bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlations between kinematic profiles and cerebral hemodynamics suggest changes of motor coordination in single and bilateral finger movement
Authors: Zhou Guangquan , Chen Yuzhao , Wang Xiaohan , Wei Hao , Huang Qinghua , Li Le
Published: August 2022

Objective

The correlation between the performance of coordination movement and brain activity is still not fully understood. The current study aimed to identify activated brain regions and brain network connectivity changes for several coordinated finger movements with different difficulty levels and to correlate the brain hemodynamics and connectivity with kinematic performance.

Methods

Twenty-one right-dominant-handed subjects were recruited and asked to complete circular motions of single and bilateral fingers in the same direction (in-phase, IP) and in opposite directions (anti-phase, AP) on a plane. Kinematic data including radius and angular velocity at each task and synchronized blood oxygen concentration data using functional near-infrared spectroscopy (fNIRS) were recorded covering six brain regions including the prefrontal cortex, motor cortex, and occipital lobes. A general linear model was used to locate activated brain regions, and changes compared with baseline in blood oxygen concentration were used to evaluate the degree of brain region activation. Small-world properties, clustering coefficients, and efficiency were used to measure information interaction in brain activity during the movement.

Result

It was found that the radius error of the dominant hand was significantly lower than that of the non-dominant hand (p < 0.001) in both clockwise and counterclockwise movements. The fNIRS results confirmed that the contralateral brain region was activated during single finger movement and the dominant motor area was activated in IP movement, while both motor areas were activated simultaneously in AP movement. The Δhbo were weakly correlated with radius errors (p = 0.002). Brain information interaction in IP movement was significantly larger than that from AP movement in the brain network (p < 0.02) in the right prefrontal cortex. Brain activity in the right motor cortex reduces motor performance (p < 0.001), while the right prefrontal cortex region promotes it (p < 0.05).

Conclusion

Our results suggest there was a significant correlation between motion performance and brain activation level, as well as between motion deviation and brain functional connectivity. The findings may provide a basis for further exploration of the operation of complex brain networks.
Learning populations with hubs govern the initiation and propagation of spontaneous bursts in neuronal networks after learning
Authors: Jia Xiaoli , Shao Wenwei , Hu Nan , Shi Jianxin , Fan Xiu , Chen Chong , Wang Youwei , Chen Liqun , Qiao Huanhuan , Li Xiaohong
Published: August 2022

Spontaneous bursts in neuronal networks with propagation involving a large number of synchronously firing neurons are considered to be a crucial feature of these networks both in vivo and in vitro. Recently, learning has been shown to improve the association and synchronization of spontaneous events in neuronal networks by promoting the firing of spontaneous bursts. However, little is known about the relationship between the learning phase and spontaneous bursts. By combining high-resolution measurement with a 4,096-channel complementary metal-oxide-semiconductor (CMOS) microelectrode array (MEA) and graph theory, we studied how the learning phase influenced the initiation of spontaneous bursts in cultured networks of rat cortical neurons in vitro. We found that a small number of selected populations carried most of the stimulus information and contributed to learning. Moreover, several new burst propagation patterns appeared in spontaneous firing after learning. Importantly, these “learning populations” had more hubs in the functional network that governed the initiation of spontaneous burst activity. These results suggest that changes in the functional structure of learning populations may be the key mechanism underlying increased bursts after learning. Our findings could increase understanding of the important role that synaptic plasticity plays in the regulation of spontaneous activity.
Increased cerebral cortex activation in stroke patients during electrical stimulation of cerebellar fastigial nucleus with functional near-infrared spectroscopy
Authors: Ma Haiyun , Zhai Yujia , Xu Zhen , Fan Shengnuo , Wu Xian , Xu Jing , Wu Shaoling , Ma Chao
Published: August 2022

Background

Electrical stimulation of the cerebellar fastigial nucleus (FNS) has been shown to protect animals against cerebral ischemic injury. However, the changes in cortical activation as a response to FNS have not been illustrated in humans.

Objective

This study aims to detect functional connectivity changes in the brain of stroke patients, and investigate the cortical activation caused by FNS through measuring the oxygenated hemoglobin concentration (HBO) in the cerebral cortex of stroke patients and healthy controls (HCs).

Methods

This study recruited 20 patients with stroke and 20 HCs with all the following factors matched: age, gender and BMI. The experiment session was made up of the pre-task baseline, FNS task period, and post-task baseline. FNS task period contains 5 blocks, each block encompassing the resting state (30 s) and the FNS state (30 s). HBO signals were acquired by functional near-infrared spectroscopy (fNIRS) from the Prefrontal Cortex (PFC), the Motor Cortex (MC) and the Occipital Cortex (OC) throughout the experiment. The Pearson correlation coefficient was used to calculate the resting-state functional connectivity strength between the two groups, and the general linear model (GLM) was used to calculate the activation of 39 fNIRS channels during FNS in stroke patients and HCs, respectively.

Results

The coupling strength of stroke patients were significantly decreased in the following regions: right MC and left MC (t = 4.65, p = 0.0007), right MC and left OC (t = 2.93, p = 0.04), left MC and left OC (t = 2.81, p = 0.04). In stroke patients, the changes in cerebral oxygenated hemoglobin (ΔHBO) among 12 channels (CH) in the bilateral PFC and bilateral MC regions were significantly increased during the FNS state (FDR corrected p < 0.05) compared with the resting state. In HCs, only 1 channel was increased (FDR corrected p < 0.05) in the left PFC during FNS.

Conclusion

By using the FNS and fNIRS techniques, the characteristics of functional connectivity were found to decrease in stroke patients. It was also noticed that FNS activates the PFC and MC regions. These findings may help to guide functional rehabilitation in stroke patients.
Prediction of balance function for stroke based on EEG and fNIRS features during ankle dorsiflexion
Authors: Liang Jun , Song Yanxin , Belkacem Abdelkader Nasreddine , Li Fengmin , Liu Shizhong , Chen Xiaona , Wang Xinrui , Wang Yueyun , Wan Chunxiao
Published: August 2022

Balance rehabilitation is exceedingly crucial during stroke rehabilitation and is highly related to the stroke patients’ secondary injuries (caused by falling). Stroke patients focus on walking ability rehabilitation during the early stage. Ankle dorsiflexion can activate the brain areas of stroke patients, similar to walking. The combination of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) was a new method, providing more beneficial information. We extracted the event-related desynchronization (ERD), oxygenated hemoglobin (HBO), and Phase Synchronization Index (PSI) features during ankle dorsiflexion from EEG and fNIRS. Moreover, we established a linear regression model to predict Berg Balance Scale (BBS) values and used an eightfold cross validation to test the model. The results showed that ERD, HBO, PSI, and age were critical biomarkers in predicting BBS. ERD and HBO during ankle dorsiflexion and age were promising biomarkers for stroke motor recovery.
Neural substrates in patients with visual-spatial neglect recovering from right-hemispheric stroke
Authors: Cao Lei , Ye Linlin , Xie Huanxin , Zhang Yichen , Song Weiqun
Published: August 2022

Visual-spatial attention disorder after stroke seriously affects recovery and quality of life in stroke patients. Previous studies have shown that some patients recovery rapidly from visual-spatial neglect (VSN), but the brain networks underlying this recovery are not well understood. Using functional magnetic resonance imaging, we aimed to identify network differences between patients who rapidly recovered from VSN and those with persistent VSN. The study included 30 patients with VSN who suffered subacute stroke. Patients were examined 2–4 weeks after stroke onset and 4 weeks after the initial assessment. At the last evaluation, patients in the persistent VSN (n = 15) and rapid recovery (n = 15) groups underwent paper-and-pencil tests. We defined the bilateral frontal eye fields, bilateral intraparietal sulcus in the dorsal attention network, and right temporoparietal junction and ventral frontal cortex areas in the ventral attention network as regions of interest (ROI) and measured whole-brain ROI-based functional connectivity (FC) and amplitude of low-frequency fluctuations (ALFF) in subacute right-hemisphere stroke patients. VSN recovery was associated with changes in the activation of multiple bilateral attentional brain regions. Specifically, persistent VSN was associated with lower FC in the right superior frontal gyrus, right inferior temporal gyrus, right medial orbitofrontal cortex, left precuneus, right inferior parietal gyrus, right medial frontal gyrus, right rectus gyrus, left superior frontal gyrus, left middle cingulate gyrus, right superior temporal pole, right postcentral gyrus, and right posterior cingulate gyrus compared to that in those with rapid recovery, whereas ALFF in the left cerebellum were decreased in patients with persistent VSN. Our results demonstrate that the DAN rather than the VAN, plays a more important role in recovery from VSN, and that the cerebellum is involved in recovery. We believe that our results supplement those of previous studies on recovery from VSN.
Trends in added sugars intake and sources among U.S. adults using the National Health and Nutrition Examination Survey (NHANES) 2001–2018
Authors: DiFrancesco Loretta , Fulgoni Victor L. , Gaine P. Courtney , Scott Maria O. , Ricciuto Laurie
Published: August 2022

Research on trends over time in added sugars intake is important to help gain insights into how population intakes change with evolving dietary guidelines and policies on reducing added sugars. The purpose of this study was to provide an analysis of dietary trends in added sugars intakes and sources among U.S. adults from 2001 to 2018, with a focus on variations according to the sociodemographic factors, age, sex, race and ethnicity and income, and the health-related factors, physical activity and body weight. Data from nine consecutive 2 year cycles of the National Health and Nutrition Examination Survey (NHANES) were combined and regression analyses were conducted to test for trends in added sugars intake and sources from 2001 to 2018. Trends were examined in the whole sample (19+ years) and in subsamples stratified by age (19–50, 51+ years), sex, race and ethnicity (Asian, Black, Hispanic, White), household income (poverty income ratio low, medium, high), physical activity level (sedentary, moderate, vigorous) and body weight status (normal, overweight, obese). From 2001 to 2018, added sugars intake (% kcal) decreased significantly (P < 0.01), from 16.2 to 12.7% among younger adults (19–50 years), mainly due to declines in added sugars from sweetened beverages, which remained the top source. There were no changes in intake among older adults, and by 2018, the 23% difference in intake between younger and older adults that existed in 2001 almost disappeared. Declines in added sugars intake were similar among Black and White individuals, and all income, physical activity and body weight groups. Population-wide reductions in added sugars intake among younger adults over an 18 year time span coincide with the increasing public health focus on reducing added sugars intake. With the updated Nutrition Facts label now displaying added sugars content, it remains to be seen how added sugars intake trends carry forward in the future.
Using combined CT-clinical radiomics models to identify epidermal growth factor receptor mutation subtypes in lung adenocarcinoma
Authors: Huo Ji-wen , Luo Tian-you , Diao Le , Lv Fa-jin , Chen Wei-dao , Yu Rui-ze , Li Qi
Published: August 2022

Background

To investigate the value of computed tomography (CT)-based radiomics signatures in combination with clinical and CT morphological features to identify epidermal growth factor receptor (EGFR)-mutation subtypes in lung adenocarcinoma (LADC).

Methods

From February 2012 to October 2019, 608 patients were confirmed with LADC and underwent chest CT scans. Among them, 307 (50.5%) patients had a positive EGFR-mutation and 301 (49.5%) had a negative EGFR-mutation. Of the EGFR-mutant patients, 114 (37.1%) had a 19del -mutation, 155 (50.5%) had a L858R-mutation, and 38 (12.4%) had other rare mutations. Three combined models were generated by incorporating radiomics signatures, clinical, and CT morphological features to predict EGFR-mutation status. Patients were randomly split into training and testing cohorts, 80% and 20%, respectively. Model 1 was used to predict positive and negative EGFR-mutation, model 2 was used to predict 19del and non-19del mutations, and model 3 was used to predict L858R and non-L858R mutations. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate their performance.

Results

For the three models, model 1 had AUC values of 0.969 and 0.886 in the training and validation cohorts, respectively. Model 2 had AUC values of 0.999 and 0.847 in the training and validation cohorts, respectively. Model 3 had AUC values of 0.984 and 0.806 in the training and validation cohorts, respectively.

Conclusion

Combined models that incorporate radiomics signature, clinical, and CT morphological features may serve as an auxiliary tool to predict EGFR-mutation subtypes and contribute to individualized treatment for patients with LADC.
Relationship between metabolic reprogramming and drug resistance in breast cancer
Authors: Lv Linlin , Yang Shilei , Zhu Yanna , Zhai Xiaohan , Li Shuai , Tao Xufeng , Dong Deshi
Published: August 2022

Breast cancer is the leading cause of cancer death in women. At present, chemotherapy is the main method to treat breast cancer in addition to surgery and radiotherapy, but the process of chemotherapy is often accompanied by the development of drug resistance, which leads to a reduction in drug efficacy. Furthermore, mounting evidence indicates that drug resistance is caused by dysregulated cellular metabolism, and metabolic reprogramming, including enhanced glucose metabolism, fatty acid synthesis and glutamine metabolic rates, is one of the hallmarks of cancer. Changes in metabolism have been considered one of the most important causes of resistance to treatment, and knowledge of the mechanisms involved will help in identifying potential treatment deficiencies. To improve women’s survival outcomes, it is vital to elucidate the relationship between metabolic reprogramming and drug resistance in breast cancer. This review analyzes and investigates the reprogramming of metabolism and resistance to breast cancer therapy, and the results offer promise for novel targeted and cell-based therapies.
Deep learning-based low-dose CT for adaptive radiotherapy of abdominal and pelvic tumors
Authors: Gong Wei , Yao Yiming , Ni Jie , Jiang Hua , Jia Lecheng , Xiong Weiqi , Zhang Wei , He Shumeng , Wei Ziquan , Zhou Juying
Published: August 2022

The shape and position of abdominal and pelvic organs change greatly during radiotherapy, so image-guided radiation therapy (IGRT) is urgently needed. The world’s first integrated CT-linac platform, equipped with fan beam CT (FBCT), can provide a diagnostic-quality FBCT for achieve adaptive radiotherapy (ART). However, CT scans will bring the risk of excessive scanning radiation dose. Reducing the tube current of the FBCT system can reduce the scanning dose, but it will lead to serious noise and artifacts in the reconstructed images. In this study, we proposed a deep learning method, Content-Noise Cycle-Consistent Generative Adversarial Network (CNCycle-GAN), to improve the image quality and CT value accuracy of low-dose FBCT images to meet the requirements of adaptive radiotherapy. We selected 76 patients with abdominal and pelvic tumors who received radiation therapy. The patients received one low-dose CT scan and one normal-dose CT scan in IGRT mode during different fractions of radiotherapy. The normal dose CT images (NDCT) and low dose CT images (LDCT) of 70 patients were used for network training, and the remaining 6 patients were used to validate the performance of the network. The quality of low-dose CT images after network restoration (RCT) were evaluated in three aspects: image quality, automatic delineation performance and dose calculation accuracy. Taking NDCT images as a reference, RCT images reduced MAE from 34.34 ± 5.91 to 20.25 ± 4.27, PSNR increased from 34.08 ± 1.49 to 37.23 ± 2.63, and SSIM increased from 0.92 ± 0.08 to 0.94 ± 0.07. The P value is less than 0.01 of the above performance indicators indicated that the difference were statistically significant. The Dice similarity coefficients (DCS) between the automatic delineation results of organs at risk such as bladder, femoral heads, and rectum on RCT and the results of manual delineation by doctors both reached 0.98. In terms of dose calculation accuracy, compared with the automatic planning based on LDCT, the difference in dose distribution between the automatic planning based on RCT and the automatic planning based on NDCT were smaller. Therefore, based on the integrated CT-linac platform, combined with deep learning technology, it provides clinical feasibility for the realization of low-dose FBCT adaptive radiotherapy for abdominal and pelvic tumors.
Epigenetic regulation of cutaneous T-cell lymphoma is mediated by dysregulated lncRNA MALAT1 through modulation of tumor microenvironment
Authors: Guo Wei , Liu Guang-Ming , Guan Ji-Yu , Chen Yu-Jia , Zhao Yang-Zhi , Wang Kun , Bai Ou
Published: August 2022

Cutaneous T-Cell Lymphoma (CTCL) is a rare non-Hodgkin lymphoma marked by migration of T-lymphocytes to the skin. It has many subtypes some of which are aggressive with documented metastasis. We investigated a possible role of lncRNA MALAT1 in CTCL cells because of its documented involvement in cancer metastasis. A screening of MALAT1 in CTCL patients revealed its elevated levels in the patients, compared to healthy individuals. For our investigation, we employed HH and H9 CTCL cells and silenced MALAT1 to understand the MALAT1 mediated functions. Such silencing of MALAT1 resulted in reversal of EMT and inhibition of cancer stem cell phenotype, along with reduced cell growth and proliferation. EMT reversal was established through increased E-cadherin and reduced N-cadherin while inhibition of cancer stem cell phenotype was evident through reduced Sox2 and Nanog. CTCL patients had higher circulating levels of IL-6, IL-8, IL-10, TGFβ, PGE2 and MMP7 which are factors released by tumor-associated macrophages in tumor microenvironment. MALAT1 sponged miR-124 as this tumor suppressive miRNA was de-repressed upon MALAT1 silencing. Moreover, downregulation of miR-124 attenuated MALAT1 silencing effects. Our study provides a rationale for further studies focused on an evaluation of MALAT1-miR-124 in CTCL progression.
Intravesical recurrence factors and outcome after radical nephroureterectomy for upper tract urothelial carcinoma: Multivariate analysis with propensity score matching
Authors: Zhao Hang , Jiao Binbin , Liu Kunpeng , Luo Zhenkai , Ding Zhenshan , Lai Shicong , Ren Jian , Zhang Guan
Published: August 2022

Objective

The risk factors for intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) remain inconsistent and unclear. Thus, the risk factors of IVR after RNU and the prognostic significance of the risk indicators were explored herein.

Methods

We retrospectively analyzed UTUC patients upon RNU in our center from January 2009 to December 2019. After propensity score matching, 139 patients were included in this study. Univariate and multivariate Cox proportional hazard regressions were used to estimate the hazard ratio and 95% confidence intervals. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were measured using the Kaplan–Meier curve with a log-rank test. A P-value < 0.05 was considered statistically significant.

Results

We included 139 patients with a median follow-up of 42 months, of which 48 patients had an intravesical recurrence. Multivariate Cox regression analysis showed cytological abnormalities in urine (HR=3.101, P=0.002), hydronephrosis (HR=1.852, P=0.042), adjuvant chemotherapy (HR=0.242, P<0.001), and previous history of bladder cancer (HR=5.51, P<0.001) were independent risk factors for IVR. As for clinical outcomes, OS and CSS suggested disadvantages in patients with IVR compared with patients without recurrence (P=0.042 for OS, P<0.0001 for CSS), OS of patients with abnormal urine cytology and OS and CSS of patients receiving adjuvant chemotherapy did not present clinical significance, and other risk factors all affected the clinical outcome.

Conclusion

In this propensity-score matching study, cytological abnormality of urine, hydronephrosis, adjuvant chemotherapy and previous history of bladder cancer were shown to be independent risk factors for IVR. Moreover, risk factors also influence clinical outcomes, thereby rendering it necessary to adopt more active postoperative surveillance and treatment strategies for these patients, which may help improve treatment outcomes.
Machine learning model for the prediction of prostate cancer in patients with low prostate-specific antigen levels: A multicenter retrospective analysis
Authors: Deng Xiaobin , Li Tianyu , Mo Linjian , Wang Fubo , Ji Jin , He Xing , Mohamud Bashir Hussein , Pradhan Swadhin , Cheng Jiwen
Published: August 2022

Objective

The aim of this study was to develop a predictive model to improve the accuracy of prostate cancer (PCa) detection in patients with prostate specific antigen (PSA) levels ≤20 ng/mL at the initial puncture biopsy.

Methods

A total of 146 patients (46 with Pca, 31.5%) with PSA ≤20 ng/mL who had undergone transrectal ultrasound-guided 12+X prostate puncture biopsy with clear pathological results at the First Affiliated Hospital of Guangxi Medical University (November 2015 to December 2021) were retrospectively evaluated. The validation group was 116 patients drawn from Changhai Hospital(52 with Pca, 44.8%). Age, body mass index (BMI), serum PSA, PSA-derived indices, several peripheral blood biomarkers, and ultrasound findings were considered as predictive factors and were analyzed by logistic regression. Significant predictors (P < 0.05) were included in five machine learning algorithm models. The performance of the models was evaluated by receiver operating characteristic curves. Decision curve analysis (DCA) was performed to estimate the clinical utility of the models. Ten-fold cross-validation was applied in the training process.

Results

Prostate-specific antigen density, alanine transaminase-to-aspartate transaminase ratio, BMI, and urine red blood cell levels were identified as independent predictors for the differential diagnosis of PCa according to multivariate logistic regression analysis. The RandomForest model exhibited the best predictive performance and had the highest net benefit when compared with the other algorithms, with an area under the curve of 0.871. In addition, DCA had the highest net benefit across the whole range of cut-off points examined.

Conclusion

The RandomForest-based model generated showed good prediction ability for the risk of PCa. Thus, this model could help urologists in the treatment decision-making process.
Case report: Idiopathic subglottic stenosis in a girl; successful treatment with macrolides
Authors: Tebbe Wolfgang , Wittkowski Helmut , Tebbe Johannes , Hülskamp Georg
Published: August 2022

An 8-year-old girl presented with treatment-refractory cough and inspiratory stridor. Bronchoscopies showed progressive scarring leading to narrowing of the proximal trachea (Myer-Cotton Grade 2) and epithelial metaplasia of the tracheal and bronchial mucosa. After excluding other causes of congenital and acquired tracheal stenosis, an idiopathic subglottic tracheal stenosis (iSGS) was diagnosed. Because of the patient's young age, a judicious therapeutic approach seemed appropriate. Therapy with azithromycin, followed by roxithromycin, was started. Symptoms almost completely subsided, spirometry normalized, and endoscopic and histologic findings improved considerably. Therapy has been continued for more than 3 years with normal lung function values, and no compromise on physical activities and development. In instances of iSGS, therapy with macrolides is worth considering before more invasive procedures such as dilatation, laser, intralesional injections, or surgical resection are performed.
Minimally invasive surgery for pediatric renal and ureteric stones: A therapeutic update
Authors: Peng Tao , Zhong Hongcai , Hu Baohui , Zhao Shankun
Published: August 2022

The incidence of pediatric urolithiasis (PU) is growing worldwide. The corresponding therapeutic methods have become a research hot spot in pediatric urology. PU has the characteristics of abnormal metabolism, easy recurrence, and immature urinary system development, which make its treatment different from that of adults. Pediatric urologists should select the optimal treatment modality to completely remove the stones to prevent recurrence. Currently, the curative treatments of PU include extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, retrograde intrarenal surgery, percutaneous nephrolithotomy (PCNL), laparoscopic, robot-assisted laparoscopic, and open surgery. This review aims to conduct a therapeutic update on the surgical interventions of both pediatric renal and ureteric stones. It accentuates that pediatric surgeons or urologists should bear in mind the pros and cons of various minimally invasive surgical treatments under different conditions. In the future, the treatment of PU will be more refined due to the advancement of technology and the development of surgical instruments. However, a comprehensive understanding of the affected factors should be taken into account by pediatric urologists to select the most beneficial treatment plan for individual children to achieve precise treatment.
Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19
Authors: Çaǧlayan Şengül , Sönmez Hafize Emine , Otar Yener Gülçin , Baǧlan Esra , Öztürk Kübra , Ulu Kadir , Guliyeva Vafa , Demirkol Demet , Çakan Mustafa , Özdel Semanur , Bukulmez Hulya , Aktay Ayaz Nuray , Sözeri Betül
Published: August 2022

Objective

The study aimed to report the efficacy and safety of anakinra treatment in patients with the refractory multisystemic inflammatory syndrome in children (MIS-C).

Methods

This is a cross-sectional retrospective study consisting of pediatric patients diagnosed with MIS-C who were treated with anakinra.

Results

Among the 378 patients diagnosed with MIS-C, 82 patients (21.6%) who were treated with anakinra were included in the study. The median age of patients was 115 (6-214) months. The median duration of hospitalization was 15 (6-42) days. Sixty patients (73.1%) were admitted to the pediatric intensive care unit. Patients were treated with a median dose of 2.7 mg/kg/day anakinra concomitant with IVIG and steroids. Intravenous anakinra was applied to 12 patients while 70 patients received it subcutaneously. Twenty-eight patients required high dose (4–10 mg/kg/day) anakinra. The median day of anakinra initiation was 2 (1-14) days and the median duration of anakinra use was 7 (1-41) days. No injection site reactions were observed while elevated transaminase levels were detected in 13 patients. Seventy-three patients (89.1%) were discharged without any sequela or morbidity. Seven patients (1.8%) died. Abnormal echocardiographic findings continued in two patients (2.4%) (coronary artery dilatation in one, low ejection fraction in one) at discharge and became normal on the 2nd month.

Conclusion

Based on the results of the study, anakinra was associated with clinical improvements and was safe for most patients with refractory MIS-C.
Birth during on-call period: Impact of care organization on mortality and morbidity of very premature neonates
Authors: Cambonie Gilles , Theret Bénédicte , Badr Maliha , Fournier Patricia , Combes Clémentine , Picaud Jean-Charles , Gavotto Arthur
Published: August 2022

Objectives

The evidence that risks of morbidity and mortality are higher when very premature newborns are born during the on-call period is inconsistent. This study aimed to assess the impact of this situation among other determinants of outcomes, particularly newborn characteristics and care organization.

Methods

Observational study including all infants born < 30 weeks’ gestation in a French tertiary perinatal center between 2007 and 2020. On-call period corresponded to weekdays between 6:30 p.m. and 8:30 a.m., weekends, and public holidays. The primary endpoint was survival without severe morbidity, including grade 3–4 intraventricular hemorrhage (IVH), cystic periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity. The relationship between admission and outcome was assessed by an adjusted odds ratio (aOR) on the propensity of being born during on-call period and expressed vs. weekday. Secondary analyses were carried out in extremely preterm newborns (<27 weeks’ gestation), in cases of early death (within 7 days), and before (2007–2013, 51.5% of the cohort) vs. after (2014–2020, 48.5% of the cohort) the implementation of a pediatrician-nurse team dedicated to newborn care in the delivery room.

Results

A total of 1,064 infants [27.9 (26.3; 28.9) weeks, 947 (760; 1,147) g] were included: 668 during the on-call period (63%) and 396 (37%) on weekdays. For infants born on weekdays, survival without severe morbidity was 54.5% and mortality 19.2%. During on-call, these rates were 57.3% [aOR 1.08 (0.84–1.40)] and 18.4% [aOR 0.93 (0.67–1.29)]. Comparable rates of survival without severe morbidity [aOR 1.42 (0.87–2.34)] or mortality [aOR 0.76 (0.47–1.22)] were observed in extremely preterm infants. The early death rate was 6.4% on weekdays vs. 8.2% during on-call [aOR 1.44 (0.84–2.48)]. Implementation of the dedicated team was associated with decreased rates of mortality [aOR 0.57 (0.38, 0.85)] and grade 3–4 IVH [aOR 0.48 (0.30, 0.75)], and an increased rate of severe BPD [aOR 2.16 (1.37, 3.41)], for infants born during on-call.

Conclusion

In this cohort, most births of very premature neonates occurred during the on-call period. A team dedicated to newborn care in the delivery room may have a favorable effect on the outcome of infants born in this situation.
High-yield bioactive triterpenoid production by heterologous expression in Nicotiana benthamiana using the Tsukuba system
Authors: Romsuk Jutapat , Yasumoto Shuhei , Fukushima Ery Odette , Miura Kenji , Muranaka Toshiya , Seki Hikaru
Published: August 2022

Oleanolic acid is a pentacyclic triterpenoid found in numerous plant species and is a precursor to several bioactive triterpenoids with commercial potential. However, oleanolic acid accumulates at low levels in plants, and its chemical synthesis is challenging. Here, we established a method for producing oleanolic acid in substantial quantities via heterologous expression of pathway enzymes in Nicotiana benthamiana. The “Tsukuba system” is one of the most efficient agroinfiltration-based transient protein expression systems using the vector pBYR2HS, which contains geminiviral replication machinery and a double terminator for boosting expression. Additionally, the pBYR2HS vector contains an expression cassette for the gene-silencing suppressor p19 protein from tomato bushy stunt virus, which can also contribute to enhancing the expression of target proteins. In this study, we evaluated the applicability of this system to heterologous triterpenoid production in N. benthamiana. Medicago truncatula cytochrome P450 monooxygenase (CYP) 716A12 is the first enzyme to be functionally characterized as β-amyrin C-28 oxidase producing oleanolic acid. A mutant CYP716A12 (D122Q) with improved catalytic activity engineered in our previous study was co-expressed with other enzymes in N. benthamiana leaves. Using pBYR2HS, oleanolic acid yield was increased 13.1-fold compared with that using the conventional binary vector, indicating the advantage of the Tsukuba system. We also demonstrated the efficacy of co-expressing a mutant Arabidopsis thaliana HMGR1 catalytic domain, additional NADPH-cytochrome P450 reductase (CPR) transferring electrons to heterologous CYPs, and application of ascorbic acid for preventing leaf necrosis after agroinfiltration, to improve product yield. As a result, the product yields of both simple (β-amyrin) and oxidized (oleanolic acid and maslinic acid) triterpenoids were significantly improved compared with the previously reported yield in heterologous triterpenoid production in N. benthamiana leaves.
Overexpression of leucoanthocyanidin reductase or anthocyanidin reductase elevates tannins content and confers cassava resistance to two-spotted spider mite
Authors: Chen Qing , Liang Xiao , Wu Chunling , Liu Ying , Liu Xiaoqiang , Zhao Huiping , Li Kaimian , Chen Songbi , Wang Haiyan , Han Zhiling , Wu Mufeng , Yao Xiaowen , Shui Jun , Qiao Yang , Zhan Xue , Zhang Yao
Published: August 2022

The two-spotted spider mite (TSSM) is a destructive cassava pest. Intensive demonstration of resistance mechanism greatly facilitates the creation of TSSM-resistant cassava germplasm. Gene to metabolite network plays a crucial role in modulating plant resistance, but little is known about the genes and related metabolites which are responsible for cassava resistance to TSSM. Here, a highly resistant (HR) and a highly susceptible (HS) cassava cultivar were used, integrative and comparative transcriptomic and metabolomic analyses between these two cultivars after TSSM infestation revealed that several genes and metabolites were closely related and significantly different in abundance. In particular, the expression of leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR) genes showed a high positive correlation with most of the metabolites in the tannin biosynthesis pathway. Furthermore, transgenic cassava lines overexpressing either of the genes elevated tannin concentrations and conferred cassava resistance to TSSM. Additionally, different forms of tannins possessed distinct bioactivity on TSSM, of which total condensed tannins (LC50 = 375.68 mg/l) showed maximum lethal effects followed by procyanidin B1 (LC50 = 3537.10 mg/l). This study accurately targets LAR, ANR and specific tannin compounds as critical genes and metabolites in shaping cassava resistance to TSSM, which could be considered as biomarkers for evaluation and creation of pest-resistant cassava germplasm.
Stair walking effects on feelings of energy and fatigue: Is 4-min enough for benefits?
Authors: Carmichael Kaitlyn E. , O’Connor Patrick J. , Gay Jennifer L.
Published: August 2022

Purpose

Even low intensity exercise bouts of at least 15 min can improve feelings of energy (FOE) and reduce systolic blood pressure. However, little is known about the psychological outcomes of briefer exercise bouts, particularly for modes of exercise that are more intense than level walking, and readily available to many working adults. This study assessed the effects of a 4-min bout of stair walking on FOE and feelings of fatigue (FOF).

Methods

Thirty-six young adult participants were randomized to either stair walking or seated control groups. All participants walked on level-ground from a laboratory to a nearby stairwell (~90 s) and were seated for 4 min before beginning their experimental condition. Stair-walking participants walked up and down one flight of 16 stairs at their own pace for 4 min, while control participants remained seated during that time. Participants walked back to the laboratory for post-condition assessments. Measures of blood pressure, heart rate, rated perceived exertion (RPE), and the intensity of feelings of mental energy, mental fatigue, physical energy, and physical fatigue were assessed pre-and post-condition. Separate one-way ANOVAs were conducted on change scores for all variables.

Results

The stair climbing group experienced significant increases in heart rate [F(1,34) = 13.167, p < 0.001] and RPE [F(1,34) = 93.844, p < 0.001] that were not observed in the seated control group. Four minutes of self-paced stair climbing resulted in small changes and non-significant differences within and between groups in blood pressure as well as FOE and FOF.

Conclusion

Although a 4-min self-paced exercise bout can convey short-term physiological health benefits, a 4-min bout of self-paced indoor stair walking in a stairwell was insufficient to lower blood pressure or change subjective FOE and fatigue in a sample that exhibited better than typical FOE and FOF at the pre-test.
Psychometric properties and measurement invariance across gender of the Italian version of the tempest self-regulation questionnaire for eating adapted for young adults
Authors: Diotaiuti Pierluigi , Girelli Laura , Mancone Stefania , Valente Giuseppe , Bellizzi Fernando , Misiti Francesco , Cavicchiolo Elisa
Published: August 2022

The prevalence of overweight and obesity in young adults has increased dramatically in recent decades. The unhealthy eating habits that develop at this time can often lead to negative health consequences in the future. It is therefore important to learn about self-regulation and self-control strategies and help young adults to have healthy eating behaviours. This study aims to present an Italian version of the Tempest Self-Regulation Questionnaire for Eating (TESQ-E) adapted for young adults. The instrument assesses self-regulation and self-control strategies to counteract the desire and temptation to eat unhealthy food and to choose healthy foods. A total of 645 students (271 males and 374 females with an average age of 24.82 and SD = 4.34) took part in the study. The results of the confirmatory factor analysis supported the six first-order factors model concerning specific self-regulation strategies and a higher-order structure of the TESQ-E [χ2 (152) = 336.480, p < 0.001; CFI = 0.95; RMSEA = 0.04; SRMR = 0.04]: three correlated second-order factors (addressing the temptation directly, addressing the psychological meaning of temptation, and addressing the goal directly) and one-third-order factor (self-regulatory competence). The results also confirmed the strong measurement invariance of the TESQ-E across gender. To have reliable comparisons across males and females, the latent mean differences tests were performed on the six specific self-regulation strategies. The analysis showed that females appear to prefer strategies that directly address the goal by expressing explicit intentions or plans to eat in a healthy way. Convergence validity was tested through correlations with Eating-Self-Efficacy Brief Scale (ESEBS), Emotional Eating Scale (EES), Scale of Attitudes towards Healthy Eating (SAHE), and Body Mass Index (BMI). In conclusion, the TESQ-E appears to be a psychometrically sound questionnaire that can be effectively used with young adults to measure self-regulation strategies in eating in order to plan personalised interventions for the prevention and control of the metabolic syndrome, and to reduce a wide range of diet-related diseases.
Lower serum levels of IL-1β and IL-6 cytokines in adolescents with anorexia nervosa and their association with gut microbiota in a longitudinal study
Authors: Specht Hannah E. , Mannig Nina , Belheouane Meriem , Andreani Nadia Andrea , Tenbrock Klaus , Biemann Ronald , Borucki Katrin , Dahmen Brigitte , Dempfle Astrid , Baines John F. , Herpertz-Dahlmann Beate , Seitz Jochen
Published: August 2022

Introduction

Anorexia nervosa (AN) is an often chronic and debilitating psychiatric disease whose etiology is not completely understood. Recently, a potential role of inflammation has emerged in other psychiatric diseases, such as depression, PTSD and schizophrenia. The first results in adults with AN seemed to confirm a low-grade proinflammatory state until recent studies presented more differential findings. Studying adolescents with a shorter illness duration and fewer confounding factors might help elucidate the role of inflammation in the underlying pathophysiology of AN; however, the few available studies in adolescents remain ambiguous, and no longitudinal data are available in this age range.

Methods

We examined the proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, IL-15, and the cytokine-receptor IL-6 Receptor alpha (IL-6 Rα) in the serum of twenty-two hospitalized female adolescent patients with AN longitudinally at admission and discharge and compared their results to nineteen healthy controls (HC). We also collected clinical data and stool samples that were analyzed with 16S rRNA amplicon sequencing to explore potential influencing factors of cytokine changes.

Results

TNF-α serum levels were significantly elevated in patients with AN at admission, while IL-1β and IL-6 levels were lower at admission and discharge than in HC. After treatment, we also found significantly elevated levels of IL-6 Rα compared to HC, while IL-15 did not show significant changes. Exploratory analyses revealed positive associations of cytokine and genus-level changes between admission and discharge for IL-1β (Bacteroides) and IL-15 (Romboutsia), and negative associations for IL-15 (Anaerostipes) and TNF-α (uncultured Lachnospiraceae).

Conclusion

We confirmed a previous finding of elevated levels of TNF-α also in adolescents with AN; however, the reduced IL-1β and IL-6 levels differed from the mostly increased levels found in adults. A mixed pro- and anti-inflammatory state appears to be present in adolescents, potentially due to their shorter illness duration. The gut microbiota, with its regulatory function on cytokine production, might play a role in mediating these inflammatory processes in AN and could offer targets for new therapeutic approaches.
Investigation of the genetic effect of 56 tobacco-smoking susceptibility genes on DNA methylation and RNA expression in human brain
Authors: Yang Zhongli , Yang Jiekun , Mao Ying , Li Ming D.
Published: August 2022

Although various susceptibility genes have been revealed to influence tobacco smoking, the underlying regulatory mechanisms between genetic variants and smoking are poorly understood. In this study, we investigated cis-expression quantitative trait loci (cis-eQTLs) and methylation quantitative trait loci (mQTLs) for 56 candidate smoking-linked genes using the BrainCloud cohort samples. An eQTL was revealed to significantly affect EGLN2 expression in the European sample and two mQTLs were respectively detected in CpG sites in NRXN1 and CYP2A7. Interestingly, we found for the first time that the minor allele of the single nucleotide polymorphism (SNP) rs3745277 located in CYP2A7P1 (downstream of CYP2B6) significantly decreased methylation at the CpG site for CYP2A7 (cg25427638; P = 5.31 × 10–7), reduced expression of CYP2B6 (P = 0.03), and lowered the percentage of smokers (8.8% vs. 42.3%; Odds Ratio (OR) = 0.14, 95% Confidence Interval (CI): 0.02–0.62; P = 4.47 × 10–3) in a dominant way for the same cohort sample. Taken together, our findings resulted from analyzing genetic variation, DNA methylation, mRNA expression, and smoking status together using the same participants revealed a regulatory mechanism linking mQTLs to the smoking phenotype. Moreover, we demonstrated the presence of different regulatory effects of low-frequency and common variants on mRNA expression and DNA methylation.
Exploring the adult sexual wellbeing and behavior during the COVID-19 pandemic. A systematic review and meta-analysis
Authors: Mourikis Iraklis , Kokka Ioulia , Koumantarou-Malisiova Elli , Kontoangelos Konstantinos , Konstantakopoulos George , Papageorgiou Charalabos
Published: August 2022

Implemented social distancing measures may have forestalled the spread of COVID-19, yet they suppressed the natural human need for contact. The aim of this systematic review was to explore the impact of the COVID-19 pandemic on adult sexual wellbeing and sexual behavior. An extensive search in Pubmed, Scopus, and PsycInfo databases based on PRISMA guidelines was conducted. After applying specific eligibility criteria, screening resulted in 38 studies. Results were drawn from 31,911 subjects and outlined the negative effect of the pandemic in sexual frequency, function, satisfaction, and the behavioral changes regarding masturbation and internet-based practices. Meta-analyses of the drawn data on 1,343 female, and 1,372 male subjects quantified the degree of sexual function change during the COVID-19 pandemic vs. prior the pandemic. A random effects model revealed the significant negative impact of the pandemic on female sexual function (SMD: 0.76, 95% CI:0.74 to 1.59), while no significant change was found for the males (SMD: 0.25, 95% Cl: −0.03 to 0.52). Significant heterogeneity was identified across included studies (p < 0.00001, I2 = 97%, I2 = 90% for females and males, respectively). As part of the global health, sexual wellbeing should be on the focus of clinicians and researchers.
Gastrointestinal complaints in patients with anorexia nervosa in the timecourse of inpatient treatment
Authors: Riedlinger Caroline , Mazurak Nazar , Schäffeler Norbert , Stengel Andreas , Giel Katrin Elisabeth , Zipfel Stephan , Enck Paul , Mack Isabelle
Published: August 2022

Background

In patients with anorexia nervosa (AN), gastrointestinal (GI) symptoms are common and usually improve during or after nutritional rehabilitation. It is unclear when exactly GI symptoms change in the timecourse of treatment and to which extent. In this study, we analyzed the timecourse of GI symptoms and their relation to disease-specific, demographic, anthropometric, and psychological factors in inpatients with AN.

Methods

In weekly intervals, the Gastrointestinal Symptom Rating Scale (GSRS) was completed, and body weight was measured over a mean of 9.5 weeks in inpatients with AN. A total of four self-report questionnaires assessing psychological factors were completed before and after inpatient treatment. Data from 38 inpatients with AN were analyzed using mixed linear models.

Results

Abdominal pain and constipation improved significantly in the timecourse with 0.085 (p = 0.002) and 0.101 (p = 0.004) points per week on the GSRS and were predicted to normalize after 13 (p = 0.002) and 17 (p = 0.004) weeks, respectively. Total GI symptoms tended to normalize after 25 weeks (p = 0.079). Indigestion (borborygmus, abdominal distension, eructation, flatulence) was the most severely pathological symptom at admission and did not improve significantly (p = 0.197). Diarrhea and reflux were, on average, not pathological at admission and remained stable during treatment. In addition to treatment time, the strongest predictors were ED pathology at admission for the development of abdominal pain, constipation, reflux, and total GI symptoms; stress for the development of constipation and total GI symptoms; and depression for constipation.

Conclusions

Informing patients with AN about the course of GI symptoms and their improvement during weight rehabilitation may help support compliance during treatment.