transport between two insulating parallel plates. Using a beam intensity of approximately 20 pA, measurements of the incoming and transmitted beams provide quantitative temporal information about the charge deposited on the plates and the guiding probability. Using a smaller beam intensity (~ 1 pA) plate charging and discharging properties were studied as a function of time. These data imply that both the charge deposition and decay along the surface and through the bulk need to be modeled as acting independently. A further reduction of beam intensity to ~ 25 fA allowed temporal imaging studies of the positions and intensities of the guided beam plus two bypass beams to be performed. SIMION software was used to simulate trajectories of the guided and bypass beams, to provide information about the amount and location of deposited charge and, as a function of charge patch voltage, the probability of beam guiding and how much the bypass beams are deflected plus to provide information about the electric fields. An equivalent electric circuit model of the parallel plates, used to associate the deposited charge with the patch voltage implies that the deposited charge is distributed primarily on the inner surface of the plates, transverse to the beam direction, rather than being distributed throughout the entire plate.
Unexpected malocclusion in a 13,000-Year-old Late Pleistocene young woman from Mexico
Authors: Herrera-Atoche José Rubén , Chatters James C. , Cucina Andrea
Published: March 2022

To analyze the etiological factors behind the malocclusion of a Late Pleistocene woman (named Naia), who is the best-preserved of the earliest individuals of the American continent. The examination of Naia’s malocclusion was performed through cephalometric and occlusal analyses, and by measuring her mandible. Her data were then compared to published data for modern, medieval, and postmedieval samples and seven Late Pleistocene individuals. Naia presented her permanent dentition fully erupted, except for the impacted mandibular third molars. She presented a class II molar malocclusion with crowding. The dental widths and mandible measurements were similar to or smaller than modern standards. The degree of dental wear was light. The cephalometric analysis confirmed a skeletal class II relationship, with a retrusive mandible and protruded upper incisors. Naia’s mild level of dental wear is consistent with a low masticatory force, in a time when the norm was a high amount of grinding. The low masticatory forces help explain Naia’s small jaws and crowding. However, it does not clarify Angle’s class II relationship. Naia is an example that environmental factors are insufficient to explain the onset of malocclusions and emphasizes the importance of understanding hereditary factors’ role.
HELP-DKT: an interpretable cognitive model of how students learn programming based on deep knowledge tracing
Authors: Liang Yu , Peng Tianhao , Pu Yanjun , Wu Wenjun
Published: March 2022

Student cognitive models are playing an essential role in intelligent online tutoring for programming courses. These models capture students’ learning interactions and store them in the form of a set of binary responses, thereby failing to utilize rich educational information in the learning process. Moreover, the recent development of these models has been focused on improving the prediction performance and tended to adopt deep neural networks in building the end-to-end prediction frameworks. Although this approach can provide an improved prediction performance, it may also cause difficulties in interpreting the student’s learning status, which is crucial for providing personalized educational feedback. To address this problem, this paper provides an interpretable cognitive model named HELP-DKT, which can infer how students learn programming based on deep knowledge tracing. HELP-DKT has two major advantages. First, it implements a feature-rich input layer, where the raw codes of students are encoded to vector representations, and the error classifications as concept indicators are incorporated. Second, it can infer meaningful estimation of student abilities while reliably predicting future performance. The experiments confirm that HELP-DKT can achieve good prediction performance and present reasonable interpretability of student skills improvement. In practice, HELP-DKT can personalize the learning experience of novice learners.
Evaluation of microbiome enrichment and host DNA depletion in human vaginal samples using Oxford Nanopore’s adaptive sequencing
Authors: Marquet Mike , Zöllkau Janine , Pastuschek Jana , Viehweger Adrian , Schleußner Ekkehard , Makarewicz Oliwia , Pletz Mathias W. , Ehricht Ralf , Brandt Christian
Published: March 2022

Metagenomic sequencing is promising for clinical applications to study microbial composition concerning disease or patient outcomes. Alterations of the vaginal microbiome are associated with adverse pregnancy outcomes, like preterm premature rupture of membranes and preterm birth. Methodologically these samples often have to deal with low relative amounts of prokaryotic DNA and high amounts of host DNA (> 90%), decreasing the overall microbial resolution. Nanopore's adaptive sampling method offers selective DNA depletion or target enrichment to directly reject or accept DNA molecules during sequencing without specialized sample preparation. Here, we demonstrate how selective ‘human host depletion’ resulted in a 1.70 fold (± 0.27 fold) increase in total sequencing depth, providing higher taxonomic profiling sensitivity. At the same time, the microbial composition remains consistent with the control experiments. The complete removal of all human host sequences is not yet possible and should be considered as an ethical approval statement might still be necessary. Adaptive sampling increased microbial sequencing yield in all 15 sequenced clinical routine vaginal samples, making it a valuable tool for clinical surveillance and medical-based research, which can be used in addition to other host depletion methods before sequencing.
Adaptation, psychometric properties and factor structure of the Spanish Quality in Psychiatric Care-Outpatient Staff (QPC-OPS) instrument
Authors: Tomás-Jiménez Manuel , Roldán-Merino Juan , Sanchez-Balcells Sara , Schröder Agneta , Lundqvist Lars-Olov , Puig-Llobet Montserrat , Moreno-Poyato Antonio R. , Domínguez del Campo Marta , Lluch-Canut Maria Teresa
Published: March 2022

Quality of care is a multidimensional concept that should include the perspectives of all parties involved. There are few instruments with adequate psychometric properties for the assessment of the quality of psychiatric care in community mental health. Quality in Psychiatric Care-Outpatient Staff (QPC-OPS) instrument has adequate psychometric properties to evaluate the quality of psychiatric care from the perspective of professionals. The aim of this study was to validate the Spanish version of the QPC-OPS instrument. The instrument was translated and back-translated, and then was administered to 260 professionals from distinct community mental health services. To assess test–retest reliability, it was re-administered after 7–14 days (n = 157). Confirmatory factor analysis revealed an 8-factor-structure identical to the original version, showing the good fit of the model. The internal consistency coefficient (Cronbach’s alpha) was 0.885. The intraclass correlation coefficient was 0.847 (95% IC 0.790–0.888), which was higher than 0.70 in all factors bar one. The NT394 General Satisfaction Scale was used for analysis of convergent validity showing a rho correlation of 0.31 (p < 0.0001). Results show that the Spanish version of the QPC-OPS instrument is valid and reliable for the assessment of the quality of psychiatric care in the community setting.
The curious case of the photochemistry of 2-hydroxyphenylazo-3,5-dimethylisoxazole: unravelling the process among tautomerization, photoisomerization, and conformational changes
Authors: Sah Chitranjan , Mahadevan Anjali , Kumar Pravesh , Venkataramani Sugumar
Published: March 2022

Matrix isolation infrared spectropscopy and computational investigations on the photochemistry of 2-hydroxyphenylazo-3,5-dimethylisoxazole (HPAI).
An accurate many-body expansion potential energy surface for SiH2 (11 A′) using a switching function formalism
Authors: Wang Hainan , Lü Yanling , Chen Jiaxin , Song Yuzhi , Zhang Chengyuan , Li Yongqing
Published: March 2022

The two potential energy curves for H–H bond stretching when r1 = 25 a0 at the MRCI(Q)/AV(Q+d)Z level dissociate inconsistently. A switching function formalism has been utilized to warrant the correct behavior at the Si (1D) + H2 (X1Σ+g) dissociation channels.