bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral and Neural Activity-Dependent Recanalization of Plugged Capillaries in the Brain of Adult and Aged Mice
Authors: Reeson Patrick , Schager Ben , Van Sprengel Myrthe , Brown Craig E.
Published: June 2022

The capillaries of the brain, owing to their small diameter and low perfusion pressure, are vulnerable to interruptions in blood flow. These tiny occlusions can have outsized consequences on angioarchitecture and brain function; especially when exacerbated by disease states or accumulate with aging. A distinctive feature of the brain’s microvasculature is the ability for active neurons to recruit local blood flow. The coupling of neural activity to blood flow could play an important role in recanalizing obstructed capillaries. To investigate this idea, we experimentally induced capillary obstructions in mice by injecting fluorescent microspheres and then manipulated neural activity levels though behavioral or pharmacologic approaches. We show that engaging adult and aged mice with 12 h exposure to an enriched environment (group housing, novel objects, exercise wheels) was sufficient to significantly reduce the density of obstructed capillaries throughout the forebrain. In order to more directly manipulate neural activity, we pharmacologically suppressed or increased neuronal activity in the somatosensory cortex. When we suppressed cortical activity, recanalization was impaired given the density of obstructed capillaries was significantly increased. Conversely, increasing cortical activity improved capillary recanalization. Since systemic cardiovascular factors (changes in heart rate, blood pressure) could explain these effects on recanalization, we demonstrate that unilateral manipulations of neural activity through whisker trimming or injection of muscimol, still had significant and hemisphere specific effects on recanalization, even in mice exposed to enrichment where cardiovascular effects would be evident in both hemispheres. In summary, our studies reveal that neural activity bi-directionally regulates the recanalization of obstructed capillaries. Further, we show that stimulating brain activity through behavioral engagement (i.e., environmental enrichment) can promote vascular health throughout the lifespan.
The Basolateral Amygdala to Ventral Hippocampus Circuit Controls Anxiety-Like Behaviors Induced by Morphine Withdrawal
Authors: Deji Cuola , Yan Peng , Ji Yuanyuan , Yan Xinyue , Feng Yue , Liu Jincen , Liu Yige , Wei Shuguang , Zhu Yongsheng , Lai Jianghua
Published: June 2022

Anxiety is one of the most common comorbid conditions reported in people with opioid dependence. The basolateral amygdala (BLA) and ventral hippocampus (vHip) are critical brain regions for fear and anxiety. The kappa opioid receptor (KOR) is present in the mesolimbic regions involved in emotions and addiction. However, the precise circuits and molecular basis underlying anxiety associated with chronic opioid use are poorly understood. Using a mouse model, we demonstrated that anxiety-like behaviors appeared in the first 2 weeks after morphine withdrawal. Furthermore, the BLA and vHip were activated in mice experiencing anxiety after morphine withdrawal (Mor-A). KORs in the BLA to vHip projections were significantly increased in the Mor-A group. Optogenetic/chemogenetic inhibition of BLA inputs ameliorated anxiety-like behaviors and facilitated conditioned place preference (CPP) extinction in Mor-A mice. Knockdown of the BLA to vHip circuit KOR alleviated the anxiety-like behaviors but did not affect CPP extinction or reinstatement. Furthermore, combined treatment of inhibition of the BLA to vHip circuit and KOR antagonists mitigated anxiety-like behaviors and prevented stress-induced CPP reinstatement after morphine withdrawal. These results revealed a previously unknown circuit associated with the emotional component of opioid withdrawal and indicated that restoration of synaptic deficits with KOR antagonists might be effective in the treatment of anxiety associated with morphine withdrawal.
Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development
Authors: Thomason Elizabeth J. , Suárez-Pozos Edna , Afshari Fatemah S. , Rosenberg Paul A. , Dupree Jeffrey L. , Fuss Babette
Published: June 2022

The sodium-dependent glutamate transporter GLT-1 (EAAT2, SLC1A2) has been well-described as an important regulator of extracellular glutamate homeostasis in the central nervous system (CNS), a function that is performed mainly through its presence on astrocytes. There is, however, increasing evidence for the expression of GLT-1 in CNS cells other than astrocytes and in functional roles that are mediated by mechanisms downstream of glutamate uptake. In this context, GLT-1 expression has been reported for both neurons and oligodendrocytes (OLGs), and neuronal presynaptic presence of GLT-1 has been implicated in the regulation of glutamate uptake, gene expression, and mitochondrial function. Much less is currently known about the functional roles of GLT-1 expressed by OLGs. The data presented here provide first evidence that GLT-1 expressed by maturing OLGs contributes to the modulation of developmental myelination in the CNS. More specifically, using inducible and conditional knockout mice in which GLT-1 was deleted in maturing OLGs during a peak period of myelination (between 2 and 4 weeks of age) revealed hypomyelinated characteristics in the corpus callosum of preferentially male mice. These characteristics included reduced percentages of smaller diameter myelinated axons and reduced myelin thickness. Interestingly, this myelination phenotype was not found to be associated with major changes in myelin gene expression. Taken together, the data presented here demonstrate that GLT-1 expressed by maturing OLGs is involved in the modulation of the morphological aspects associated with CNS myelination in at least the corpus callosum and during a developmental window that appears of particular vulnerability in males compared to females.
Pulsed Radiofrequency Combined With Methylene Blue Paravertebral Nerve Block Effectively Treats Thoracic Postherpetic Neuralgia
Authors: Ji Meiduan , Yao Peng , Han Zhenkai , Zhu Danlin
Published: June 2022

Objective

To compare the effect, safety, and patient satisfaction of pulsed radiofrequency combined with methylene blue paravertebral nerve block and pulsed radiofrequency alone in the treatment of thoracic postherpetic neuralgia (PHN).

Methods

A total of seventy-two patients with PHN diagnosed in the Department of Pain Management of Shengjing Hospital at China Medical University, from September 2019 to April 2021, were enrolled in the study. Patients were randomly divided into two groups. Group A (n = 36) received pulsed radiofrequency treatment. Group B (n = 36) received pulsed radiofrequency + methylene blue paravertebral nerve block. Patients were followed-up at 1 day, 1 week, 1 month, 3 months, and 6 months after treatment. Observation at each follow-up included basic patient characteristics, Visual Analog Scale (VAS), Hospital Anxiety and Depression Scale (HAD), the Insomnia Severity Index (ISI), patient satisfaction, complications, and side effects.

Results

Compared with preoperative values, the VAS scores significantly decreased in both groups at each postoperative time point (1 day, 1 week, and 1, 3, and 6 months; all p < 0.05). Compared with group A, VAS scores in group B were significantly lower 1 week and 1 month after surgery (p < 0.05). Patients in group B had lower HAD scores than those in group A 1 week after surgery (p < 0.05). Patients in group B had lower ISI scores than those in group A 1 day, 1 week, and 1, 3, and 6 months after surgery (p < 0.05). The pregabalin dosage in group B was lower than that in group A at 1 and 6 months after surgery (p < 0.05). Patient satisfaction was higher in group B than in group A at 1 week and 6 months after surgery (p < 0.05). There were no serious complications or side effects in either group.

Conclusion

Pulsed radiofrequency combined with methylene blue paravertebral nerve block is superior to pulsed radiofrequency alone in the treatment of thoracic PHN, which can significantly relieve PHN and improve the condition of sleep and emotional disorders. Therefore, it is a safe and effective treatment method.
Gray Matter Structural and Functional Alterations in Idiopathic Blepharospasm: A Multimodal Meta-Analysis of VBM and Functional Neuroimaging Studies
Authors: Zhang Meng , Huang Xiang , Li Boyi , Shang Huifang , Yang Jing
Published: June 2022

Background

Neuroimaging studies have shown gray matter structural and functional alterations in patients with idiopathic blepharospasm (iBSP) but with variations. Here we aimed to investigate the specific and common neurostructural/functional abnormalities in patients with iBSP.

Methods

A systematic literature search from PubMed, Web of Science and Embase was conducted to identify relevant publications. We conducted separate meta-analysis for whole-brain voxel-based morphometry (VBM) studies and for functional imaging studies, and a multimodal meta-analysis across VBM and functional studies in iBSP, using anisotropic effect size-based signed differential mapping.

Results

The structural database comprised 129 patients with iBSP and 144 healthy controls whilst the functional database included 183 patients with iBSP and 253 healthy controls. The meta-analysis of VBM studies showed increased gray matter in bilateral precentral and postcentral gyri, right supplementary motor area and bilateral paracentral lobules, while decreased gray matter in right superior and inferior parietal gyri, left inferior parietal gyrus, left inferior temporal gyrus, left fusiform gyrus and parahippocampal gyrus. The meta-analysis of functional studies revealed hyperactivity in right dorsolateral superior frontal gyrus, left thalamus and right fusiform gyrus, while hypoactivity in left temporal pole, left insula, left precentral gyrus, bilateral precuneus and paracentral lobules, right supplementary motor area and middle frontal gyrus. The multimodal meta-analysis identified conjoint anatomic and functional changes in left precentral gyrus, bilateral supplementary motor areas and paracentral lobules, right inferior occipital gyrus and fusiform gyrus.

Conclusions

The patterns of conjoint and dissociated gray matter alterations identified in the meta-analysis may enhance our understanding of the pathophysiological mechanisms underlying iBSP.
Usability of a Hybrid System Combining P300-Based Brain-Computer Interface and Commercial Assistive Technologies to Enhance Communication in People With Multiple Sclerosis
Authors: Riccio Angela , Schettini Francesca , Galiotta Valentina , Giraldi Enrico , Grasso Maria Grazia , Cincotti Febo , Mattia Donatella
Published: June 2022

Brain-computer interface (BCI) can provide people with motor disabilities with an alternative channel to access assistive technology (AT) software for communication and environmental interaction. Multiple sclerosis (MS) is a chronic disease of the central nervous system that mostly starts in young adulthood and often leads to a long-term disability, possibly exacerbated by the presence of fatigue. Patients with MS have been rarely considered as potential BCI end-users. In this pilot study, we evaluated the usability of a hybrid BCI (h-BCI) system that enables both a P300-based BCI and conventional input devices (i.e., muscular dependent) to access mainstream applications through the widely used AT software for communication “Grid 3.” The evaluation was performed according to the principles of the user-centered design (UCD) with the aim of providing patients with MS with an alternative control channel (i.e., BCI), potentially less sensitive to fatigue. A total of 13 patients with MS were enrolled. In session I, participants were presented with a widely validated P300-based BCI (P3-speller); in session II, they had to operate Grid 3 to access three mainstream applications with (1) an AT conventional input device and (2) the h-BCI. Eight patients completed the protocol. Five out of eight patients with MS were successfully able to access the Grid 3 via the BCI, with a mean online accuracy of 83.3% (± 14.6). Effectiveness (online accuracy), satisfaction, and workload were comparable between the conventional AT inputs and the BCI channel in controlling the Grid 3. As expected, the efficiency (time for correct selection) resulted to be significantly lower for the BCI with respect to the AT conventional channels (Z = 0.2, p < 0.05). Although cautious due to the limited sample size, these preliminary findings indicated that the BCI control channel did not have a detrimental effect with respect to conventional AT channels on the ability to operate an AT software (Grid 3). Therefore, we inferred that the usability of the two access modalities was comparable. The integration of BCI with commercial AT input devices to access a widely used AT software represents an important step toward the introduction of BCIs into the AT centers’ daily practice.
Role of the Contra-Lesional Corticoreticular Tract in Motor Recovery of the Paretic Leg in Stroke: A Mini-Narrative Review
Authors: Jang Sung Ho , Cho Min Jye
Published: June 2022

This review discusses the role of the contra-lesional corticoreticular tract (CRT) in motor recovery of the paretic leg in stroke patients by reviewing related diffusion tensor tractography studies. These studies suggest that the contra-lesional CRT can contribute to the motor recovery of the paretic leg in stroke patients, particularly in patients with complete injuries of the ipsilesional corticospinal tract and CRT. Furthermore, a review study reported that the motor recovery of the paretic ankle dorsiflexor, which is mandatory for achieving a good gait pattern without braces in hemiparetic stroke patients, was closely related to the contra-lesional CRT. These results could be clinically important in neuro-rehabilitation. For example, the contra-lesional CRT could be a target for neuromodulation therapies in patients with complete injuries of the ipsilesional corticospinal tract and CRT. On the other hand, only three studies were reviewed in this review and one was a case report. Although the CRT has been suggested to be one of the ipsilateral motor pathways from the contra-lesional cerebral cortex to the paretic limbs in stroke, the role of the CRT has not been elucidated clearly. Therefore, further prospective follow-up studies combining functional neuroimaging and transcranial magnetic stimulation for the paretic leg with diffusion tensor tractography will be useful for elucidating the role of the contra-lesional CRT in stroke patients.
Real-Time Functional Magnetic Resonance Imaging Dyadic Neurofeedback for Emotion Regulation: A Proof-of-Concept Study
Authors: Kerr Kara L. , Ratliff Erin L. , Cohen Zsofia P. , Fuller Stormie , Cosgrove Kelly T. , DeVille Danielle C. , Misaki Masaya , Morris Amanda Sheffield , Bodurka Jerzy
Published: June 2022

Real-time fMRI (rt-fMRI) neurofeedback can be used to non-invasively modulate brain activity and has shown initial effectiveness in symptom reduction for psychiatric disorders. Neurofeedback paradigms often target the neurocircuitry underlying emotion regulation, as difficulties with emotion regulation are common across many psychiatric conditions. Adolescence is a key period for the development of emotion regulation, with the parent-adolescent relationship providing an important context for learning how to modulate one’s emotions. Here, we present evidence for a novel extension of rt-fMRI neurofeedback wherein a second person (the parent) views neurofeedback from the focal participant (adolescent) and attempts to regulate the other person’s brain activity. In this proof-of-concept study, mother-adolescent dyads (n = 6; all female) participated in a dyadic neurofeedback protocol, during which they communicated via active noise-canceling microphones and headphones. During the scan, adolescents described current emotionally upsetting situations in their lives, and their mothers responded while viewing neurofeedback from the adolescent’s right anterior insular cortex (aIC)—a key hub for emotion-related processing. The mother was instructed to supportively respond to her daughter’s negative emotions and attempt to downregulate the aIC activity. Mean right aIC activation during each run was calculated for each adolescent participant, and results revealed a downward trend across the session (β = −0.17, SEβ = 0.19, Cohen’s f2 = 0.03). Results of this proof-of-concept study support further research using dyadic neurofeedback to target emotion-related processing. Future applications may include therapist-client dyads and continued research with parents and children.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03929263].
The Influence of Media in Purchasing Decisions for Recycled Construction and Demolition Waste Products: An Functional Near Infrared Spectroscopy Study
Authors: Ding Zhikun , Zhang Zhiyu , Chen Weilin
Published: June 2022

The increasing hazards caused by construction and demolition (C&D) waste is an inevitable problem in the development of the construction industry. Many countries have successively launched many policies to encourage and guide the recycling of C&D waste, which has greatly improved the recycling rate of C&D waste. However, most of these policies only regulate contractors but do not promote C&D waste recycling products enough. It has led to an increase in the production of C&D waste recycling products while the acceptance in the market is generally low. Consumers believe that products made with “garbage” may have problems such as quality defects. In order to explore a measure that can mitigate this problem, this study uses functional near infrared spectroscopy (fNIRS) to investigate whether the influence of media can increase consumers’ willingness to purchase products for recycling construction and demolition waste, and thus increase consumers’ choice to purchase products for C&D recycling waste. This experiment consists of two phases. First, a pre-test experiment to obtain pre-intervention brain images characterizing consumers’ original attitudes toward C&D recycling waste products through a functional near-infrared imaging brain technique and a questionnaire. Second, The post-test builds on the pre-test to investigate the effectiveness of the intervention. The activation mechanism of the consumer purchase decision is further investigated by fNIRS data. The behavioral results showed that the choice of recycled C&D waste products was significantly higher after the intervention. The fNIRS results further revealed the significantly higher activation of the dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC) after the intervention. These findings suggest that consumers’ purchase willingness is significantly improved after intervention, and their purchase behavior changed substantially. This study also demonstrates the great potential of fNIRS for interdisciplinary research in engineering management and neuroscience.
Texture Analysis Based on Vascular Ultrasound to Identify the Vulnerable Carotid Plaques
Authors: Zhang Lianlian , Lyu Qi , Ding Yafang , Hu Chunhong , Hui Pinjing
Published: June 2022

Vulnerable carotid plaques are closely related to the occurrence of ischemic stroke. Therefore, accurate and rapid identification of the nature of carotid plaques is essential. This study aimed to determine whether texture analysis based on a vascular ultrasound can be applied to identify vulnerable plaques. Data from a total of 150 patients diagnosed with atherosclerotic plaque (AP) by carotid ultrasound (CDU) and high-resolution magnetic resonance imaging (HRMRI) were collected. HRMRI is the in vivo reference to assess the nature of AP. MaZda software was used to delineate the region of interest and extract 303 texture features from ultrasonic images of plaques. Following regression analysis using the least absolute shrinkage and selection operator (LASSO) algorithm, the overall cohort was randomized 7:3 into the training (n = 105) and testing (n = 45) sets. In the training set, the conventional ultrasound model, the texture feature model, and the conventional ultrasound-texture feature combined model were constructed. The testing set was used to validate the model’s effectiveness by calculating the area under the curve (AUC), accuracy, sensitivity, and specificity. Based on the combined model, a nomogram risk prediction model was established, and the consistency index (C-index) and the calibration curve were obtained. In the training and testing sets, the AUC of the prediction performance of the conventional ultrasonic-texture feature combined model was higher than that of the conventional ultrasonic model and the texture feature model. In the training set, the AUC of the combined model was 0.88, while in the testing set, AUC was 0.87. In addition, the C-index results were also favorable (0.89 in the training set and 0.84 in the testing set). Furthermore, the calibration curve was close to the ideal curve, indicating the accuracy of the nomogram. This study proves the performance of vascular ultrasound-based texture analysis in identifying the vulnerable carotid plaques. Texture feature extraction combined with CDU sonogram features can accurately predict the vulnerability of AP.
Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning
Authors: Lin Yi-Cheng , Lien Yun R. , Lin Shang-Hua N. , Kung Yi-Chia , Huang Chu-Chung , Lin Ching-Po , Chang Li-Hung
Published: June 2022

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research.
Assessing Neurokinematic and Neuromuscular Connectivity During Walking Using Mobile Brain-Body Imaging
Authors: Zhao Mingqi , Bonassi Gaia , Samogin Jessica , Taberna Gaia Amaranta , Porcaro Camillo , Pelosin Elisa , Avanzino Laura , Mantini Dante
Published: June 2022

Gait is a common but rather complex activity that supports mobility in daily life. It requires indeed sophisticated coordination of lower and upper limbs, controlled by the nervous system. The relationship between limb kinematics and muscular activity with neural activity, referred to as neurokinematic and neuromuscular connectivity (NKC/NMC) respectively, still needs to be elucidated. Recently developed analysis techniques for mobile high-density electroencephalography (hdEEG) recordings have enabled investigations of gait-related neural modulations at the brain level. To shed light on gait-related neurokinematic and neuromuscular connectivity patterns in the brain, we performed a mobile brain/body imaging (MoBI) study in young healthy participants. In each participant, we collected hdEEG signals and limb velocity/electromyography signals during treadmill walking. We reconstructed neural signals in the alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–50 Hz) frequency bands, and assessed the co-modulations of their power envelopes with myogenic/velocity envelopes. Our results showed that the myogenic signals have larger discriminative power in evaluating gait-related brain-body connectivity with respect to kinematic signals. A detailed analysis of neuromuscular connectivity patterns in the brain revealed robust responses in the alpha and beta bands over the lower limb representation in the primary sensorimotor cortex. There responses were largely contralateral with respect to the body sensor used for the analysis. By using a voxel-wise analysis of variance on the NMC images, we revealed clear modulations across body sensors; the variability across frequency bands was relatively lower, and below significance. Overall, our study demonstrates that a MoBI platform based on hdEEG can be used for the investigation of gait-related brain-body connectivity. Future studies might involve more complex walking conditions to gain a better understanding of fundamental neural processes associated with gait control, or might be conducted in individuals with neuromotor disorders to identify neural markers of abnormal gait.
Impaired Duration Perception in Patients With Unilateral Vestibulopathy During Whole-Body Rotation
Authors: Kwon Eunjin , Lee Ju-Young , Song Jung-Mi , Kim Hyo-Jung , Lee Jong-Hee , Choi Jeong-Yoon , Kim Ji-Soo
Published: June 2022

This study aimed to evaluate vestibular perception in patients with unilateral vestibulopathy. We recruited 14 patients (9 women, mean age = 59.3 ± 14.3) with unilateral vestibulopathy during the subacute or chronic stage (disease duration = 6 days to 25 years). For the evaluation of position perception, the patients had to estimate the position after whole-body rotation in the yaw plane. The velocity/acceleration perception was evaluated by acquiring decisions of patients regarding which direction would be the faster rotation after a pair of ipsi- and contra-lesional rotations at various velocity/acceleration settings. The duration perception was assessed by collecting decisions of patients for longer rotation directions at each pair of ipsi- and contra-lesional rotations with various velocities and amplitudes. Patients with unilateral vestibulopathy showed position estimates and velocity/acceleration discriminations comparable to healthy controls. However, in duration discrimination, patients had a contralesional bias such that they had a longer perception period for the healthy side during the equal duration and same amplitude rotations. For the complex duration task, where a longer duration was assigned to a smaller rotation amplitude, the precision was significantly lower in the patient group than in the control group. These results indicate persistent impairments of duration perception in unilateral vestibulopathy and favor the intrinsic and distributed timing mechanism of the vestibular system. Complex perceptual tasks may be helpful to disclose hidden perceptual disturbances in unilateral vestibular hypofunction.
Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain
Authors: Notartomaso Serena , Boccella Serena , Antenucci N. , Ricciardi Flavia , Fazio Francesco , Liberatore F. , Scarselli P. , Scioli M. , Mascio Giada , Bruno V. , Battaglia Giuseppe , Nicoletti Ferdinando , Maione Sabatino , Luongo Livio
Published: June 2022

Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the regulation of pain thresholds. Systemic administration of low doses of CA (0.125 and 0.25 mg/kg, i.p.) reduced nocifensive behaviour in the second phase of the formalin test. CA-induced analgesia was abrogated in mGlu4 receptor knockout mice, but was unaffected by treatment with the Ah receptor antagonist, CH223191 (1 mg/Kg, s.c.). Acute injection of low doses of CA (0.25 mg/kg, i.p.) also caused analgesia in mice subjected to Chronic Constriction Injury (CCI) of the sciatic nerve. Electrophysiological recording showed no effect of CA on spinal cord nociceptive neurons and a trend to a lowering effect on the frequency and duration of excitation of the rostral ventromedial medulla (RVM) ON cells in CCI mice. However, local application of CH223191 or the group-III mGlu receptor antagonist, MSOP disclosed a substantial lowering and enhancing effect of CA on both populations of neurons, respectively. When repeatedly administered to CCI mice, CA retained the analgesic activity only when combined with CH223191. Repeated administration of CA plus CH223191 restrained the activity of both spinal nociceptive neurons and RVM ON cells, in full agreement with the analgesic activity. These findings suggest that CA is involved in the regulation of pain transmission, and its overall effect depends on the recruitment of mGlu4 and Ah receptors.
Effects of Probiotic Intervention on Markers of Inflammation and Health Outcomes in Women of Reproductive Age and Their Children
Authors: Kwok Kah Onn , Fries Lisa R. , Silva-Zolezzi Irma , Thakkar Sagar K. , Iroz Alison , Blanchard Carine
Published: June 2022

The human intestinal microbiota has been shown to be modulated during inflammatory conditions. Probiotic administration has been shown to affect the immune system and cytokine expression which can affect inflammation and health outcomes. There seems to be an association between the mother's intestinal microbiota and inflammation biomarkers, both of which may contribute to newborn early life immune and metabolic programming and impact short and long-term health outcomes. Probiotic supplementation during pregnancy has been shown to influence metabolic health, immunity, and gastrointestinal health of the mother, and can also have carry-over benefits to infants such as infant allergy risk reduction. Therefore, this review focuses on the evidence of probiotic administration in women of reproductive age, including during pregnancy and its impact on inflammatory markers and on maternal and infant health. We performed a PubMed search for articles published in English in the last 20 years. Immune markers were narrowed to serum and breast milk levels of TNF-α, IL-6 and TGF-β, IgA, and IL-10. Studies that investigated the beneficial effects of interventions in women with gestational diabetes mellitus, polycystic ovarian syndrome, and infant allergy management are summarized. These results show a beneficial or neutral effect on selected health outcomes and that it is safe for woman and their infants. The effect of probiotics on modulation of inflammatory markers was probiotic specific. More research is needed to further our understanding of the mechanisms underlying the effects of probiotics on inflammation and how these effects improve health outcomes.
Evaluating 12 Years of Implementing a Multidisciplinary Specialist Child and Adolescent Obesity Treatment Service: Patient-Level Outcomes
Authors: Wyse Cathy , Case Lucinda , Walsh Órla , Shortall Catherine , Jordan Norah , McCrea Lois , O'Malley Grace
Published: June 2022

Introduction

Childhood obesity is a chronic disease that requires multidisciplinary and specialist intervention to address its complex pathophysiology, though access to treatment is limited globally. Evaluating the impact of evidence-based interventions implemented in real-world clinical settings is essential, in order to increase the translation of research into practice and enhance child health outcomes. In Ireland, the National Model of Care for Obesity highlighted the need to develop and improve healthcare services for children and adolescents with obesity.

Aims

This study aims to evaluate the impact of a family-based, Tier 3 multi-disciplinary child and adolescent obesity outpatient service (www.w82go.ie) on standardized body mass index (BMI-SDS).

Methods

Following referral by pediatricians, patients were assessed by a pediatric multidisciplinary team (physiotherapist, dietician, and psychologist) and personalized obesity treatment plans were developed. Anthropometric and demographic information were recorded at baseline and final visit. Descriptive statistics were used to explore distribution, central tendency and variation in the demographic data, change in BMI-SDS over time was assessed using a t-test, and multiple linear regression analysis was used to investigate the association of demographic factors on the change in BMI-SDS.

Results

The overall mean BMI-SDS reduction across the whole cohort (n = 692) was −0.17 (95% CI = −0.20, −0.13; P < 0.001). Younger age at admission and longer duration of treatment were associated with greater BMI-SDS reduction but there was no significant association between change in BMI-SDS and any of the other parameters (deprivation score, treatment type, sex, obesity category at admission or presence of comorbid condition).

Conclusion

Engagement in a specialist Tier 3 pediatric obesity service was associated with reductions in BMI-SDS in children and adolescents with obesity.
Quality Markers of Dendrobium officinale by “Oligosaccharide-Spectrum-Effect” Relationships
Authors: Liu Ruimin , Shi Songshan , Xiong Si , Su Juan , Gan Xiaona , Wu Jianjun , Wang Huijun , Wang Shunchun
Published: June 2022

Dendrobium officinale Kimura et Migo has been used as a traditional Chinese medicine (TCM) and a functional food for thousands of years. Carbohydrate is one of the most important effective substances and indicative components in D. officinale. However, since the qualitative and quantitative analysis of polysaccharides in D. officinale remains a challenge and limitation, herein, an oligosaccharide-quality marker approach was newly developed for quality assessment of D. officinale by spectrum–effect relationships between high performance liquid chromatographic (HPLC) fingerprints and anti-inflammatory effects. The HPLC fingerprints of 48 batches of oligosaccharides from D. officinale (DOOS) were developed and analyzed with similarity analysis (SA) and hierarchical cluster analysis (HCA), and eight common peaks were identified. In vitro screening experiment indicated that DOOS potentially inhibited nitric oxide (NO) production and effectively reduced the release of inflammatory cytokines, such as TNF-α, IL-6, and IL-1β in RAW 264.7 cells, thereby reducing the inflammatory response of cells. Finally, the HPLC fingerprint of different batches of DOOS was combined with in vitro anti-inflammatory activity to assess the spectrum–effect relationships of DOOS by gray correlation analysis (GCA), in addition, the purified oligosaccharide components were identified and validated for NO inhibitory activity. Our results showed four DOOS (maltotetraose, maltopentaose, maltohexaose, and mannohexaose) were relevant to anti-inflammatory effects and could be as quality markers for the quality control of D. officinale. It suggests that the “oligosaccharide-spectrum-effect” relationships approach is a simple and reliable method for the quality control of herb medicines or nutritious foods.
A Novel Secreted Protein-Related Gene Signature Predicts Overall Survival and Is Associated With Tumor Immunity in Patients With Lung Adenocarcinoma
Authors: Chen Shuaijun , Zhang Jun , Li Qian , Xiao Lingyan , Feng Xiao , Niu Qian , Zhao Liqin , Ma Wanli , Ye Hong
Published: June 2022

Secreted proteins are important proteins in the human proteome, accounting for approximately one-tenth of the proteome. However, the prognostic value of secreted protein-related genes has not been comprehensively explored in lung adenocarcinoma (LUAD). In this study, we screened 379 differentially expressed secretory protein genes (DESPRGs) by analyzing the expression profile in patients with LUAD from The Cancer Genome Atlas database. Following univariate Cox regression and least absolute shrinkage and selection operator method regression analysis, 9 prognostic SPRGs were selected to develop secreted protein-related risk score (SPRrisk), including CLEC3B, C1QTNF6, TCN1, F2, FETUB, IGFBP1, ANGPTL4, IFNE, and CCL20. The prediction accuracy of the prognostic models was determined by Kaplan–Meier survival curve analysis and receiver operating characteristic curve analysis. Moreover, a nomogram with improved accuracy for predicting overall survival was established based on independent prognostic factors (SPRrisk and clinical stage). The DESPRGs were validated by quantitative real-time PCR and enzyme-linked immunosorbent assay by using our clinical samples and datasets. Our results demonstrated that SPRrisk can accurately predict the prognosis of patients with LUAD. Patients with a higher risk had lower immune, stromal, and ESTIMATE scores and higher tumor purity. A higher SPRrisk was also negatively associated with the abundance of CD8+ T cells and M1 macrophages. In addition, several genes of the human leukocyte antigen family and immune checkpoints were expressed in low levels in the high-SPRrisk group. Our results provided some insights into assessing individual prognosis and choosing personalized treatment modalities.
KRAS Gene Copy Number as a Negative Predictive Biomarker for the Treatment of Metastatic Rectal Cancer With Cetuximab: A Case Report
Authors: Xiong Qunli , Zeng Zhu , Yang Yang , Wang Ya , Xu Yongfeng , Zhou Ying , Liu Jinlu , Zhang Zhiwei , Qiu Meng , Zhu Qing
Published: June 2022

Background

Close to one third of colorectal cancer (CRC) patients are diagnosed with metastatic CRC (mCRC). Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy containing cetuximab. Overall, 30–50% of mCRC patients are reported to harbor RAS mutations, and RAS mutation status should be assessed when considering EGFR inhibitor treatment according to mCRC biomarker guidelines. Of note, 0.67–2% of patients with CRC harbored a KRAS amplification. Here we reported a case of advanced rectal cancer with wild-type RAS and BRAF in a male patient who harbored a KRAS amplification during anti-EGFR treatment.

Case Presentation

A 46-year-old man was diagnosed with rectal adenocarcinoma with liver metastases (cT3NxM1a, stage IVA). After receiving first-line irinotecan- fluorouracil chemotherapy (FOLFIRI) plus cetuximab, second-line capecitabine- oxaliplatin chemotherapy (XELOX) plus bevacizumab, and third-line regorafenib, he rechallenged FOLFIRI and cetuximab for seven cycles, achieving a prolonged survival of at least 5 months. The KRAS copy number of circulating tumor DNA (ctDNA) was assessed during treatment. Notably, apart from serum carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA), the change of plasm Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) copy number appeared to strongly correlate with treatment response.

Conclusion

Our findings suggest that the dynamic change of KRAS copy number on ctDNA during treatment might be a negative predictive biomarker. Additionally, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab “rechallenged” strategy.
Radiomic Signatures for Predicting Receptor Status in Breast Cancer Brain Metastases
Authors: Luo Xiao , Xie Hui , Yang Yadi , Zhang Cheng , Zhang Yijun , Li Yue , Yang Qiuxia , Wang Deling , Luo Yingwei , Mai Zhijun , Xie Chuanmiao , Yin Shaohan
Published: June 2022

Backgrounds

A significant proportion of breast cancer patients showed receptor discordance between primary cancers and breast cancer brain metastases (BCBM), which significantly affected therapeutic decision-making. But it was not always feasible to obtain BCBM tissues. The aim of the present study was to analyze the receptor status of primary breast cancer and matched brain metastases and establish radiomic signatures to predict the receptor status of BCBM.

Methods

The receptor status of 80 matched primary breast cancers and resected brain metastases were retrospectively analyzed. Radiomic features were extracted using preoperative brain MRI (contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2 fluid-attenuated inversion recovery, and combinations of these sequences) collected from 68 patients (45 and 23 for training and test sets, respectively) with BCBM excision. Using least absolute shrinkage selection operator and logistic regression model, the machine learning-based radiomic signatures were constructed to predict the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of BCBM.

Results

Discordance between the primary cancer and BCBM was found in 51.3% of patients, with 27.5%, 27.5%, and 5.0% discordance for ER, PR, and HER2, respectively. Loss of receptor expression was more common (33.8%) than gain (18.8%). The radiomic signatures built using combination sequences had the best performance in the training and test sets. The combination model yielded AUCs of 0.89, 0.88, and 0.87, classification sensitivities of 71.4%, 90%, and 87.5%, specificities of 81.2%, 76.9%, and 71.4%, and accuracies of 78.3%, 82.6%, and 82.6% for ER, PR, and HER2, respectively, in the test set.

Conclusions

Receptor conversion in BCBM was common, and radiomic signatures show potential for noninvasively predicting BCBM receptor status.
Identification of LINC00654-NINL Regulatory Axis in Diffuse Large B-Cell Lymphoma In Silico Analysis
Authors: Chen Yinchu , Li Chen , Wang Nana , Wu Zhenghao , Zhang Jin , Yan Jiawei , Wei Yuanfeng , Peng Qunlong , Qi Jing
Published: June 2022

Background

The long non-coding RNA (lncRNA)-mRNA regulation network plays an important role in the development of diffuse large B-cell lymphoma (DLBCL). This study uses bioinformatics to find an innovative regulation axis in DLBCL that will provide a positive reference for defining the mechanism of disease progression.

Methods

Batch Cox regression was used to screen prognosis-related lncRNAs, and a random forest model was used to identify hub lncRNA. The clinical value of the lncRNA was evaluated and Spearman correlation analysis was used to predict the candidate target genes. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were used to define the biological function of the lncRNA. A batch Cox regression model, expression validation, and Spearman correlation analysis were used to select the best downstream target genes. The expression and prognostic value validation of this gene was conducted using public data. Gene Set Enrichment Analysis (GSEA) was performed to explore potential mechanisms for this gene in DLBCL.

Results

LINC00654 was identified as the hub lncRNA and 1443 mRNAs were selected as downstream target genes of the lncRNA. The target genes were enriched in the regulation of GTPase and Notch signaling pathways. After validation, the ninein-like (NINL) gene was selected as the potential target of LINC00654 and the LINC00654-NINL axis was constructed. Patients with better responses to therapy were shown to have high NINL gene expression (p-value = 0.036). NINL also had high expression in the DB cell line and low expression in the OCILY3 cell line. Survival analysis showed that high NINL expression was a risk factor for overall survival (OS) and disease-specific survival (DSS) within older patients and those with advanced-stage cancer. GSEA results showed that NINL may be involved in neutrophil-mediated immunity and NF-κB signaling.

Conclusion

This study identified a novel LncRNA00654-NINL regulatory axis in DLBCL, which could provide a favorable reference for exploring the possible mechanisms of disease progression.
Effectiveness and Safety of Therapeutic Vaccines for Precancerous Cervical Lesions: A Systematic Review and Meta-Analysis
Authors: Cai Shan , Tan Xiaoyu , Miao Ke , Li Dantong , Cheng Si , Li Pei , Zeng Xueyang , Sun Feng
Published: June 2022

Objective

This study systematically evaluated the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions, providing evidence for future research.

Methods

We systematically searched the literature in 10 databases from inception to February 18, 2021. Studies on the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions were included. Then, we calculated the overall incidence rates of four outcomes, for which we used the risk ratio (RR) and 95% confidence interval (95% CI) to describe the effects of high-grade squamous intraepithelial lesions (HSILs) on recurrence.

Results

A total of 39 studies were included, all reported in English, published from 1989 to 2021 in 16 countries. The studies covered 22,865 women aged 15–65 years, with a total of 5,794 vaccinated, and 21 vaccines were divided into six types. Meta-analysis showed that the overall incidence rate of HSIL regression in vaccine therapies was 62.48% [95% CI (42.80, 80.41)], with the highest rate being 72.32% for viral vector vaccines [95% CI (29.33, 99.51)]. Similarly, the overall incidence rates of HPV and HPV16/18 clearance by vaccines were 48.59% [95% CI (32.68, 64.64)] and 47.37% [95% CI (38.00, 56.81)], respectively, with the highest rates being 68.18% [95% CI (45.13, 86.14)] for bacterial vector vaccines and 55.14% [95% CI (42.31, 67.66)] for DNA-based vaccines. In addition, a comprehensive analysis indicated that virus-like particle vaccines after conization reduced the risk of HSIL recurrence with statistical significance compared to conization alone [RR = 0.46; 95% CI (0.29, 0.74)]. Regarding safety, only four studies reported a few severe adverse events, indicating that vaccines for precancerous cervical lesions are generally safe.

Conclusion

Virus-like particle vaccines as an adjuvant immunotherapy for conization can significantly reduce the risk of HSIL recurrence. Most therapeutic vaccines have direct therapeutic effects on precancerous lesions, and the effectiveness in HSIL regression, clearance of HPV, and clearance of HPV16/18 is great with good safety. That is, therapeutic vaccines have good development potential and are worthy of further research.

Systematic Review Registration

PROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021275452.