bluuebunny/crossref_metadata_2025 huggingface dataset:
Limb Preference and Skill Level Dependence During the Imagery of a Whole-Body Movement: A Functional Near Infrared Spectroscopy Study
Authors: Wriessnegger Selina C. , Unterhauser Kris , Bauernfeind Günther
Published: June 2022

In the past years motor imagery (MI) turned out to be also an innovative and effective tool for motor learning and improvement of sports performance. Whereas many studies investigating sports MI focusing on upper or lower limbs involvement, knowledge about involved neural structures during whole-body movements is still limited. In the present study we investigated brain activity of climbers during a kinesthetic motor imagery (KMI) climbing task with different difficulties by means of functional near infrared spectroscopy (fNIRS). Twenty healthy participants were split into two groups according to their climbing skill level. The aim of the current study is investigating neural correlates of a whole-body sports MI task with an additional focus on skill level dependency. Climbing experts and non-experts imagined bouldering an “easy” and “difficult” route from a first-person perspective while hemodynamic responses were recorded simultaneously. We found significant differences between the two climbing routes, easy and difficult within participants as well as between the two groups of different climbing skill levels. Overall beginners showed increased hemodynamic responses compared to experts in all defined regions of interest (ROI) supporting the claim of the neural efficiency hypothesis (NEH). Even though climbing is a complex, coordinated movement of upper and lower limbs we found a stronger activation focus of the upper limbs, especially of the dominant hand-area, while the foot area seems to be deactivated or inhibited simultaneously. Summarizing, these findings provide novel insights into brain activation during the imagery of a whole-body movement and its relation to climbing expertise.
Gray Matter Volume Abnormality in Chronic Pain Patients With Depressive Symptoms: A Systemic Review and Meta-Analysis of Voxel-Based Morphometry Studies
Authors: Ma Teng , Ji Yuan-Yuan , Yan Lin-Feng , Lin Jia-Ji , Li Ze-Yang , Wang Wen , Li Jin-Lian , Cui Guang-Bin
Published: June 2022

Background

Gray matter volume (GMV) alteration in specific brain regions has been widely regarded as one of the most important neuroplasticity features in chronic pain patients with depressive symptoms (CP-D). However, the consistent and significant results were still lacking. Thus, further exploration was suggested to be performed.

Objectives

This study aimed to comprehensively collect the voxel-based morphometry (VBM) studies on GMV alteration between CP-D and healthy controls (HCs). And a systemic review and meta-analysis were made to explore the characteristic brain regions in chronic pain and depression comorbidity.

Methods

Search of PubMed, MEDLINE, Web of Science, and Cochrane Library databases updated to July 13, 2021. The altered GMV between CP-D and HCs in VBM studies was included in this meta-analysis. In total, 18 studies (20 datasets) and 1320 participants (520 patients and 800 HCs) were included. The significant coordinate information (x, y, z) reported in standard space and the effect size (t-value or z-score) were extracted and analyzed by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software.

Results

According to the main analysis results, CP-D showed significant and consistent increased GMV in the left hippocampus (HIP. L) and decreased GMV in the medial part of the left superior frontal gyrus (SFG. L, BA 10) compared to HCs. Subgroup analysis showed significant decreased GMV in the medial orbital part of SFG.R (BA 10) in neuropathic pain, as well as significant increased GMV in the right parahippocampal gyrus (PHG.R, BA 35), left hippocampus (HIP.L, BA 20), and right middle frontal gyrus (MFG.R) in musculoskeletal pain. Furthermore, meta-regression showed a positive relationship between the decreased GMV in the medial part of SFG.L and the percentage of female patients.

Conclusion

GMV abnormality in specific brain areas (e.g., HIP.L and SFG) was robust and reproducible, which could be significantly involved in this comorbidity disease. The findings in this study may be a valuable reference for future research.

Systematic Review Registration

[www.crd.york.ac.uk/prospero/].
Human Stiffness Perception and Learning in Interacting With Compliant Environments
Authors: Takahashi Chie , Azad Morteza , Rajasekaran Vijaykumar , Babič Jan , Mistry Michael
Published: June 2022

Humans are capable of adjusting their posture stably when interacting with a compliant surface. Their whole-body motion can be modulated in order to respond to the environment and reach to a stable state. In perceiving an uncertain external force, humans repetitively push it and learn how to produce a stable state. Research in human motor control has led to the hypothesis that the central nervous system integrates an internal model with sensory feedback in order to generate accurate movements. However, how the brain understands external force through exploration movements, and how humans accurately estimate a force from their experience of the force, is yet to be fully understood. To address these questions, we tested human behaviour in different stiffness profiles even though the force at the goal was the same. We generated one linear and two non-linear stiffness profiles, which required the same force at the target but different forces half-way to the target; we then measured the differences in the learning performance at the target and the differences in perception at the half-way point. Human subjects learned the stiffness profile through repetitive movements in reaching the target, and then indicated their estimation of half of the target value (position and force separately). This experimental design enabled us to probe how perception of the force experienced in different profiles affects the participants’ estimations. We observed that the early parts of the learning curves were different for the three stiffness profiles. Secondly, the position estimates were accurate independent of the stiffness profile. The estimation in position was most likely influenced by the external environment rather than the profile itself. Interestingly, although visual information about the target had a large influence, we observed significant differences in accuracy of force estimation according to the stiffness profile.
Forward Electric Stimulation-Induced Interference in Intracochlear Electrocochleography of Acoustic Stimulation in the Cochlea of Guinea Pigs
Authors: Min Shiyao , Lu Tianhao , Chen Min , Mao Jiabao , Hu Xuerui , Li Shufeng
Published: June 2022

Electric-acoustic stimulation (EAS) uses amplified sound by a hearing aid to stimulate an apical low-frequency region of the cochlea and electrical current from a cochlear implant (CI) to stimulate the basal high-frequency region. EAS recipients had significantly improved speech perception, music appreciation, and hearing function in noise compared to those relying on CI electrical stimulation (ES) alone. However, the interaction between basal ES and apical acoustic stimulation (AS) in the cochlea potentially affects EAS advantages. To investigate ES-AS interaction, we designed a system that recorded the electrically evoked compound action potential (ECAP) and the auditory evoked potential (AEP). We used an intracochlear electrode array to deliver ES at the basal cochlea and detect intracochlear electrocochleography (iECochG) generated from apical AS. Within iECochG, 3 or 6 dB (double or quadruple intensity of ECAP threshold) electric stimulation, 1 ms-forward ES significantly increased CAP amplitudes of 4 kHz/20 dB AS compared to 0 dB ES. Notably, 1 ms-forward 3 dB ES significantly increased CAP amplitudes of 4 kHz/20 dB AS, while 3 or 5 ms-forward ES did not change the CAP amplitudes. The elevation in CAP amplitude of 40 dB/4 kHz AS induced by 1 ms-forward 3 dB ES was significantly lower than that in 20 dB/4 kHz AS. With 1 ms-forward 3 dB ES, AS frequency and stimulating electrode location have no significant impact on relative CAP amplitudes of 20 dB AS. These results suggest that the basal forward ES and the following apical AS could produce a cumulative effect on the auditory nerve response.
Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder
Authors: Constable Paul A. , Marmolejo-Ramos Fernando , Gauthier Mercedes , Lee Irene O. , Skuse David H. , Thompson Dorothy A.
Published: June 2022

Background

To evaluate the electroretinogram waveform in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) using a discrete wavelet transform (DWT) approach.

Methods

A total of 55 ASD, 15 ADHD and 156 control individuals took part in this study. Full field light-adapted electroretinograms (ERGs) were recorded using a Troland protocol, accounting for pupil size, with five flash strengths ranging from –0.12 to 1.20 log photopic cd.s.m–2. A DWT analysis was performed using the Haar wavelet on the waveforms to examine the energy within the time windows of the a- and b-waves and the oscillatory potentials (OPs) which yielded six DWT coefficients related to these parameters. The central frequency bands were from 20–160 Hz relating to the a-wave, b-wave and OPs represented by the coefficients: a20, a40, b20, b40, op80, and op160, respectively. In addition, the b-wave amplitude and percentage energy contribution of the OPs (%OPs) in the total ERG broadband energy was evaluated.

Results

There were significant group differences (p < 0.001) in the coefficients corresponding to energies in the b-wave (b20, b40) and OPs (op80 and op160) as well as the b-wave amplitude. Notable differences between the ADHD and control groups were found in the b20 and b40 coefficients. In contrast, the greatest differences between the ASD and control group were found in the op80 and op160 coefficients. The b-wave amplitude showed both ASD and ADHD significant group differences from the control participants, for flash strengths greater than 0.4 log photopic cd.s.m–2 (p < 0.001).

Conclusion

This methodological approach may provide insights about neuronal activity in studies investigating group differences where retinal signaling may be altered through neurodevelopment or neurodegenerative conditions. However, further work will be required to determine if retinal signal analysis can offer a classification model for neurodevelopmental conditions in which there is a co-occurrence such as ASD and ADHD.
Acoustic Change Complex Evoked by Horizontal Sound Location Change in Young Adults With Normal Hearing
Authors: Fan Zhi-Tong , Zhao Zi-Hui , Sharma Mridula , Valderrama Joaquin T. , Fu Qian-Jie , Liu Jia-Xing , Fu Xin , Li Huan , Zhao Xue-Lei , Guo Xin-Yu , Fu Luo-Yi , Wang Ning-Yu , Zhang Juan
Published: June 2022

Acoustic change complex (ACC) is a cortical auditory-evoked potential induced by a change of continuous sound stimulation. This study aimed to explore: (1) whether the change of horizontal sound location can elicit ACC; (2) the relationship between the change of sound location and the amplitude or latency of ACC; (3) the relationship between the behavioral measure of localization, minimum audible angle (MAA), and ACC. A total of 36 normal-hearing adults participated in this study. A 180° horizontal arc-shaped bracket with a 1.2 m radius was set in a sound field where participants sat at the center. MAA was measured in a two-alternative forced-choice setting. The objective electroencephalography recording of ACC was conducted with the location changed at four sets of positions, ±45°, ±15°, ±5°, and ±2°. The test stimulus was a 125–6,000 Hz broadband noise of 1 s at 60 ± 2 dB SPL with a 2 s interval. The N1′–P2′ amplitudes, N1′ latencies, and P2′ latencies of ACC under four positions were evaluated. The influence of electrode sites and the direction of sound position change on ACC waveform was analyzed with analysis of variance. Results suggested that (1) ACC can be elicited successfully by changing the horizontal sound location position. The elicitation rate of ACC increased with the increase of location change. (2) N1′–P2′ amplitude increased and N1′ and P2′ latencies decreased as the change of sound location increased. The effects of test angles on N1′–P2′ amplitude [F(1.91,238.1) = 97.172, p < 0.001], N1′ latency [F(1.78,221.90) = 96.96, p < 0.001], and P2′ latency [F(1.87,233.11) = 79.97, p < 0.001] showed a statistical significance. (3) The direction of sound location change had no significant effect on any of the ACC peak amplitudes or latencies. (4) Sound location discrimination threshold by the ACC test (97.0% elicitation rate at ±5°) was higher than MAA threshold (2.08 ± 0.5°). The current study results show that though the ACC thresholds are higher than the behavioral thresholds on MAA task, ACC can be used as an objective method to evaluate sound localization ability. This article discusses the implications of this research for clinical practice and evaluation of localization skills, especially for children.
How Widespread Are the “Young” Neurons of the Mammalian Brain?
Authors: Ghibaudi Marco , Bonfanti Luca
Published: June 2022

After the discovery of adult neurogenesis (stem cell-driven production of new neuronal elements), it is conceivable to find young, undifferentiated neurons mixed with mature neurons in the neural networks of the adult mammalian brain. This “canonical” neurogenesis is restricted to small stem cell niches persisting from embryonic germinal layers, yet, the genesis of new neurons has also been reported in various parenchymal brain regions. Whichever the process involved, several populations of “young” neurons can be found at different locations of the brain. Across the years, further complexity emerged: (i) molecules of immaturity can also be expressed by non-dividing cells born during embryogenesis, then maintaining immature features later on; (ii) remarkable interspecies differences exist concerning the types, location, amount of undifferentiated neurons; (iii) re-expression of immaturity can occur in aging (dematuration). These twists are introducing a somewhat different definition of neurogenesis than normally assumed, in which our knowledge of the “young” neurons is less sharp. In this emerging complexity, there is a need for complete mapping of the different “types” of young neurons, considering their role in postnatal development, plasticity, functioning, and interspecies differences. Several important aspects are at stake: the possible role(s) that the young neurons may play in maintaining brain efficiency and in prevention/repair of neurological disorders; nonetheless, the correct translation of results obtained from laboratory rodents. Hence, the open question is: how many types of undifferentiated neurons do exist in the brain, and how widespread are they?
The Use of Bioelectrical Impedance Analysis Measures for Predicting Clinical Outcomes in Critically Ill Children
Authors: Xiong Zi-Hong , Zheng Xue-Mei , Zhang Guo-Ying , Wu Meng-Jun , Qu Yi
Published: June 2022

Background

The study aimed to investigate the association of bioelectrical impedance analysis (BIA) for predicting clinical outcomes in critically ill children.

Methods

This single-center prospective observational study included patients admitted to a mixed Pediatric Intensive Care Unit (PICU). All patients underwent anthropometric measurement and BIA measurements in the first 24 h of admission. The patients were classified into different groups based on body mass index (BMI) for age. Electronic hospital medical records were reviewed to collect clinical data for each patient. All the obtained data were analyzed by the statistical methods.

Results

There were 231 patients enrolled in our study, of which 31.6% were diagnosed with malnutrition. The phase angle (PhA) of 90-day survivors was significantly higher than that of the non-survivors (4.3° ± 1.1°vs. 3.1° ± 0.9°, P = 0.02). The age-adjusted Spearman partial correlation analysis showed a weak negative correlation between PhA and duration of medical ventilation (rs = -0.42, P < 0.05). Furthermore, length of stay in PICU has a very weak correlation with ECW/TBW (rs = 0.29, P < 0.05), and a negative correlation with protein (rs = -0.27, P < 0.05). Multivariate analysis found that PhA was a significant predictor associated with the 90-day mortality when it was adjusted for PRISM III score (adjusted OR = 1.51, CI: 1.10–2.07, p = 0.01). The area under the ROC (AUROC) of PhA for predicting 90-day mortality was 0.69 (95% CI: 0.53–0.85, p < 0.05), and the cutoff value of PhA was 3.0°, with a sensitivity and specificity of 83 and 53%, respectively.

Conclusion

BIA-derived PhA was found to be an independent predictor of 90-day mortality among critically ill children. A low PhA was associated with a prolonged duration of medical ventilation.
A Novel Combined Nomogram Model for Predicting the Pathological Complete Response to Neoadjuvant Chemotherapy in Invasive Breast Carcinoma of No Specific Type: Real-World Study
Authors: Zhu Xuelin , Shen Jing , Zhang Huanlei , Wang Xiulin , Zhang Huihui , Yu Jing , Zhang Qing , Song Dongdong , Guo Liping , Zhang Dianlong , Zhu Ruiping , Wu Jianlin
Published: June 2022

Objective

To explore the value of a predictive model combining the multiparametric magnetic resonance imaging (mpMRI) radiomics score (RAD-score), clinicopathologic features, and morphologic features for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in invasive breast carcinoma of no specific type (IBC-NST).

Methods

We enrolled, retrospectively and consecutively, 206 women with IBC-NST who underwent surgery after NAC and obtained pathological results from August 2018 to October 2021. Four RAD-scores were constructed for predicting the pCR based on fat-suppression T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (T1WI+C) and their combination, which was called mpMRI. The best RAD-score was combined with clinicopathologic and morphologic features to establish a nomogram model through binary logistic regression. The predictive performance of the nomogram was evaluated using the area under receiver operator characteristic (ROC) curve (AUC) and calibration curve. The clinical net benefit of the model was evaluated using decision curve analysis (DCA).

Results

The mpMRI RAD-score had the highest diagnostic performance, with AUC of 0.848 among the four RAD-scores. T stage, human epidermal growth factor receptor-2 (HER2) status, RAD-score, and roundness were independent factors for predicting the pCR (P < 0.05 for all). The combined nomogram model based on these factors achieved AUCs of 0.930 and 0.895 in the training cohort and validation cohort, respectively, higher than other models (P < 0.05 for all). The calibration curve showed that the predicted probabilities of the nomogram were in good agreement with the actual probabilities, and DCA indicated that it provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and validation datasets.

Conclusion

The combined nomogram model based on the mpMRI RAD-score combined with clinicopathologic and morphologic features may improve the predictive performance for the pCR of NAC in patients with IBC-NST.
Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
Authors: Salvetti Chiara , Vitale Candida , Griggio Valentina , Drandi Daniela , Jones Rebecca , Bonello Lisa , Bomben Riccardo , Bragoni Alberto , Bagnara Davide , Fais Franco , Gattei Valter , Cavallo Federica , Zamò Alberto , Coscia Marta
Published: June 2022

Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CLL) and RS clones, characterizes patients with a poor prognosis. Due to method sensitivity, this categorization is performed without considering the possibility of small-size ancillary clones, sharing the same phenotype with the preexisting predominant CLL clone, but with different IGHV rearrangements. Here we describe and molecularly profile the peculiar case of a patient with a CLL-like monoclonal B-cell lymphocytosis (MBL), who sequentially developed a DLBCL, which occurred concomitantly to progression of MBL to CLL, and a subsequent HL. Based on standard IGHV clonality analysis, DLBCL was considered clonally unrelated to the concomitantly expanded CLL clone and treated as a de novo lymphoma, achieving a persistent response. Three years later, the patient further developed a clonally unrelated HL, refractory to bendamustine, which was successfully treated with brentuximab vedotin and radiotherapy, and later with pembrolizumab. We retrospectively performed additional molecular testing, by applying next-generation sequencing (NGS) of immunoglobulin repertoire (Ig-rep) techniques and a more sensitive allele-specific oligonucleotide-droplet digital PCR (ASO-ddPCR) strategy, in order to quantitatively investigate the presence of the rearranged IGHV genes in tumor specimens collected during the disease course. In this highly complex case, the application of modern and sensitive molecular technologies uncovered that DLBCL, initially considered as a de novo lymphoma, was instead the result of the transformation of a preexisting ancillary B-cell clone, which was already present at the time of first MBL diagnosis. A similar approach was also applied on the HL sample, showing its clonal unrelatedness to the previous MBL and DLBCL.
ANO1: More Than Just Calcium-Activated Chloride Channel in Cancer
Authors: Guo Saisai , Zhang Linna , Li Na
Published: June 2022

ANO1, a calcium-activated chloride channel (CACC), is also known as transmembrane protein 16A (TMEM16A). It plays a vital role in the occurrence, development, metastasis, proliferation, and apoptosis of various malignant tumors. This article reviews the mechanism of ANO1 involved in the replication, proliferation, invasion and apoptosis of various malignant tumors. Various molecules and Stimuli control the expression of ANO1, and the regulatory mechanism of ANO1 is different in tumor cells. To explore the mechanism of ANO1 overexpression and activation of tumor cells by studying the different effects of ANO1. Current studies have shown that ANO1 expression is controlled by 11q13 gene amplification and may also exert cell-specific effects through its interconnected protein network, phosphorylation of different kinases, and signaling pathways. At the same time, ANO1 also resists tumor apoptosis and promotes tumor immune escape. ANO1 can be used as a promising biomarker for detecting certain malignant tumors. Further studies on the channels and the mechanism of protein activity of ANO1 are needed. Finally, the latest inhibitors of ANO1 are summarized, which provides the research direction for the tumor-promoting mechanism of ANO1.
Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets
Authors: Arruza Luis , Barata Lorena , Vierge Eva , Rodríguez Maria José , Del Pozo Aaron , Hind William , Martínez-Orgado José
Published: June 2022

Aim

To assess the effects of cannabidiol (CBD) on lung damage in a piglet model of meconium aspiration syndrome (MAS).

Materials and Methods

Meconium aspiration syndrome was modelled in newborn piglets via intratracheal instillation of 20% meconium in saline collected from healthy newborn humans. Piglets were treated i.v. with 5 mg/kg CBD (MAS + CBD) or Vehicle (MAS + VEH) 30 min after MAS induction and monitored for 6 h. Ventilated piglets without meconium instillation served as controls (CTL). Ventilatory and haemodynamic monitoring, histological and biochemical studies assessed the effects of treatment.

Results

Post-insult administration of CBD reduced MAS-induced deterioration of gas exchange, improving respiratory acidosis (final pH 7.38 ± 0.02, 7.22 ± 0.03 and 7.33 ± 0.03 and final pCO2 39.8 ± 1.3, 60.4 ± 3.8 and 45.7 ± 3.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). These beneficial effects were obtained despite the less aggressive ventilatory settings required for CBD-treated animals (final minute volume 230 ± 30, 348 ± 33 and 253 ± 24 mL/kg/min and final Oxygenation Index 1.64 ± 0.04, 12.57 ± 3.10 and 7.42 ± 2.07 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). CBD’s beneficial effects on gas exchange were associated with reduced histological lung damage, reduced leucocyte infiltration and oedema (histopathological score 1.6 ± 0.3, 8.6 ± 1.4 and 4.6 ± 0.7 points for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05), as well as reduced TNFα production (0.04 ± 0.01, 0.34 ± 0.06 and 0.12 ± 0.02 A.U. for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). Moreover, CBD improved blood pressure stability (final mean blood pressure 74.5 ± 0.2, 62.2 ± 6.2, and 78.67 ± 4.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05).

Conclusion

Cannabidiol reduces histologic lung damage and inflammation in a piglet model of MAS. This translates into improved gas exchange and blood pressure stability.
The Activity of Antimicrobial Peptides in Pediatric Celiac Disease
Authors: Kamilova Altinoy T. , Azizova Gulnoza K. , Umarnazarova Zulkhumar E. , Abdullaeva Dilrabo A. , Geller Svetlana I.
Published: June 2022

Background

Celiac disease (CD) is an immune-mediated disorder of the gut in which innate and adaptive responses are involved. Antimicrobial peptides (AMPs) constitute an arsenal of innate immunity regulators of paramount importance in the gut. However, the role of AMPs in CD is unclear.

Aims

To evaluate the levels of fecal β-defensin-2, fecal calprotectin (FC), and antibodies against bactericidal/permeability-increasing protein (BPI) in the serum of children with active CD and to compare them with those of healthy controls (HCs).

Methods

We examined 76 children with recently diagnosed CD between the age of 2–10 years (average age: 6.1 ± 1.2 years) and 32 HC (average age: 6.2 ± 3.8 years) in this study. We evaluated the level of fecal β-defensin-2 and FC levels in coprofiltrates, and the level of anti-BPI antibodies in blood serum. Correlation relationships between the parameters were assessed according to Pearson correlation coefficient.

Results

Fecal β-defensin-2 concentration was greater in the CD group than in HC group, amounting to 99.6 ± 15.5 ng/mL and 64.0 ± 2.4 ng/mL, respectively (p < 0.02). The level of FC in the CD children was 35.4 ± 8.1 μg/g, while that in the control group was 19.1 ± 1.1 μg/g, (p < 0.05), representing a slightly increase. The concentration of anti-BPI antibodies in the CD and HC groups was 35.9 ± 10.1 U/mL and 5.2 ± 3.2 U/mL, respectively (p < 0.002). There was a strong and direct correlation between fecal β-defensin-2 and FC (r = 0.69), as well as a direct but weak relationship between fecal β-defensin-2 and anti-BPI antibodies (r = 0.35).

Conclusions

Our data reinforce that fecal β-defensin-2 and anti-BPI antibodies are greatly increased in patients with active CD. These biomarkers may be components of epithelial innate immunity in the intestine, with each having a distinct functional role in intestinal6 mucosal defense.
Higher Levels of Plasma Hyaluronic Acid and N-terminal Propeptide of Type III Procollagen Are Associated With Lower Kidney Function in Children With Non-alcoholic Fatty Liver Disease
Authors: Mosca Antonella , Mantovani Alessandro , Crudele Annalisa , Panera Nadia , Comparcola Donatella , De Vito Rita , Bianchi Marzia , Byrne Christopher D. , Targher Giovanni , Alisi Anna
Published: June 2022

Objective

Hyaluronic acid (HA) and N-terminal propeptide of type III procollagen (PIIINP) are two non-invasive biomarkers of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). We examined the relationships of plasma levels of HA and PIIINP with kidney function in children with NAFLD.

Methods

Plasma HA and PIIINP levels were measured using two commercially available enzyme-linked immunosorbent assay kits in a cohort of 106 Caucasian overweight or obese children with biopsy-proven NAFLD. Glomerular filtration rate (eGFR) was estimated using the Bedside Schwartz equation. Genotyping for the patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 variant was performed using an allelic discrimination assay.

Results

Children with fibrosis F2 had significantly higher plasma PIIINP and HA levels than those with F0 or F1 fibrosis. Liver fibrosis was positively associated with plasma HA and PIIINP, as well as with the presence of the risk allele G of PNPLA3 rs738409 variant, and negatively with eGFR. Moreover, eGFR showed significant inverse associations with HA and PIIINP levels, as well as the presence of G of PNPLA3 rs738409, and liver fibrosis stage. Notably, our multivariable regression models showed that higher plasma PIIINP (standardized beta coefficient: −0.206, P = 0.011) and HA levels (standardized beta coefficient: −0.531, P < 0.0001) were associated with lower eGFR values, even after adjustment for age, sex, systolic blood pressure, PNPLA3 rs738409 genotype, and any stage of liver fibrosis.

Conclusions

Higher levels of HA and PIIINP were associated with lower eGFR values in Caucasian children with biopsy-proven NAFLD, independently of PNPLA3 rs738409 genotype and other potential confounding factors.
Chromosomal Abnormalities and Pregnancy Outcomes for Fetuses With Gastrointestinal Tract Obstructions
Authors: Wu Xiaoqing , Su Linjuan , Shen Qingmei , Guo Qun , Li Ying , Xu Shiyi , Lin Na , Huang Hailong , Xu Liangpu
Published: June 2022

Fetal gastrointestinal tract obstruction (GITO) is the most frequently encountered gastrointestinal defect in the prenatal period. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies that were referred for invasive prenatal testing because of fetal GITO. According to the level of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, or anal atresia. Traditional karyotyping was performed on all the 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel. Traditional karyotyping revealed twelve (17.1%) chromosomal abnormalities, including 11 cases of trisomy 21 (Down syndrome), and one case of a supernumerary marker chromosome related to Cat eye syndrome. According to the absence or presence of other ultrasound anomalies, they were categorized into isolated GITO (n = 36) and non-isolated GITO (n = 34). The rate of chromosomal abnormalities in the non-isolated GITO pregnancies was significantly higher than that in the isolated GITO pregnancies (29.4 vs. 5.5%, p < 0.05); the survival rate in the isolated group was significantly higher than that in the non-isolated group (67.6 vs. 34.4%, p < 0.05). Among the 32 cases where CMA was performed, an additional one (3.1%) copy number variant with clinical significance was noted in a fetus with normal karyotype. The microduplication on 7q12 was considered to be the genetic etiology of duodenal stenosis, although it was inherited from a phenotypically normal mother. Our study supports the strong association between Down syndrome and fetal GITO, especially duodenal stenosis. Our findings suggested that the risk of chromosomal abnormalities was increased when GITO was accompanied by other ultrasound anomalies; thus, chromosomal abnormalities and fetal anatomy should be carefully evaluated for pregnancy management of fetal GITO.
Impact of National Volume-Based Procurement on the Procurement Volumes and Spending for Antiviral Medications of Hepatitis B Virus
Authors: Yuan Jing , Lu Z. Kevin , Xiong Xiaomo , Lee Tai-Ying , Huang Huang , Jiang Bin
Published: June 2022

Introduction: Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines are becoming salient. The national volume-based procurement (NVBP) was piloted in China and led to substantial reduction in the list price of prescription drugs. To examine the impact of NVBP on selected antiviral medication costs per defined daily dose (DDD), procurement volumes, and spending.

Methods: We employed an interrupted time series design to examine changes in cost per defined daily dose (DDD), procurement volumes, and spending for NVBP bid-winning antiviral medications (tenofovir disoproxil fumarate and entecavir) in 11 pilot cities from 2017 to 2020. Procurement transaction data were obtained from 9,454 hospitals in the Chinese Hospital Pharmaceutical Audit (CHPA) database. In the secondary analysis, the control group comprised two non-NVBP drugs (adefovir and lamivudine) procured in 11 cities not exposed to the NVBP.

Results: Cost per DDD of the two hepatitis B virus (HBV) antiviral medications reduced by CNY1.598 (p = 0.002) immediately following the implementation of NVBP, dropping from an average cost of CNY16.483 per DDD at baseline to CNY6.420 at the end of the observation period. NVBP implementation resulted in a substantial reduction in daily costs of antivirals and an increase in monthly procurement volumes by 6.674 million DDDs (p = 0.017), while monthly spending was reduced by CNY138.26 million (p = 0.002). In the secondary ITS analysis with a control group, the average cost per DDD of the NVBP bid-winning antivirals declined by CNY4.537 (p < 0.001), monthly procurement volumes increased by 7.209 million DDDs (p = 0.002), and monthly spending dropped by CNY138.83 million (p < 0.001).

Conclusion: Volume-based procurement piloted in China may be effective for reducing price and total expenditures and improving drug utilization, which is especially important for HBV patients who need constant access to antiviral therapies.
Population Pharmacokinetics of Vancomycin in Pregnant Women
Authors: Goyal Rahul K. , Moffett Brady S. , Gobburu Jogarao V. S. , Al Mohajer Mayar
Published: June 2022

Objective: Vancomycin is a glycopeptide antibacterial indicated for serious gram-positive infections. Pharmacokinetics (PK) of vancomycin have not been described in pregnant women. This study aims to characterize the PK disposition of vancomycin in pregnant women based on data acquired from a database of routine hospital care for therapeutic drug monitoring to better inform dosing decisions.

Methods: In this study, plasma drug concentration data from 34 pregnant hospitalized women who were administered intravenous vancomycin was analyzed. A population pharmacokinetic (PPK) model was developed using non-linear mixed effects modeling. Model selection was based on statistical criterion, graphical analysis, and physiologic relevance. Using the final model AUC0-24 (PK efficacy index of vancomycin) was compared with non-pregnant population.

Results: Vancomycin PK in pregnant women were best described by a two-compartment model with first-order elimination and the following parameters: clearance (inter individual variability) of 7.64 L/hr (32%), central volume of 67.35 L, inter-compartmental clearance of 9.06 L/h, and peripheral volume of 37.5 L in a typical patient with 175 ml/min creatinine clearance (CRCL) and 45 kg fat-free mass (FFM). The calculated geometric mean of AUC0-24 for the pregnant population was 223 ug.h/ ml and 226 ug.h/ ml for the non-pregnant population.

Conclusion: Our analysis suggests that vancomycin PK in pregnant women is consistent with non-pregnant adults and the dosing regimens used for non-pregnant patients may also be applicable to pregnant patients.
Sanghuang Tongxie Formula Ameliorates Insulin Resistance in Drosophila Through Regulating PI3K/Akt Signaling
Authors: Cao Xuqing , La Xiaojin , Zhang Biwei , Wang Zhigang , Li Yinghong , Bo Yanping , Chang Hong , Gao Xiujuan , Tian Chunyu , Wu Chenxi , Li Ji-an
Published: June 2022

Insulin resistance (IR) is a pivotal pathological characteristic that affects the occurrence and development of type 2 diabetes mellitus (T2DM). Thus, the effective control of IR is of great significance for diabetes prevention and treatment. Traditional Chinese medicine (TCM) represents a valuable tool handed down to the world by the Chinese nation and has a long history of use for diabetes clinical therapy. In this study, we focused on a self-drafted TCM-patented formula, Sanghuang Tongxie Formula (SHTXF), which exhibits clinical efficacy in the treatment of diabetes. To explore the effect and molecular mechanism of SHTXF on IR in vivo, Drosophila melanogaster was used and a (Collagen) Cg > InRK1409A diabetic IR fly model was established. SHTXF water extract was found to contribute toward carbohydrate clearance from the circulating system by converting it into triglycerides (TAG), not glycogen, for nutrient storage. In addition, SHTXF activated phosphatidylinositol-3-kinase (PI3K) activity and improved protein kinase B (PKB, also termed Akt) phosphorylation. Finally, SHTXF promoted Drosophila Forkhead Box O (dFoxO) cytoplasmic localization and inhibited its transcriptional activity. Taken together, these findings not only highlight the positive role of SHTXF in ameliorating IR via the PI3K/Akt pathway but also provide potential drug targets and key insights for use in T2DM clinical treatment strategies.
Predicting Adverse Events During Six-Minute Walk Test Using Continuous Physiological Signals
Authors: Wang Jiachen , Zang Yaning , Wu Qian , She Yingjia , Xu Haoran , Zhang Jian , Cai Shan , Li Yuzhu , Zhang Zhengbo
Published: June 2022

Background and Objective: The 6-min walk test (6MWT) is a common functional assessment test, but adverse events during the test can be potentially dangerous and can lead to serious consequences and low quality of life. This study aimed to predict the occurrence of adverse events during 6MWT, using continuous physiological parameters combined with demographic variables.

Methods: 578 patients with respiratory disease who had performed standardized 6MWT with wearable devices from three hospitals were included in this study. Adverse events occurred in 73 patients (12.6%). ECG, respiratory signal, tri-axial acceleration signals, oxygen saturation, demographic variables and scales assessment were obtained. Feature extraction and selection of physiological signals were performed during 2-min resting and 1-min movement phases. 5-fold cross-validation was used to assess the machine learning models. The predictive ability of different models and scales was compared.

Results: Of the 16 features selected by the recursive feature elimination method, those related to blood oxygen were the most important and those related to heart rate were the most numerous. Light Gradient Boosting Machine (LightGBM) had the highest AUC of 0.874 ± 0.063 and the AUC of Logistic Regression was AUC of 0.869 ± 0.067. The mMRC (Modified Medical Research Council) scale and Borg scale had the lowest performance, with an AUC of 0.733 and 0.656 respectively.

Conclusion: It is feasible to predict the occurrence of adverse event during 6MWT using continuous physiological parameters combined with demographic variables. Wearable sensors/systems can be used for continuous physiological monitoring and provide additional tools for patient safety during 6MWT.
A High Soldier Proportion Encouraged the Greater Antifungal Immunity in a Subterranean Termite
Authors: Zeng Wenhui , Shen Danni , Chen Yong , Zhang Shijun , Wu Wenjing , Li Zhiqiang
Published: June 2022

Termites possess a mighty social immune system, serving as one of the key obstacles to controlling them biologically. However, the dynamic mechanism coordinating the social immunologic defense and caste distribution of the termites remains elusive. This study used the Coptotermes formosanus Shiraki and an entomopathogenic fungus as a host–pathogen system and experimentally manipulated a series of groups with different caste compositions of workers and soldiers. Then, the impact of demography on the behavior and innate immunity of termites was explored by analyzing the fungus susceptibility of the respective caste, efficiencies, and caste preferences of sanitary care, as well as the expression of the immune genes and phenoloxidase activity. Overall, to ensure the general health and survival of a group, the infected workers were found to sacrifice their survivorship for maintaining the soldier proportion of the group. If soldier proportion was limited within a threshold, both the survivorship of the workers and soldiers were not significantly affected by the infection. Correspondingly, the infected group with a higher proportion of soldiers stimulated the higher efficiency of a non-caste-biased sanitary care of the workers to the nestmate workers and soldiers. Moreover, the innate immunities of the infected workers were found to be more intensely upregulated in the group with higher soldier proportions. This suggested that the adjustable non-caste-biased sanitary care and innate immunity of the workers would contribute to the flexibility of the worker–soldier caste ratio in C. formosanus. This study, therefore, enhanced our understanding of the functional adaptation mechanism between pathogen-driven social immunity and the demography of the termites.
Compositions and Functions of Mitochondria-Associated Endoplasmic Reticulum Membranes and Their Contribution to Cardioprotection by Exercise Preconditioning
Authors: Lv Yuhu , Cheng Lin , Peng Fenglin
Published: June 2022

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are important components of intracellular signaling and contribute to the regulation of intracellular Ca2+/lipid homeostasis, mitochondrial dynamics, autophagy/mitophagy, apoptosis, and inflammation. Multiple studies have shown that proteins located on MAMs mediate cardioprotection. Exercise preconditioning (EP) has been shown to protect the myocardium from adverse stimuli, but these mechanisms are still being explored. Recently, a growing body of evidence points to MAMs, suggesting that exercise or EP may be involved in cardioprotection by modulating proteins on MAMs and subsequently affecting MAMs. In this review, we summarize the latest findings on MAMs, analyzing the structure and function of MAMs and the role of MAM-related proteins in cardioprotection. We focused on the possible mechanisms by which exercise or EP can modulate the involvement of MAMs in cardioprotection. We found that EP may affect MAMs by regulating changes in MFN2, MFN1, AMPK, FUNDC1, BECN1, VDAC1, GRP75, IP3R, CYPD, GSK3β, AKT, NLRP3, GRP78, and LC3, thus playing a cardioprotective role. We also provided direction for future studies that may be of interest so that more in-depth studies can be conducted to elucidate the relationship between EP and cardioprotection.
Association of the Recessive Allele vrn-D1 With Winter Frost Tolerance in Bread Wheat
Authors: Zhang Hongjun , Xue Xinhui , Guo Jie , Huang Yiwen , Dai Xuran , Li Teng , Hu Jinghuang , Qu Yunfeng , Yu Liqiang , Mai Chunyan , Liu Hongwei , Yang Li , Zhou Yang , Li Hongjie
Published: June 2022

Winter frost has been considered the primary limiting factor in wheat production. Shimai 12 is an elite wheat cultivar grown in central and southern Hebei province of China, but sensitive to winter frost. In this study, the winter frost tolerant cultivar Lunxuan 103 was bred by introducing the recessive allele vrn-D1 from winter wheat Shijiazhuang 8 (frost tolerance) into Shimai 12 using marker-assisted selection (MAS). Different from Shimai 12, Lunxuan 103 exhibited a winter growth habit with strong winter frost tolerance. In the Shimai 12 × Shijiazhuang 8 population, the winter progenies (vrn-D1vrn-D1) had significantly lower winter-killed seedling/tiller rates than spring progenies (Vrn-D1aVrn-D1a), and the consistent result was observed in an association population. Winter frost damage caused a significant decrease in grain yield and spike number/m2 in Shimai 12, but not in Lunxuan 103 and Shijiazhuang 8. The time-course expression analysis showed that the transcript accumulation levels of the cold-responsive genes were higher in Lunxuan 103 and Shijiazhuang 8 than in Shimai 12. Lunxuan 103 possessed the same alleles as its parents in the loci for plant height, vernalization, and photoperiod, except for the vernalization gene Vrn-D1. An analysis of genomic composition showed that the two parents contributed similar proportions of genetic compositions to Lunxuan 103. This study provides an example of the improvement of winter frost tolerance by introducing the recessive vernalization gene in bread wheat.
Structure-Based Modulation of the Ligand Sensitivity of a Tomato Dimeric Abscisic Acid Receptor Through a Glu to Asp Mutation in the Latch Loop
Authors: Infantes Lourdes , Rivera-Moreno Maria , Daniel-Mozo Miguel , Benavente Juan Luis , Ocaña-Cuesta Javier , Coego Alberto , Lozano-Juste Jorge , Rodriguez Pedro L. , Albert Armando
Published: June 2022

The binding of the plant phytohormone Abscisic acid (ABA) to the family of ABA receptors (PYR/PYL/RCAR) triggers plant responses to abiotic stress. Thus, the implementation of genetic or chemical strategies to modulate PYR/PYL activity might be biotechnologically relevant. We have employed the available structural information on the PYR/PYL receptors to design SlPYL1, a tomato receptor, harboring a single point mutation that displays enhanced ABA dependent and independent activity. Interestingly, crystallographic studies show that this mutation is not directly involved in ABA recognition or in the downstream phosphatase (PP2C) inhibitory interaction, rather, molecular dynamic based ensemble refinement restrained by crystallographic data indicates that it enhances the conformational variability required for receptor activation and it is involved in the stabilization of an active form of the receptor. Moreover, structural studies on this receptor have led to the identification of niacin as an ABA antagonist molecule in vivo. We have found that niacin blocks the ABA binding site by mimicking ABA receptor interactions, and the niacin interaction inhibits the biochemical activity of the receptor.