bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Serum Follicle-Stimulating Hormone and Sarcopenia and Physical Disability Among Older Chinese Men: Evidence From a Cross-Sectional Study
Authors: Ke Yingying , Xu Jun , Zhang Xiaoyan , Guo Qihao , Zhu Yunxia
Published: January 2022

Background: Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass, function and quality and associated with a range of adverse health outcomes including disability. Despite a negative correlation between muscle mass and follicle-stimulating hormone (FSH) levels in postmenopausal women, it is unclear if FSH is associated with sarcopenia and its poor outcomes, especially in older men.

Methods: We used cross-sectional data from 360 men aged over 80 who participated in health check-ups to investigate correlations between serum FSH and sarcopenia, individual sarcopenia components, low physical performance (gait speed ≤ 0.8 m/s) and instrumental activities of daily living (IADL) disability. Sarcopenia and severe sarcopenia were diagnosed according to the revised definition of the European Working Group on Sarcopenia in Old People (EWGSOP2).

Results: The prevalence of sarcopenia was 17.8% in this population. In binary logistic regression analysis, compared with higher FSH group, lower FSH group showed a significant reduction in the risk of low calf circumference (a surrogate for muscle mass; OR 0.308, 95% CI 0.109–0.868, P = 0.026) after adjusting potential confounders including age, waist circumference, education, exercise, associated biochemical parameters, other sex hormones and high-sensitivity C-reactive protein. The correlation between FSH and low handgrip strength was marginally significant (OR 0.390, 95% CI 0.151–1.005, P = 0.051). No associations were observed between FSH and sarcopenia, severe sarcopenia, and disability in adjusted models.

Conclusion: In older men, circulating FSH was not associated with sarcopenia, sarcopenia severity, the majority of its components and adverse health outcome (IADL disability), with the exception of low calf circumference. Further work is needed to better elucidate the association of FSH and low muscle quantity by adopting more accurate measurement method of appendicular skeletal muscle mass such as DXA, CT or MRI.
Case Report: A Case of COVID Vaccine-Induced Thrombotic Thrombocytopenia Manifested as Pulmonary Embolism and Hemorrhagia. A First Reported Case From Slovakia
Authors: Ihnatko Martin , Truchla Ivana , Ihnatková L'udmila , Prohászka Zoltán , Lazúrová Ivica
Published: January 2022

COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector (ChAdOx1 nCoV-19) vaccine administration. It is presented as thrombocytopenia and thrombotic manifestations in various sites, especially in cerebral veins. Pulmonary emboli have been reported rarely. We present a case of a young male patient who developed severe thrombocytopenia and pulmonary embolism 12 days after the first dose of the vaccine. Severe thrombocytopenia, skin hematomas, and segmental pulmonary emboli were detected. Anti-platelet factor 4 (aPF-4) antibody was highly positive supporting the diagnosis of VITT. Prompt treatment with fondaparinux, intravenous immunoglobulin, and prednisone led to a marked improvement of clinical condition and thrombocytes count. We report the first known case of VITT in Slovakia.
Choroidal Morphologic and Vascular Features in Patients With Myopic Choroidal Neovascularization and Different Levels of Myopia Based on Image Binarization of Optical Coherence Tomography
Authors: Wang Xinglin , Yang Jiarui , Liu Yushi , Yang Luling , Xia Huaqin , Ren Xiaotong , Hou Qingyi , Ge Yimeng , Wang Changguan , Li Xuemin
Published: January 2022

Purpose: To characterize the choroidal morphologic and vascular features in different levels of myopes and patients with myopic choroidal neovascularization (mCNV).

Methods: A total of 148 subjects were enrolled in this cross-sectional study, including 78 low-to-moderate myopes (LMM), 53 high myopes (HM), and 17 high myopic patients with mCNV. Ocular biometrics were measured using an optical low-coherence reflectometry device. Retinal and choroidal imaging was performed using enhanced depth imaging (EDI) spectral domain optical coherence tomography (OCT). Retinal parameters including retinal thickness and retinal volume were obtained from a built-in software. Binarization technique was adopted to investigate choroidal parameters including choroidal thickness (CT), vascular area, stromal area, and choroidal vascularity index (CVI). Choroidal parameters were measured at five locations to cover as much area of choroid as possible, and their patterns of distribution were further analyzed.

Results: Patients with mCNV had an atrophic retina of comparable thickness to HM (273.65 ± 17.28 vs. 276.49 ± 13.29 μm, p = 0.47), but the choroid was thinner than that of HM (153.94 ± 15.12 vs. 236.09 ± 38.51 μm, p < 0.001). Subfoveal CVI was greatest in the mCNV eyes (0.651 ± 0.009), followed by HM (0.645 ± 0.012) and LMM eyes (0.636 ± 0.012). Similar to CT, CVI was also found significantly different among these three groups at all five locations (p for trend < 0.001 for all locations). Axial length (AL) was negatively correlated with retinal volume (r = −0.236, p = 0.009), which is the only significant finding in associations between ocular factors and retinal parameters. Strong, negative correlations were identified between AL and subfoveal choroidal thickness (SFCT, r = −0.820, p < 0.001). However, AL was positively correlated with subfoveal CVI (r = 0.668, p < 0.001). CVI was greater in myopic eyes with thinner choroid (r = −0.578, p < 0.001). BCVA exhibited no significant association with CVI (r = 0.139, p = 0.092), but was negatively correlated with SFCT (r = −0.386, p < 0.001) and positively correlated with AL (r = 0.351, p < 0.001).

Conclusion: Choroid in patients with mCNV was thinner yet more vascularized than that in HM and LMM subjects. CVI increased with a longer AL which was associated with a smaller SFCT, choroidal vascular area (VA), and total choroidal area (TCA). Better BCVA was achieved in subjects with thicker SFCT and shorter AL.
Plasma Cyclic Guanosine Monophosphate Is a Promising Biomarker of Clinically Significant Portal Hypertension in Patients With Liver Cirrhosis
Authors: Sturm Lukas , Bettinger Dominik , Roth Lisa , Zoldan Katharina , Stolz Laura , Gahm Chiara , Huber Jan Patrick , Reincke Marlene , Kaeser Rafael , Boettler Tobias , Kreisel Wolfgang , Thimme Robert , Schultheiss Michael
Published: January 2022

Introduction: Despite intensive research, reliable blood-derived parameters to detect clinically significant portal hypertension (CSPH) in patients with cirrhosis are lacking. As altered homeostasis of cyclic guanosine monophosphate (cGMP), the central mediator of vasodilatation, is an essential factor in the pathogenesis of portal hypertension, the aim of our study was to evaluate plasma cGMP as potential biomarker of cirrhotic portal hypertension.

Methods: Plasma cGMP was analyzed in cirrhotic patients with CSPH (ascites, n = 39; esophageal varices, n = 31), cirrhotic patients without CSPH (n = 21), patients with chronic liver disease without cirrhosis (n = 11) and healthy controls (n = 8). cGMP was evaluated as predictor of CSPH using logistic regression models. Further, the effect of transjugular intrahepatic portosystemic shunt (TIPS) placement on plasma cGMP was investigated in a subgroup of cirrhotic patients (n = 13).

Results: Plasma cGMP was significantly elevated in cirrhotic patients with CSPH compared to cirrhotic patients without CSPH [78.1 (67.6–89.2) pmol/ml vs. 39.1 (35.0–45.3) pmol/l, p < 0.001]. Of note, this effect was consistent in the subgroup of patients with esophageal varices detected at screening endoscopy who had no prior manifestations of portal hypertension (p < 0.001). Cirrhotic patients without CSPH displayed no significant elevation of plasma cGMP compared to patients without cirrhosis (p = 0.347) and healthy controls (p = 0.200). Regression analyses confirmed that cGMP was an independent predictor of CSPH (OR 1.042, 95% CI 1.008–1.078, p = 0.016). Interestingly, portal decompression by TIPS implantation did not lead to normalization of plasma cGMP levels (p = 0.101).

Conclusions: Plasma cGMP is a promising biomarker of CSPH in patients with cirrhosis, especially with respect to screening for esophageal varices. The lacking normalization of plasma cGMP after portal decompression suggests that elevated plasma cGMP in cirrhotic portal hypertension is mainly a correlate of systemic and splanchnic vasodilatation, as these alterations have been shown to persist after TIPS implantation.
Estimating the Postmortem Interval of Carcasses in the Water Using the Carrion Insect, Brain Tissue RNA, Bacterial Biofilm, and Algae
Authors: Wang Yu , Wang Man , Xu Wang , Wang Yinghui , Zhang Yanan , Wang Jiangfeng
Published: January 2022

The accurate estimation of postmortem interval (PMI) is crucial in the investigation of homicide cases. Unlike carcasses on land, various biological and abiotic factors affect the decomposition of carcasses in water. In addition, the insect evidence (e.g., blow flies) that is commonly used to estimate the PMI are unavailable before the carcasses float on water. Therefore, it is difficult to estimate the PMI of a carcass in water. This study aimed to explore an effective way of estimating the PMI of a carcass in water. Carrion insects, brain tissue RNA, bacterial biofilm on the skin surface, and algae in water with PMI were studied using 45 rat carcasses in a small river. The results showed that carrion insects might not be suitable for the estimation of PMI of a carcass in water since they do not have a regular succession pattern as a carcass on land, and the flies only colonized six of the carcasses. The target genes (β-actin, GAPDH, and 18S) in the brain tissue were associated with the PMI in a time-dependent manner within 1 week after death. A polynomial regression analysis was used to assess the relationship between the gene expression profiles and PMI. The correlation coefficient R2 of each regression equation was ≥ 0.924. A third-generation sequencing analysis showed that the bacteria on the skin surface of the carcass and the algae in the water samples around the carcass had a regular succession pattern, where Cryptomonas and Placoneis incased and decreased, respectively, within first 9 days. The results of this study provide a promising way to use the brain tissue RNA, bacterial biofilm, and algae to estimate the PMI of a carcass in water.
Different Shades of Listeria monocytogenes: Strain, Serotype, and Lineage-Based Variability in Virulence and Stress Tolerance Profiles
Authors: Muchaamba Francis , Eshwar Athmanya K. , Stevens Marc J. A. , Stephan Roger , Tasara Taurai
Published: January 2022

Listeria monocytogenes is a public health and food safety challenge due to its virulence and natural stress resistance phenotypes. The variable distribution of L. monocytogenes molecular subtypes with respect to food products and processing environments and among human and animal clinical listeriosis cases is observed. Sixty-two clinical and food-associated L. monocytogenes isolates were examined through phenome and genome analysis. Virulence assessed using a zebrafish infection model revealed serotype and genotype-specific differences in pathogenicity. Strains of genetic lineage I serotype 4b and multilocus sequence type clonal complexes CC1, CC2, CC4, and CC6 grew and survived better and were more virulent than serotype 1/2a and 1/2c lineage II, CC8, and CC9 strains. Hemolysis, phospholipase activity, and lysozyme tolerance profiles were associated with the differences observed in virulence. Osmotic stress resistance evaluation revealed serotype 4b lineage I CC2 and CC4 strains as more osmotolerant, whereas serotype 1/2c lineage II CC9 strains were more osmo-sensitive than others. Variable tolerance to the widely used quaternary ammonium compound benzalkonium chloride (BC) was observed. Some outbreak and sporadic clinical case associated strains demonstrated BC tolerance, which might have contributed to their survival and transition in the food-processing environment facilitating food product contamination and ultimately outbreaks or sporadic listeriosis cases. Genome comparison uncovered various moderate differences in virulence and stress associated genes between the strains indicating that these differences in addition to gene expression regulation variations might largely be responsible for the observed virulence and stress sensitivity phenotypic differences. Overall, our study uncovered strain and genotype-dependent variation in virulence and stress resilience among clinical and food-associated L. monocytogenes isolates with potential public health risk implications. The extensive genome and phenotypic data generated provide a basis for developing improved Listeria control strategies and policies.
Mucormycosis Amid COVID-19 Crisis: Pathogenesis, Diagnosis, and Novel Treatment Strategies to Combat the Spread
Authors: Dogra Shreya , Arora Akanksha , Aggarwal Aashni , Passi Gautam , Sharma Akanksha , Singh Gurpal , Barnwal Ravi P.
Published: January 2022

The havoc unleashed by COVID-19 pandemic has paved way for secondary ominous fungal infections like Mucormycosis. It is caused by a class of opportunistic pathogens from the order Mucorales. Fatality rates due to this contagious infection are extremely high. Numerous clinical manifestations result in damage to multiple organs subject to the patient’s underlying condition. Lack of a proper detection method and reliable treatment has made the management of this infection troublesome. Several reports studying the behavior pattern of Mucorales inside the host by modulation of its defense mechanisms have helped in understanding the pathogenesis of this angio-invasive infection. Many recent advances in diagnosis and treatment of this fungal infection have not been much beneficial. Therefore, there is a need to foster more viable strategies. This article summarizes current and imminent approaches that could aid effective management of these secondary infections in these times of global pandemic. It is foreseen that the development of newer antifungal drugs, antimicrobial peptides, and nanotechnology-based approaches for drug delivery would help combat this infection and curb its spread.
From Synapses to Circuits, Astrocytes Regulate Behavior
Authors: Lyon Krissy A. , Allen Nicola J.
Published: January 2022

Astrocytes are non-neuronal cells that regulate synapses, neuronal circuits, and behavior. Astrocytes ensheath neuronal synapses to form the tripartite synapse where astrocytes influence synapse formation, function, and plasticity. Beyond the synapse, recent research has revealed that astrocyte influences on the nervous system extend to the modulation of neuronal circuitry and behavior. Here we review recent findings on the active role of astrocytes in behavioral modulation with a focus on in vivo studies, primarily in mice. Using tools to acutely manipulate astrocytes, such as optogenetics or chemogenetics, studies reviewed here have demonstrated a causal role for astrocytes in sleep, memory, sensorimotor behaviors, feeding, fear, anxiety, and cognitive processes like attention and behavioral flexibility. Current tools and future directions for astrocyte-specific manipulation, including methods for probing astrocyte heterogeneity, are discussed. Understanding the contribution of astrocytes to neuronal circuit activity and organismal behavior will be critical toward understanding how nervous system function gives rise to behavior.
Therapeutic Benefits of Short-Arm Human Centrifugation in Multiple Sclerosis–A New Approach
Authors: Kourtidou-Papadeli Chrysoula , Frantzidis Christos A. , Bakirtzis Christos , Petridou Anatoli , Gilou Sotiria , Karkala Aliki , Machairas Ilias , Kantouris Nikolaos , Nday Christiane M. , Dermitzakis Emmanouil V. , Bakas Eleftherios , Mougios Vassilis , Bamidis Panagiotis D. , Vernikos Joan
Published: January 2022

Short-arm human centrifugation (SAHC) is proposed as a robust countermeasure to treat deconditioning and prevent progressive disability in a case of secondary progressive multiple sclerosis. Based on long-term physiological knowledge derived from space medicine and missions, artificial gravity training seems to be a promising physical rehabilitation approach toward the prevention of musculoskeletal decrement due to confinement and inactivity. So, the present study proposes a novel infrastructure based on SAHC to investigate the hypothesis that artificial gravity ameliorates the degree of disability. The patient was submitted to a 4-week training programme including three weekly sessions of 30 min of intermittent centrifugation at 1.5–2 g. During sessions, cardiovascular, muscle oxygen saturation (SmO2) and electroencephalographic (EEG) responses were monitored, whereas neurological and physical performance tests were carried out before and after the intervention. Cardiovascular parameters improved in a way reminiscent of adaptations to aerobic exercise. SmO2 decreased during sessions concomitant with increased g load, and, as training progressed, SmO2 of the suffering limb dropped, both effects suggesting increased oxygen use, similar to that seen during hard exercise. EEG showed increased slow and decreased fast brain waves, with brain reorganization/plasticity evidenced through functional connectivity alterations. Multiple-sclerosis-related disability and balance capacity also improved. Overall, this study provides novel evidence supporting SAHC as a promising therapeutic strategy in multiple sclerosis, based on mechanical loading, thereby setting the basis for future randomized controlled trials.
Contribution of Inflammation and Hypoperfusion to White Matter Hyperintensities-Related Cognitive Impairment
Authors: Huang Chao-Juan , Zhou Xia , Yuan Xin , Zhang Wei , Li Ming-Xu , You Meng-Zhe , Zhu Xiao-Qun , Sun Zhong-Wu
Published: January 2022

White matter hyperintensities (WMHs) of presumed vascular origin are one of the most important neuroimaging markers of cerebral small vessel disease (CSVD), which are closely associated with cognitive impairment. The aim of this study was to elucidate the pathogenesis of WMHs from the perspective of inflammation and hypoperfusion mechanisms. A total of 65 patients with WMHs and 65 healthy controls were enrolled in this study. Inflammatory markers measurements [hypersensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)], cognitive evaluation, and pseudocontinuous arterial spin labeling (PCASL) MRI scanning were performed in all the subjects. The multivariate logistic regression analysis showed that Lp-PLA2 was an independent risk factor for WMHs. Cerebral blood flow (CBF) in the whole brain, gray matter (GM), white matter (WM), left orbital medial frontal gyrus [MFG.L (orbital part)], left middle temporal gyrus (MTG.L), and right thalamus (Tha.R) in the patients was lower than those in the controls and CBF in the left triangular inferior frontal gyrus [IFG.L (triangular part)] was higher in the patients than in the controls. There was a significant correlation between Lp-PLA2 levels and CBF in the whole brain (R = −0.417, p < 0.001) and GM (R = −0.278, p = 0.025), but not in the WM in the patients. Moreover, CBF in the MFG.L (orbital part) and the Tha.R was, respectively, negatively associated with the trail making test (TMT) and the Stroop color word test (SCWT), suggesting the higher CBF, the better executive function. The CBF in the IFG.L (triangular part) was negatively correlated with attention scores in the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) subitems (R = −0.288, p = 0.020). Our results revealed the vascular inflammation roles in WMHs, which may through the regulation of CBF in the whole brain and GM. Additionally, CBF changes in different brain regions may imply a potential role in the modulation of cognitive function in different domains.
Individual Optimal Attentional Strategy in Motor Learning Tasks Characterized by Steady-State Somatosensory and Visual Evoked Potentials
Authors: Sakurada Takeshi , Yoshida Masataka , Nagai Kiyoshi
Published: January 2022

Focus of attention is one of the most influential factors facilitating motor performance. Previous evidence supports that the external focus (EF) strategy, which directs attention to movement outcomes, is associated with better motor performance than the internal focus (IF) strategy, which directs attention to body movements. However, recent studies have reported that the EF strategy is not effective for some individuals. Furthermore, neuroimaging studies have demonstrated that the frontal and parietal areas characterize individual optimal attentional strategies for motor tasks. However, whether the sensory cortices are also functionally related to individual optimal attentional strategy remains unclear. Therefore, the present study examined whether an individual’s sensory processing ability would reflect the optimal attentional strategy. To address this point, we explored the relationship between responses in the early sensory cortex and individuals’ optimal attentional strategy by recording steady-state somatosensory evoked potentials (SSSEP) and steady-state visual evoked potentials (SSVEP). Twenty-six healthy young participants first performed a motor learning task with reaching movements under IF and EF conditions. Of the total sample, 12 individuals showed higher after-effects under the IF condition than the EF condition (IF-dominant group), whereas the remaining individuals showed the opposite trend (EF-dominant group). Subsequently, we measured SSSEP from bilateral primary somatosensory cortices while presenting vibrotactile stimuli and measured SSVEP from bilateral primary visual cortices while presenting checkerboard visual stimuli. The degree of increasing SSSEP response when the individuals in the IF-dominant group directed attention to vibrotactile stimuli was significantly more potent than those in the EF-dominant individuals. By contrast, the individuals in the EF-dominant group showed a significantly larger SSVEP increase while they directed attention to visual stimuli compared with the IF-dominant individuals. Furthermore, a significant correlation was observed such that individuals with more robust IF dominance showed more pronounced SSSEP attention modulation. These results suggest that the early sensory areas have crucial brain dynamics to characterize an individual’s optimal attentional strategy during motor tasks. The response characteristics may reflect the individual sensory processing ability, such as control of priority to the sensory inputs. Considering individual cognitive traits based on the suitable attentional strategy could enhance adaptability in motor tasks.
EEG Delta/Theta Ratio and Microstate Analysis Originating Novel Biomarkers for Malnutrition-Inflammation Complex Syndrome in ESRD Patients
Authors: Jatupornpoonsub Tirapoot , Thimachai Paramat , Supasyndh Ouppatham , Wongsawat Yodchanan
Published: January 2022

The Malnutrition-Inflammation Score (MIS) was initially proposed to evaluate malnutrition-inflammation complex syndrome (MICS) in end-stage renal disease (ESRD) patients. Although MICS should be routinely evaluated to reduce the hospitalization and mortality rate of ESRD patients, the inconvenience of the MIS might limit its use. Cerebral complications in ESRD, possibly induced by MICS, were previously assessed by using spectral electroencephalography (EEG) via the delta/theta ratio and microstate analysis. Correspondingly, EEG could be used to directly assess MICS in ESRD patients, but the relationships among MICS and these EEG features remain inconclusive. Thus, we aimed to investigate the delta/theta ratio and microstates in ESRD patients with high and low risks of MICS. We also attempted to identify the correlation among the MIS, delta/theta ratio, and microstate parameters, which might clarify their relationships. To achieve these objectives, a total of forty-six ESRD subjects were willingly recruited. We collected their blood samples, MIS, and EEGs after receiving written informed consent. Sixteen women and seven men were allocated to low risk group (MIS ≤ 5, age 57.57 ± 14.88 years). Additionally, high risk group contains 15 women and 8 men (MIS > 5, age 59.13 ± 11.77 years). Here, we discovered that delta/theta ratio (p < 0.041) and most microstate parameters (p < 0.001) were significantly different between subject groups. We also found that the delta/theta ratio was not correlated with MIS but was strongly with the average microstate duration (ρ = 0.708, p < 0.001); hence, we suggested that the average microstate duration might serve as an alternative encephalopathy biomarker. Coincidentally, we noticed positive correlations for most parameters of microstates A and B (0.54 ≤ ρ ≤ 0.68, p < 0.001) and stronger negative correlations for all microstate C parameters (−0.75 ≤ ρ ≤ −0.61, p < 0.001). These findings unveiled a novel EEG biomarker, the MIC index, that could efficiently distinguish ESRD patients at high and low risk of MICS when utilized as a feature in a binary logistic regression model (accuracy of train-test split validation = 1.00). We expected that the average microstate duration and MIC index might potentially contribute to monitor ESRD patients in the future.
Voluntary Behavior and Training Conditions Modulate in vivo Extracellular Glucose and Lactate in the Mouse Primary Motor Cortex
Authors: Béland-Millar Alexandria , Messier Claude
Published: January 2022

Learning or performing new behaviors requires significant neuronal signaling and is metabolically demanding. The metabolic cost of performing a behavior is mitigated by exposure and practice which result in diminished signaling and metabolic requirements. We examined the impact of novel and habituated wheel running, as well as effortful behaviors on the modulation of extracellular glucose and lactate using biosensors inserted in the primary motor cortex of mice. We found that motor behaviors produce increases in extracellular lactate and decreases in extracellular glucose in the primary motor cortex. These effects were modulated by experience, novelty and intensity of the behavior. The increase in extracellular lactate appears to be strongly associated with novelty of a behavior as well as the difficulty of performing a behavior. Our observations are consistent with the view that a main function of aerobic glycolysis is not to fuel the current neuronal activity but to sustain new bio-infrastructure as learning changes neural networks, chiefly through the shuttling of glucose derived carbons into the pentose phosphate pathway for the biosynthesis of nucleotides.
Objective Recognition of Tinnitus Location Using Electroencephalography Connectivity Features
Authors: Li Zhaobo , Wang Xinzui , Shen Weidong , Yang Shiming , Zhao David Y. , Hu Jimin , Wang Dawei , Liu Juan , Xin Haibing , Zhang Yalun , Li Pengfei , Zhang Bing , Cai Houyong , Liang Yueqing , Li Xihua
Published: January 2022

Purpose: Tinnitus is a common but obscure auditory disease to be studied. This study will determine whether the connectivity features in electroencephalography (EEG) signals can be used as the biomarkers for an efficient and fast diagnosis method for chronic tinnitus.

Methods: In this study, the resting-state EEG signals of tinnitus patients with different tinnitus locations were recorded. Four connectivity features [including the Phase-locking value (PLV), Phase lag index (PLI), Pearson correlation coefficient (PCC), and Transfer entropy (TE)] and two time-frequency domain features in the EEG signals were extracted, and four machine learning algorithms, included two support vector machine models (SVM), a multi-layer perception network (MLP) and a convolutional neural network (CNN), were used based on the selected features to classify different possible tinnitus sources.

Results: Classification accuracy was highest when the SVM algorithm or the MLP algorithm was applied to the PCC feature sets, achieving final average classification accuracies of 99.42 or 99.1%, respectively. And based on the PLV feature, the classification result was also particularly good. And MLP ran the fastest, with an average computing time of only 4.2 s, which was more suitable than other methods when a real-time diagnosis was required.

Conclusion: Connectivity features of the resting-state EEG signals could characterize the differentiation of tinnitus location. The connectivity features (PCC and PLV) were more suitable as the biomarkers for the objective diagnosing of tinnitus. And the results were helpful for clinicians in the initial diagnosis of tinnitus.
Abnormal Somatosensory Behaviors Associated With a Gain-of-Function Mutation in TRPV3 Channels
Authors: Fatima Mahar , Slade Hannah , Horwitz Lorraine , Shi Angela , Liu Jingyi , McKinstry Delaney , Villani Troy , Xu Haoxing , Duan Bo
Published: January 2022

Thermosensitive transient receptor potential V3 (TRPV3) is a polymodal receptor implicated in nociceptive, thermoceptive, pruritoceptive, and inflammatory pathways. Reports focused on understanding the role of TRPV3 in thermoception or nociception are not conclusive. Previous studies also show that aberrant hyperactivity of TRPV3 channels results in spontaneous itch and dermatitis-like symptoms, but the resultant behavior is highly dependent on the background of the animal and the skin microbiome. To determine the function of hyperactive TRPV3 channels in somatosensory sensations, we tested different somatosensory behaviors using a genetic mouse model that carries a gain-of-function point mutation G573S in the Trpv3 gene (Trpv3G573S). Here we report that Trpv3G573S mutants show reduced perception of cold, acetone-induced cooling, punctate, and sharp mechanical pain. By contrast, locomotion, noxious heat, touch, and mechanical itch are unaffected in Trpv3G573S mice. We fail to observe any spontaneous itch responses and/or dermatitis in Trpv3G573S mutants under specific pathogen (Staphylococcus aureus)-free conditions. However, we find that the scratching events in response to various pruritogens are dramatically decreased in Trpv3G573S mice in comparison to wild-type littermates. Interestingly, we observe sensory hypoinnervation of the epidermis in Trpv3G573S mutants, which might contribute to the deficits in acute mechanical pain, cool, cold, and itch sensations.
Gut Microbiome and Plasma Metabolome Signatures in Middle-Aged Mice With Cognitive Dysfunction Induced by Chronic Neuropathic Pain
Authors: Hua Dongyu , Li Shan , Li Shiyong , Wang Xuan , Wang Yue , Xie Zheng , Zhao Yilin , Zhang Jie , Luo Ailin
Published: January 2022

Patients with chronic neuropathic pain (CNP) often complain about their terrible memory, especially the speed of information processing. Accumulating evidence suggests a possible link between gut microbiota and pain processing as well as cognitive function via the microbiota-gut-brain axis. This study aimed at exploring the fecal microbiome and plasma metabolite profiles in middle-aged spared nerve injury (SNI) mice model with cognitive dysfunction (CD) induced by CNP. The hierarchical cluster analysis of performance in the Morris water maze test was used to classify SNI mice with CD or without CD [i.e., non-CD (NCD)] phenotype. 16S rRNA sequencing revealed a lower diversity of gut bacteria in SNI mice, and the increase of Actinobacteria, Proteus, and Bifidobacterium might contribute to the cognitive impairment in the CNP condition. The plasma metabolome analysis showed that the endocannabinoid (eCB) system, disturbances of lipids, and amino acid metabolism might be the dominant signatures of CD mice. The fecal microbiota transplantation of the Sham (not CD) group improved allodynia and cognitive performance in pseudo-germ-free mice via normalizing the mRNA expression of eCB receptors, such as cn1r, cn2r, and htr1a, reflecting the effects of gut bacteria on metabolic activity. Collectively, the findings of this study suggest that the modulation of gut microbiota and eCB signaling may serve as therapeutic targets for cognitive deficits in patients with CNP.
Use of Branded Food Composition Databases for the Exploitation of Food Fortification Practices: A Case Study on Vitamin D in the Slovenian Food Supply
Authors: Krušič Sanja , Hribar Maša , Hafner Edvina , Žmitek Katja , Pravst Igor
Published: January 2022

Vitamin D deficiency is a worldwide public health concern, which can be addressed with voluntary or mandatory food fortification. The aim of this study was to determine if branded food composition databases can be used to investigate voluntary fortification practices. A case study was conducted using two nationally representative cross-sectional datasets of branded foods in Slovenia, collected in 2017 and 2020, and yearly sales data. Using food labeling data we investigated prevalence of fortification and average vitamin D content, while nutrient profiling was used to investigate overall nutritional quality of the foods. In both datasets, the highest prevalence of vitamin D fortification was observed in meal replacements (78% in 2017; 100% in 2020) and in margarine, corresponding to high market share. Other food categories commonly fortified with vitamin D are breakfast cereals (5% in 2017; 6% in 2020), yogurts and their imitates (5% in 2017; 4% in 2020), and baby foods (18% in both years). The highest declared average content of vitamin D was observed in margarine and foods for specific dietary use (7–8 μg/100g), followed by breakfast cereals (4 μg/100g), while the average content in other foods was below 2 μg/100g. Only minor differences were observed between 2017 and 2020. Major food-category differences were also observed in comparison of the overall nutritional quality of the fortified foods; higher overall nutritional quality was only observed in fortified margarine. Our study showed that branded food composition databases are extremely useful resources for the investigation and monitoring of fortification practices, particularly if sales data can also be used. In the absence of mandatory or recommended fortification in Slovenia, very few manufacturers decide to add vitamin D, and even when this is the case, such products are commonly niche foods with lower market shares. We observed exceptions in imported foods, which can be subject to fortification policies introduced in other countries.
Physicochemical Properties and Biological Activities of Silver Carp Scale Peptide and Its Nanofiltration Fractions
Authors: Zu Xiao-yan , Zhao Ya-jing , Fu Shi-ming , Liao Tao , Li Hai-lan , Xiong Guang-quan
Published: January 2022

To explore the physicochemical properties and biological functions of silver carp scale peptide (SCSP), its molecular-weight fractions SCSP-I, II, and III obtained by nanofiltration were assessed for their solubility, emulsibility, free radical scavenging ability, effect on the proliferation of mouse B16 cells. The results showed that the solubility of each fraction of SCSP was higher than 90%, SCSP-II and III were higher than 95%. The antioxidant powers on ⦁OH, O2-⦁ and Fe3+ were ranked as SCSP-III > SCSP-II > SCSP-I > SCSP. All fractions of SCSP had no toxic or side effects in mouse B16 melanoma cells experiments in vitro. At a concentration of 0.01 mg/mL, the tyrosinase activity of B16 cells in the SCSP-II fraction was significantly lower than that of the α-arbutin (P < 0.05), at 65.37%. The molecular weight distribution of SCSP was 399–1404 Dalton and 13 peptide sequences were detected. Among them, SCSP-II contained many hydrophobic amino acids, and SCSP-III stood out for combining arginine with hydrophobic amino acids. This may be the reason why the low molecular-weight SCSPs show the strong antioxidant activity and strong tyrosinase inhibition. The work provides a data base for the development of SCSP and increases the possibility of its application.
Reconstruction With 3D-Printed Prostheses After Sacroiliac Joint Tumor Resection: A Retrospective Case-Control Study
Authors: Pu Feifei , Liu Jianxiang , Shi Deyao , Huang Xin , Zhang Jingtao , Wang Baichuan , Wu Qiang , Zhang Zhicai , Shao Zengwu
Published: January 2022

Background

Sacroiliac joint tumor is rare, and the reconstruction after tumor resection is difficult. We aimed to analyze and compare the clinical effects of three-dimensional (3D) printed prostheses and bone cement combined with screws for bone defect reconstruction after sacroiliac joint tumor resection.

Methods

Twelve patients with sacroiliac joint tumors who underwent tumor resection and received 3D-printed prostheses to reconstruct bone defects in our hospital from January 2014 to December 2020 were included in the study group Twelve matched patients who underwent sacroiliac joint tumor resection and reconstruction with bone cement and screws in the same time period were selected as the control group.

Results

In the 3D-printing group, six cases were extensively excised, and six cases were marginally excised. All patients were followed up for 6–90 months, and the median follow-up time was 21 months. Among them, nine patients had disease-free survival, two survived with tumor recurrence, and one died due to tumor metastasis. The MSTS-93 score of the surviving patients was 24.1 ± 2.8. The operation time was 120.30 ± 14.50 min, and the intraoperative bleeding was 625.50 ± 30.00 ml. In the control group, seven cases were extensively excised, and five cases were marginally excised. All patients were followed up for 6–90 months, with a median follow-up time of 20 months. Among them, nine patients had disease-free survival, one survived with tumor recurrence, and two died due to tumor metastasis. The MSTS-93 score of the patients was 18.9 ± 2.6. The operation time was 165.25 ± 15.00 min, and the intraoperative bleeding was 635.45 ± 32.00 ml. There was no significant difference in survival status, intraoperative blood loss, or complications between the two groups (P>0.05). However, there were statistically significant differences in operative time and postoperative MSTS-93 scores between the two groups (P<0.05).

Conclusions

After resection of the sacroiliac joint tumor, reconstruction using 3D printed prostheses was shorter and resulted in better movement function.
Charged Particle Irradiation for Pancreatic Cancer: A Systematic Review of In Vitro Studies
Authors: Wang Dandan , Liu Ruifeng , Zhang Qiuning , Luo Hongtao , Chen Junru , Dong Meng , Wang Yuhang , Ou Yuhong , Liu Zhiqiang , Sun Shilong , Yang Kehu , Tian Jinhui , Li Zheng , Wang Xiaohu
Published: January 2022

Purpose

Given the higher precision accompanied by optimized sparing of normal tissue, charged particle therapy was thought of as a promising treatment for pancreatic cancer. However, systematic preclinical studies were scarce. We aimed to investigate the radiobiological effects of charged particle irradiation on pancreatic cancer cell lines.

Methods

A systematic literature search was performed in EMBASE (OVID), Medline (OVID), and Web of Science databases. Included studies were in vitro English publications that reported the radiobiological effects of charged particle irradiation on pancreatic cancer cells.

Results

Thirteen carbon ion irradiation and seven proton irradiation in vitro studies were included finally. Relative biological effectiveness (RBE) values of carbon ion irradiation and proton irradiation in different human pancreatic cancer cell lines ranged from 1.29 to 4.5, and 0.6 to 2.1, respectively. The mean of the surviving fraction of 2 Gy (SF2) of carbon ion, proton, and photon irradiation was 0.18 ± 0.11, 0.48 ± 0.11, and 0.57 ± 0.13, respectively. Carbon ion irradiation induced more G2/M arrest and a longer-lasting expression of γH2AX than photon irradiation. Combination therapies enhanced the therapeutic effects of pancreatic cell lines with a mean standard enhancement ratio (SER) of 1.66 ± 0.63 for carbon ion irradiation, 1.55 ± 0.27 for proton irradiation, and 1.52 ± 0.30 for photon irradiation. Carbon ion irradiation was more effective in suppressing the migration and invasion than photon irradiation, except for the PANC-1 cells.

Conclusions

Current in vitro evidence demonstrates that, compared with photon irradiation, carbon ion irradiation offers superior radiobiological effects in the treatment of pancreatic cancer. Mechanistically, high-LET irradiation may induce complex DNA damage and ultimately promote genomic instability and cell death. Both carbon ion irradiation and proton irradiation confer similar sensitization effects in comparison with photon irradiation when combined with chemotherapy or targeted therapy.
Genomic Effects Associated With Response to Placebo Treatment in a Randomized Trial of Irritable Bowel Syndrome
Authors: Wang Rui-Sheng , Lembo Anthony J. , Kaptchuk Ted J. , Cheng Vivian , Nee Judy , Iturrino Johanna , Rao Meenakshi , Loscalzo Joseph , Silvester Jocelyn A. , Hall Kathryn T.
Published: January 2022

Background and Aims: Irritable bowel syndrome (IBS), a functional pain disorder of gut-brain interactions, is characterized by a high placebo response in randomized clinical trials (RCTs). Catechol-O-methyltransferase (COMT) rs4680, which encodes high-activity (val) or low-activity (met) enzyme variants, was previously associated with placebo response to sham-acupuncture in an IBS RCT. Examining COMT effects and identifying novel genomic factors that influence response to placebo pills is critical to identifying underlying mechanisms and predicting and managing placebos in RCTs.

Methods: Participants with IBS (N = 188) were randomized to three placebo-related interventions, namely, double-blind placebo (DBP), open-label placebo (OLP), or simply trial enrollment without placebo treatment [no placebo (i.e., no pill) treatment control (NPC)], for 6 weeks. COMT rs4680, gene-set, and genome-wide suggestive (p < 10−5) loci effects on irritable bowel symptom severity score (IBS-SSS) across all participants were examined.

Results: Participants with IBS homozygous for rs4680 met (met/met) had the greatest improvement across all arms, with significantly greater improvement compared to val/val in DBP (beta (SE), −89.4 (42.3); p = 0.04). Twelve genome-wide suggestive loci formed a gene regulatory network highly connected to EGR1, a transcription factor involved in placebo-related processes of learning, memory, and response to stress and reward. EGR1 gene expression in peripheral blood mononuclear cells (PBMC) was significantly reduced at the endpoint across all treatment arms (log fold-change, −0.15; p = 0.02). Gene-set enrichment analysis returned three genome-wide significant ontology terms (GO:0032968, GO:0070934, and GO:0070937) linked to transcription regulation and GO:0003918 associated with DNA topoisomerase regulation.

Conclusion: These results suggest common molecular mechanisms in response to varying forms of placebo that may inform personalized IBS treatment and placebo response prediction.

Clinical Trial Registration:ClinicalTrials.gov, Identifier: NCT0280224.
Autonomic Nervous System Dysfunction Is Associated With Re-hospitalization in Pediatric Septic Shock Survivors
Authors: Badke Colleen M. , Swigart Lindsey , Carroll Michael S. , Weese-Mayer Debra E. , Sanchez-Pinto L. Nelson
Published: January 2022

Objective: Re-hospitalization after sepsis can lead to impaired quality of life. Predictors of re-hospitalization could help identify sepsis survivors who may benefit from targeted interventions. Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors.

Materials and Methods: This was a retrospective, observational cohort study of patients admitted between 6/2012 and 10/2020 at a single institution. Patients admitted to the pediatric intensive care unit with septic shock who had continuous heart rate data available from the bedside monitors and survived their hospitalization were included. HRV was measured using age-normalized z-scores of the integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 s over 5 consecutive minutes. The 24-h median HRVi was assessed on two different days: the last 24 h of PICU admission (“last HRVi”) and the 24-h period with the lowest median HRVi (“lowest HRVi”). The change between the lowest and last HRVi was termed “delta HRVi.” The primary outcome was re-hospitalization within 1 year of discharge, including both emergency department encounters and hospital readmission, with sensitivity analyses at 30 and 90 days. Kruskal-Wallis, logistic regression, and Poisson regression evaluated the association between HRVi and re-hospitalizations and adjusted for potential confounders.

Results: Of the 463 patients who met inclusion criteria, 306 (66%) were re-hospitalized, including 270 readmissions (58%). The last HRVi was significantly lower among re-hospitalized patients compared to those who were not (p = 0.02). There was no difference in the lowest HRVi, but patients who were re-hospitalized showed a smaller recovery in their delta HRVi compared to those who were not re-hospitalized (p = 0.02). This association remained significant after adjusting for potential confounders. In the sensitivity analysis, a smaller recovery in delta HRVi was consistently associated with a higher likelihood of re-hospitalization.

Conclusion: In pediatric septic shock survivors, a smaller recovery in HRV during the index admission is significantly associated with re-hospitalization. This continuous physiologic measure could potentially be used as a predictor of patients at risk for re-hospitalization and lower health-related quality of life.
Incidence and Prevalence Trends of Pediatric Inflammatory Bowel Disease in the Daegu-Kyungpook Province From 2017 to 2020
Authors: Choe Jae Young , Choi Sujin , Song Ki Hwan , Jang Hyo-Jeong , Choi Kwang-Hae , Yi Dae Yong , Hong Suk Jin , Hwang Jun Hyun , Cho Seung-Man , Kim Young Jin , Choe Byung-Ho , Kang Ben
Published: January 2022

Background and Aim: There is paucity of data regarding the epidemiology of pediatric IBD in Asia compared to that of Western countries. We aimed to investigate the incidence and prevalence trends of pediatric inflammatory bowel disease (IBD) in the Daegu-Kyungpook province of South Korea from 2017 to 2020.

Methods: This study was a multicenter, retrospective study conducted in eight IBD referral centers located in the Daegu-Kyungpook province. Children and adolescents of ≤18 years who were initially diagnosed with IBD between 2017 and 2020 were included. The annual number of children and adolescents newly diagnosed with IBD and the annual resident population of children and adolescents ≤18 years of age in the Daegu-Kyungpook province were investigated to calculate the annual incidence and prevalence in the region.

Results: A total 304 children and adolescents that had been diagnosed with IBD were included in this study. Among these patients, 71.4% had been diagnosed with Crohn's disease (CD), and 28.6% with ulcerative colitis (UC). The population based annual incidences of IBD from 2017 to 2020 were each 7.24, 6.82, 10.27, and 13.33 per 100,000, respectively (P for trend <0.001), 4.48, 5.26, 7.39, and 9.8 per 100,000, respectively, for CD (P for trend <0.001), and 2.76, 1.56, 2.88, and 3.53 per 100,000, respectively, for UC (P for trend = 0.174).

Conclusion: Pediatric IBD, especially CD has significantly increased recently in the Daegu-Kyungpook province. Epidemiology studies from other regions of Asia are required to better elucidate this trend of increase in Asia.