bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactory Stimulation Modulates Visual Perception Without Training
Authors: Tsushima Yoshiaki , Nishino Yurie , Ando Hiroshi
Published: August 2021

Considerable research shows that olfactory stimulations affect other modalities in high-level cognitive functions such as emotion. However, little known fact is that olfaction modulates low-level perception of other sensory modalities. Although some studies showed that olfaction had influenced on the other low-level perception, all of them required specific experiences like perceptual training. To test the possibility that olfaction modulates low-level perception without training, we conducted a series of psychophysical and neuroimaging experiments. From the results of a visual task in which participants reported the speed of moving dots, we found that participants perceived the slower motions with a lemon smell and the faster motions with a vanilla smell, without any specific training. In functional magnetic resonance imaging (fMRI) studies, brain activities in the visual cortices [V1 and human middle temporal area (hMT)] changed based on the type of olfactory stimulation. Our findings provide us with the first direct evidence that olfaction modulates low-level visual perception without training, thereby indicating that olfactory-visual effect is not an acquired behavior but an innate behavior. The present results show us with a new crossmodal effect between olfaction and vision, and bring a unique opportunity to reconsider some fundamental roles of olfactory function.
Interaction and Subcellular Association of PRRT1/SynDIG4 With AMPA Receptors
Authors: Martin Emily Eischen , Wleklinski Erica , Hoang Hanh T. M. , Ahmad Mohiuddin
Published: August 2021

AMPA receptors (AMPAR) are organized into supramolecular complexes in association with other membrane proteins that provide exquisite regulation of their biophysical properties and subcellular trafficking. Proline-rich transmembrane protein 1 (PRRT1), also named as SynDIG4, is a component of native AMPAR complexes in multiple brain regions. Deletion of PRRT1 leads to altered surface levels and phosphorylation status of AMPARs, as well as impaired forms of synaptic plasticity. Here, we have investigated the mechanisms underlying the observed regulation of AMPARs by investigating the interaction properties and subcellular localization of PRRT1. Our results show that PRRT1 can interact physically with all AMPAR subunits GluA1-GluA4. We decipher the membrane topology of PRRT1 to find that contrary to the predicted dual membrane pass, only the second hydrophobic segment spans the membrane completely, and is involved in mediating the interaction with AMPARs. We also report a physical interaction of PRRT1 with phosphatase PP2B that dephosphorylates AMPARs during synaptic plasticity. Our co-localization analysis in primary neuronal cultures identifies that PRRT1 associates with AMPARs extrasynaptically where it localizes to early and recycling endosomes as well as to the plasma membrane. These findings advance the understanding of the mechanisms by which PRRT1 regulates AMPARs under basal conditions and during synaptic plasticity.
Anticonvulsant vs. Proconvulsant Effect of in situ Deep Brain Stimulation at the Epileptogenic Focus
Authors: Chou Ping , Kuo Chung-Chin
Published: August 2021

Since deep brain stimulation (DBS) at the epileptogenic focus (in situ) denotes long-term repetitive stimulation of the potentially epileptogenic structures, such as the amygdala, the hippocampus, and the cerebral cortex, a kindling effect and aggravation of seizures may happen and complicate the clinical condition. It is, thus, highly desirable to work out a protocol with an evident quenching (anticonvulsant) effect but free of concomitant proconvulsant side effects. We found that in the basolateral amygdala (BLA), an extremely wide range of pulsatile stimulation protocols eventually leads to the kindling effect. Only protocols with a pulse frequency of ≤1 Hz or a direct current (DC), with all of the other parameters unchanged, could never kindle the animal. On the other hand, the aforementioned DC stimulation (DCS), even a pulse as short as 10 s given 5 min before the kindling stimuli or a pulse given even to the contralateral BLA, is very effective against epileptogenicity and ictogenicity. Behavioral, electrophysiological, and histological findings consistently demonstrate success in seizure quenching or suppression as well as in the safety of the specific DBS protocol (e.g., no apparent brain damage by repeated sessions of stimulation applied to the BLA for 1 month). We conclude that in situ DCS, with a novel and rational design of the stimulation protocol composed of a very low (∼3% or 10 s/5 min) duty cycle and assuredly devoid of the potential of kindling, may make a successful antiepileptic therapy with adequate safety in terms of little epileptogenic adverse events and tissue damage.
Nutrition in Pediatric Extracorporeal Membrane Oxygenation: A Narrative Review
Authors: Toh Theresa S. W. , Ong Chengsi , Mok Yee Hui , Mallory Palen , Cheifetz Ira M. , Lee Jan Hau
Published: August 2021

Extracorporeal membrane oxygenation (ECMO) support is increasingly utilized in quaternary pediatric intensive care units. Metabolic derangements and altered nutritional requirements are common in critically ill children supported on ECMO. However, there remains no consensus on the optimal approach to the prescription of nutrition in these patients. This narrative review aims to summarize the current medical literature on various aspects of nutrition support in pediatric patients on ECMO. These include: (1) nutritional adequacy, (2) pros and cons of feeding on ECMO, (3) enteral vs. parenteral nutrition, and (4) proposed recommendations and future directions for research in this area.
Efficacy of a Novel Bi-Steric mTORC1 Inhibitor in Models of B-Cell Acute Lymphoblastic Leukemia
Authors: Lee Bianca J. , Mallya Sharmila , Dinglasan Nuntana , Fung Amos , Nguyen Tram , Herzog Lee-or , Thao Joshua , Lorenzana Edward G. , Wildes David , Singh Mallika , Smith Jacqueline A. M. , Fruman David A.
Published: August 2021

The mechanistic target of rapamycin (mTOR) is a kinase whose activity is elevated in hematological malignancies. mTOR-complex-1 (mTORC1) phosphorylates numerous substrates to promote cell proliferation and survival. Eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) are mTORC1 substrates with an integral role in oncogenic protein translation. Current pharmacological approaches to inhibit mTORC1 activity and 4E-BP phosphorylation have drawbacks. Recently we described a series of bi-steric compounds that are potent and selective inhibitors of mTORC1, inhibiting 4E-BP phosphorylation at lower concentrations than mTOR kinase inhibitors (TOR-KIs). Here we report the activity of the mTORC1-selective bi-steric inhibitor, RMC-4627, in BCR-ABL-driven models of B-cell acute lymphoblastic leukemia (B-ALL). RMC-4627 exhibited potent and selective inhibition of 4E-BP1 phosphorylation in B-ALL cell lines without inhibiting mTOR-complex-2 (mTORC2) activity. RMC-4627 suppressed cell cycle progression, reduced survival, and enhanced dasatinib cytotoxicity. Compared to a TOR-KI compound, RMC-4627 was more potent, and its effects on cell viability were sustained after washout in vitro. Notably, a once-weekly, well tolerated dose reduced leukemic burden in a B-ALL xenograft model and enhanced the activity of dasatinib. These preclinical studies suggest that intermittent dosing of a bi-steric mTORC1-selective inhibitor has therapeutic potential as a component of leukemia regimens, and further study is warranted.
Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE
Authors: Atkinson Charlotte , Ganeshan Balaji , Endozo Raymond , Wan Simon , Aldridge Matthew D. , Groves Ashley M. , Bomanji Jamshed B. , Gaze Mark N.
Published: August 2021

Purpose

Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value.

Methods

The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis.

Results

Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS.

Conclusion

These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.
Perioperative Intravenous Lidocaine and Metastatic Cancer Recurrence - A Narrative Review
Authors: Wall Thomas P. , Buggy Donal J.
Published: August 2021

Cancer is a major global health problem and the second leading cause of death worldwide. When detected early, surgery provides a potentially curative intervention for many solid organ tumours. Unfortunately, cancer frequently recurs postoperatively. Evidence from laboratory and retrospective clinical studies suggests that the choice of anaesthetic and analgesic agents used perioperatively may influence the activity of residual cancer cells and thus affect subsequent recurrence risk. The amide local anaesthetic lidocaine has a well-established role in perioperative therapeutics, whether used systemically as an analgesic agent or in the provision of regional anaesthesia. Under laboratory conditions, lidocaine has been shown to inhibit cancer cell behaviour and exerts beneficial effects on components of the inflammatory and immune responses which are known to affect cancer biology. These findings raise the possibility that lidocaine administered perioperatively as a safe and inexpensive intravenous infusion may provide significant benefits in terms of long term cancer outcomes. However, despite the volume of promising laboratory data, robust prospective clinical evidence supporting beneficial anti-cancer effects of perioperative lidocaine treatment is lacking, although trials are planned to address this. This review provides a state of the art summary of the current knowledge base and recent advances regarding perioperative lidocaine therapy, its biological effects and influence on postoperative cancer outcomes.
Case Report: A Novel Heterozygous Mutation of CD2AP in a Chinese Family With Proteinuria Leads to Focal Segmental Glomerulosclerosis
Authors: Liu Yu-Xing , Zhang Ai-Qian , Luo Fang-Mei , Sheng Yue , Wang Chen-Yu , Dong Yi , Fan Liangliang , Liu Lv
Published: August 2021

Idiopathic focal segmental glomerulosclerosis (FSGS) is a relatively frequent kidney disorder that manifest clinically as proteinuria and progressive loss of renal function. Genetic factors play a dominant role in the occurrence of FSGS. CD2-associated protein (CD2AP) is an adapter molecule and is essential for the slit-diaphragm assembly and function. Mutations in the CD2AP gene can contribute to FSGS development. Here, we describe a Chinese family of four generations with unexplained proteinuria. The proband, a 12-year-old boy, was diagnosed as FSGS. Whole-exome sequencing (WES) revealed an unknown frameshift insertion mutation (p.K579Efs*7) of CD2AP gene that leads to a truncation of CD2AP protein. Bioinformatics strategies predicted that the novel mutation was pathogenic. The mutation was absent in either healthy family members or our 200 healthy controls. In summary, we used WES to explore the genetic lesion of FSGS patients and identified a novel mutation in CD2AP gene. This work broadens the mutation spectrum of CD2AP gene and provides data for genetic counseling to additional FSGS patients.
Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis
Authors: Hanafin Patrick O. , Sermet-Gaudelus Isabelle , Griese Matthias , Kappler Matthias , Ellemunter Helmut , Schwarz Carsten , Wilson John , Tan Marsha , Velkov Tony , Rao Gauri G. , Schneider-Futschik Elena K.
Published: August 2021

Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited.

Methods: Secondary objectives were to identify (1) patient characteristics and (2) the interactions between ivacaftor-lumacaftor responsible for interindividual variability (IIV).

Results: Peak plasma concentrations (Cmax) of ivacaftor - lumacaftor were >10 fold lower than expected compared to label information. The one-way ANOVA indicated that the patient site had an effect on Cmax values of ivacaftor metabolites ivacaftor-M1, ivacaftor-M6, and lumacaftor (p < 0.001, p < 0.001, and p < 0.001, respectively). The Spearman’s rho test indicated that patient weight and age have an effect on the Cmax of lumacaftor (p = 0.003 and p < 0.001, respectively) and ivacaftor metabolite M1 (p = 0.020 and p < 0.001, respectively). Age (p < 0.001) was found to effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p = 0.026). A large impact of patient characteristics on the IIV of PK parameters Cmax and Tmax, was observed among the CF patients.

Conclusion: Understanding the many sources of variability can help reduce this individual patient variability and ensure consistent patient outcomes.
Molecular and Biomechanical Adaptations to Mechanical Stretch in Cultured Myotubes
Authors: Ren Dapeng , Song Jing , Liu Ran , Zeng Xuemin , Yan Xiao , Zhang Qiang , Yuan Xiao
Published: August 2021

Myotubes are mature muscle cells that form the basic structural element of skeletal muscle. When stretching skeletal muscles, myotubes are subjected to passive tension as well. This lead to alterations in myotube cytophysiology, which could be related with muscular biomechanics. During the past decades, much progresses have been made in exploring biomechanical properties of myotubes in vitro. In this review, we integrated the studies focusing on cultured myotubes being mechanically stretched, and classified these studies into several categories: amino acid and glucose uptake, protein turnover, myotube hypertrophy and atrophy, maturation, alignment, secretion of cytokines, cytoskeleton adaption, myotube damage, ion channel activation, and oxidative stress in myotubes. These biomechanical adaptions do not occur independently, but interconnect with each other as part of the systematic mechanoresponse of myotubes. The purpose of this review is to broaden our comprehensions of stretch-induced muscular alterations in cellular and molecular scales, and to point out future challenges and directions in investigating myotube biomechanical manifestations.
Lung Inflation With Hydrogen During the Cold Ischemia Phase Alleviates Lung Ischemia-Reperfusion Injury by Inhibiting Pyroptosis in Rats
Authors: Zheng Panpan , Kang Jiyu , Xing Entong , Zheng Bin , Wang Xueyao , Zhou Huacheng
Published: August 2021

Background: Lung inflation with hydrogen is an effective method to protect donor lungs from lung ischemia-reperfusion injury (IRI). This study aimed to examine the effect of lung inflation with 3% hydrogen during the cold ischemia phase on pyroptosis in lung grafts of rats.

Methods: Adult male Wistar rats were randomly divided into the sham group, the control group, the oxygen (O2) group, and the hydrogen (H2) group. The sham group underwent thoracotomy but no lung transplantation. In the control group, the donor lungs were deflated for 2 h. In the O2 and H2 groups, the donor lungs were inflated with 40% O2 + 60% N2 and 3% H2 + 40% O2 + 57% N2, respectively, at 10 ml/kg, and the gas was replaced every 20 min during the cold ischemia phase for 2 h. Two hours after orthotopic lung transplantation, the recipients were euthanized.

Results: Compared with the control group, the O2 and H2 groups improved oxygenation indices, decreases the inflammatory response and oxidative stress, reduced lung injury, and improved pressure-volume (P-V) curves. H2 had a better protective effect than O2. Furthermore, the levels of the pyroptosis-related proteins selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase)-1 p20, and the N-terminal of gasdermin D (GSDMD-N) were decreased in the H2 group.

Conclusion: Lung inflation with 3% hydrogen during the cold ischemia phase inhibited the inflammatory response, oxidative stress, and pyroptosis and improved the function of the graft. Inhibiting reactive oxygen species (ROS) production may be the main mechanism of the antipyroptotic effect of hydrogen.
Extracting the Auditory Attention in a Dual-Speaker Scenario From EEG Using a Joint CNN-LSTM Model
Authors: Kuruvila Ivine , Muncke Jan , Fischer Eghart , Hoppe Ulrich
Published: August 2021

Human brain performs remarkably well in segregating a particular speaker from interfering ones in a multispeaker scenario. We can quantitatively evaluate the segregation capability by modeling a relationship between the speech signals present in an auditory scene, and the listener's cortical signals measured using electroencephalography (EEG). This has opened up avenues to integrate neuro-feedback into hearing aids where the device can infer user's attention and enhance the attended speaker. Commonly used algorithms to infer the auditory attention are based on linear systems theory where cues such as speech envelopes are mapped on to the EEG signals. Here, we present a joint convolutional neural network (CNN)—long short-term memory (LSTM) model to infer the auditory attention. Our joint CNN-LSTM model takes the EEG signals and the spectrogram of the multiple speakers as inputs and classifies the attention to one of the speakers. We evaluated the reliability of our network using three different datasets comprising of 61 subjects, where each subject undertook a dual-speaker experiment. The three datasets analyzed corresponded to speech stimuli presented in three different languages namely German, Danish, and Dutch. Using the proposed joint CNN-LSTM model, we obtained a median decoding accuracy of 77.2% at a trial duration of 3 s. Furthermore, we evaluated the amount of sparsity that the model can tolerate by means of magnitude pruning and found a tolerance of up to 50% sparsity without substantial loss of decoding accuracy.
Auricular Neuromodulation for Mass Vagus Nerve Stimulation: Insights From SOS COVID-19 a Multicentric, Randomized, Controlled, Double-Blind French Pilot Study
Authors: Rangon Claire-Marie , Barruet Régine , Mazouni Abdelmadjid , Le Cossec Chloé , Thevenin Sophie , Guillaume Jessica , Léguillier Teddy , Huysman Fabienne , Luis David
Published: August 2021

Importance: An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and could improve the clinical outcomes as an adjunct treatment. We proposed to test it by the stimulation of the auricular branch of the vagus nerve, i.e., auricular neuromodulation (AN), a non-invasive procedure through the insertion of semipermanent needles on the ears.

Objective: The aim of this study was to assess the effect of AN on the clinical outcomes in patients affected by COVID-19.

Design, Setting, and Participants: A multicenter, randomized, placebo-controlled, double-blind clinical trial included 31 patients with respiratory failure due to COVID-19 requiring hospitalization. Within 72 h after admission, patients received either AN (n = 14) or sham neuromodulation (SN, n = 15) in addition to the conventional treatments.

Main Outcome and Measures: The primary endpoint of the study was the rate of a clinical benefit conferred by AN at Day 14 (D14) as assessed by a 7-point Clinical Progression Scale. The secondary endpoint of the study was the impact of AN on the rate of transfer to the intensive care unit (ICU) and on the survival rate at D14.

Results: The AN procedure was well-tolerated without any reported side effects but with no significant improvement for the measures of both primary (p > 0.3) and secondary (p > 0.05) endpoints at the interim analysis. None of the AN-treated patients died but one in the SN group did (81 years). Two AN-treated patients (73 and 79 years, respectively) and one SN-treated patient (59 years) were transferred to ICU. Remarkably, AN-treated patients were older with more representation by males than in the SN arm (i.e., the median age of 75 vs. 65 years, 79% male vs. 47%).

Conclusion: The AN procedure, which was used within 72 h after the admission of patients with COVID-19, was safe and could be successfully implemented during the first two waves of COVID-19 in France. Nevertheless, AN did not significantly improve the outcome of the patients in our small preliminary study. It is pertinent to explore further to validate AN as the non-invasive mass vagal stimulation solution for the forthcoming pandemics.

Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT04341415].
Genetic and Physiological Effects of Insulin on Human Urate Homeostasis
Authors: Mandal Asim K. , Leask Megan P. , Estiverne Christopher , Choi Hyon K. , Merriman Tony R. , Mount David B.
Published: August 2021

Insulin and hyperinsulinemia reduce renal fractional excretion of urate (FeU) and play a key role in the genesis of hyperuricemia and gout, via uncharacterized mechanisms. To explore this association further we studied the effects of genetic variation in insulin-associated pathways on serum urate (SU) levels and the physiological effects of insulin on urate transporters. We found that urate-associated variants in the human insulin (INS), insulin receptor (INSR), and insulin receptor substrate-1 (IRS1) loci associate with the expression of the insulin-like growth factor 2, IRS1, INSR, and ZNF358 genes; additionally, we found genetic interaction between SLC2A9 and the three loci, most evident in women. We also found that insulin stimulates the expression of GLUT9 and increases [14C]-urate uptake in human proximal tubular cells (PTC-05) and HEK293T cells, transport activity that was effectively abrogated by uricosurics or inhibitors of protein tyrosine kinase (PTK), PI3 kinase, MEK/ERK, or p38 MAPK. Heterologous expression of individual urate transporters in Xenopus oocytes revealed that the [14C]-urate transport activities of GLUT9a, GLUT9b, OAT10, OAT3, OAT1, NPT1 and ABCG2 are directly activated by insulin signaling, through PI3 kinase (PI3K)/Akt, MEK/ERK and/or p38 MAPK. Given that the high-capacity urate transporter GLUT9a is the exclusive basolateral exit pathway for reabsorbed urate from the renal proximal tubule into the blood, that insulin stimulates both GLUT9 expression and urate transport activity more than other urate transporters, and that SLC2A9 shows genetic interaction with urate-associated insulin-signaling loci, we postulate that the anti-uricosuric effect of insulin is primarily due to the enhanced expression and activation of GLUT9.
Upregulation of Calcium Homeostasis Modulators in Contractile-To-Proliferative Phenotypical Transition of Pulmonary Arterial Smooth Muscle Cells
Authors: Rodriguez Marisela , Chen Jiyuan , Jain Pritesh P. , Babicheva Aleksandra , Xiong Mingmei , Li Jifeng , Lai Ning , Zhao Tengteng , Hernandez Moises , Balistrieri Angela , Parmisano Sophia , Simonson Tatum , Breen Ellen , Valdez-Jasso Daniela , Thistlethwaite Patricia A. , Shyy John Y. -J. , Wang Jian , Garcia Joe G. N. , Makino Ayako , Yuan Jason X. -J.
Published: August 2021

Excessive pulmonary artery (PA) smooth muscle cell (PASMC) proliferation and migration are implicated in the development of pathogenic pulmonary vascular remodeling characterized by concentric arterial wall thickening and arteriole muscularization in patients with pulmonary arterial hypertension (PAH). Pulmonary artery smooth muscle cell contractile-to-proliferative phenotypical transition is a process that promotes pulmonary vascular remodeling. A rise in cytosolic Ca2+ concentration [(Ca2+)cyt] in PASMCs is a trigger for pulmonary vasoconstriction and a stimulus for pulmonary vascular remodeling. Here, we report that the calcium homeostasis modulator (CALHM), a Ca2+ (and ATP) channel that is allosterically regulated by voltage and extracellular Ca2+, is upregulated during the PASMC contractile-to-proliferative phenotypical transition. Protein expression of CALHM1/2 in primary cultured PASMCs in media containing serum and growth factors (proliferative PASMC) was significantly greater than in freshly isolated PA (contractile PASMC) from the same rat. Upregulated CALHM1/2 in proliferative PASMCs were associated with an increased ratio of pAKT/AKT and pmTOR/mTOR and an increased expression of the cell proliferation marker PCNA, whereas serum starvation and rapamycin significantly downregulated CALHM1/2. Furthermore, CALHM1/2 were upregulated in freshly isolated PA from rats with monocrotaline (MCT)-induced PH and in primary cultured PASMC from patients with PAH in comparison to normal controls. Intraperitoneal injection of CGP 37157 (0.6 mg/kg, q8H), a non-selective blocker of CALHM channels, partially reversed established experimental PH. These data suggest that CALHM upregulation is involved in PASMC contractile-to-proliferative phenotypical transition. Ca2+ influx through upregulated CALHM1/2 may play an important role in the transition of sustained vasoconstriction to excessive vascular remodeling in PAH or precapillary PH. Calcium homeostasis modulator could potentially be a target to develop novel therapies for PAH.
Iron Deficiency Leads to Chlorosis Through Impacting Chlorophyll Synthesis and Nitrogen Metabolism in Areca catechu L.
Authors: Li Jia , Cao Xianmei , Jia Xiaocheng , Liu Liyun , Cao Haowei , Qin Weiquan , Li Meng
Published: August 2021

Deficiency of certain elements can cause leaf chlorosis in Areca catechu L. trees, which causes considerable production loss. The linkage between nutrient deficiency and chlorosis phenomenon and physiological defect in A. catechu remains unclear. Here, we found that low iron supply is a determinant for chlorosis of A. catechu seedling, and excessive iron supply resulted in dark green leaves. We also observed morphological characters of A. catechu seedlings under different iron levels and compared their fresh weight, chlorophyll contents, chloroplast structures and photosynthetic activities. Results showed that iron deficiency directly caused chloroplast degeneration and reduced chlorophyll synthesis in chlorosis leaves, while excessive iron treatment can increase chlorophyll contents, chloroplasts sizes, and inflated starch granules. However, both excessive and deficient of iron decreases fresh weight and photosynthetic rate in A. catechu seedlings. Therefore, we applied transcriptomic and metabolomic approaches to understand the effect of different iron supply to A. catechu seedlings. The genes involved in nitrogen assimilation pathway, such as NR (nitrate reductase) and GOGAT (glutamate synthase), were significantly down-regulated under both iron deficiency and excessive iron. Moreover, the accumulation of organic acids and flavonoids indicated a potential way for A. catechu to endure iron deficiency. On the other hand, the up-regulation of POD-related genes was assumed to be a defense strategy against the excessive iron toxicity. Our data demonstrated that A. catechu is an iron-sensitive species, therefore the precise control of iron level is believed to be the key point for A. catechu cultivation.
Study of Effective Corridor Design to Improve Wayfinding in Underground Malls
Authors: Zhang Shaoqing , Park Soobeen
Published: August 2021

In retail space, wayfinding difficulties can cause problems, such as loss of time, stress, or discomfort, negatively affecting the shopping experience of consumers and even their patronage intentions. Although studies have reported that space configuration may facilitate navigation, there has been a lack of detailed discussion, particularly in underground malls, where people often encounter wayfinding issues. In this study, a series of exit-finding tasks in virtual malls were simulated to determine if it was practical to encourage turn taking by changing the corridor width, length, height, or angle. The results showed that people have a right-turn preference during exit finding. Moreover, exit-finders mostly prefer taking the upward pathway via stairs followed by corridors with broader widths or curved corners, exhibiting visible and similar navigation effects. Shorter corridors have a visible but relatively small affinity. This study provides some empirical evidence of how the corridor configuration influences the turn taking of people and provides a theoretical reference for adding a guiding function to the spatial arrangement in underground malls.
When the Idiom Advantage Comes Up Short: Eye-Tracking Canonical and Modified Idioms
Authors: Kyriacou Marianna , Conklin Kathy , Thompson Dominic
Published: August 2021

The literature on idioms often talks about an “idiom advantage,” such that familiar idioms (spill the beans) are generally processed faster than comparable literal phrases (burn the beans). More recently, researchers have explored the processing of idiom modification and while a few studies indicate that familiarity benefits the processing of modified forms, the extent of this facilitation is unknown. In an eye-tracking study, we explored whether familiar idioms and modified versions with 1 or 2 adjectives {spill the [spicy, (red)]beans} are processed faster than matched literal phrases {burn the [spicy, (red)]beans} when both were preceded by a biasing context. The results showed that adjectives inserted in idioms induced longer fixations and were more likely to elicit a regression. However, idiom verbs and final words were processed with the same ease in all adjective conditions, implying that modifying idioms did not impede their processing. In contrast to the widely reported “idiom advantage,” the results demonstrated that canonical and modified idioms wereslowerto read relative to matched literal controls. This was taken to reflect the competition between an idiom’s literal and figurative meaning, and subsequently the need to select and integrate the contextually appropriate one. In contrast, meaning integration in literal, unambiguous phrases was easier. We argue that processing costs associated with meaning selection may only manifest when idioms are preceded by a biasing context that allows disambiguation to occur in the idiom region, and/or when literal control phrases are contextually appropriate and carefully matched to idioms. Thus, idiom recognition/activation may elicit the well attested idiom advantage, while meaning selection and integration may come at a cost, and idiom modifications may simply add to the cognitive load.
Investigating Links Between Fear of COVID-19, Neuroticism, Social Networks Use Disorder, and Smartphone Use Disorder Tendencies
Authors: Montag Christian , Sindermann Cornelia , Rozgonjuk Dmitri , Yang Shixin , Elhai Jon D. , Yang Haibo
Published: August 2021

The present study investigates links between fear of COVID-19, the personality trait of neuroticism, social networks use disorder, and smartphone use disorder (SNUD and SmUD, respectively) tendencies. In an online survey, N = 932 participants recruited at a Chinese University (237 males and 695 females) completed self-reports on fear of COVID-19, neuroticism (and other personality traits from the Big Five Inventory-44), the Bergen Social Media Addiction Scale (assessing tendencies toward SNUD), and the Smartphone Addiction Scale short version—assessing individual differences in tendencies toward SmUD.

Our findings showed that all variables of main interest were positively correlated with each other. A mediation model suggested that SNUD (in parts) mediated the association between fear of COVID-19 and SmUD. Although neuroticism was robustly correlated with all mentioned variables, no moderation effect could be observed on the investigated fear-of-COVID-19-SNUD-link.

The findings of this work provide further evidence that the smartphone itself is only a device giving individuals access to software applications, which might be excessively used. Beyond that, the present data indicate neuroticism to be a risk factor with respect to fear of COVID-19, SNUD, and SmUD, although the study is limited by its cross-sectional study design.
Therapy Management of Metabolic Disorder Comorbidity With Depression
Authors: Luo Hua , Jiang Zheng-Li , Ren Yu
Published: August 2021

Depression is a common disease that seriously endangers the physical and mental health of human beings, and it often coexists with other metabolic disorders such as diabetes and cancer. There have been endless reports on the mechanism, prevention, and cure of comorbidity because of its high incidence and poor prognosis and the increased burden on the family and society. There may be a specific comorbid basis and causal relationship between depression and metabolic diseases. Depression in patients with metabolic disorders can be effectively alleviated through psychotherapy and medication. The timely and effective treatment of depression can significantly improve the quality of life of patients with metabolic disorders, reduce their psychological burden, and promote the effective treatment of metabolic diseases. This study reorganized the research progress on the management of metabolic disorder comorbidity with depression.
Impact of Perceived Severity of COVID-19 (SARS-COV-2) on Mental Health of University Students of Pakistan: The Mediating Role of Muslim Religiosity
Authors: Saleem Muhammad , Bakar Abou , Durrani Areeha Khan , Manzoor Zubair
Published: August 2021

Background: Perceived severity of COVID-19 (SARS-COV-2) is known to be associated with mental health of people in general and health professionals in particular in Western societies. However, its association with the mental health of students in Pakistan, which is predominantly a Muslim society, remains unclear so far. Moreover, the role of Muslim religiosity for such an association has not yet been investigated. We aimed to examine the association and report findings on the impact of perceived severity on mental health with a sample of students from all five provinces of Pakistan.

Methods: We did a cross-sectional online survey from 1,525 Pakistani students in March 2020 using standardized measurement tools. We then determined the prevalence of perceived severity among students and its impact on their mental health. The strength of associations between these variables was estimated using generalized linear models, with appropriate distribution and link functions. Structural equation modeling through SmartPLS (3.0) software was utilized to analyze the results.

Findings: The perceived severity of COVID-19 is significantly associated with mental health of Pakistani students, whereas Muslim religiosity is a strong mediator between perceived severity and mental health of Pakistani students.

Conclusions: Though the perceived severity of COVID-19 is associated with mental health, this relationship can be better explained by the role of Muslim religiosity. When tested individually, the perceived severity accounted for only 18% variance in mental health that increased up to 57% by the mediating role of Muslim religiosity. This difference clearly indicates the mediating role of Muslim religiosity in the association between perceived severity and mental health for Pakistani students.
Conflicts Between Women's Religiosity and Sense of Free Will in the Context of Elective Abortion: A Qualitative Study in the Worst Period of Italy's COVID-19 Crisis
Authors: Testoni Ines , Finco Nicoletta , Keisari Shoshi , Orkibi Hod , Azoulay Bracha
Published: August 2021

This qualitative study considers the relationship between abortion, bereavement, and the effects of the COVID-19 lockdown nine women who had undergone an elective abortion, which is voluntarily termination of a pregnancy at the woman's request. These women were interviewed in three time points (1 month, 6 months, and 1 year after the event) to consider the possible evolution of their experience. The third phase was concurrent with the COVID-19 pandemic and particularly with Pope Francis's Easter declaration against abortion. All the interviews were conducted and analysed through qualitative research in psychology. Results showed that the abortion experience led to physical, relational, and psychological suffering, similar to perinatal grief. Participants were non-practising Catholics and religiosity did not help them to overcome their sorrow. Though religiosity is a possible resilience factor in other stressful conditions, in this case it is a factor that aggravated suffering. Finally, we discuss the difficulties experienced by Catholic women who choose to have an abortion and assert the necessity of psychological and spiritual interventions to support these women.
Developing a Tool to Measure Person-Centered Care in Service Planning
Authors: Stanhope Victoria , Baslock Daniel , Tondora Janis , Jessell Lauren , Ross Abigail M. , Marcus Steven C.
Published: August 2021

Background: Delivering person-centered care is a key component of health care reform. Despite widespread endorsement, medical and behavioral health settings struggle to specify and measure person-centered care objectively. This study presents the validity and reliability of the Person-Centered Care Planning Assessment Measure (PCCP-AM), an objective measure of the extent to which service planning is person-centered.

Methods: Based upon the recovery-oriented practice of person-centered care planning, the 10-item PCCP-AM tool rates service plans on the inclusion of service user strengths, personal life goals, natural supports, self-directed actions and the promotion of community integration. As part of a large randomized controlled trial of person-centered care planning, service plans completed by community mental health clinic providers were rated using the PCCP-AM. Reliability was tested by calculating inter-rater reliability across 168 plans and internal consistency across 798 plans. To test concurrent validity, PCCP-AM scores for 84 plans were compared to expert rater scores on a separate instrument.

Results: Interrater reliability for each of the 10 PCCP-AM items as measured by Kendall's W ranged from W = 0.77 to W = 0.89 and percent of scores within ± 1 point of each other ranged from 85.7 to 100%. Overall internal consistency as measured by Cronbach's alpha across 798 plans was α = 0.72. Concurrent validity as measured by Kendall's W ranged from W = 0.55 to W = 0.74 and percent of item scores within ± 1 point of expert rater scores ranged from 73.8 to 86.8%.

Conclusions: Findings demonstrated that the 10-item PCCP-AM was a valid and reliable objective measure of person-centered care. Using the service plan as an indicator of multiple domains of person-centered care, the measure provides a valuable tool to inform clinical supervision and quality improvement across programs. More psychometric testing is needed to strengthen the measure for research purposes.
Brain-Specific Oxysterols and Risk of Schizophrenia in Clinical High-Risk Subjects and Patients With Schizophrenia
Authors: Sun Zuoli , Zhao Lei , Bo Qijing , Mao Zhen , He Yi , Jiang Tao , Li Yuhong , Wang Chuanyue , Li Rena
Published: August 2021

Accumulating evidence from clinical, genetic, and epidemiologic studies suggest that schizophrenia might be a neuronal development disorder. While oxysterols are important factors in neurodevelopment, it is unknown whether oxysterols might be involved in development of schizophrenia. The present study investigated the relationship between tissue-specifically originated oxysterols and risk of schizophrenia. A total of 216 individuals were recruited in this study, including 76 schizophrenia patients, 39 clinical high-risk (CHR) subjects, and 101 healthy controls (HC). We investigated the circulating levels of brain-specific oxysterol 24(S)-hydroxycholesterol (24OHC) and peripheral oxysterol 27-hydroxycholesterol (27OHC) in all participants and analyzed the potential links between the oxysterols and specific clinical symptoms in schizophrenic patients and CHR. Our data showed an elevation of 24OHC in both schizophrenia patients and CHR than that in HC, while a lower level of 27OHC in the schizophrenia group only. The ratio of 24OHC to 27OHC was only increased in the schizophrenic group compared with CHR and HC. For the schizophrenic patients, the circulating 24OHC levels are significantly associated with disease duration, positively correlated with the positive and negative syndrome total scores, while the 27OHC levels were inversely correlated with the positive symptom scores. Together, our data demonstrated the disruption of tissue-specifically originated cholesterol metabolism in schizophrenia and CHR, suggesting the circulating 24OHC or 24OHC/27OHC ratio might not only be a potential indicator for risk for schizophrenia but also be biomarkers for functional abnormalities in neuropathology of schizophrenia.
An Exploration of Child–Staff Interactions That Promote Physical Activity in Pre-School
Authors: Kippe Karin Oddbjørg , Fossdal Tom Stian , Lagestad Pål Arild
Published: August 2021

A previous study identified a significant association between the average physical activity levels of pre-school staff and children during pre-school hours but did not determine if this association was initiated by pre-school staff or children. The present study aimed to explore the interactions between children and staff to better understand the conditions of such a relationship. Observations using the Environment and Policy Assessment and Observation (EPAO) protocol were carried out in three pre-schools, and a focus-group interview and semiformal interviews were conducted with five pre-school staff in one of the three pre-schools to examine the research question. Both the observations and the interview data revealed that physical activity by pre-school staff initiated physical activity among the children. The findings pointing to the importance of pre-school staff as organizers of the physical activity of children and the willingness of staff to join a physical activity initiated by the children also appear to be important. The findings also indicate that most of the physical activity took place outdoors. The study highlights the importance of pre-school staff as major contributors to the physical activity of pre-school children.
Impact of COVID-19 Related Lockdown on the Frequency of Acute and Oncological Surgeries—Lessons Learned From an Austrian University Hospital
Authors: Abram Julia , Gasteiger Lukas , Putzer Gabriel , Spraider Patrick , Mathis Simon , Hell Tobias , Martini Judith
Published: August 2021

Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.
Exploring Pathways of Socioeconomic Inequity in Vegetable Expenditure Among Consumers Participating in a Grocery Loyalty Program in Quebec, Canada, 2015–2017
Authors: Ma Yu , McRae Cameron , Wu Yun-Hsuan , Dubé Laurette
Published: August 2021

Vegetable consumption remains consistently low despite supportive policy and investments across the world. Vegetables are available in great variety, ranging in their processing level, availability, cost, and arguably, nutritional value. A retrospective longitudinal study was conducted in Quebec, Canada to explore pathways of socioeconomic inequity in vegetable expenditure. Data was obtained for consumers who participated in a grocery loyalty program from 2015 to 2017 and linked to the 2016 Canadian census. Vegetable expenditure share (%) was examined as a fraction of the overall food basket and segmented by processing level. Panel random effects and tobit models were used overall and to estimate the stratified analysis by median income split. Consumers allocated 8.35% of their total food expenditure to vegetables, which was mostly allocated to non-processed fresh (6.88%). Vegetable expenditure share was the highest in early winter and lowest in late summer. In the stratified analysis, the low-income group exhibited less seasonal variation, allocated less to fresh vegetables, and spent more on canned and frozen compared to the high-income group. Measures of socioeconomic status were all significant drivers of overall vegetable consumption. Consumers with high post-secondary education in the low-income group spent 2% more on vegetables than those with low education. The complexity of observed expenditure patterns points to a need for more specific vegetable consumption guidelines that include provisions by processing level. Implications for education, marketing, intersectional policies, and the role of government are discussed. Governments can scale present efforts and catalyze health-promoting investments across local, state, national, and global food systems.