bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurological, neurobehavioral, and radiological alterations in patients with mucopolysaccharidosis III (Sanfilippo's syndrome) in Brazil
Authors: Valle Daniel Almeida do , Santos Mara Lúcia Schmitz Ferreira , Telles Bruno Augusto , Cordeiro Mara L.
Published: November 2022

Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is the most common form of MPS, in which neurological involvement in all stages of the disease is prominent. The current study aimed to comprehensively describe the neurological profile of children and adolescents with MPS III who visited the largest pediatric hospital in South America. A prospective/retrospective cohort analysis was performed on 10 patients with MPS III from eight unrelated families. Most patients <12 months of age had achieved development milestones within the expected range for their age, with delay in walking independently and first single word acquisition. Behavioral symptoms were reported in seven patients. Eight patients (80%) developed profound intellectual disabilities. Six patients (60%) had epilepsy, among whom 75% had their first seizure between 2 and 4 years of age; the frequency of which increased with age. Monotherapy was effective in 60% of patients. Two patients, both aged <8 years, had normal baseline electroencephalographic activity. Epileptiform activity was observed in three patients. Cortical atrophy was visualized using magnetic resonance imaging in 71% patients; all but one of these patients were aged >6 years. Neurological abnormalities increased in prevalence and severity with age. Anti-seizure drug resistance was uncommon. Dysmorphological and systemic manifestations were uncommon and mild and did not correlate with neurological involvement. Despite high allelic heterogeneity, neurodegeneration was similar among all patients. Overall, these data contribute to the scarce literature from developing countries.
Investigating the role of human frontal eye field in the pupil light reflex modulation by saccade planning and working memory
Authors: Hsu Tzu-Yu , Wang Hsin-Yi , Chen Jui-Tai , Wang Chin-An
Published: November 2022

The pupil constricts in response to an increase in global luminance level, commonly referred to as the pupil light reflex. Recent research has shown that these reflex responses are modulated by high-level cognition. There is larger pupil constriction evoked by a bright stimulus when the stimulus location spatially overlaps with the locus of attention, and these effects have been extended to saccade planning and working memory (here referred to as pupil local-luminance modulation). Although research in monkeys has further elucidated a central role of the frontal eye field (FEF) and superior colliculus in the pupil local-luminance modulation, their roles remain to be established in humans. Through applying continuous theta-burst transcranial magnetic stimulation over the right FEF (and vertex) to inhibit its activity, we investigated the role of the FEF in human pupil local-luminance responses. Pupil light reflex responses were transiently evoked by a bright patch stimulus presented during the delay period in the visual- and memory-delay tasks. In the visual-delay task, larger pupil constriction was observed when the patch location was spatially aligned with the target location in both stimulation conditions. More interestingly, after FEF stimulation, larger pupil constriction was obtained when the patch was presented in the contralateral, compared to the ipsilateral visual field of the stimulation. In contrast, FEF stimulation effects were absence in the memory-delay task. Linear mixed model results further found that stimulation condition, patch location consistency, and visual field significantly modulated observed pupil constriction responses. Together, our results constitute the first evidence of FEF modulation in human pupil local-luminance responses.
Effect of music intervention on subjective scores, heart rate variability, and prefrontal hemodynamics in patients with chronic pain
Authors: Du Jiahao , Shi Ping , Fang Fanfu , Yu Hongliu
Published: November 2022

Introduction

Music interventions have been proposed in recent years as a treatment for chronic pain. However, the mechanisms by which music relieves pain are unclear, and the effects of music intervention on physiological indicators in patients with chronic pain remain to be explored. This study aimed to explore whether a music intervention would have effects on subjective pain ratings, heart rate variability, and functional connectivity of the cerebral cortex in patients with chronic pain.

Methods

A randomized controlled study was conducted on 37 pain patients aged 18–65 years, with the control group receiving usual care, and the intervention group receiving music intervention (8–150 Hz, 50–70 dB) for 30 min before bedtime for 7 days on top of usual care. Pain visual analog scale and heart rate variability were used as subjective and objective physiological indices before and after the music intervention, respectively. Changes in oxyhemoglobin and deoxyhemoglobin concentrations in the cerebral cortex were measured by functional near-infrared spectroscopy, and whole-brain correlation analysis was used to quantify the connectivity of prefrontal brain regions associated with the pain response.

Results

Results showed that patients with chronic pain in the intervention group had significantly lower visual assessment scale scores, as well as significantly lower overall voluntary mobility during pain episodes, resulting in relatively higher vagal innervation compared to the control group. In addition, connections between the bilateral dorsolateral prefrontal cortex (BA9, BA46) and frontal areas (BA10) were significantly higher in the intervention group.

Discussion

This study demonstrates the effectiveness of the combined application of music interventions with usual care in reducing pain levels in patients with chronic pain and provides insight into the pathological mechanisms of music interventions for analgesia, providing direction for new baseline indicators for quantitative clinical assessment of pain. The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100052993).

Clinical trial registration

[https://www.chictr.org.cn/showproj.aspx?proj=136268], identifier [ChiCTR2100052993].
Abnormal resting-state functional connectome in methamphetamine-dependent patients and its application in machine-learning-based classification
Authors: Li Yadi , Cheng Ping , Liang Liang , Dong Haibo , Liu Huifen , Shen Wenwen , Zhou Wenhua
Published: November 2022

Brain resting-state functional connectivity (rsFC) has been widely analyzed in substance use disorders (SUDs), including methamphetamine (MA) dependence. Most of these studies utilized Pearson correlation analysis to assess rsFC, which cannot determine whether two brain regions are connected by direct or indirect pathways. Moreover, few studies have reported the application of rsFC-based graph theory in MA dependence. We evaluated alterations in Tikhonov regularization-based rsFC and rsFC-based topological attributes in 46 MA-dependent patients, as well as the correlations between topological attributes and clinical variables. Moreover, the topological attributes selected by least absolute shrinkage and selection operator (LASSO) were used to construct a support vector machine (SVM)-based classifier for MA dependence. The MA group presented a subnetwork with increased rsFC, indicating overactivation of the reward circuit that makes patients very sensitive to drug-related visual cues, and a subnetwork with decreased rsFC suggesting aberrant synchronized spontaneous activity in subregions within the orbitofrontal cortex (OFC) system. The MA group demonstrated a significantly decreased area under the curve (AUC) for the clustering coefficient (Cp) (Pperm < 0.001), shortest path length (Lp) (Pperm = 0.007), modularity (Pperm = 0.006), and small-worldness (σ, Pperm = 0.004), as well as an increased AUC for global efficiency (E.glob) (Pperm = 0.009), network strength (Sp) (Pperm = 0.009), and small-worldness (ω, Pperm < 0.001), implying a shift toward random networks. MA-related increased nodal efficiency (E.nodal) and altered betweenness centrality were also discovered in several brain regions. The AUC for ω was significantly positively associated with psychiatric symptoms. An SVM classifier trained by 36 features selected by LASSO from all topological attributes achieved excellent performance, cross-validated prediction area under the receiver operating characteristics curve, accuracy, sensitivity, specificity, and kappa of 99.03 ± 1.79, 94.00 ± 5.78, 93.46 ± 8.82, 94.52 ± 8.11, and 87.99 ± 11.57%, respectively (Pperm < 0.001), indicating that rsFC-based topological attributes can provide promising features for constructing a high-efficacy classifier for MA dependence.
Wearable super-resolution muscle–machine interfacing
Authors: Wang Huxi , Zuo Siming , Cerezo-Sánchez María , Arekhloo Negin Ghahremani , Nazarpour Kianoush , Heidari Hadi
Published: November 2022

Muscles are the actuators of all human actions, from daily work and life to communication and expression of emotions. Myography records the signals from muscle activities as an interface between machine hardware and human wetware, granting direct and natural control of our electronic peripherals. Regardless of the significant progression as of late, the conventional myographic sensors are still incapable of achieving the desired high-resolution and non-invasive recording. This paper presents a critical review of state-of-the-art wearable sensing technologies that measure deeper muscle activity with high spatial resolution, so-called super-resolution. This paper classifies these myographic sensors according to the different signal types (i.e., biomechanical, biochemical, and bioelectrical) they record during measuring muscle activity. By describing the characteristics and current developments with advantages and limitations of each myographic sensor, their capabilities are investigated as a super-resolution myography technique, including: (i) non-invasive and high-density designs of the sensing units and their vulnerability to interferences, (ii) limit-of-detection to register the activity of deep muscles. Finally, this paper concludes with new opportunities in this fast-growing super-resolution myography field and proposes promising future research directions. These advances will enable next-generation muscle-machine interfaces to meet the practical design needs in real-life for healthcare technologies, assistive/rehabilitation robotics, and human augmentation with extended reality.
Triple network activation causes tinnitus in patients with sudden sensorineural hearing loss: A model-based volume-entropy analysis
Authors: Lee Seung Jae , Park Jaemin , Lee Sang-Yeon , Koo Ja-Won , Vanneste Sven , De Ridder Dirk , Lim Seonhee , Song Jae-Jin
Published: November 2022

Tinnitus can be defined as the conscious perception of phantom sounds in the absence of corresponding external auditory signals. Tinnitus can develop in the setting of sudden sensorineural hearing loss (SSNHL), but the underlying mechanism is largely unknown. Using electroencephalography, we investigated differences in afferent node capacity between 15 SSNHL patients without tinnitus (NT) and 30 SSNHL patients with tinnitus (T). Where the T group showed increased afferent node capacity in regions constituting a “triple brain network” [default mode network (DMN), central executive network (CEN), and salience network (SN)], the NT group showed increased information flow in regions implicated in temporal auditory processing and noise-canceling pathways. Our results demonstrate that when all components of the triple network are activated due to sudden-onset auditory deprivation, tinnitus ensues. By contrast, auditory processing-associated and tinnitus-suppressing networks are highly activated in the NT group, to overcome the activation of the triple network and effectively suppress the generation of tinnitus.
Disrupted metabolic and spontaneous neuronal activity of hippocampus in sepsis associated encephalopathy rats: A study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging
Authors: Li Haojia , Liao Hongsen , Zhang Chen , Xu Yajie , Xu Xiaomin , Chen Yuchen , Song Shaozheng , Li Qian , Si Yanna , Bao Hongguang
Published: November 2022

Background

The diagnosis of sepsis associated encephalopathy (SAE) remains challenging in clinical settings because of a lack of specific biomarkers. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) can be used to aid in the diagnosis of cognition related diseases. This study investigated changes in functional activities and brain metabolites in the hippocampus in SAE rats by fMRI and 1H-MRS.

Materials and methods

Sepsis associated encephalopathy rats underwent cecal ligation and perforation (CLP) surgery. The Morris water maze (MWM) test was then used to evaluate cognitive function. Resting state-fMRI and 1H-MRS scanning were performed 7 and 14 days after CLP surgery to reveal spontaneous neuronal activity and metabolite changes in the hippocampus. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate spontaneous neuronal activity in the hippocampus. Creatine (Cr), Myo-inositol (mI), and glutamine/glutamate (Glx) levels were measured with 1H-MRS scanning. Immunofluorescence and levels of interleukin (IL)-1β, interleukin (IL)-6, and C-reactive protein (CRP) in the hippocampus were additionally detected to evaluate microglial mediated inflammatory responses. Statistical analysis was performed to evaluate correlations between hippocampal metabolism and behavioral findings.

Results

Cecal ligation and perforation treated rats exhibited impaired learning and memory function in the MWM test at days 7 and 14. Elevation of IL-1β in the hippocampus, as well as immunofluorescence results, confirmed severe neuro inflammation in the hippocampus in SAE rats. Compared with the sham group, the ALFF of the right CA-1 area of the hippocampus was higher at day 7after CLP surgery. The Glx/Cr and mI/Cr ratios were enhanced at day 7 after CLP surgery and slightly lower at day 14 after CLP surgery. The ALFF value, and Glx/Cr and mI/Cr ratios were negatively correlated with time spent in the target quadrant in the MWM test.

Conclusion

Spontaneous neuronal activity and metabolites showed significant alterations in SAE rats. The elevated ALFF value, Glx/Cr ratio, and mI/Cr ratio in the hippocampus were positively associated with cognitive deficits. Changes in ALFF and metabolites in hippocampus may serve as potential neuroimaging biomarkers of cognitive disorders in patients with SAE.
Accelerating cutaneous healing in a rodent model of type II diabetes utilizing non-invasive focused ultrasound targeted at the spleen
Authors: Morton Christine , Cotero Victoria , Ashe Jeffrey , Ginty Fiona , Puleo Christopher
Published: November 2022

Healing of wounds is delayed in Type 2 Diabetes Mellitus (T2DM), and new treatment approaches are urgently needed. Our earlier work showed that splenic pulsed focused ultrasound (pFUS) alters inflammatory cytokines in models of acute endotoxemia and pneumoniaviamodulation of the cholinergic anti-inflammatory pathway (CAP) (ref below). Based on these earlier results, we hypothesized that daily splenic exposure to pFUS during wound healing would accelerate closure rateviaaltered systemic cytokine titers. In this study, we applied non-invasive ultrasound directed to the spleen of a rodent model [Zucker Diabetic Sprague Dawley (ZDSD) rats] of T2DM with full thickness cutaneous excisional wounds in an attempt to accelerate wound healingvianormalization of T2DM-driven aberrant cytokine expression. Daily (1x/day, Monday-Friday) pFUS pulses were targeted externally to the spleen area for 3 min over the course of 15 days. Wound diameter was measured daily, and levels of cytokines were evaluated in spleen and wound bed lysates. Non-invasive splenic pFUS accelerated wound closure by up to 4.5 days vs. sham controls. The time to heal in all treated groups was comparable to that of healthy rats from previously published studies (ref below), suggesting that the pFUS treatment restored a normal wound healing phenotype to the ZDSD rats. IL-6 was lower in stimulated spleen (-2.24 ± 0.81 Log2FC,p= 0.02) while L-selectin was higher in the wound bed of stimulated rodents (2.53 ± 0.72 Log2FC,p= 0.003). In summary, splenic pFUS accelerates healing in a T2DM rat model, demonstrating the potential of the method to provide a novel, non-invasive approach for wound care in diabetes.
Mapping trends and hotspot regarding gastrointestinal microbiome and neuroscience: A bibliometric analysis of global research (2002–2022)
Authors: Yang Jingjing , Deng Yihui , Cai Yuzhe , Liu Yixuan , Peng Lanyu , Luo Zheng , Li Dingxiang
Published: November 2022

Background

Scholars have long understood that gastrointestinal microorganisms are intimately related to human disorders. The literature on research involving the gut microbiome and neuroscience is emerging. This study exposed the connections between gut microbiota and neuroscience methodically and intuitively using bibliometrics and visualization. This study’s objectives were to summarize the knowledge structure and identify emerging trends and potential hotspots in this field.

Materials and methods

On October 18, 2022, a literature search was conducted utilizing the Web of Science Core Collection (WoSCC) database for studies on gut microbiota and neuroscience studies from 2002 to 2022 (August 20, 2022). VOSviewer and CiteSpace V software was used to conduct the bibliometrics and visualization analysis.

Results

From 2002 to 2022 (August 20, 2022), 2,275 publications in the WoSCC database satisfied the criteria. The annual volume of publications has rapidly emerged in recent years (2016–2022). The most productive nation (n = 732, 32.18%) and the hub of inter-country cooperation (links: 38) were the United States. University College Cork had the most research papers published in this area, followed by McMaster University and Harvard Medical School. Cryan JF, Dinan TG, and Clarke G were key researchers with considerable academic influence. The journals with the most publications are “Neurogastroenterology and Motility” and “Brain Behavior and Immunity.” The most cited article and co-cited reference was Cryan JF’s 2012 article on the impact of gut microbiota on the brain and behavior. The current research hotspot includes gastrointestinal microbiome, inflammation, gut-brain axis, Parkinson’s disease (PD), and Alzheimer’s disease (AD). The research focus would be on the “gastrointestinal microbiome, inflammation: a link between obesity, insulin resistance, and cognition” and “the role of two important theories of the gut-brain axis and microbial-gut-brain axis in diseases.” Burst detection analysis showed that schizophrenia, pathology, and psychiatric disorder may continue to be the research frontiers.

Conclusion

Research on “gastrointestinal microbiome, inflammation: a link between obesity, insulin resistance, and cognition” and “the role of two important theories of the gut-brain axis and microbial-gut-brain axis in diseases” will continue to be the hotspot. Schizophrenia and psychiatric disorder will be the key research diseases in the field of gut microbiota and neuroscience, and pathology is the key research content, which is worthy of scholars’ attention.
Structural network alterations in patients with nasopharyngeal carcinoma after radiotherapy: A 1-year longitudinal study
Authors: Zhang Xinyuan , Pan Jie , Lin Yuhao , Fu Gui , Xu Pu , Liang Jiahui , Ye Chenfei , Peng Jie , Lv Xiaofei , Yang Yadi , Feng Yanqiu
Published: November 2022

This longitudinal study explored the changed patterns of structural brain network after radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). Diffusion tensor imaging (DTI) data were gathered from 35 patients with NPC at four time points: before RT (baseline), 0∼3 (acute), 6 (early delayed), and 12 months (late-delayed) after RT. The graph theory was used to characterize the dynamic topological properties after RT and the significant changes were detected over time at the global, regional and modular levels. Significantly altered regional metrics (nodal efficiency and degree centrality) were distributed in the prefrontal, temporal, parietal, frontal, and subcortical regions. The module, that exhibited a significantly altered within-module connectivity, had a high overlap with the default mode network (DMN). In addition, the global, regional and modular metrics showed a tendency of progressive decrease at the acute and early delayed stages, and a partial/full recovery at the late-delayed stage. This changed pattern illustrated that the radiation-induced brain damage began at the acute reaction stage and were aggravated at the early-delayed stage, and then partially recovered at the late-delayed stage. Furthermore, the spearman’s correlations between the abnormal nodal metrics and temporal dose were calculated and high correlations were found at the temporal (MTG.R and HES.L), subcortical (INS.R), prefrontal (ORBinf.L and ACG.L), and parietal (IPL.R) indicating that these regions were more sensitive to dose and should be mainly considered in radiotherapy treatment plan.
Alterations of presynaptic proteins in autism spectrum disorder
Authors: Yeo Xin Yi , Lim Yi Tang , Chae Woo Ri , Park Chungwon , Park Hyokeun , Jung Sangyong
Published: November 2022

The expanded use of hypothesis-free gene analysis methods in autism research has significantly increased the number of genetic risk factors associated with the pathogenesis of autism. A further examination of the implicated genes directly revealed the involvement in processes pertinent to neuronal differentiation, development, and function, with a predominant contribution from the regulators of synaptic function. Despite the importance of presynaptic function in synaptic transmission, the regulation of neuronal network activity, and the final behavioral output, there is a relative lack of understanding of the presynaptic contribution to the pathology of autism. Here, we will review the close association among autism-related mutations, autism spectrum disorders (ASD) phenotypes, and the altered presynaptic protein functions through a systematic examination of the presynaptic risk genes relating to the critical stages of synaptogenesis and neurotransmission.
Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons
Authors: Hosoi Yasushi , Akita Tenpei , Watanabe Miho , Ito Takashi , Miyajima Hiroaki , Fukuda Atsuo
Published: November 2022

Fetal and infant brains are rich in maternally derived taurine. We previously demonstrated that taurine action regulates the cation-chloride cotransporter activity and the differentiation and radial migration of pyramidal neuron progenitors in the developing neocortex of rodent fetuses. Here we examined the effects of fetal and infantile taurine depletion caused by knockout of the taurine transporter Slc6a6 on firing properties of layer II/III pyramidal neurons in the mouse somatosensory cortex at 3 weeks of postnatal age, using the whole-cell patch-clamp technique. The membrane excitability under resting conditions was similar between the neurons in knockout mice and those in wildtype littermates. However, the frequency of repetitive spike firing during moderate current injection was significantly lower, along with lower membrane voltage levels during interspike intervals in knockout neurons. When strong currents were injected, by which repetitive firing was rapidly abolished due to inactivation of voltage-gated Na+ channels in wildtype neurons, the firing in knockout neurons lasted for a much longer period than in wildtype neurons. This was due to much lower membrane voltage levels during interspike intervals in knockout neurons, promoting greater recovery of voltage-gated Na+ channels from inactivation. Thus, taurine depletion in pyramidal neurons blunted neuronal responses to external stimuli through increasing the stability of repetitive firing, presumably mediated by larger increases in membrane K+ conductance during interspike intervals.
Image discrimination reversal learning is impaired by sleep deprivation in rats: Cognitive rigidity or fatigue?
Authors: Strobel Brian K. , Schmidt Michelle A. , Harvey Daniel O. , Davis Christopher J.
Published: November 2022

Introduction

Insufficient sleep is pervasive worldwide, and its toll on health and safety is recapitulated in many settings. It is thus important to understand how poor sleep affects the brain and decision making. A robust literature documents the adverse effects of sleep deprivation on cognitive processes including cognitive flexibility, which is the capacity to appraise new feedback and make behavioral adjustments to respond appropriately. Animal models are often used to unravel the molecules, genes and neural circuits that are altered by sleep loss. Herein we take a translational approach to model the effects of sleep deprivation on cognitive rigidity, i.e., impaired cognitive flexibility in rats.

Methods

There are several approaches to assess cognitive rigidity; in the present study, we employ a pairwise discrimination reversal task. To our knowledge this is the first time this paradigm has been used to investigate sleep deprivation. In this touchscreen operant platform, we trained rats to select one of two images to claim a sucrose pellet reward. If the non-rewarded image was selected the rats proceeded to a correction trial where both images were presented in the same position as before. This image presentation continued until the rat selected the correct image. Once rats reached performance criteria, the reward contingencies were reversed. In one group of rats the initial reversal session was preceded by 10 h of sleep deprivation. We compared those rats to controls with undisturbed sleep on the number of sessions to reach performance criteria, number of trials per session, response latencies, correct responses, errors, perseverative errors and perseveration bouts in the initial training and reversal phases.

Results

We report that on reversal session one, sleep deprived rats completed a fraction of the trials completed by controls. On subsequent reversal sessions, the sleep deprived rats struggled to adapt to the reversed contingencies despite completing a similar number of trials, suggesting an effect of cognitive rigidity separate from fatigue.

Discussion

We discuss the delayed performance dynamics incurred by sleep loss in the context of fatigue and the implications of using pairwise discrimination reversal as a model to further examine the effects of sleep loss on adaptive decision making.
Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: Thoughts on iron supplementation in pregnant women with thalassemia genes
Authors: Wang Min , Zhang Xiaozhuang , Zhao Yanhong , Zhang Yubin , Lin Yan , Xiao Meifang , Li Ling
Published: November 2022

Background

There are limited studies on iron-deficiency anemia (IDA) in carriers of various thalassemia genotypes. However, for pregnant women (PW) with high iron demand, ignoring the phenomenon of carrying the thalassemia genes combined with IDA may lead to adverse pregnancy outcomes.

Methods

The hematological phenotype indexes of 15,051 PW who received a prenatal diagnosis of thalassemia in our hospital were analyzed, and the plasma ferritin (PF) of 714 anemic pregnant women (APW) was determined.

Results

The results showed that 87.43% of APW without thalassemia suffered from IDA. Among APW with various thalassemia genotypes, we found that 40.00∼77.78% of subjects with α-thalassemia silent genotypes [αCS (or QS)α/αα (40.00%), –α3.7(or4.2)/αα (57.65%), and αWSα/αα (77.78%)] and 18.18∼84.21% of subjects with α-thalassemia minor genotypes [αCS (or QS)α/–α3.7(or4.2) (18.18%), –α3.7(or4.2)/–α3.7(or4.2) (40.00%), αα/–SEA (44.55%), and αWSα/–α3.7(or4.2) (84.21%)] developed IDA, while in subjects with α-thalassemia intermedia genotypes, only αWSα/–SEA was associated with IDA, with an incidence of 16.67%. However, the incidence of IDA in APW with common β-thalassemia minor genotypes (βCD17(A>T)/β, βCD41/42 (–TTCT)/β, βCD71/72(+A)/β, βIVS–II–654(C>T)/β, and β–28(A>G)/β) was less than 10.85%. In addition, the APW with β-thalassemia minor had a higher PF level than the APW without thalassemia.

Conclusion

Our study is the first to reveal differences in the prevalence of IDA among PW with various thalassemia genotypes, indicating that the possibility of IDA should be fully considered when managing PW with α-thalassemia silent or minor genotypes in high-risk areas, and that iron supplementation should be monitored dynamically for PW with β-thalassemia minor genotypes.
Effects of a nutritional intervention on impaired behavior and cognitive function in an emphysematous murine model of COPD with endotoxin-induced lung inflammation
Authors: Pelgrim Charlotte E. , van Ark Ingrid , van Berkum Ronja E. , Schuitemaker-Borneman Anne M. , Flier Inge , Leusink-Muis Thea , Janbazacyabar Hamed , Diks Mara A. P. , Gosker Harry R. , Kelders Marco C. J. M. , Langen Ramon C. J. , Schols Annemie M. W. J. , Hageman Robert J. J. , Braber Saskia , Garssen Johan , Folkerts Gert , van Helvoort Ardy , Kraneveld Aletta D.
Published: November 2022

One cluster of the extrapulmonary manifestations in chronic obstructive pulmonary disease (COPD) is related to the brain, which includes anxiety, depression and cognitive impairment. Brain-related comorbidities are related to worsening of symptoms and increased mortality in COPD patients. In this study, a murine model of COPD was used to examine the effects of emphysema and repetitive pulmonary inflammatory events on systemic inflammatory outcomes and brain function. In addition, the effect of a dietary intervention on brain-related parameters was assessed. Adult male C57Bl/6J mice were exposed to elastase or vehicle intratracheally (i.t.) once a week on three consecutive weeks. Two weeks after the final administration, mice were i.t. exposed to lipopolysaccharide (LPS) or vehicle for three times with a 10 day interval. A dietary intervention enriched with omega-3 PUFAs, prebiotic fibers, tryptophan and vitamin D was administered from the first LPS exposure onward. Behavior and cognitive function, the degree of emphysema and both pulmonary and systemic inflammation as well as blood-brain barrier (BBB) integrity and neuroinflammation in the brain were assessed. A lower score in the cognitive test was observed in elastase-exposed mice. Mice exposed to elastase plus LPS showed less locomotion in the behavior test. The enriched diet seemed to reduce anxiety-like behavior over time and cognitive impairments associated with the presented COPD model, without affecting locomotion. In addition, the enriched diet restored the disbalance in splenic T-helper 1 (Th1) and Th2 cells. There was a trend toward recovering elastase plus LPS-induced decreased expression of occludin in brain microvessels, a measure of BBB integrity, as well as improving expression levels of kynurenine pathway markers in the brain by the enriched diet. The findings of this study demonstrate brain-associated comorbidities – including cognitive and behavioral impairments – in this murine model for COPD. Although no changes in lung parameters were observed, exposure to the specific enriched diet in this model appeared to improve systemic immune disbalance, BBB integrity and derailed kynurenine pathway which may lead to reduction of anxiety-like behavior and improved cognition.
Structural characterization of a new high molecular weight polysaccharide from jujube fruit
Authors: Ji Xiaolong , Wang Zhiwen , Hao Xiyu , Zhu Yingying , Lin Yan , Li Guoli , Guo Xudan
Published: November 2022

From Ziziphus Jujuba cv. Muzao fruit, a new polysaccharide (PZMP3-1) with high molecular weight was isolated. Constructional characterization revealed that PZMP3-1 comprized 2.56 rhamnose, 7.70 arabinoses, 3.73 galactose, and 6.73 galactose, and it has a 241 kDa average molecular weight. The principal structural components of PZMP3-1 were 1,2,4 and 1,4-linked GalpA, 1,4-linked Galp, 1,3 and 1,5-linked Araf, and 1-linked Rhap based on methylation and nuclear magnetic resonance spectroscopy (NMR) analyses. X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), atomic force microscopy (AFM), and scanning electron microscopy (SEM) structural analysis of PZMP3-1 revealed a tangled and branching pattern. Overall, these structural results suggested that PZMP3-1 could have unique bioactivities and be widely used in nutritional supplements.
Effect of aflatoxin B1 exposure on the progression of depressive-like behavior in rats
Authors: Subramaniam Syarminie , Sabran Mohd-Redzwan , Stanslas Johnson , Kirby Brian P.
Published: November 2022

While it is well documented that aflatoxin B1 (AFB1); one of the most toxic food contaminants is linked to the development of depression. However, the mechanism on how it affects the gut and brain health leading to depressive-like behavior remains unclear. This study was conducted to determine the effect of AFB1 on the progression of depressive-like behavior. Thirty-two (n = 32) male Sprague Dawley rats were randomly allocated into four groups: control, low-dose (5 μg AFB1/kg), high-dose (25 μg AFB1/kg) and positive control group; exposed on chronic unpredictable mild stress (CUMS). After 4 weeks of exposure, sucrose preference test (SPT) and force swim test (FST) were used to measure behavioral despair. Fecal samples were selectively cultured to profile the bacteria. Body weight and relative organs weights were compared among groups. AFB1 and CUMS caused reduction in body weight and food intake as well as increased relative weight of adrenal glands, liver, and brain. Rats in AFB1 and CUMS groups had suppressed sucrose preference and prolonged immobility time in FST, wherein this could indicate anhedonia. Besides, fecal count of Lactobacillus spp. was significantly low following AFB1 exposure, with increasing count of Bifidobacterium spp, in comparison to the control. Indeed, further biochemical analysis and metagenomic approach are warranted to explore the underlying mechanisms on the role of gut microbiota dysbiosis and dysregulation of gut-brain axis due to AFB1 neurotoxicity on the progression of depressive-like behavior.
Recent advances in structural characterization of biomacromolecules in foods via small-angle X-ray scattering
Authors: Sun Yang , Li Xiujuan , Chen Ruixin , Liu Fei , Wei Song
Published: November 2022

Small-angle X-ray scattering (SAXS) is a method for examining the solution structure, oligomeric state, conformational changes, and flexibility of biomacromolecules at a scale ranging from a few Angstroms to hundreds of nanometers. Wide time scales ranging from real time (milliseconds) to minutes can be also covered by SAXS. With many advantages, SAXS has been extensively used, it is widely used in the structural characterization of biomacromolecules in food science and technology. However, the application of SAXS in charactering the structure of food biomacromolecules has not been reviewed so far. In the current review, the principle, theoretical calculations and modeling programs are summarized, technical advances in the experimental setups and corresponding applications of in situ capabilities: combination of chromatography, time-resolved, temperature, pressure, flow-through are elaborated. Recent applications of SAXS for monitoring structural properties of biomacromolecules in food including protein, carbohydrate and lipid are also highlighted, and limitations and prospects for developing SAXS based on facility upgraded and artificial intelligence to study the structural properties of biomacromolecules are finally discussed. Future research should focus on extending machine time, simplifying SAXS data treatment, optimizing modeling methods in order to achieve an integrated structural biology based on SAXS as a practical tool for investigating the structure-function relationship of biomacromolecules in food industry.
The estimated burden of ultra-processed foods on cardiovascular disease outcomes in Brazil: A modeling study
Authors: Nilson Eduardo Augusto Fernandes , Ferrari Gerson , Louzada Maria Laura da Costa , Levy Renata Bertazzi , Monteiro Carlos Augusto , Rezende Leandro F. M.
Published: November 2022

Introduction

Ultra-processed foods (UPF) have been associated with an increased risk of cardiovascular diseases (CVD). This study aimed to estimate CVD premature deaths, incident cases, and disability adjusted life-years (DALYs) attributable to the consumption of UPF in Brazilian adults in 2019.

Methods

A validated a comparative risk assessment model was adapted to estimate the burden of major CVD outcomes (coronary heart disease and stroke) attributable to the consumption of UPF in Brazilian adults aged 30 to 69 years. The model inputs included nationally representative data of the UPF contribution to the total energy of the diet, national official demographic records, CVD outcomes (incidence, deaths and DALYs) from the Global Burden of Disease study for 2019, and relative risks from meta-analysis studies.

Results

We estimated that approximately 19,200 premature deaths (95% uncertainty intervals – UI, 7,097 to 32,353), 74,900 new cases (95% UI, 25,983 to 128,725), and 883,000 DALYs/year (95% UI, 324,279 to 1,492,593) from CVD were attributable to the consumption of UPF in Brazil, corresponding to about 22% of the premature deaths from CVD and to 33% of the total premature all-cause deaths attributable to UPF intake among Brazilian adults. Reducing UPF consumption by 10% in the adult population would avert approximately 11% of the premature CVD deaths, equivalent to 2,100 deaths/year (95% UI, 697 to 4,511). A 20% reduction in UPF intake would avert approximately 21% of the premature CVD deaths or 4,100 deaths (95% UI, 1,413 to 8,047), and a 50% reduction in UPF intake would avert about 52% of the premature CVD deaths, corresponding to 9,900 deaths/year (95% UI, 3,682 to 17,820). If UPF consumption among adults was reduced to that of the first quintile of UPF intake in the baseline scenario, approximately 81% of the premature CVD deaths would be averted, corresponding to some 15,600 deaths/year (95% UI, 5,229 to 27,519).

Conclusion

Our study estimated a high burden of premature CVD outcomes attributable to the consumption of UPF in Brazil. Our findings support food policies aimed at reducing the consumption of UPF, such as fiscal and regulatory policies, which are imperative to prevent CVD in Brazil.
Association between serum arginine levels and cancer risk: A community-based nested case-control study
Authors: Liu Tong , Wang Xiaomeng , Jia Pingping , Liu Chenan , Wei Yaping , Song Yun , Li Shuqun , Liu Lishun , Wang Binyan , Shi Hanping
Published: November 2022

Objective

The effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants.

Materials and methods

A nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer.

Results

Compared with matched controls, cancer patients had higher levels of arginine (21.41 μg/mL vs. 20.88 μg/mL,p< 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis.

Conclusion

We found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.
Association between malnutrition and contrast-associated acute kidney injury in congestive heart failure patients following coronary angiography
Authors: Ying Ming , Yang Junqing , Huang Zhidong , Ling Yihang , Wang Bo , Huang Haozhang , Li Qiang , Liu Jin , Liu Yong , Chen Zhujun
Published: November 2022

Background

Previous studies have shown that malnutrition is very common in patients with congestive heart failure (CHF) and is closely related to the occurrence of acute kidney injury. However, the relationship between malnutrition and contrast-associated acute kidney injury (CA-AKI) is unclear.

Method and results

We obtained data from 842 patients who were diagnosed with CHF following coronary angiography (CAG) or percutaneous coronary angiography (PCI) and had follow-up information from January 2013 to February 2016. The patients were divided into 3 groups according to the Controlling Nutritional Status Score before CAG or PCI procedure (Group 1: Normal; Group 2: Mild Malnutrition; Group 3: Moderate to Severe Malnutrition). The main endpoint was CA-AKI. Univariate and multivariable logistic regression analyses were performed. 556 (60.0%) patients suffered from malnutrition before CAG or PCI. During a median follow-up of 2.1 years, A total of 49 (5.82%) patients developed CA-AKI. Additionally, 5 (1.75%), 26 (6.27%) and 18 (12.77%) events were documented in patients with normal, mild and moderate or severe malnutrition, respectively (p < 0.01). In multivariable-adjusted models, patients with malnutrition showed a significantly higher incidence of CA-AKI than those in the normal group.

Conclusion

Malnutrition is an independent risk factor for CA-AKI in CHF patients following CAG.
Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques
Authors: Anttinen Mikael , Blanco Sequeiros Roberto , Boström Peter J. , Taimen Pekka
Published: November 2022

Established therapies for prostate cancer (PCa), surgery and radiotherapy, treat the entire gland regardless of the location of the cancerous lesion within the prostate. Although effective, these methods include a significant risk of worsening genitourinary outcomes. Targeted image-guided cancer therapy has gained acceptance through improved PCa detection, localization, and characterization by magnetic resonance imaging (MRI). Minimally-invasive ablative techniques aim to achieve comparable oncological outcomes to radical treatment while preserving genitourinary function. Transurethral ultrasound ablation (TULSA) and next-generation transrectal high-intensity focused ultrasound (HIFU) utilize MRI guidance to thermally ablate prostate tissue under real-time MRI monitoring and active temperature feedback control. Previous trials performed by our group and others, including a large multicenter study in men with localized favorable-risk disease, have demonstrated that TULSA provides effective prostate ablation with a favorable safety profile and low impact on quality of life. Recently, MRI-guided HIFU focal therapy was also shown as a safe and effective treatment of intermediate-risk PCa. Here we review the current literature on ablative techniques in the treatment of localized PCa with a focus on TULSA and HIFU methods.
Current concepts of anti-EGFR targeting in metastatic colorectal cancer
Authors: Doleschal Bernhard , Petzer Andreas , Rumpold Holger
Published: November 2022

Anti-EGFR targeting is one of the key strategies in the treatment of metastatic colorectal cancer (mCRC). For almost two decades oncologists have struggled to implement EGFR antibodies in the mCRC continuum of care. Both sidedness and RAS mutational status rank high among the predictive factors for the clinical efficacy of EGFR inhibitors. A prospective phase III trial has recently confirmed that anti-EGFR targeting confers an overall survival benefit only in left sided RAS-wildtype tumors when given in first line. It is a matter of discussion if more clinical benefit can be reached by considering putative primary resistance mechanisms (e.g., HER2, BRAF, PIK3CA, etc.) at this early stage of treatment. The value of this procedure in daily routine clinical utility has not yet been clearly delineated. Re-exposure to EGFR antibodies becomes increasingly crucial in the disease journey of mCRC. Yet re- induction or re-challenge strategies have been problematic as they relied on mathematical models that described the timely decay of EGFR antibody resistant clones. The advent of liquid biopsy and the implementation of more accurate next-generation sequencing (NGS) based high throughput methods allows for tracing of EGFR resistant clones in real time. These displays the spatiotemporal heterogeneity of metastatic disease compared to the former standard radiographic assessment and re-biopsy. These techniques may move EGFR inhibition in mCRC into the area of precision medicine in order to apply EGFR antibodies with the increase or decrease of EGFR resistant clones. This review critically discusses established concepts of tackling the EGFR pathway in mCRC and provides insight into the growing field of liquid biopsy guided personalized approaches of EGFR inhibition in mCRC.
Single-cell transcriptomic analysis of the tumor ecosystem of adenoid cystic carcinoma
Authors: Lin Quanquan , Fang Zhanjie , Sun Jinlong , Chen Fei , Ren Yipeng , Fu Zhenhong , Yang Sefei , Feng Lin , Wang Feng , Song Zhigang , Chen Wei , Yu Wenjun , Wang Chen , Shi Yixin , Liang Yue , Zhang Haizhong , Qu Hongzhu , Fang Xiangdong , Xi Qing
Published: November 2022

Adenoid cystic carcinoma (ACC) is a malignant tumor that originates from exocrine gland epithelial cells. We profiled the transcriptomes of 49,948 cells from paracarcinoma and carcinoma tissues of three patients using single-cell RNA sequencing. Three main types of the epithelial cells were identified into myoepithelial-like cells, intercalated duct-like cells, and duct-like cells by marker genes. And part of intercalated duct-like cells with special copy number variations which altered with MYB family gene and EN1 transcriptomes were identified as premalignant cells. Developmental pseudo-time analysis showed that the premalignant cells eventually transformed into malignant cells. Furthermore, MYB and MYBL1 were found to belong to two different gene modules and were expressed in a mutually exclusive manner. The two gene modules drove ACC progression into different directions. Our findings provide novel evidence to explain the high recurrence rate of ACC and its characteristic biological behavior.
Extracellular RNA as a kind of communication molecule and emerging cancer biomarker
Authors: Wu Danny , Tao Tao , Eshraghian Emily A. , Lin Peixu , Li Zesong , Zhu Xiao
Published: November 2022

Extracellular RNA (exRNA) is a special form of RNA in the body. RNA carries information about genes and metabolic regulation in the body, which can reflect the real-time status of cells. This characteristic renders it a biomarker for disease diagnosis, treatment, and prognosis. ExRNA is transported through extracellular vesicles as a signal medium to mediate communication between cells. Tumor cells can release more vesicles than normal cells, thereby promoting tumor development. Depending on its easy detection, the advantages of non-invasive molecular diagnostic technology can be realized. In this systematic review, we present the types, vectors, and biological value of exRNA. We briefly describe new methods of tumor diagnosis and treatment, as well as the difficulties faced in the progress of such research. This review highlights the groundbreaking potential of exRNA as a clinical biomarker.