bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multidisciplinary Guidelines for Diagnosis and Referral in Cerebral Visual Impairment
Authors: Boonstra Frouke N. , Bosch Daniëlle G. M. , Geldof Christiaan J. A. , Stellingwerf Catharina , Porro Giorgio
Published: June 2022

Introduction

Cerebral visual impairment (CVI) is an important cause of visual impairment in western countries. Perinatal hypoxic-ischemic damage is the most frequent cause of CVI but CVI can also be the result of a genetic disorder. The majority of children with CVI have cerebral palsy and/or developmental delay. Early diagnosis is crucial; however, there is a need for consensus on evidence based diagnostic tools and referral criteria. The aim of this study is to develop guidelines for diagnosis and referral in CVI according to the grade method.

Patients and Methods

We developed the guidelines according to the GRADE method 5 searches on CVI (children, developmental age ≤ 18 years) were performed in the databases Medline, Embase, and Psychinfo, each with a distinct topic.

Results

Based on evidence articles were selected on five topics: 1. Medical history and CVI-questionnaires 23 (out of 1,007). 2. Ophthalmological and orthoptic assessment 37 (out of 816). 3. Neuropsychological assessment 5 (out of 716). 4. Neuroradiological evaluation and magnetic resonance imaging (MRI) 9 (out of 723). 5. Genetic assessment 5 (out of 458).

Conclusion

In medical history taking, prematurity low birth weight and APGAR (Appearance, Pulse, Grimace, Activity, Respiration) Scores (<5) are important. Different questionnaires are advised for children under the age of 3 years, older children and for specific risk groups (extremely preterm). In ophthalmological examination, eye movements, specially saccades, accommodation, crowding, contrast sensitivity and visual fields should be evaluated. OCT can show objective signs of trans-synaptic degeneration and abnormalities in fixation and saccades can be measured with eye tracking. Screening of visual perceptive functioning is recommended and can be directive for further assessment. MRI findings in CVI in Cerebral Palsy can be structured in five groups: Brain maldevelopment, white and gray matter lesions, postnatal lesions and a normal MRI. In children with CVI and periventricular leukomalacia, brain lesion severity correlates with visual function impairment. A differentiation can be made between cortical and subcortical damage and related visual function impairment. Additional assessments (neurological or genetic) can be necessary to complete the diagnosis of CVI and/or to reveal the etiology.
The Effect of Hemoglobin Concentration on Hyperbaric Oxygen and Non-hyperbaric Oxygen in the Treatment of Hypertensive Intracerebral Hemorrhage After Operation at the High Altitude
Authors: Wei Linjie , Lin Chi , Xue Xingsen , Jila Shiju , Dai Yalan , Pan Li , Wei Wei , Dun Guodong , Shen Yong , Zong Taoxi , Wu Jingjing , Li Yafang , Wu Lixia , Xian Jishu , Yu Anyong
Published: June 2022

Background

The prognosis of hypertensive intracerebral hemorrhage (HICH) is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen (HBO) can improve the results of computed tomography perfusion (CTP) imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration.

Method

The patients with HICH were treated with puncture and drainage. Twenty-one patients (51.22% of 41 patients in total) were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic (ROC) curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months.

Results

Forty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group’s hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale (GOS) scores of the HBO group were significantly higher than those of the control group (p < 0.05).

Conclusions

HBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission.
Characterizing Pelvic Floor Muscle Activity During Walking and Jogging in Continent Adults: A Cross-Sectional Study
Authors: Williams Alison M. M. , Sato-Klemm Maya , Deegan Emily G. , Eginyan Gevorg , Lam Tania
Published: June 2022

Introduction

The pelvic floor muscles (PFM) are active during motor tasks that increase intra-abdominal pressure, but little is known about how the PFM respond to dynamic activities, such as gait. The purpose of this study was to characterize and compare PFM activity during walking and jogging in continent adults across the entire gait cycle.

Methods

17 able-bodied individuals (8 females) with no history of incontinence participated in this study. We recorded electromyography (EMG) from the abdominal muscles, gluteus maximus (GM), and PFM while participants performed attempted maximum voluntary contractions (aMVC) of all muscles and completed 60–70 strides in four gait conditions: slow walk (1 km/h); regular walk (self-selected comfortable pace); transition walk (self-selected fastest walking pace); jog (same speed as transition walking). We quantified activity throughout the whole gait cycle (%aMVCGC) and during periods of bursting (%aMVCBR) for each participant, and analyzed the timing of PFM bursting periods to explore when the PFM were most active in the gait cycle. We also conducted a phase metric analysis on the PFM and GM burst timings. We performed a Spearman's rank-order correlation to examine the effect of speed on %aMVCGC, %aMVCBR, and phase metric score, and used the Wilcoxon Signed-Rank test to evaluate the effect of gait modality, matched for speed (walking vs. jogging), on these variables.

Results

The PFM were active throughout the gait cycle, with bursts typically occurring during single-leg support. The PFM and GM were in phase for 44–69% of the gait cycle, depending on condition. There was a positive correlation between gait speed and both %aMVCGC and %aMVCBR (p < 0.001). Phase metric scores were significantly higher during jogging than transition walking (p = 0.005), but there was no difference between gait modality on %aMVCGC or %aMVCBR (p = 0.059). Where possible we disaggregated data by sex, although were unable to make statistical comparisons due to low sample sizes.

Conclusion

The PFM are active during walking and jogging, with greater activity at faster speeds and with bursts in activity around single-leg support. The PFM and GM co-activate during gait, but are not completely in phase with each other.
The Effect of Neuroepo on Cognition in Parkinson’s Disease Patients Is Mediated by Electroencephalogram Source Activity
Authors: Bringas Vega Maria L. , Pedroso Ibáñez Ivonne , Razzaq Fuleah A. , Zhang Min , Morales Chacón Lilia , Ren Peng , Galan Garcia Lidice , Gan Peng , Virues Alba Trinidad , Lopez Naranjo Carlos , Jahanshahi Marjan , Bosch-Bayard Jorge , Valdes-Sosa Pedro A.
Published: June 2022

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson’s disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG.
Multiple-Kernel Support Vector Machine for Predicting Internet Gaming Disorder Using Multimodal Fusion of PET, EEG, and Clinical Features
Authors: Jeong Boram , Lee Jiyoon , Kim Heejung , Gwak Seungyeon , Kim Yu Kyeong , Yoo So Young , Lee Donghwan , Choi Jung-Seok
Published: June 2022

Internet gaming disorder (IGD) has become an important social and psychiatric issue in recent years. To prevent IGD and provide the appropriate intervention, an accurate prediction method for identifying IGD is necessary. In this study, we investigated machine learning methods of multimodal neuroimaging data including Positron Emission Tomography (PET), Electroencephalography (EEG), and clinical features to enhance prediction accuracy. Unlike the conventional methods which usually concatenate all features into one feature vector, we adopted a multiple-kernel support vector machine (MK-SVM) to classify IGD. We compared the prediction performance of standard machine learning methods such as SVM, random forest, and boosting with the proposed method in patients with IGD (N = 28) and healthy controls (N = 24). We showed that the prediction accuracy of the optimal MK-SVM using three kinds of modalities was much higher than other conventional machine learning methods, with the highest accuracy being 86.5%, the sensitivity 89.3%, and the specificity 83.3%. Furthermore, we deduced that clinical variables had the highest contribution to the optimal IGD prediction model and that the other two modalities were also indispensable. We found that more efficient integration of multimodal data through kernel combination could contribute to better performance of the prediction model. This study is a novel attempt to integrate each method from different sources and suggests that integrating each method, such as self-administrated reports, PET, and EEG, improves the prediction of IGD.
Distinct Phenotypes of Inflammation Associated Macrophages and Microglia in the Prefrontal Cortex Schizophrenia Compared to Controls
Authors: Zhu Yunting , Webster Maree J. , Murphy Caitlin E. , Middleton Frank A. , Massa Paul T. , Liu Chunyu , Dai Rujia , Weickert Cyndi Shannon
Published: June 2022

Approximately 40% of people with schizophrenia are classified as having “high inflammation.” This subgroup has worse neuropathology than patients with “low inflammation.” Thus, one would expect the resident microglia and possibly monocyte-derived macrophages infiltrating from the periphery to be “activated” in those with schizophrenia with elevated neuroinflammation. To test whether microglia and/or macrophages are associated with increased inflammatory signaling in schizophrenia, we measured microglia- and macrophage-associated transcripts in the postmortem dorsolateral prefrontal cortex of 69 controls and 72 people with schizophrenia. Both groups were stratified by neuroinflammatory status based on cortical mRNA levels of cytokines and SERPINA3. We found microglial mRNAs levels were either unchanged (IBA1 and Hexb, p > 0.20) or decreased (CD11c, <62% p < 0.001) in high inflammation schizophrenia compared to controls. Conversely, macrophage CD163 mRNA levels were increased in patients, substantially so in the high inflammation schizophrenia subgroup compared to low inflammation subgroup (>250%, p < 0.0001). In contrast, high inflammation controls did not have elevated CD163 mRNA compared to low inflammation controls (p > 0.05). The pro-inflammatory macrophage marker (CD64 mRNA) was elevated (>160%, all p < 0.05) and more related to CD163 mRNA in the high inflammation schizophrenia subgroup compared to high inflammation controls, while anti-inflammatory macrophage and cytokine markers (CD206 and IL-10 mRNAs) were either unchanged or decreased in schizophrenia. Finally, macrophage recruitment chemokine CCL2 mRNA was increased in schizophrenia (>200%, p < 0.0001) and CCL2 mRNA levels positively correlated with CD163 mRNA (r = 0.46, p < 0.0001). Collectively, our findings support the co-existence of quiescent microglia and increased pro-inflammatory macrophages in the cortex of people with schizophrenia.
A Strength Endurance Exercise Paradigm Mitigates Deficits in Hypoglossal-Tongue Axis Function, Strength, and Structure in a Rodent Model of Hypoglossal Motor Neuron Degeneration
Authors: Murphy Erika R. , Thompson Rebecca , Osman Kate L. , Haxton Chandler , Brothers Margaret , Lee Li , Warncke Kristen , Smith Catherine L. , Keilholz Amy N. , Hamad Ali , Golzy Mojgan , Bunyak Filiz , Ma Lixin , Nichols Nicole L. , Lever Teresa E.
Published: June 2022

The tongue plays a crucial role in the swallowing process, and impairment can lead to dysphagia, particularly in motor neuron diseases (MNDs) resulting in hypoglossal-tongue axis degeneration (e.g., amyotrophic lateral sclerosis and progressive bulbar palsy). This study utilized our previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis. This model was created by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Our goal was to investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure in four groups of male rats: (1) control + sham exercise (n = 13); (2) control + exercise (n = 10); (3) CTB-SAP + sham exercise (n = 13); and (4) CTB-SAP + exercise (n = 12). For each group, a custom spout with adjustable lick force requirement for fluid access was placed in the home cage overnight on days 4 and 6 post-tongue injection. For the two sham exercise groups, the lick force requirement was negligible. For the two exercise groups, the lick force requirement was set to ∼40% greater than the maximum voluntary lick force for individual rats. Following exercise exposure, we evaluated the effect on hypoglossal-tongue axis function (via videofluoroscopy), strength (via force-lickometer), and structure [via Magnetic Resonance Imaging (MRI) of the brainstem and tongue in a subset of rats]. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted. MRI revealed corresponding degenerative changes in the hypoglossal-tongue axis that were mitigated by tongue exercise. These collective findings suggest that high-repetition/low-resistance tongue exercise in our model is a safe and effective treatment to prevent/diminish signs of hypoglossal-tongue axis degeneration. The next step is to leverage our rat model to optimize exercise dosing parameters and investigate corresponding treatment mechanisms of action for future translation to MND clinical trials.
Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice
Authors: Aomine Yoshiatsu , Sakurai Koki , Macpherson Tom , Ozawa Takaaki , Miyamoto Yoichi , Yoneda Yoshihiro , Oka Masahiro , Hikida Takatoshi
Published: June 2022

Importin α3 (Gene: Kpna3, the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP) in the KPNA3 gene are associated with the occurrence of several psychiatric disorders accompanied by abnormal reward-related behavior, including schizophrenia, major depression, and substance addiction. However, the precise roles of importin α3 in controlling reward processing and motivation are still unclear. In this study, we evaluated the behavioral effects of Kpna3 knockout (KO) in mice on performance in touchscreen operant chamber-based tasks evaluating simple (fixed-ratio) and effortful (progressive-ratio) reward-seeking behaviors. While Kpna3 KO mice showed no significant differences in operant reward learning on a fixed-ratio schedule, they demonstrated significantly increased motivation (increased break point) to instrumentally respond for sucrose on a progressive-ratio schedule. We additionally measured the number of c-Fos-positive cells, a marker of neural activity, in 20 regions of the brain and identified a network of brain regions based on their interregional correlation coefficients. Network and graph-theoretic analyses suggested that Kpna3 deficiency enhanced overall interregional functional connectivity. These findings suggest the importance of Kpna3 in motivational control and indicate that Kpna3 KO mice may be an attractive line for modeling motivational abnormalities associated with several psychiatric disorders.
Abnormal Voxel-Based Degree Centrality in Patients With Postpartum Depression: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Zhang Shufen , Li Bo , Liu Kai , Hou Xiaoming , Zhang Ping
Published: June 2022

Postpartum depression (PPD) is a major public health concern with significant consequences for mothers, their children, and their families. However, less is known about its underlying neuropathological mechanisms. The voxel-based degree centrality (DC) analysis approach provides a new perspective for exploring the intrinsic dysconnectivity pattern of whole-brain functional networks of PPD. Twenty-nine patients with PPD and thirty healthy postpartum women were enrolled and received resting-state functional magnetic resonance imaging (fMRI) scans in the fourth week after delivery. DC image, clinical symptom correlation, and seed-based functional connectivity (FC) analyses were performed to reveal the abnormalities of the whole-brain functional network in PPD. Compared with healthy controls (HCs), patients with PPD exhibited significantly increased DC in the right hippocampus (HIP.R) and left inferior frontal orbital gyrus (ORBinf.L). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the above two brain regions is all over 0.7. In the seed-based FC analyses, the PPD showed significantly decreased FC between the HIP.R and right middle frontal gyrus (MFG.R), between the HIP.R and left median cingulate and paracingulate gyri (DCG.L), and between the ORBinf.L and the left fusiform (FFG.L) compared with HCs. The PPD showed significantly increased FC between the ORBinf.L and the right superior frontal gyrus, medial (SFGmed.R) compared with HCs. Mean FC between the HIP.R and DCG.L positively correlated with EDPS scores in the PPD group. This study provided evidence of aberrant DC and FC within brain regions in patients with PPD, which was associated with the default mode network (DMN) and limbic system (LIN). Identification of these above-altered brain areas may help physicians to better understand neural circuitry dysfunction in PPD.
Whole-Blood MicroRNA Sequence Profiling and Identification of Specific miR-21 for Adolescents With Postural Tachycardia Syndrome
Authors: Lin Jing , Shen Jie , Liu Juan , Cheng Wenjie , Li Lintian , Jiao Fuyong
Published: June 2022

Objective

The aim of the study was to establish whether whole-blood microRNA (miRNA) profiles differ between postural tachycardia syndrome (POTS) sufferers and control subjects and to identify the miRNA that regulates plasma H2S.

Study Design

High-throughput sequencing was used to obtain whole-blood miRNA expression profiles for 20 POTS sufferers and 20 normal children.The thresholds for defining differentially expressed miRNAs (DEmiRNAs) were an adjusted DESeq P of <0.05 and a log2 fold variation of ≥3. The DEmiRNA target genes were identified using RNAhybrid and miRanda, and only those identified by both were considered. The combined effects of the DEmiRNAs were determined using KEGG pathway analysis. Another 40 POTS and 20 normal patients were used as validation subjects. Plasma H2S was determined with a sulfide electrode, and flow-mediated vasodilation (FMD) was performed with a color Doppler ultrasound system. miRNAs were analyzed using qRT-PCR.

Results

Totally, 13 DEmiRNAs were identified through high-throughput sequencing. In the 60-member validation group, the 13 miRNAs were verified again, and it turned out that miR-21 was significantly elevated and could diagnose POTS with a 100% specificity and 92.5% sensitivity. Overall, 198 and 481 genes, respectively, were shown to be targeted by the 13 DEmiRNAs when P values of 0.01 and 0.05 were used. The target gene of hsa-miR-21-5p was SP1 when the P-value is <0.01. DEmiRNAs were significantly enriched in 36 pathways (P < 0.05), in which PI3K/Akt signaling was closely related to vascular function. In the validation subjects, the plasma H2S and FMD were higher in the POTS sufferers (P < 0.05).

Conclusion

Elevated whole-blood miR-21 levels serve as an indicator for POTS and may explain the increased plasma H2S observed in POTS sufferers.
New Retinal Pigment Epithelial Cell Model to Unravel Neuroprotection Sensors of Neurodegeneration in Retinal Disease
Authors: Asatryan Aram , Calandria Jorgelina M. , Kautzmann Marie-Audrey I. , Jun Bokkyoo , Gordon William C. , Do Khanh V. , Bhattacharjee Surjyadipta , Pham Thang L. , Bermúdez Vicente , Mateos Melina Valeria , Heap Jessica , Bazan Nicolas G.
Published: June 2022

Retinal pigment epithelial (RPE) cells sustain photoreceptor integrity, and when this function is disrupted, retinal degenerations ensue. Herein, we characterize a new cell line from human RPE that we termed ABC. These cells remarkably recapitulate human eye native cells. Distinctive from other epithelia, RPE cells originate from the neural crest and follow a neural development but are terminally differentiated into “epithelial” type, thus sharing characteristics with their neuronal lineages counterparts. Additionally, they form microvilli, tight junctions, and honeycomb packing and express distinctive markers. In these cells, outer segment phagocytosis, phagolysosome fate, phospholipid metabolism, and lipid mediator release can be studied. ABC cells display higher resistance to oxidative stress and are protected from senescence through mTOR inhibition, making them more stable in culture. The cells are responsive to Neuroprotectin D1 (NPD1), which downregulates inflammasomes and upregulates antioxidant and anti-inflammatory genes. ABC gene expression profile displays close proximity to native RPE lineage, making them a reliable cell system to unravel signaling in uncompensated oxidative stress (UOS) and retinal degenerative disease to define neuroprotection sites.
Linear Frequency Modulation of NbO2-Based Nanoscale Oscillator With Li-Based Electrochemical Random Access Memory for Compact Coupled Oscillatory Neural Network
Authors: Lee Donguk , Kwak Myonghoon , Lee Jongwon , Woo Jiyong , Hwang Hyunsang
Published: June 2022

Oscillatory neural network (ONN)-based classification of clustered data relies on frequency synchronization to injected signals representing input data, showing a more efficient structure than a conventional deep neural network. A frequency tunable oscillator is a core component of the network, requiring energy-efficient, and area-scalable characteristics for large-scale hardware implementation. From a hardware viewpoint, insulator-metal transition (IMT) device-based oscillators are attractive owing to their simple structure and low power consumption. Furthermore, by introducing non-volatile analog memory, non-volatile frequency programmability can be obtained. However, the required device characteristics of the oscillator for high performance of coupled oscillator have not been identified. In this article, we investigated the effect of device parameters of IMT oscillator with non-volatile analog memory on coupled oscillators network for classification of clustered data. We confirmed that linear conductance response with identical pulses is crucial to accurate training. In addition, considering dispersed clustered inputs, a wide synchronization window achieved by controlling the hold voltage of the IMT shows resilient classification. As an oscillator that satisfies the requirements, we evaluated the NbO2-based IMT oscillator with non-volatile Li-based electrochemical random access memory (Li-ECRAM). Finally, we demonstrated a coupled oscillator network for classifying spoken vowels, achieving an accuracy of 85%, higher than that of a ring oscillator-based system. Our results show that an NbO2-based oscillator with Li-ECRAM has the potential for an area-scalable and energy-efficient network with high performance.
Patch-to-Seq and Transcriptomic Analyses Yield Molecular Markers of Functionally Distinct Brainstem Serotonin Neurons
Authors: Mouradian Gary C. , Liu Pengyuan , Nakagawa Pablo , Duffy Erin , Gomez Vargas Javier , Balapattabi Kirthikaa , Grobe Justin L. , Sigmund Curt D. , Hodges Matthew R.
Published: June 2022

Acute regulation of CO2 and pH homeostasis requires sensory feedback from peripheral (carotid body) and central (central) CO2/pH sensitive cells – so called respiratory chemoreceptors. Subsets of brainstem serotonin (5-HT) neurons in the medullary raphe are CO2 sensitive or insensitive based on differences in embryonic origin, suggesting these functionally distinct subpopulations may have unique transcriptional profiles. Here, we used Patch-to-Seq to determine if the CO2 responses in brainstem 5-HT neurons could be correlated to unique transcriptional profiles and/or unique molecular markers and pathways. First, firing rate changes with hypercapnic acidosis were measured in fluorescently labeled 5-HT neurons in acute brainstem slices from transgenic, Dahl SS (SSMcwi) rats expressing T2/ePet-eGFP transgene in Pet-1 expressing (serotonin) neurons (SSePet1–eGFP rats). Subsequently, the transcriptomic and pathway profiles of CO2 sensitive and insensitive 5-HT neurons were determined and compared by single cell RNA (scRNAseq) and bioinformatic analyses. Low baseline firing rates were a distinguishing feature of CO2 sensitive 5-HT neurons. scRNAseq of these recorded neurons revealed 166 differentially expressed genes among CO2 sensitive and insensitive 5-HT neurons. Pathway analyses yielded novel predicted upstream regulators, including the transcription factor Egr2 and Leptin. Additional bioinformatic analyses identified 6 candidate gene markers of CO2 sensitive 5-HT neurons, and 2 selected candidate genes (CD46 and Iba57) were both expressed in 5-HT neurons determined via in situ mRNA hybridization. Together, these data provide novel insights into the transcriptional control of cellular chemoreception and provide unbiased candidate gene markers of CO2 sensitive 5-HT neurons. Methodologically, these data highlight the utility of the patch-to-seq technique in enabling the linkage of gene expression to specific functions, like CO2 chemoreception, in a single cell to identify potential mechanisms underlying functional differences in otherwise similar cell types.
Unilateral Perforant Path Transection Does Not Alter Lateral Entorhinal Cortical or Hippocampal CA3 Arc Expression
Authors: Cooper Tara L. , Thompson John J. , Turner Sean M. , Watson Cory , Lubke Katelyn N. , Logan Carly N. , Maurer Andrew P. , Burke Sara N.
Published: June 2022

It is well established that degradation of perforant path fibers is associated with age-related cognitive dysfunction and CA3 hyperactivity. Whether this fiber loss triggers a cascade of other functional changes within the hippocampus circuit has not been causatively established, however. Thus, the current study evaluated the effect of perforant path fiber loss on neuronal activity in CA3 and layer II of the lateral entorhinal cortex (LEC) in relation to mnemonic similarity task performance. Expression of the immediate early gene Arc was quantified in rats that received a unilateral right hemisphere transection of the perforant path or sham surgery that cut the cortex but left the fibers intact. Behavior-related expression of Arc mRNA was measured to test the hypothesis that fiber loss leads to elevated activation of CA3 and LEC neurons, as previously observed in aged rats that were impaired on the mnemonic similarity task. Transection of perforant path fibers, which has previously been shown to lead to a decline in mnemonic similarity task performance, did not alter Arc expression. Arc expression in CA3, however, was correlated with task performance on the more difficult discrimination trials across both surgical groups. These observations further support a link between CA3 activity and mnemonic similarity task performance but suggest the reduced input from the entorhinal cortex to the hippocampus, as observed in old age, does not causatively elevate CA3 activity.
An Indicator Measuring the Influence of the Online Public Food Environment: An Analytical Framework and Case Study
Authors: Cong Na , Zhao Ai , Kwan Mei-Po , Yang Jun , Gong Peng
Published: June 2022

The online public food environment (OPFE) has had a considerable impact on people's lifestyles over the past decade; however, research on its exposure is sparse. The results of the existing research on the impact of the food environment on human health are inconsistent. In response to the lack of food elements in the definition of the food environment and the lack of a clear method to assess the health attributes and the impact degree of the food environment, we proposed a new analytical framework based on the latest disease burden research, combining the characteristics of China's current food environment, from the perspective of environmental science. We redefined the food environment and proposed that food and its physical space are two core elements of the food environment. Accordingly, we extracted four domains of characteristics to describe the basic components of the food environment. Using the sales records, we designed an approach by referring to the standard process of environmental health indicators, including the health attributes and the impact degree of the food environment, to measure the OPFE of takeaway food outlets. Further, we conducted a case study and extracted three domains of characteristics for more than 18,000 effective takeaway meals from 812 takeaway food outlets located in 10 administrative subdivisions in the Haidian District and Xicheng District of Beijing Municipality. The results showed that more than 60% of single meals sold by takeaway food outlets were considered as healthy, and only 15% of takeaway food outlets sold healthy meals exclusively. Additionally, there were significant differences in health effects among different types of food environments, and high-risk areas of different types of food environments can be spatially identified. Compared with the counting method in the availability of food environment, the proposed new approach can depict food environment characteristics not only in the macro-scale like the counting method but also in the meal-scale. The indicators could be useful for large-scale and long-term monitoring of food environmental changes due to their simple calculation and design depending on the food delivery platform.
Body Mass Index Combined With Possible Sarcopenia Status Is Better Than BMI or Possible Sarcopenia Status Alone for Predicting All-Cause Mortality Among Asian Community-Dwelling Older Adults
Authors: Chalermsri Chalobol , Aekplakorn Wichai , Srinonprasert Varalak
Published: June 2022

Background

Body mass index (BMI) and sarcopenia are common indicators of nutritional status. Possible sarcopenia, defined as low muscle strength or performance, was recently introduced by the Asian Working Group for Sarcopenia (AWGS) in 2019. We investigated for association between all-cause mortality and BMI combined with possible sarcopenia severity in Asian older adults.

Methods

This study included a subpopulation (8,195 participants aged ≥60 years; male gender: 49.4%; mean age: 69.2 ± 6.8 years) from the Fourth Thai National Health Examination Survey (NHES-IV). BMI was classified using Asia-Pacific cut-offs. Possible sarcopenia was defined using quadriceps strength based on AWGS 2019 criteria, and possible sarcopenia severity was determined using study population quartile cut-offs. All-cause mortality data was derived from the national vital registry in 2020.

Results

The prevalence of underweight status and possible sarcopenia was 11.8 and 38.9%, respectively. Multivariate analysis showed underweight individuals with severe possible sarcopenia to be at highest risk for increased mortality [adjusted hazard ratio (aHR): 3.98, 95% confidence interval (CI): 2.89–5.48], and higher risk was found in men compared to women (aHR: 5.35, 95% CI: 1.19–8.97). Obese status without possible sarcopenia was an independent protective factor (aHR: 0.61, 95% CI: 0.38–0.97).

Conclusion

BMI combined with possible sarcopenia severity is a better predictor of mortality risk than either parameter alone.
Comparison of Diabetes Mellitus Risk Factors in Mexico in 2003 and 2014
Authors: López Sánchez Guillermo F. , López-Bueno Rubén , Villaseñor-Mora Carlos , Pardhan Shahina
Published: June 2022

Objective

The prevalence of diabetes mellitus in Mexico is very high. This study aimed to compare the risk factors of diabetes mellitus in Mexican adults in 2003 and in 2014.

Methods

This study had a repeated cross-sectional design. Data from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) from Mexico (Wave 0, 2003, and Wave 2, 2014) were compared. Self-reported diabetes mellitus (outcome) was evaluated with the yes/no question: “Have you ever been diagnosed with diabetes mellitus (high blood sugar)?” Bivariate analyses and multivariable logistic regression analyses adjusted for potential risk factors were conducted.

Results

In 11 years (2003–2014), the prevalence of self-reported diabetes mellitus in Mexican adults increased by 2.6 times in those younger than 50 years (2003: 2.1%; 2014: 5.5%) and by 1.9 times in those ≥50 years (2003: 12.7%; 2014: 24.2%). In 2003, the risk factors associated with diabetes mellitus were female sex (OR 1.344, 95% CI 1.176–1.536), age ≥50 years (OR 6.734, 95% CI 5.843–7.760), being overweight (OR 1.359, 95% CI 1.175–1.571), obesity (OR 1.871, 95% CI 1.583–2.211), and lower physical activity of <600 MET-minutes/week (OR 1.349, 95% CI 1.117–1.630). In 2014, the exposure characteristics significantly associated with diabetes mellitus were female sex (OR 1.244, 95% CI 1.025–1.511), older age ≥50 years (OR 4.608, 95% CI 3.260–6.515), being overweight (OR 1.649, 95% CI 1.305–2.083), obesity (OR 1.778, 95% CI 1.398–2.261), and in those who had not attended/completed primary school (OR 1.360, 95% CI 1.042–1.773).

Conclusion

The prevalence of diabetes mellitus in Mexico significantly increased from 2003 to 2014. Female sex, age older than 50 years, and being overweight or obese were significant risk factors in both 2003 and 2014. Not having completed primary school was a new significant risk factor in 2014. Public health policies and strategies should prioritize decreasing the high levels of overweight and obesity, and improve health literacy in Mexico.
Intra- and Inter-individual Differences in the Human Intestinal Microbial Conversion of (-)-Epicatechin and Bioactivity of Its Major Colonic Metabolite 5-(3′,4′-Dihydroxy-Phenyl)-γ-Valerolactone in Regulating Nrf2-Mediated Gene Expression
Authors: Liu Chen , Boeren Sjef , Rietjens Ivonne M. C. M.
Published: June 2022

(-)-Epicatechin (EC) is one of the most popular polyphenols present in various food products in daily life. Upon intake, it is intensively metabolized by microbiota in the large intestine. In the present study, intra- and inter-individual variations in this gut microbial conversion of EC and the concomitant formation of its major metabolites, including 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (3,4-diHPV), were identified and quantified via liquid chromatography triple quadrupole mass spectrometry (LC-TQ-MS) in anaerobic fecal incubations. In addition, the bioactivity of EC and 3,4-diHPV in activating Nrf2-mediated gene expression was tested quantifying their effects in the U2OS Nrf2 CALUX assay (a reporter gene assay that is used to test the potency of chemicals in activation of Nrf2 signaling), and on the expression levels of Nrf2-related proteins in Hepa1c1c7 and Caco-2 cells via nanoLC-MSMS. A quantitative real-time polymerase chain reaction (RT-qPCR) was carried out to confirm selected Nrf2-regulated gene expressions at the mRNA level. Results obtained show that both intra- and inter-individual differences exist in human gut microbial EC degradation and 3,4-diHPV formation, with inter-individual differences being more distinct than intra-individual differences. The metabolite, 3,4-diHPV, showed higher potency in the U2OS Nrf2 CALUX assay than EC itself. Among the obviously altered Nrf2-related proteins, 14 and 10 Nrf2-associated proteins were upregulated to a higher extent upon 3,4-diHPV treatment than in the EC treated group for Hepa1c1c7 and Caco-2 cells, respectively. While only three and four of these Nrf2-associated proteins were induced at a higher level upon EC than upon 3,4-diHPV treatment for Hepa1c1c7 and Caco-2 cells, respectively. RT-qPCR results showed that indeed Nrf2-mediated genes (e.g., Nqo1 and Ugt1a) were only induced significantly in 3,4-diHPV treated and not in EC treated Hepa1c1c7 cells. Taken together, the results suggest that the major colonic EC metabolite, 3,4-diHPV, was more capable of inducing Nrf2-mediated gene expression than its parent compound EC. This implies that the evident inter- and intra-individual differences in the microbial conversion of EC to this major metabolite 3,4-diHPV may affect the overall health-promoting effects of EC consumption related to the Nrf2 pathway activation.
Association of Retinol and Carotenoids Content in Diet and Serum With Risk for Colorectal Cancer: A Meta-Analysis
Authors: Han Xiaoyong , Zhao Rangyin , Zhang Guangming , Jiao Yajun , Wang Yongfeng , Wang Da , Cai Hui
Published: June 2022

Background

Colorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them.

Methods

From 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software.

Results

A total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: β-carotene (OR = 0.89, 95% CI: 0.78–1.03), α-carotene (OR = 0.87, 95% CI: 0.72–1.03), lycopene (OR = 0.93, 95% CI: 0.81–1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87–1.07), β-cryptoxanthin (OR = 0.70, 95% CI: 0.48–1.01), total carotenoids (OR = 0.97, 95% CI: 0.81–1.15), retinol (OR = 0.99, 95% CI: 0.89–1.10), serum carotenoids (OR = 0.73, 95% CI: 0.58–0.93), serum retinol (OR = 0.62, 95% CI: 0.26–1.49). Subgroup analysis was performed according to tumor type, study type and sex.

Conclusion

Total carotenoid intake and Lutein/Zeaxanthin intake were not associated with CRC risk. High β-carotene, α-carotene, lycopene, and β-cryptoxanthin all tended to reduce CRC risk. Serum carotenoid concentrations were significantly inversely associated with CRC risk.
Maternal Stress and Human Milk Antibodies During the COVID-19 Pandemic
Authors: Juncker Hannah G. , Ruhé Eliza J. M. , Korosi Aniko , van Goudoever Johannes B. , van Gils Marit J. , van Keulen Britt J.
Published: June 2022

Importance

SARS-CoV-2-specific antibodies in human milk might protect the breastfed infant against COVID-19. One of the factors that may influence human milk antibodies is psychological stress, which is suggested to be increased in lactating women during the COVID-19 pandemic.

Objective

To determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of SARS-CoV-2-specific antibodies in human milk.

Design

Population-based prospective cohort study.

Setting

Data collection took place in the Netherlands between October 2020 and February 2021.

Participants

Lactating women living in the Netherlands were eligible to participate in this study. In total, 2310 women were included.

Exposures

Stress exposure during the COVID-19 pandemic was determined using the Perceived Stress Scale (PSS) questionnaire and maternal lifetime stress was determined by the Life Stressor Checklist – revised (LSC-r) questionnaire.

Main Outcome(s) and Measure(s)

Stress experience during the COVID-19 pandemic was compared with a pre-pandemic cohort. SARS-CoV-2-specific antibodies in human milk were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) with the Spike protein of SARS-CoV-2. The association between maternal stress and human milk antibodies was determined using a multiple regression model.

Results

The PSS score of lactating mothers was not increased during the pandemic compared to the PSS score in the prepandemic cohort. Six hundred ninety-one participants had SARS-CoV-2-specific antibodies and were included in the regression models to assess the association between maternal stress and human milk antibodies. No association was found between PSS scores and human milk antibodies. In contrast, the LSC-r score was negatively associated with SARS-CoV-2-specific IgA in human milk (β = 0.98, 95% CI: 0.96–0.997, p = 0.03).

Conclusions and Relevance

Our results suggest that lactating women in the Netherlands did not experience higher stress levels during the COVID-19 pandemic. Breastfed infants of mothers with high chronic stress levels receive lower amounts of antibodies through human milk, which possibly makes them more vulnerable to respiratory infections. This emphasizes the importance of psychological wellbeing during lactation.
Rapid Screening of 22 Polycyclic Aromatic Hydrocarbons Residues in Vegetable Oils by Gas Chromatography-Electrostatic Field Orbitrap High Resolution Mass Spectrometry
Authors: Meng Zhijuan , Fan Sufang , Yuan Xiaoxuan , Li Qiang , Huang Yunxia , Niu Lisha , Shi Guohua , Zhang Yan
Published: June 2022

A method for simultaneous determination of 22 polycyclic aromatic hydrocarbons (PAHs) residues in vegetable oils by gas chromatography-electrostatic field orbitrap high resolution mass spectrometry (Orbitrap GC-MS) was established. The samples were vortexed with acetonitrile, centrifuged at 8,000 r/min for 5 min, and frozen at −70°C for 10 min. The extracts of upper layer were poured out, dried with nitrogen at 40°C, redissolved in dichloromethane, and measured by Orbitrap GC-MS. The matrix interference in vegetable oil could be effectively removed by determining the accurate mass number of target compounds under the full scan mode. Six typical vegetable oil samples (soybean oil, sesame oil, peanut oil, olive oil, rapeseed oil, sunflower oil) were used for method validation. The calibration curve displayed good linearity in the range of 1–100 ng/mL, with correlation coefficients > 0.9950. The limits of detection (LODs) were in the range of 0.10–0.60 μg/kg, and the limits of quantification (LOQs) were in the range of 0.35–2.00 μg/kg. The average spiked recoveries of 22 PAHs in 6 matrices at 5, 50 and 100 μg/kg levels were 76.4–115.4%, and the average relative standard deviations (RSDs) were 1.8–10.8%. The results showed that 22 PAHs were detected in 6 types of 90 edible vegetable oil samples in the Chinese market by this method. Meanwhile, the abundance of light PAHs (LPAHs) was higher than that of heavy PAHs (HPAHs), and its relative contribution of LPAHs to the total PAHs was higher. All levels of BaP conformed to the Chinese requirement of upper limit, 10 μg/kg. However, 13.3 and 11.1% of the samples exceeded the maximum limits of BaP and PAH4 set by EU, 2 and 10 μg/kg, respectively. The total concentrations of 22 PAHs (defined as PAH22) varies greatly among different oil species, and the average PAH22 contents were listed in descending order as follows: peanut oil > sesame oil > olive oil > rapeseed oil > soybean oil > sunflower seed oil. The established method effectively avoided interference from large amounts of lipids and pigments. Therefore, the method is simple, sensitive and suitable for rapid screening and confirmation of PAHs in vegetable oil.
Hypoxia-Mediated ATF4 Induction Promotes Survival in Detached Conditions in Metastatic Murine Mammary Cancer Cells
Authors: Kiesel Violet A. , Sheeley Madeline P. , Hicks Emily M. , Andolino Chaylen , Donkin Shawn S. , Wendt Michael K. , Hursting Stephen D. , Teegarden Dorothy
Published: June 2022

Regions of hypoxia are common in solid tumors and drive changes in gene expression that increase risk of cancer metastasis. Tumor cells must respond to the stress of hypoxia by activating genes to modify cell metabolism and antioxidant response to improve survival. The goal of the current study was to determine the effect of hypoxia on cell metabolism and markers of oxidative stress in metastatic (metM-Wntlung) compared with nonmetastatic (M-Wnt) murine mammary cancer cell lines. We show that hypoxia induced a greater suppression of glutamine to glutamate conversion in metastatic cells (13% in metastatic cells compared to 7% in nonmetastatic cells). We also show that hypoxia increased expression of genes involved in antioxidant response in metastatic compared to nonmetastatic cells, including glutamate cysteine ligase catalytic and modifier subunits and malic enzyme 1. Interestingly, hypoxia increased the mRNA level of the transaminase glutamic pyruvic transaminase 2 (Gpt2, 7.7-fold) only in metM-Wntlung cells. The change in Gpt2 expression was accompanied by transcriptional (4.2-fold) and translational (6.5-fold) induction of the integrated stress response effector protein activating transcription factor 4 (ATF4). Genetic depletion ATF4 demonstrated importance of this molecule for survival of hypoxic metastatic cells in detached conditions. These findings indicate that more aggressive, metastatic cancer cells utilize hypoxia for metabolic reprogramming and induction of antioxidant defense, including activation of ATF4, for survival in detached conditions.