bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Hebbian-Type Stimulation to Rescue Arm Function After Stroke: Study Protocol for a Randomized Clinical Trial
Authors: Xu Rong , Zhu Guang-Yue , Zhu Jun , Wang Yong , Xing Xiang-Xin , Chen Lin-Yu , Li Jie , Shen Fu-Qiang , Chen Jian-Bing , Hua Xu-Yun , Xu Dong-Sheng
Published: February 2022

Background

Upper-extremity hemiplegia after stroke remains a significant clinical problem. The supplementary motor area (SMA) is vital to the motor recovery outcomes of chronic stroke patients. Therefore, rebuilding the descending motor tract from the SMA to the paralyzed limb is a potential approach to restoring arm motor function after stroke. Paired associative stimulation (PAS), which is based on Hebbian theory, is a potential method for reconstructing the connections in the impaired motor neural circuits. The study described in this protocol aims to assess the effects of cortico–peripheral Hebbian-type stimulation (HTS), involving PAS, for neural circuit reconstruction to rescue the paralyzed arm after stroke.

Methods

The study is a 4-month double-blind randomized sham-controlled clinical trial. We will recruit 90 post-stroke individuals with mild to moderate upper limb paralysis. Based on a 1:1 ratio, the participants will be randomly assigned to the HTS and sham groups. Each participant will undergo 5-week HTS or sham stimulation. Assessments will be conducted at baseline, immediately after the 5-week treatment, and at a 3-month follow-up. The primary outcome will be the Wolf Motor Function Test (WMFT). The secondary outcomes will be Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Functional Independence Measure (FIM), and functional near-infrared spectroscopy (fNIRS) parameters. The adverse events will be recorded throughout the study.

Discussion

Upper-limb paralysis in stroke patients is due to neural circuit disruption, so the reconstruction of effective motor circuits is a promising treatment approach. Based on its anatomical structure and function, the SMA is thought to compensate for motor dysfunction after focal brain injury at the cortical level. Our well-designed randomized controlled trial will allow us to analyze the clinical efficacy of this novel Hebbian theory-based neuromodulation strategy regarding promoting the connection between the cortex and peripheral limb. The results may have significance for the development and implementation of effective neurorehabilitation treatments.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [ChiCTR2000039949].
Recurrent Excitatory Feedback From Mossy Cells Enhances Sparsity and Pattern Separation in the Dentate Gyrus via Indirect Feedback Inhibition
Authors: Galloni Alessandro R. , Samadzelkava Aya , Hiremath Kiran , Oumnov Reuben , Milstein Aaron D.
Published: February 2022

It is generally appreciated that storing memories of specific events in the mammalian brain, and associating features of the environment with behavioral outcomes requires fine-tuning of the strengths of connections between neurons through synaptic plasticity. It is less understood whether the organization of neuronal circuits comprised of multiple distinct neuronal cell types provides an architectural prior that facilitates learning and memory by generating unique patterns of neuronal activity in response to different stimuli in the environment, even before plasticity and learning occur. Here we simulated a neuronal network responding to sensory stimuli, and systematically determined the effects of specific neuronal cell types and connections on three key metrics of neuronal sensory representations: sparsity, selectivity, and discriminability. We found that when the total amount of input varied considerably across stimuli, standard feedforward and feedback inhibitory circuit motifs failed to discriminate all stimuli without sacrificing sparsity or selectivity. Interestingly, networks that included dedicated excitatory feedback interneurons based on the mossy cells of the hippocampal dentate gyrus exhibited improved pattern separation, a result that depended on the indirect recruitment of feedback inhibition. These results elucidate the roles of cellular diversity and neural circuit architecture on generating neuronal representations with properties advantageous for memory storage and recall.
The Effects of Safinamide Adjunct Therapy on Depression and Apathy in Patients With Parkinson's Disease: Post-hoc Analysis of a Japanese Phase 2/3 Study
Authors: Hattori Nobutaka , Kogo Yuki , Koebis Michinori , Ishida Takayuki , Suzuki Ippei , Tsuboi Yoshio , Nomoto Masahiro
Published: February 2022

Background and Purpose

Neuropsychiatric symptoms in Parkinson's disease (PD) have been shown to significantly affect quality of life (QOL). We investigated the impact of safinamide on depression and apathy when administered as an adjunct to levodopa in Japanese patients with PD.

Methods

This was a post-hoc analysis of data from a phase 2/3 clinical study of safinamide in Japanese patients with PD experiencing wearing-off (JapicCTI-153056; https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-153056). Patients received placebo, safinamide 50 mg, or safinamide 100 mg as an adjunct therapy. The endpoints for this analysis were changes from baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I item 3 (depression) and item 4 (apathy) scores and the Parkinson's Disease Questionnaire (PDQ-39) “emotional well-being” domain score. Subgroup analyses investigated the relationship between neuropsychologic symptoms and improvements in motor fluctuation and assessed which patient populations might be expected to obtain neuropsychologic benefit from safinamide.

Results

Compared with placebo, safinamide (both doses) significantly improved UPDRS Part I item 3 scores in the overall analysis population, and the 100-mg dose improved UPDRS Part I item 4 scores in the population with apathy at baseline. Changes in the PDQ-39 “emotional well-being” score showed numerical, but not significant, dose-related improvements. Notable reductions in depression were associated with a change in daily ON-time ≥1 h, pain during OFF-time at baseline, and female sex.

Conclusions

The results from this post-hoc analysis of the Japanese phase 2/3 study suggest that safinamide could bring benefits to patients with PD who have mild depression, pain during the OFF phase. In addition, safinamide might provide particular benefits for patients with PD who have mild apathy and female.
Hormonal Therapy for Infantile Spasms: A Systematic Review and Meta-Analysis
Authors: Guang Shiqi , Mao Leilei , Zhong Linxiu , Liu Fangyun , Pan Zou , Yin Fei , Peng Jing
Published: February 2022

Objective

The limitations of adrenocorticotrophic hormone (ACTH) treatment for infantile spasms (ISs), such as high costs, limited availability, and adverse effects (AEs), make it necessary to explore whether corticosteroids are optimal alternatives. Many other compelling treatments have gone through trials due to the suboptimal effectiveness of hormonal therapy. A systematic review and meta-analysis were performed to evaluate the effectiveness and safety of hormonal therapy for patients with ISs.

Methods

EMBASE, Ovid MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and online registers were searched through April 2021 for randomized controlled trials (RCTs).

Results

A total of 19 RCTs (N = 1,279) were included. There was no significant difference in the effectiveness of oral corticosteroids and ACTH in electro-clinical response (risk ratio [RR] = 0.85, 95% CI 0.41–1.76). Low-dose ACTH had similar effectiveness in electro-clinical response compared to usual-dose group (RR = 0.94, 95% CI 0.60–1.47) but conferred a lower risk of AEs (RR = 1.71, 95% CI 1.08–2.71). ACTH was more beneficial in controlling spasms than vigabatrin (VGB) (RR = 1.31, 95% CI 1.05–1.64) for patients without tuberous sclerosis complex (TSC). All RCTs were connected through network meta-analysis, and we found that ketogenic diet (KD), zonisamide, methylprednisolone, or combined treatment of hormonal therapy with topiramate (TPM) or pyridoxine was not different in electro-clinical response compared to usual-dose ACTH.

Conclusion

Our analysis showed that oral corticosteroids could be optional alternatives when ACTH is not applicable, and ACTH is more beneficial for patients without TSC. Moreover, low-dose ACTH is recommended due to comparative effectiveness but lower risk of AEs. However, due to the high heterogeneity of included patients and treatment protocols, these results must be interpreted with caution. RCTs with multicentric involvement and larger sample size are needed for solid evaluation of other alternative treatments.
A Comparison of Local Endolymphatic Sac Decompression, Endolymphatic Mastoid Shunt, and Wide Endolymphatic Sac Decompression in the Treatment of Intractable Meniere's Disease: A Short-Term Follow-Up Investigation
Authors: Zheng Guiliang , Liu Yupeng , He Jingchun , Li Shuna , Zhang Qing , Duan Maoli , Yang Jun , Jin Yulian
Published: February 2022

Background

Meniere's disease (MD) is an inner ear disorder, characterized by recurrent attacks of vertigo, low-frequency sensorineural hearing loss, tinnitus, and aural fullness. Endolymphatic sac surgery is an effective treatment to control vertigo attacks but without causing a hearing loss for intractable MD. However, the methods and effects of endolymphatic sac surgery have been controversial for many years, and the relationship between the vertigo control rates of different endolymphatic sac surgery methods is not well-documented.

Objectives

This study compared the vertigo control rate, hearing outcome, and quality of life (QOL) among different endolymphatic sac surgery, such as local endolymphatic sac decompression (LESD), endolymphatic sac mastoid shunt (ESMS), and wide endolymphatic sac decompression (WESD).

Materials and Methods

We retrospectively analyzed the patients who underwent endolymphatic sac surgery from January 2008 to June 2019. The control rate of vertigo and QOL scores were compared after 2 years of follow-up. The QOL was scored with validation of the MD patient-oriented symptom-severity index (MDPOSI). The pure tone thresholds of all patients at pre- and postoperation were also compared.

Results

In total, 83 MD patients with complete follow-up data were included in the study, i.e., 20 patients with LESD, 28 patients with ESMS, and 35 patients with WESD. Results showed a better vertigo control with WESD than the other groups (70% with LESD, 71.4% with ESMS, and 88.6% with WESD). The QOL was improved after surgery in all groups in which the difference was statistically significant (QOL, preoperative vs. postoperative, 38.2 vs. 10.1 with LESD, 37.8 vs. 9.6 with ESMS, and 37.6 vs. 8.3 with WESD), respectively. After endolymphatic sac surgery, the hearing was well-preserved in the three groups [pure tone averages (PTAs), dB, preoperative vs. postoperative, 41.0 ± 19.3 vs. 40.8 ± 17.9 with LESD, 39.7 ± 16.4 vs. 40.8 ± 18.2 with ESMS, and 38.5 ± 18.7 vs. 36.6 ± 19.5 with WESD].

Conclusion

Wide endolymphatic sac decompression has a higher vertigo control rate, better improvement of QOL, and relatively higher hearing stability or improvement rate after surgery in patients with MD compared with LESD and ESMS.
Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment
Authors: Wang Xiaoyu , Hu Jiangqi , Jiang Qingsong
Published: February 2022

Background

There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VaD). Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood.

Objective

To conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms.

Methods

“Tooth Loss,” “Edentulous,” “Tooth Extraction and Memory Loss,” “Cognition Impairment,” and “Dementia” were used as keywords to search PubMed, Embase, SCI, ScienceDirect, and OpenGrey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE'S risk of bias tool.

Results

The putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: (1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; (2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and (3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system.

Conclusion

The loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.
The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder
Authors: Zhou Cui-Hong , Xue Fen , Shi Qing-Qing , Xue Shan-Shan , Zhang Tian , Ma Xin-Xu , Yu Li-Sheng , Liu Chuang , Wang Hua-Ning , Peng Zheng-Wu
Published: February 2022

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.
Clinical Outcomes of Transcranial and Endoscopic Endonasal Surgery for Craniopharyngiomas: A Single-Institution Experience
Authors: Nie Chuansheng , Ye Youfan , Wu Jingnan , Zhao Hongyang , Jiang Xiaobing , Wang Haijun
Published: February 2022

Objective

Craniopharyngioma has always been a challenge for the neurosurgeon, and there is no consensus on optimal treatment. The objective of this study was to compare surgical outcomes and complications between transcranial surgery (TCS) and endoscopic endonasal surgery (EES) of craniopharyngiomas.

Methods

A retrospective review of patients who underwent craniopharyngioma resection at Wuhan Union Hospital between January 2010 and December 2019 was performed. A total of 273 patients were enrolled in this retrospective study. All patients were analyzed with surgical effects, endocrinologic outcomes, complications, and follow-up results.

Results

A total of 185 patients underwent TCS and 88 underwent EES. There were no significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between the two groups. The mean follow-up was 30.5 months (range 8–51 months). The EES group had a greater gross total resection (GTR) rate (89.8% EES vs. 77.3% TCS, p < 0.05) and lower rate of hypopituitarism (53.4% EES vs. 68.1% TCS, p < 0.05) and diabetes insipidus (DI) (51.1% EES vs. 72.4% TCS, p < 0.05). More postoperative cerebrospinal fluid (CSF) leaks occurred in the EES group (4.5% EES vs. 0% TCS, p < 0.05). More patients in the EES group with preoperative visual deficits experienced improvement after surgery (74.5% EES vs. 56.3% TCS, p < 0.05). There were statistical differences in the recurrence rates (12.5% EES vs. 23.8% TCS, p < 0.05) between the 2 groups.

Conclusion

These data support the view that EES is a safe and effective minimally invasive surgery compared to TCS. Compared to TCS, EES has fewer surgical complications and a lower recurrence rate.
Impact of BCR-ABL1 Transcript Type on Outcome in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors: A Pairwise and Bayesian Network Meta-Analysis
Authors: Chen Kangkang , Ruan Yingying , Tian Kewei , Xiong Peisheng , Xia Nan , Li Jin , Huang Wen , Cao Feiyan , Chen Qifeng
Published: February 2022

Purpose

To evaluate the impact of BCR-ABL1 transcript type on outcome in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).

Methods

PubMed, Embase and Cochrane library were systematically searched for relevant studies. Outcomes assessed were: major molecular response (MMR) at 6, 12, 18 and 60 months, deep molecular response (DMR) at 6, 12, 18 and 60 months, event-free survival (EFS), progression-free survival (PFS), overall survival (OS) and treatment-free remission (TFR). Odds ratios (ORs) and hazard ratios (HRs) were estimated and pooled using a random effect model.

Results

A total of 16 retrospective cohort studies involving 5,411 patients were included in this study. Compared with e13a2 transcripts, there was a statistically significant advantage for patients with e14a2 (alone or with co-expressed e13a2) in terms of MMR and DMR at 6, 12 and 18 months. This benefit was sustained up to 5 years for patients with e14a2 transcripts (OR 1.60, 1.23-2.07 and 2.21, 1.71-2.87, respectively), but not for patients with both transcripts. The expression of e14a2 also improved EFS (HR 0.71, 0.53-0.94) and OS (HR 0.76, 0.57-1.00) throughout treatment period. Importantly, having e14a2 transcripts were associated with a higher rate of TFR (OR 2.94, 1.70-5.08) in CML patients attempting TKI discontinuation. Bayesian network meta-analysis showed that e14a2 had the highest probability to be the most favorable transcript type for all outcomes, followed by both and e13a2.

Conclusions

The expression of e14a2 had a positive impact on MMR, DMR, EFS, OS and TFR. We suggest that in the future, the e14a2 transcript can be added to the list of prognostic factors to guide clinical decisions in treating CML.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/#myprospero], identifier PROSPERO (CRD42021288440).
A CT-Based Radiomics Nomogram to Predict Complete Ablation of Pulmonary Malignancy: A Multicenter Study
Authors: Zhang Guozheng , Yang Hong , Zhu Xisong , Luo Jun , Zheng Jiaping , Xu Yining , Zheng Yifeng , Wei Yuguo , Mei Zubing , Shao Guoliang
Published: February 2022

Objective

Thermal ablation is a minimally invasive procedure for the treatment of pulmonary malignancy, but the intraoperative measure of complete ablation of the tumor is mainly based on the subjective judgment of clinicians without quantitative criteria. This study aimed to develop and validate an intraoperative computed tomography (CT)-based radiomic nomogram to predict complete ablation of pulmonary malignancy.

Methods

This study enrolled 104 individual lesions from 92 patients with primary or metastatic pulmonary malignancies, which were randomly divided into training cohort (n=74) and verification cohort (n=30). Radiomics features were extracted from the original CT images when the study clinicians determined the completion of the ablation surgery. Minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were adopted for the dimensionality reduction of high-dimensional data and feature selection. The prediction model was developed based on the radiomics signature combined with the independent clinical predictors by multiple logistic regression analysis. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive performance of the model. Decision curve analysis (DCA) was applied to estimate the clinical usefulness and net benefit of the nomogram for decision making.

Results

Thirteen CT features were selected to construct radiomics prediction model, which exhibits good predictive performance for determination of complete ablation of pulmonary malignancy. The AUCs of a CT-based radiomics nomogram that integrated the radiomics signature and the clinical predictors were 0.88 (95% CI 0.80-0.96) in the training cohort and 0.87 (95% CI: 0.71–1.00) in the validation cohort, respectively. The radiomics nomogram was well calibrated in both the training and validation cohorts, and it was highly consistent with complete tumor ablation. DCA indicated that the nomogram was clinically useful.

Conclusion

A CT-based radiomics nomogram has good predictive value for determination of complete ablation of pulmonary malignancy intraoperatively, which can assist in decision-making.
Effect of Urate-Lowering Therapy on the Progression of Kidney Function in Patients With Asymptomatic Hyperuricemia: A Systematic Review and Meta-Analysis
Authors: Zhang Lin , An Kang , Mou Xingyu , Zhang Mei , Su Qiaoli , Li Shuangqing
Published: February 2022

Background: Hyperuricemia is involved in the risk of chronic kidney disease (CKD). However, whether urate-lowering therapy (ULT) can influence the progression of kidney function in patients with asymptomatic hyperuricemia is still controversial. We conducted a systematic review and meta-analysis to evaluate the effect of ULT on the progression of kidney function in asymptomatic hyperuricemia patients.

Methods: The MEDLINE, EMBASE and Cochrane databases were searched without language, national or ethnic restrictions for randomized controlled trials published prior to November 30, 2020, that compared ULT with controlled therapy in patients with asymptomatic hyperuricemia.

Results: Eleven studies were included for qualitative synthesis. ULT did not ameliorate eGFR slopes (WMD 0.36 ml/min/1.73 m2 per year, 95% CI: −0.31, 1.04), or lead to reductions in kidney events (RR 1.26; 95% CI: 0.80, 2.00) or all-cause mortality (RR 1.00; 95% CI: 0.65, 1.55), although ULT resulted in a decrease in serum uric acid levels (WMD −2.73 mg/dl; 95% CI: −3.18, −2.28) and lowered the incidence of gout episodes (0.9 vs 2.7%, RR 0.38; 95% CI: 0.17, 0.86).

Conclusion: In patients with asymptomatic hyperuricemia, ULT did not decay the progression of kidney function. Long-term and larger sample studies are needed to verify the results.

Systematic Review Registration: [www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42020204482].
Inflammation and Cardiovascular Disease Associated With Hemodialysis for End-Stage Renal Disease
Authors: Wang Yinghui , Gao Lu
Published: February 2022

Chronic kidney disease (CKD) and cardiac insufficiency often co-exist, particularly in uremic patients on hemodialysis (HD). The occurrence of abnormal renal function in patients with cardiac insufficiency is often indicative of a poor prognosis. It has long been established that in patients with cardiac insufficiency, poorer renal function tends to indicate poorer cardiac mechanics, including left atrial reserve strain, left ventricular longitudinal strain, and right ventricular free wall strain (Unger et al., Eur J Heart Fail, 2016, 18(1), 103–12). Similarly, patients with chronic kidney disease, particularly uremic patients on HD, often have cardiovascular complications in addition to abnormal endothelial function with volume overload, persistent inflammatory states, calcium overload, and imbalances in redox responses. Cardiac insufficiency due to uremia is therefore mainly due to multifaceted non-specific pathological changes rather than pure renal insufficiency. Several studies have shown that the risk of adverse cardiovascular events is greatly increased and persistent in all patients treated with HD, especially in those who have just started HD treatment. Inflammation, as an important intersection between CKD and cardiovascular disease, is involved in the development of cardiovascular complications in patients with CKD and is indicative of prognosis (Chan et al., Eur Heart J, 2021, 42(13), 1244–1253). Therefore, only by understanding the mechanisms underlying the sequential development of inflammation in CKD patients and breaking the vicious circle between inflammation-mediated renal and cardiac insufficiency is it possible to improve the prognosis of patients with end-stage renal disease (ESRD). This review highlights the mechanisms of inflammation and the oxidative stress that co-exists with inflammation in uremic patients on dialysis, as well as the mechanisms of cardiovascular complications in the inflammatory state, and provides clinical recommendations for the anti-inflammatory treatment of cardiovascular complications in such patients.
First-In-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, a Small-Molecule Factor XIa Inhibitor in Healthy Subjects
Authors: Chen Rui , Guan Xiaoduo , Hu Pei , Dong Yanli , Zhu Yi , Zhang Tengfei , Zou Jianjun , Zhang Shuyang
Published: February 2022

Background: Targeting factor XI (FXI) is a promising therapeutic strategy for the treatment and prevention of thrombosis without increasing the risk of bleeding. Here, we assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SHR2285, a novel FXIa inhibitor, in healthy subjects.

Methods: In this randomized, double-blinded, placebo-controlled, dose-ascending single-dosing trial (NCT03769831), eligible volunteer subjects receive either SHR2285 or placebo in a 3:1 ratio. Subjects assigned to the SHR2285 group received a single oral dose of SHR2285 at 50 mg, which was subsequently escalated to 100 mg, 200 mg, and 400 mg. Safety, pharmacokinetics, and pharmacodynamics parameters were assessed. All subjects were followed for 6 days.

Results: SHR2285 was well tolerated. All adverse events were grade 1, and there was no evidence of bleeding events. The PK results revealed a rapid onset of action of SHR2285 (median time to maximum plasma concentration [Tmax] in different dose groups ranged 3.0–4.0 h) and the mean half-life ranged from 7.6 to 15.8 h. The metabolite SHR164471 had a slightly longer Tmax than the parent SHR2285, reaching a peak at a median of 6.0–7.0 h, and its mean half-life were 10.1–14.7 h in different dose groups. The sums of the area under the concentration–time curve from zero to time infinity of SHR2285 and SHR164471 in the 200 and 400 mg groups were similar, indicating the sum pharmacological activity of SHR2285 and SHR164471 showed a saturation trend between 200 and 400 mg. PD analysis showed that the inhibition of FXI activity was synchronized with prolonged activated partial thromboplastin time after SHR2285 administration, but the serum prothrombin time and international normalized ratio levels were not affected by SHR2285.

Conclusion: SHR2285 demonstrated favorable safety, PK, and PD profiles in the dose range of 50 mg–400 mg. This first-in-human study supports the further development of SHR2285 for indications requiring anticoagulation.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03769831, identifier [NCT03769831].
Individual Variation Exists Within the Psychological Response to Hypoxic Bed Rest: A Retrospective Analysis
Authors: Tobita Kunihito , Mekjavic Igor B. , McDonnell Adam C.
Published: February 2022

Individual variation is of interest to Space Agency’s, which cannot be explored with astronauts due to anonymity. We retrospectively analysed data collected throughout three projects (LunHab: 10-day male, PlanHab: 21-day male, and FemHab: 10-day female) to elucidate the potentially masked individual variation in the psychological responses to bed rest. The Profile of Mood State (POMS) and Positive and Negative Affect Schedule (PANAS) – instruments used to asses psychological state – and Lake Louise Mountain Sickness (LLMS) scores were collected prior to, following and throughout three interventions: 1: normoxic bed rest 2: hypoxic bed rest and 3: hypoxic ambulatory confinement. Total Mood Disturbance (TMD) was calculated from the POMS results, positive affect (PA), and negative affect (NA) from PANAS. The three instruments were included in a latent class mixed model. TMD, NA, and LLMS were included in a four-class model, with each class representing a specific type of response (Class 1: descending, Class 2: flat, Class 3: somewhat flat, Class 4: ascending). Responses for PA were assigned to only two classes (Classes 1 and 2). 54.55% or 24 participants were included in Class 2 (TMD, NA, and LLMS), where the responses did not change and neither hypoxia or activity level had a significant effect on emotional state. The remaining participants were allotted to Class 1, 3, or 4, where hypoxia was a significant covariate, while activity (bed rest) was significant only for class 3. For PA, 84.09% or 37 participants were assigned to class 2 indicating a significant effect of hypoxia on the participants responses with no effect of physical activity. Class 1 participants (n = 7) were not affected by hypoxia, however, physical activity improved their PA. Participants undergoing confinement, hypoxia and bed rest do not exhibit a uniform emotional response and may be categorised into 2–4 distinct classes. These results indicate significant individual emotional responses, that may be masked and underreported by traditional statistical approaches like means ± SD. The emotional state of our participants is a complex construct likely influenced by past experiences and different coping mechanisms which allowed some to adapt to the experimental environment more readily.
Mutation of Serine protease 1 Induces Male Sterility in Bombyx mori
Authors: Xu Xia , Wang Yaohui , Chen Jine , Du Xin , Yao Lusong , Xu Jun , Zhang Yong , Huang Yongping , Wang Yongqiang
Published: February 2022

Serine proteases are important in reproduction, embryonic development, cell differentiation, apoptosis, and immunity. The genes encoding some serine proteases are essential for male fertility in both humans and rodents and are functionally conserved among metazoan. For example, the Serine protease 1 (Ser1) gene determines male reproductive success in the model lepidopteran insect Bombyx mori. In this study, we explored the function of BmSer1 through transgenic CRISPR/Cas9 technology-mediated mutations in silkworm. We found that the mutation of BmSer1 gene resulted in male sterility but had no effect on female fertility. Male mutants produce normal eupyrene sperm bundles, but the sperm bundles do not dissociate into single sperm. Male sterility caused by the BmSer1 gene mutation was inherited stably through female individuals. Therefore, the serine protease encoded by BmSer1 is essential for male reproductive success in lepidopterans and is a potential target gene for biological reproductive regulation.
Assessment of Ultra-Early Administration of Sacubitril Valsartan to Improve Cardiac Remodeling in Patients With Acute Myocardial Infarction Following Primary PCI: Rational and Design of a Prospective, Multicenter, Randomized Controlled Trial
Authors: Li Zhengwei , Fu Guosheng
Published: February 2022

Background

Despite coronary re-vascularization, the common complications of acute myocardial infarction (AMI), cardiac remodeling, and heart failure (HF), is increasing globally. Sacubitril valsartan (SV), an angiotensin receptor-neprilysin inhibitor (ARNI), has been previously demonstrated to improve HF. We further hypothesize that ultra-early SV treatment is also effective in preventing cardiac remodeling for patients with AMI following primary percutaneous coronary intervention (PCI).

Methods

The Assessment of ultra-early administration of Sacubitril Valsartan to improve cardiac remodeling in patients with Acute Myocardial Infarction following primary PCI (ASV-AMI) trial is a prospective, multicenter, randomized controlled trial in China planning to enroll at least 1,942 eligible patients from 10 centers. After successful primary PCI of culprit artery within 24 h, AMI patients are randomized to 2 h group or 3–7 days group with SV treatment. The major endpoints are echocardiographic measurement, cardiothoracic ratio, and N-Terminal pro-B-Type Natriuretic Peptide (NT pro-BNP) at baseline, 1, 3, 6, and 12 months. The secondary endpoints included MACE (cardiac arrest, cardiogenic death, myocardial infarction, and target vessel re-vascularization), in-/out-patient HF, EuroQol Five Dimensions Questionnaire (EQ-5D), and Kansas City Cardiomyopathy Questionnaire (KCCQ).

Discussion

The ASV-AMI trial is the first clinical trial of ultra-early administration of SV in the treatment of post-PCI AMI, adding more clinical evidence. Early application of SV to prevent cardiac remodeling in AMI patient is a major focus of this trial.

Clinical Trial Registration

Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn; ChiCTR2100051979). Registered on 11 October 2021.
Developmental Analysis of Compound Leaf Development in Arachis hypogaea
Authors: Sun Ruiqi , Peng Zhenying , Li Shuangshuang , Mei Hongyao , Xu Yiteng , Yang Wenying , Lu Zhichao , Wang Hongfeng , Zhang Jing , Zhou Chuanen
Published: February 2022

Leaves are the primary photosynthetic structures, while photosynthesis is the direct motivation of crop yield formation. As a legume plant, peanut (Arachis hypogaea) is one of the most economically essential crops as well as an important source of edible oil and protein. The leaves of A. hypogaea are in the tetrafoliate form, which is different from the trifoliate leaf pattern of Medicago truncatula, a model legume species. In A. hypogaea, an even-pinnate leaf with a pair of proximal and distal leaflets was developed; however, only a single terminal leaflet and a pair of lateral leaflets were formed in the odd-pinnate leaf in M. truncatula. In this study, the development of compound leaf in A. hypogaea was investigated. Transcriptomic profiles revealed that the common and unique differentially expressed genes were identified in a proximal leaflet and a distal leaflet, which provided a research route to understand the leaf development in A. hypogaea. Then, a naturally occurring mutant line with leaf developmental defects in A. hypogaea was obtained, which displayed a pentafoliate form with an extra terminal leaflet. The characterization of the mutant indicated that cytokinin and class I KNOTTED-LIKE HOMEOBOX were involved in the control of compound leaf pattern in A. hypogaea. These results expand our knowledge and provide insights into the molecular mechanism underlying the formation of different compound leaf patterns among species.
Facile Labeling of Sieve Element Phloem-Protein Bodies Using the Reciprocal Oligosaccharide Probe OGA488
Authors: Azizpor Pakeeza , Sullivan Lucy , Lim Aedric , Groover Andrew
Published: February 2022

Sieve elements of many angiosperms contain structural phloem proteins (P-proteins) that can interact to create large P-protein bodies. P-protein bodies can occlude sieve plates upon injury but the range of functional and physiological roles of P-proteins remains uncertain, in part because of challenges in labeling and visualization methods. Here, we show that a reciprocal oligosaccharide probe, OGA488, can be used in rapid and sensitive labeling of P-protein bodies in Arabidopsis, poplar, snap bean and cucumber in histological sections. OGA488 labeling of knockouts of the two Arabidopsis P-protein-encoding genes, AtSEOR1 and AtSEOR2, indicated that labeling is specific to AtSEOR2. That protein bodies were labeled and visible in Atseor1 knockouts indicates that heterodimerization of AtSEOR1 and AtSEOR2 may not be necessary for P-protein body formation. Double labeling with a previously characterized stain for P-proteins, sulphorhodamine 101, confirmed P-protein labeling and also higher specificity of OGA488 for P-proteins. OGA488 is thus robust and easily used to label P-proteins in histological sections of multiple angiosperm species.
Comparative Analysis the Complete Chloroplast Genomes of Nine Musa Species: Genomic Features, Comparative Analysis, and Phylogenetic Implications
Authors: Song Weicai , Ji Chuxuan , Chen Zimeng , Cai Haohong , Wu Xiaomeng , Shi Chao , Wang Shuo
Published: February 2022

Musa (family Musaceae) is monocotyledonous plants in order Zingiberales, which grows in tropical and subtropical regions. It is one of the most important tropical fruit trees in the world. Herein, we used next-generation sequencing technology to assemble and perform in-depth analysis of the chloroplast genome of nine new Musa plants for the first time, including genome structure, GC content, repeat structure, codon usage, nucleotide diversity and etc. The entire length of the Musa chloroplast genome ranged from 167,975 to 172,653 bp, including 113 distinct genes comprising 79 protein-coding genes, 30 transfer RNA (tRNA) genes and four ribosomal RNA (rRNA) genes. In comparative analysis, we found that the contraction and expansion of the inverted repeat (IR) regions resulted in the doubling of the rps19 gene. The several non-coding sites (psbI–atpA, atpH–atpI, rpoB–petN, psbM–psbD, ndhf–rpl32, and ndhG–ndhI) and three genes (ycf1, ycf2, and accD) showed significant variation, indicating that they have the potential of molecular markers. Phylogenetic analysis based on the complete chloroplast genome and coding sequences of 77 protein-coding genes confirmed that Musa can be mainly divided into two groups. These genomic sequences provide molecular foundation for the development and utilization of Musa plants resources. This result may contribute to the understanding of the evolution pattern, phylogenetic relationships as well as classification of Musa plants.
CRISPR/Cas9-Targeted Mutagenesis of BnaFAE1 Genes Confers Low-Erucic Acid in Brassica napus
Authors: Liu Yunhao , Du Zhuolin , Lin Shengli , Li Haoming , Lu Shaoping , Guo Liang , Tang Shan
Published: February 2022

Rapeseed (Brassica napus) is an important oilseed crop widely planted in the world, providing substantial edible oil and other nutrients for mankind. The composition of fatty acids affects the edible and processing quality of vegetable oils, among which erucic acid (EA) is potentially to cause health problems. Therefore, low erucic acid (LEA) has always been a breeding trait of B. napus. Fatty acid elongase 1 (FAE1) plays a decisive role in the synthesis of EA. There are two functional homologous copies of FAE1 on the A08 and C03 chromosomes in B. napus. In this study, we used CRISPR/Cas9 technology to create targeted mutations on these two homologous copies of BnaFAE1 in three B. napus germplasms with high EA (>30%) and high oil (>50%). Our results show that the EA content was significantly reduced by more than 10 percentage points in the mutant of BnaC03.FAE1 (c03), while the double mutation of BnaA08.FAE1 and BnaC03.FAE1 (a08c03) resulted in nearly zero EA in three BnaFAE1-edited germplasms, and the oleic acid content was increased in different degrees. In addition, knockout of BnaA08.FAE1 or/and BnaC03.FAE1 mildly decreased seed oil content, but had no significant effect on other agronomic traits. In general, we successfully created low EA germplasms of B. napus, which provides a feasible way for future low EA breeding.
Interactive Design Psychology and Artificial Intelligence-Based Innovative Exploration of Anglo-American Traumatic Narrative Literature
Authors: Hou Xia , Omar Noritah , Wang Jue
Published: February 2022

The advent of the intelligence age has injected new elements into the development of literature. The synergic modification of Anglo-American (AAL) traumatic narrative (TN) literature by artificial intelligence (AI) technology and interactive design (ID) psychology will produce new possibilities in literary creation. First, by studying natural language processing (NLP) technology, this study proposes a modification language model (LM) based on the double-layered recurrent neural network (RNN) algorithm and constructs an intelligent language modification system based on the improved LM model. The results show that the performance of the proposed model is excellent; only about 30% of the respondents like AAL literature; the lack of common cultural background, appreciation difficulties, and language barriers have become the main reasons for the decline of reading willingness of AAL literature. Finally, AI technology and ID psychology are used to modify a famous TN work respectively and synergically, and the modified work is appreciated by respondents to collect their comments. The results corroborate that 62% of the respondents like original articles, but their likability scores have decreased for individually modified work by AI or ID psychology. In comparison, under the synergic modification efforts of AI and ID psychology, the popularity of the modified work has increased slightly, with 65% of the respondents showing a likability to read. Therefore, it is concluded that literary modification by single ID psychology or AI technology will reduce the reading threshold by trading off the literary value of the original work. The core of literary creation depends on human intelligence, and AI might still not be able to generate high-standard literary works independently because human minds and thoughts cannot be controlled and predicted by machines. The research results provide new ideas and improvement directions for the field of AI-assisted writing.
Physical Exercise of Primary and Middle School Students From the Perspective of Educational Psychology and Parents’ Entrepreneurship Education
Authors: Song Chao , Ge Sha , Xue Jingjing , Yao Wanxiang
Published: February 2022

The study aims to help primary and secondary school students develop a good habit of physical exercise by exploring the current situation of physical exercise of primary and secondary school students and analyzing the factors affecting their physical exercise. Then, intervention strategies are figured out for different groups of students and help them develop a good habit of physical exercise. From the perspective of educational psychology and parents’ entrepreneurship education, the research on the physical exercise of primary and secondary school students is conducted by a questionnaire survey, mathematical statistics and literature review. A total of 280 students from five schools in Tianjin are selected as the research subjects, and the current situation of students’ physical exercise in these five schools is investigated. The results show that 40.5% of boys and 39.4% of girls can take physical exercise more than three times a week; 48.9% of the students do physical exercise for more than 30 mins each time; the students who usually take regular exercise at school account for 82.1%. The physical exercise that students always do is running, badminton and table tennis, which rank the top three among the sports they do. The students usually play basketball, volleyball, and football, and they rarely do the sports like swimming, Wushu, and aerobics. This result is closely related to the characteristics and places of primary and middle school students. The survey shows that the physical exercise awareness of most primary and secondary school students is correct; most students can participate in physical exercise, but few students can do it regularly; parents’ support, parents’ habits of doing exercise, and family’s spending on physical exercise have a significant impact on developing students’ habits of doing physical exercise. Based on the above, it is concluded that the primary and secondary stage is very important for students. Physical education teachers should follow the principle of teaching different students with different methods, enrich teaching materials, and improve teaching quality. The study provides a reference for the reform of PE to guide primary and middle school students to participate in sports activities, improving students’ physical quality.
A Communication-Ecological Account of Groups
Authors: Kurilla Robin
Published: February 2022

This article presents a novel conception of groups and social processes within and among groups from a communication-ecological perspective that integrates approaches as different as Garfinkel’s ethnomethodology, Heideggerian praxeology, and Luhmann’s systems theory into an innovative social-theoretical framework. A group is understood as a social entity capable of collective action that is an object to itself and insofar possesses an identity. The elementary operations of groups consist in social processes with communicative, pre-communicative, and non-communicative episodes. Groups operate in a number of environments that are conceived of as both correlates of their own processes and providing groups with the raw materials for the fabrication of their constituents. These environments include but are not limited to spatial, discursive, emotional, institutional, semiotic-medial, psychic-personal, technical, and groupal environments. The article paves the way to combine studies on intergroup and intragroup communication in one comprehensive theoretical framework situated on such an abstract level that it can be concretized in view of utterly different cultural contexts and the emic perspectives of actors therein. Accordingly, the framework provides researchers with the conceptual devices to balance the comparability of different lifeworlds with the faithfulness to actors’ inside views. The methodological implications laid out in this article prioritize qualitative, especially ethnographic methods as a starting point for research on group communication.
Toward a Unified Framework for Positive Psychology Interventions: Evidence-Based Processes of Change in Coaching, Prevention, and Training
Authors: Ciarrochi Joseph , Hayes Steven C. , Oades Lindsay G. , Hofmann Stefan G.
Published: February 2022

Since 2000, research within positive psychology has exploded, as reflected in dozens of meta-analyses of different interventions and targeted processes, including strength spotting, positive affect, meaning in life, mindfulness, gratitude, hope, and passion. Frequently, researchers treat positive psychology processes of change as distinct from each other and unrelated to processes in clinical psychology. This paper presents a comprehensive framework for positive psychology processes that crosses theoretical orientation, links coherently to clinical psychology and its more dominantly “negative” processes, and supports practitioners in their efforts to personalize positive psychological interventions. We argue that a multi-dimensional and multi-level extended evolutionary approach can organize effective processes of change in psychosocial interventions, by focusing interventions on context-appropriate variation, selection, and retention of processes, arranged in terms of key biopsychosocial dimensions across psychological, biophysiological, and sociocultural levels of analysis. We review widely studied positive psychology constructs and programs and show how this evolutionary approach can readily accommodate them and provide a common language and framework for improving human and community flourishing. We conclude that Interventions should start with the person, not the protocol.