bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplex array analysis of serum cytokines offers minimal predictive value for cognitive function in the subacute phase after stroke
Authors: Zhang Yuling , Song Haixin , Wang Jun , Xi Xiao , Cefalo Philip , Wood Lisa J. , Luo Xun , Wang Qing Mei
Published: October 2022

Objective

The effects of inflammation on post-stroke cognitive function are still unclear. This study investigated the correlation between the Th17-related cytokines in peripheral blood and post-stroke cognitive function after ischemic stroke in the subacute phase.

Design

A retrospective cohort study.

Setting

Academic acute inpatient rehabilitation facility.

Participants

One hundred and fourteen patients with first ischemic stroke were categorized as the poor cognitive recovery group (n = 58) or good cognitive recovery group (n = 56) based on their cognitive MRFS efficiency.

Interventions

All subjects received routine physical, occupational, and speech-language pathology therapy.

Main outcome measures

Serum cytokines/chemokine (IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-17E, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GM-CSF, IFN-γ, MIP-3 α, TNF-α, and TNF-β) levels were measured in duplicate using Human Th17 magnetic bead panel and multiplex array analysis (Luminex-200 system). The primary functional outcome was a gain in functional independence measure (FIM) cognitive subscore at discharge. The secondary outcome measures were FIM total score at discharge, length of stay in the hospital, and discharge destination. Cognitive Montebello Rehabilitation Factor Score (MRFS) and cognitive MRFS efficiency were calculated. Demographic and clinical characteristics were obtained from the medical record.

Results

The good cognitive recovery group had an interesting trend of higher IL-13 than the poor cognitive recovery group (good cognitive recovery group 257.82 ± 268.76 vs. poor cognitive recovery group 191.67 ± 201.82, p = 0.049, unit: pg/ml). However, Pearson's correlation analysis showed no significant correlation between cytokine levels and gain of cognition, cognitive MRFS, or cognitive MRFS efficiency. Receiver operating characteristic (ROC) analysis of cytokines also suggested a low accuracy of prediction as a predictor for post-stroke cognitive recovery improvement.

Conclusion

Our preliminary findings suggested that the level of serum cytokines had minimal predictive value for the recovery of cognitive function during the subacute inpatient rehabilitation after stroke.
Assessment of EEG-based functional connectivity in response to haptic delay
Authors: Alsuradi Haneen , Park Wanjoo , Eid Mohamad
Published: October 2022

Haptic technologies enable users to physically interact with remote or virtual environments by applying force, vibration, or motion via haptic interfaces. However, the delivery of timely haptic feedback remains a challenge due to the stringent computation and communication requirements associated with haptic data transfer. Haptic delay disrupts the realism of the user experience and interferes with the quality of interaction. Research efforts have been devoted to studying the neural correlates of delayed sensory stimulation to better understand and thus mitigate the impact of delay. However, little is known about the functional neural networks that process haptic delay. This paper investigates the underlying neural networks associated with processing haptic delay in passive and active haptic interactions. Nineteen participants completed a visuo-haptic task using a computer screen and a haptic device while electroencephalography (EEG) data were being recorded. A combined approach based on phase locking value (PLV) functional connectivity and graph theory was used. To assay the effects of haptic delay on functional connectivity, we evaluate a global connectivity property through the small-worldness index and a local connectivity property through the nodal strength index. Results suggest that the brain exhibits significantly different network characteristics when a haptic delay is introduced. Haptic delay caused an increased manifestation of the small-worldness index in the delta and theta bands as well as an increased nodal strength index in the middle central region. Inter-regional connectivity analysis showed that the middle central region was significantly connected to the parietal and occipital regions as a result of haptic delay. These results are expected to indicate the detection of conflicting visuo-haptic information at the middle central region and their respective resolution and integration at the parietal and occipital regions.
The role of regulatory necrosis in traumatic brain injury
Authors: Nie Zhenyu , Tan Liming , Niu Jie , Wang Bing
Published: October 2022

Traumatic brain injury (TBI) is a major cause of death and disability in the population worldwide, of which key injury mechanism involving the death of nerve cells. Many recent studies have shown that regulatory necrosis is involved in the pathological process of TBI which includes necroptosis, pyroptosis, ferroptosis, parthanatos, and Cyclophilin D (CypD) mediated necrosis. Therefore, targeting the signaling pathways involved in regulatory necrosis may be an effective strategy to reduce the secondary injury after TBI. Meanwhile, drugs or genes are used as interference factors in various types of regulatory necrosis, so as to explore the potential treatment methods for the secondary injury after TBI. This review summarizes the current progress on regulatory necrosis in TBI.
A crosstalk between circular RNA, microRNA, and messenger RNA in the development of various brain cognitive disorders
Authors: He Liang , Zhang Furong , Zhu Yuling , Lu Meilin
Published: October 2022

Patients with Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), stroke, and postoperative neurocognitive disorder (POND) are commonly faced with neurocognitive disorders with limited therapeutic options. Some non-coding ribonucleic acids (ncRNAs) are involved in the development of various brain cognitive disorders. Circular RNAs (circRNAs), a typical group of ncRNAs, can function as competitive endogenous RNAs (ceRNAs) to dysregulate shared microRNAs (miRNAs) at post-transcription level, inhibiting regulation of miRNAs on their targeted messenger RNAs (mRNAs). circRNAs are abundant in central nervous system (CNS) diseases and cause brain disorders, but the exact roles of circRNAs are unclear. The crosstalk between circRNA, miRNA, and mRNA plays an important role in the pathogenesis of these neurocognitive dysfunction diseases and abnormal conditions including AD, PD, stroke, TBI, and POND. In this review, we summarized the participation of circRNA in neuroglial damage and inflammation. Finally, we aimed to highlight the regulatory mechanisms of circRNA–miRNA–mRNA networks in the development of various brain cognitive disorders and provide new insights into the therapeutics of these diseases.
Olive oil consumption and risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies
Authors: Xia Meng , Zhong Yi , Peng Yongquan , Qian Cheng
Published: October 2022

Background

Epidemiological studies have shown the preventive effects of olive oil consumption against cardiovascular events and all-cause deaths, but the results remain inconsistent. Herein, we performed a meta-analysis to elucidate this association.

Materials and methods

A systematical literature search was conducted in online databases (PubMed and Scopus) through July 31, 2022. Prospective cohort studies providing the risk of total cardiovascular disease (CVD) or all-cause mortality for olive oil consumption were included. Relative risks (RRs) and 95% confidence intervals (CIs) were aggregated using random-effect model.

Results

This meta-analysis included 13 studies comprising a total of 13 prospective cohorts. Compared with lower consumption, higher consumption of olive oil conferred a significantly reduced risk in CVD (RR: 0.85, 95% CI: 0.77–0.93,p< 0.001) and all-cause mortality (RR: 0.83, 95% CI: 0.77–0.90,p< 0.001). This beneficial effect was not modified by the potential confounders such as study country, sample size, follow-up duration, gender, and type of olive oil consumed. In dose-response meta-analysis, the summary RR of per 5-g/days increase in olive oil intake was 0.96 (95% CI: 0.93–0.99,p= 0.005) for CVD and 0.96 (95% CI: 0.95–0.96,p< 0.001) for all-cause mortality. Non-linear associations of olive oil intake with CVD and all-cause mortality were also identified (bothpfor non-linearity < 0.001), with little additional or no risk reduction observed beyond the consumption of approximately 20 g/days.

Conclusion

Olive oil consumption is inversely related to the risk of CVD and all-cause mortality. Such benefits seem to be obtained with an intake of olive oil up to 20 g/days, which deserves further exploration in future studies.
A Mendelian randomization study of the effect of tea intake on breast cancer
Authors: Deng Yuqing , Ge Wenxin , Xu Huili , Zhang Jiaming
Published: October 2022

Background

The relationship between tea consumption and the risk of breast cancer is inconsistent in previous observational studies and is still in dispute. We intended to detect the causal association between tea consumption and breast cancer risk using two-sample Mendelian randomization (MR) analysis.

Materials and methods

The summary statistics of tea consumption was obtained from the UK Biobank Consortium with 349,376 individuals and breast cancer information was obtained from the Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 non-cases). Sensitivity analyses of evaluating the influence of outliers and pleiotropy effects were performed by a variety of MR methods under different model assumptions.

Results

After potentially excluding pleiotropic single nucleotide polymorphisms (SNPs) using the MR Pleiotropy RESidual Sum and Outlier method, the odds ratio (OR) for per extra daily cup of tea intake for overall, estrogen receptor (ER)-positive, and ER-negative breast cancer risk was 1.029 [95% confidence interval (CI) = 0.983–1.077, P = 0.2086], 1.050 (95% CI = 0.994–1.109, P = 0.078), and 1.081 (95% CI = 0.990–1.103, P = 0.6513), respectively. The results were consistent with a sensitivity analysis that excluded SNPs associated with other phenotypes, manifesting that the findings were convincing and robust. Moreover, in the multivariable MR analysis, the null associations for breast cancer risk remained after adjusting for smoking and alcohol consumption separately or together.

Conclusion

Our MR results based on genetic data did not support a causal relationship between tea consumption and breast cancer risk.
Different treatment regimens in breast cancer visceral crisis: A retrospective cohort study
Authors: Yang Ruohan , Lu Guanyu , Lv Zheng , Jia Lin , Cui Jiuwei
Published: October 2022

Objective

Breast cancer visceral crisis (VC) is caused by excessive tumor burden leading to severe organ dysfunction with poor prognosis. Traditional chemotherapy reduces the quality of life of patients without significantly improving survival. The aim of this study was to investigate the clinical characteristics of patients with VC and the prognosis by using different treatment options.

Methods

According to the 5th European School of Oncology (ESO)–European Society for Medical Oncology (ESMO) international consensus guidelines for advanced breast cancer guidelines (ABC 5), patients who were treated in the First Hospital of Jilin University from 2018 to 2022 and diagnosed with breast cancer VC were retrospectively analyzed. The analysis focused on the characteristics of the patients, the treatment regimens, and prognosis.

Results

A total of 133 patients were included in this study. As for metastasis breast cancer subtype, 92 (69.18%) were hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER-2) negative, 20 (15.04%) had HER-2 overexpression, and 21 (15.78%) were triple negative. All patients had an mOS of 11.2 months (range, 1.1–107.8 months). In different types of VC, the median overall survival (mOS) of bone marrow metastasis (BMM) was 18.0 months (range, 2.0–107.8 months), that of diffuse liver metastasis (DLM) was 8.1 months (range, 1.3–30.2 months), and that of meningeal metastasis (MM) was 9.0 months (range, 1.2–53.8 months). In 92 HR+, Her-2− patients using different treatment regimens, mOS was 6.2 months (range, 1.2–29.8 months) in the chemotherapy group while it was 24.3 months (range, 3.1–107.8 months) in the endocrine therapy (ET) group. Multivariate Cox regression analysis suggested that Eastern Cooperative Oncology Group (ECOG) scores and type of VC were associated with survival.

Conclusion

Prognosis varied in different types of VC. Patients with BMM had the best prognosis, and DLM had the worst. As treatment options continue to progress, our retrospective study showed a significant prolongation of overall survival (OS) in patients with VC compared to previous studies.
Case Report: A rare case of young adult progressive familial intrahepatic cholestasis-type 3 with a novel heterozygous pathogenic variant of ABCB4
Authors: Zhu Hao , Wang Shengnan , Li Li , Geng Wenqian , Wan Xiaoqiang , Hua Rui , Wang Dong , Gao Pujun
Published: October 2022

Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive disorder with poor prognosis. It is caused by pathogenic variants of the ATP binding cassette subfamily B member 4 (ABCB4) gene and usually progresses from chronic cholestasis with or without jaundice to portal hypertension and end-stage liver disease within the first to second decade of life. Few reported PFIC-3 patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Herein, we report a 16-year-old male who was admitted to our hospital due to acute episodes of jaundice and intense pruritus, subsequently progressed to end-stage liver disease. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, drug or liver tumors. Ursodeoxycholic acid and dexamethasone did not relieve his symptoms and he underwent liver transplantation successfully. Targeted next-generation sequencing identified that the patient was a compound heterozygote for two missense mutations (c.959C > T/c.1429C > A) in the ABCB4 gene. The mutation c.1429C > A (p.Q477K) is a novel heterozygous mutation. We constructed a three-dimensional model of this novel pathogenic variant using the SWISS MODEL program and found that the patient's ABCB4 protein is an ATP hydrolysis deficient mutant. The postoperative pathological diagnosis showed intrahepatic cholestasis with progression to cirrhosis. Negative liver tissue immunohistochemistry of MDR3 was found in the explanted liver. The patient was diagnosed with PFIC-3, and his symptoms improved dramatically with liver transplantation. In conclusion, for young patients with acute cholestasis, pruritus, jaundice, growth retardation, and enlargement of the liver and spleen, the possibility of inherited metabolic liver diseases should be considered, detailed medical and family history should be collected, and metabolic screening tests as well as gene tests are necessary for correct diagnosis. Increasing the coverage of PFIC3 is meaningful and thus can improve the current understanding of this disease.
Sarcopenia in children with chronic liver disease: Prevalence and impact on liver transplant outcomes
Authors: Veraldi Silvio , Pietrobattista Andrea , Soglia Giovanna , Monti Lidia , Alterio Tommaso , Mosca Antonella , Liccardo Daniela , Basso Maria Sole , Della Corte Claudia , Russo Luca , Candusso Manila , Chiusolo Fabrizio , Tortora Francesca , Spada Marco , Maggiore Giuseppe
Published: October 2022

Sarcopenia is a clinical condition characterized by a reduction in muscle mass, which typically affects adult patients; however, it has recently been recognized in pediatric literature. Few studies in children with chronic liver disease (CLD) undergoing liver transplantation (LT) have investigated the role of sarcopenia, with controversial results. The aim of our study was to assess the prevalence and impact of sarcopenia among children with CLD who are candidates for LT. We conducted a retrospective, single-center study at Bambino Gesù Children's Hospital (Rome, Italy) from July 2016 to July 2021, evaluating all children (0–16 years old) with CLD listed for LT with an abdomen computed tomography imaging available before LT. The total psoas muscle surface area (t-PMSA) was defined as the sum of left and right psoas muscle surface area measured at L4–L5 on axial images. The t-PMSA z-score was calculated according to reference data, and sarcopenia was defined as a t-PMSA z-score of ≤−2 (1–16 years) or a psoas muscle index [PMI; PMI = t-PMSA/(100 × BSA)] of <50th percentile of the population examined (<1 year). Clinical, laboratory, and LT outcome data were collected from all the patients with CLD. 27 out 48 (56%) of the patients aged 1–16 years were sarcopenic. No differences were noted in anthropometrics, nutritional support, liver function tests, model for ESLD (MELD), or pediatric ESLD (PELD) scores between patients with and without sarcopenia. The former showed a higher prevalence of respiratory complications (66.7% vs. 42.1%) and need for inotropes (40.7% vs. 10.8%) after LT. Among patients aged 0–1 years (n: 36), those with reduced muscle mass (50%) had a longer hospitalization time (44 vs. 24 days) and higher incidences of multi-organ failure syndrome (38.9% vs. 0%) and intensive care unit-related infections (61.1% vs. 27.8%) compared to those with greater muscle mass. t-PMSA and PMI were statistically significant predictors of LT outcomes. Sarcopenia is a reliable index of frailty in children with CLD, as its presence is associated with the risk of a more challenging LT. Future studies will have to investigate the functional aspects of sarcopenia and conceive preventive measures of muscle wasting in CLD patients.
Diagnosis and management of fecal incontinence in children and adolescents
Authors: Shen Zhe-Ying , Zhang Jin , Bai Yu-Zuo , Zhang Shu-Cheng
Published: October 2022

Fecal incontinence (FI) is a commonly occurring disease of high concern. It is characterized by voluntary and involuntary defecation in children and adolescents. It is not only a physical disease but also a psychological and behavioral disorder. FI poses a serious burden on individuals and their families and therefore has become a social problem. Unfortunately, the management of FI among children is still a challenge because the etiology varies widely. Constipation has been found to be the most common cause, while sphincter dysfunction and neurogenic abnormalities may also play a role. Currently, no consensus guidelines exist, and the criteria for selecting optional methods remain unclear. It is therefore necessary to improve the efficacy of diagnosis and management strategies of FI in children. This review focused on the classification and etiology, discussed the diagnosis and management methods of FI in children and adolescents, and aimed to guide future studies.
Ultra-slim flexible bronchoscopy-guided topical hemostatic drugs administration for the management of life-threatening refractory pulmonary hemorrhage in a preterm infant: Case report
Authors: Lin Yan , Zhao Hong-fang , Xue Meng-hua , Xie Bing-jie , Zeng Ling-chao , Jiang Xun
Published: October 2022

Pulmonary hemorrhage (PH) is a rare acute catastrophic event with high mortality among neonates, especially preterm infants. Primary treatments included pulmonary surfactant, high-frequency oscillatory ventilation, epinephrine, coagulopathy management, and intermittent positive pressure ventilation. However, there are still challenges in diagnosing and treating refractory or focal pulmonary hemorrhages. Ultra-slim bronchoscopy has been widely used in the field of critically ill children and is increasingly being done in neonates with critical respiratory disease in recent years. In this study, we report a case with refractory pulmonary hemorrhage in premature infants, which was finally diagnosed as localized hemorrhage in the upper left lobe and cured by ultra-slim bronchoscopy-guided topical hemostatic drug administration. Bronchoscopy is an optional, safe, and practicable technique for early diagnosis and direct injection therapy of neonatal PH in managing life-threatening PH.
A novel heat treatment protocol for human milk
Authors: Manzardo Olimpia A. , Toll Luisa J. , Müller Katharina , Nickel Erika , Jonas Daniel , Baumgartner Jana , Wenzel Folker , Klotz Daniel
Published: October 2022

Human milk (HM) is the recommended nutrition for premature infants, but it may require processing to ensure microbial safety. The current standard is Holder pasteurisation (HoP), i.e. heating milk at 62.5 ± 0.5°C for 30 min, which eliminates bacteria but destroys heat labile bioactive HM components. We aimed to test an alternative thermal method, high-temperature short-time (HTST) pasteurisation using a modified Holder pasteurisation platform as this method has shown to preserve proteins in experimental HM flow pasteurisers. We analysed the ability of this batch process to eliminate bacterial species and to retain alkaline phosphatase, secretory immunoglobulin A and lactoferrin in HM. HTST at 81°C/5 s was as effective as HoP in bacterial count reduction while the retention of bioactive components was only improved at 62°C/5 s as compared to 72°C/5 s and HoP. HTST is a promising alternative to HoP but an optimal temperature-time combination needs to be determined for each technical platform separately.
Frankincense oil-loaded nanoemulsion formulation of paclitaxel and erucin: A synergistic combination for ameliorating drug resistance in breast cancer: In vitro and in vivo study
Authors: Kaur Harneetpal , Kaur Kirandeep , Singh Atamjit , Bedi Neena , Singh Balbir , Alturki Mansour S. , Aldawsari Mohammed F. , Almalki Atiah H. , Haque Shafiul , Lee Hae-Jeung , Yadav Dharmendra K. , Arora Saroj
Published: October 2022

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of Eruca sativa) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.
Minocycline intra-bacterial pharmacokinetic hysteresis as a basis for pharmacologic memory and a backbone for once-a-week pan-tuberculosis therapy
Authors: Deshpande Devyani , Srivastava Shashikant , Pasipanodya Jotam Garaimunashe , Gumbo Tawanda
Published: October 2022

Background: There is need for shorter duration regimens for the treatment of tuberculosis, that can treat patients regardless of multidrug resistance status (pan-tuberculosis).

Methods: We combined minocycline with tedizolid, moxifloxacin, and rifampin, in the hollow fiber system model of tuberculosis and mimicked each drugs’ intrapulmonary pharmacokinetics for 28 days. Minocycline-tedizolid was administered either as a once-a-week or a daily regimen. In order to explore a possible explanation for effectiveness of the once-a-week regimen, we measured systemic and intra-bacterial minocycline pharmacokinetics. Standard daily therapy (rifampin, isoniazid, pyrazinamide) was the comparator. We then calculated γf or kill slopes for each regimen and ranked the regimens by time-to-extinction predicted in patients.

Results: The steepest γf and shortest time-to-extinction of entire bacterial population was with daily minocycline-rifampin combination. There was no difference in γf between the minocycline-tedizolid once-a-week versus the daily therapy (p = 0.85). Standard therapy was predicted to cure 88% of patients, while minocycline-rifampin would cure 98% of patients. Minocycline concentrations fell below minimum inhibitory concentration after 2 days of once-weekly dosing schedule. The shape of minocycline intra-bacterial concentration-time curve differed from the extracellular pharmacokinetic system and lagged by several days, consistent with system hysteresis. Hysteresis explained the persistent microbial killing after hollow fiber system model of tuberculosis concentrations dropped below the minimum inhibitory concentration.

Conclusion: Minocycline could form a backbone of a shorter duration once-a-week pan-tuberculosis regimen. We propose a new concept of post-antibiotic microbial killing, distinct from post-antibiotic effect. We propose system hysteresis as the basis for the novel concept of pharmacologic memory, which allows intermittent dosing.
Iron metabolism-related genes reveal predictive value of acute coronary syndrome
Authors: Xu Cong , Li Wanyang , Li Tangzhiming , Yuan Jie , Pang Xinli , Liu Tao , Liang Benhui , Cheng Lixin , Sun Xin , Dong Shaohong
Published: October 2022

Iron deficiency has detrimental effects in patients with acute coronary syndrome (ACS), which is a common nutritional disorder and inflammation-related disease affects up to one-third people worldwide. However, the specific role of iron metabolism in ACS progression is opaque. In this study, we construct an iron metabolism-related genes (IMRGs) based molecular signature of ACS and to identify novel iron metabolism gene markers for early stage of ACS. The IMRGs were mainly collected from Molecular Signatures Database (mSigDB) and two relevant studies. Two blood transcriptome datasets GSE61144 and GSE60993 were used for constructing the prediction model of ACS. After differential analysis, 22 IMRGs were differentially expressed and defined as DEIGs in the training set. Then, the 22 DEIGs were trained by the Elastic Net to build the prediction model. Five genes, PADI4, HLA-DQA1, LCN2, CD7, and VNN1, were determined using multiple Elastic Net calculations and retained to obtain the optimal performance. Finally, the generated model iron metabolism-related gene signature (imSig) was assessed by the validation set GSE60993 using a series of evaluation measurements. Compared with other machine learning methods, the performance of imSig using Elastic Net was superior in the validation set. Elastic Net consistently scores the higher than Lasso and Logistic regression in the validation set in terms of ROC, PRC, Sensitivity, and Specificity. The prediction model based on iron metabolism-related genes may assist in ACS early diagnosis.
Cost-effectiveness of edaravone dexborneol versus edaravone for the treatment of acute ischemic stroke in China: Based on the TASTE study
Authors: Shi Fenghao , He Zixuan , Wang Lin , Su Hang , Han Sheng
Published: October 2022

Background and purpose:The TASTE trial indicated that patients with acute ischemic stroke (AIS) using edaravone dexborneol have a significantly higher proportion of 90-day good functional outcomes (mRS 0–1) than those using edaravone. This study compared the cost-effectiveness of the aforementioned interventions in treating AIS in the Chinese setting, aiming to inform treatment decisions in clinical practice.

Methods:A model combining a decision tree and a Markov model was developed to assess the cost-effectiveness of edaravone dexborneolversusedaravone for AIS over a 30-year time horizon from the Chinese healthcare system’s perspective. Both efficacy and safety data were extracted from the TASTE study. Local costs and utilities were derived from publications and open-access databases; both cost and effectiveness were discounted at a rate of 5% per year. Sensitivity analyses were conducted to ensure robustness and identify the main drivers of the result.

Results:Compared with edaravone, edaravone dexborneol for AIS was found to be cost-effective in the first year and highly cost-effective as the study time horizons extended. In the long term (30 years), edaravone dexborneol yielded a lifetime gain of 0.25 (0.07–0.45) quality-adjusted life years (QALYs) at an additional cost of CNY 2201.07 (-3,445.24–6,637.23), yielding an ICER of CNY 8823.41 per QALY gained under the willingness-to-pay (WTP) of 1.5 times per capita GDP (121,464 CNY). The result is robust in both deterministic and probabilistic sensitivity analysis (PSA) methods, with the advantage of the edaravone dexborneol strategy increasing over time. Specifically, the probability of edaravone dexborneol dominant dexborneol is 76.30%, 98.90%, and 99.50% over 1-, 5-, and 30-year time horizons.

Conclusion:Both short- and long-term economic analyses suggest that edaravone dexborneol is highly likely to be a cost-effective alternative to treat AIS compared with edaravone in China.
Quantum attacks on two-round even-mansour
Authors: Cai BinBin , Gao Fei , Leander Gregor
Published: October 2022

Even-Mansour is one of the most important constructions in symmetric cryptography, both from a theoretical and practical perspective. With the rapid development of quantum computing, the security of Even-Mansour construction in quantum setting needs to be considered. For one round Even-Mansour construction, it is well settled by classical and quantum attacks. While for the iterated scheme, the situation is much more complex. In this paper, we study the next case in line in detail and depth: quantum attacks against two rounds case. We first make an asymptotic comparison with existing classical and quantum attacks. Then we give concrete resource estimation for the proposed quantum attacks on round reduced LED cipher and AES2. The resource estimation allows to deduce the most efficient attacks based on the trade-off of the number of qubits and Toffoli depth.
Present status and challenges of underwater acoustic target recognition technology: A review
Authors: Zhufeng Lei , Xiaofang Lei , Na Wang , Qingyang Zhang
Published: October 2022

Future naval warfare has placed high demands on underwater targets’ target detection, target recognition, and opposition resistance, among other things. However, the ocean’s complex underwater acoustic environment and the evolving “stealth” technology of underwater targets pose significant challenges to target detection systems, which has become a hot topic in the field of underwater acoustic signal processing in various countries. This study introduced the mechanism of underwater target radiation noise generation, analyzed the research progress and development of underwater target radiation noise recognition by applying machine learning from three perspectives: signal acquisition, feature extraction, and signal recognition at home and abroad, and elaborated on the challenges of underwater target-radiated noise recognition technology against the backdrop of rapid computing science development, and finally, an integrated signal processing method based on the fusion of traditional feature extraction methods and deep learning is proposed for underwater target radiation noise recognition, which improves the low recognition rate of traditional methods and also circumvents the problem of deep learning requiring high computational cost, and is an important direction for future hydroacoustic signal processing.
Predicting beam transmission using 2-dimensional phase space projections of hadron accelerators
Authors: Tran Anthony , Hao Yue , Mustapha Brahim , Martinez Marin Jose L.
Published: October 2022

We present a method to compress the 2D transverse phase space projections from a hadron accelerator and use that information to predict the beam transmission. This method assumes that obtaining at least three projections of the 4D transverse phase space is possible and that an accurate simulation model is available for the beamline. Using a simulated model, we show that—a computer can train a convolutional autoencoder to reduce phase-space information which can later be used to predict the beam transmission. Finally, we argue that although using projections from a realistic nonlinear distribution produces less accurate results, the method still generalizes well.
A methodology for discriminating phase and amplitude effects on synchronization in tokamak pacing experiments
Authors: Craciunescu T. , Murari A. , Peluso E. , Lang P.T. , Harrer G. , Spolladore L. , Gelfusa M. , JET Contributors  , the ASDEX Upgrade Team
Published: October 2022

The control of macroscopic instabilities, such as Edge Localised Modes (ELMs) and sawteeth, is becoming an essential ingredient in the optimisation of scenarios in preparation for the next generation of tokamaks and the demonstrative reactor. Various pacing experiments have been indeed successfully carried out in many devices but various details of their interactions with the plasma remain poorly understood, in particular the assessment of the relative contribution of driver phase and amplitude to frequency synchronization. In this paper, a data analysis methodology for investigating the details of pacing experiments is proposed. The approach is based on the wavelet decomposition of the signals and the following implementation of information theoretic indicators, to determine the basic form of the interactions. The main analysis tool deployed is the conditional mutual information, equivalent to the informational transfer entropy, which can detect actual causal influences and not only statistical correlations between signals. The most flexible type of ELM pacing, the vertical kicks, permits to clearly confirm the potential of the analysis tools developed. In the dedicated experiments to optimise the ELMs pacing with pellets and sawteeth synchronization with ICRH modulation, the main effect is due to the influence of the amplitude of the external perturbations. Some evidence of phase synchronization has been found, in both JET and AUG, which indicates the direction of possible future optimization of the interventions. Indeed, adjusting the phase of the pacing schemes would free density and ICRH power to give more leeway to other feedback loops, an important aspect, particularly for the integrated control of the next generation of devices. The long-term objective of this line of research is therefore twofold. On the one hand, it is expected to contribute to better physical interpretation of the pacing experiments and possibly also of their target instabilities. From an operational perspective, hopefully these insights will help in the development of reactor relevant scenarios, as exemplified by examples of ELM a pacing with pellets carried out in preparation for the DT campaign on JET.
Characteristics of environmental RNAi in potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Psylloidea: Triozidae)
Authors: Mondal Mosharrof , Carver Megan , Brown Judith K.
Published: October 2022

RNA interference (RNAi) has potential to become a major tool for integrated management of insect pests of agricultural crops based on sequence-specificity and low doses of rapidly biodegradable dsRNA. Deploying ‘environmental RNAi’ for control of insect vectors of plant pathogens is of increasing interest for combatting emerging plant diseases. Hemipteran insect vectors, including psyllids, are vascular feeders, making their development difficult to control specifically by targeting with pesticidal chemistries. Psyllids transmit “Candidatus Liberibacter solanacearum” the causal organism of potato zebra chip and tomato vein greening diseases, transmitted, respectively, by the potato or tomato psyllid (PoP). Until now, the optimal effective concentration(s) of double-stranded RNA (dsRNA) required for significant gene knockdown and RNAi persistence in PoP have not been determined. The objective of this study was to optimize RNAi in young PoP adults and 3rd instars for screening by oral delivery of dsRNAs. The minimal effective dsRNA concentrations required for robust knockdown and persistence were evaluated by delivering seven concentrations spanning 0.1 ng/μL to 500 ng/μL over post ingestion-access periods (IAP) ranging from 48 h to 12 days. The PoP gene candidates evaluated as targets were vacuolar ATPase subunit A, clathrin heavy chain, and non-fermenting protein 7, which were evaluated for knockdown by qPCR amplification. The minimum and/or the second most effective dsRNA concentration resulting in effective levels of gene knockdown was 100 ng/μL for all three targets. Higher concentrations did not yield further knockdown, indicating potential RISC saturation at the higher doses. Gene silencing post-IAP of 100 ng/μL dsRNA persisted for 3–5 days in adults and nymphs, with the PoP 3rd instar, followed by teneral and mature adults, respectively, exhibiting the most robust RNAi-response.
Identification of the genes at S and Z reveals the molecular basis and evolution of grass self-incompatibility
Authors: Herridge Rowan , McCourt Tyler , Jacobs Jeanne M. E. , Mace Peter , Brownfield Lynette , Macknight Richard
Published: October 2022

Self-incompatibility (SI) is a feature of many flowering plants, whereby self-pollen is recognized and rejected by the stigma. In grasses (Poaceae), the genes controlling this phenomenon have not been fully elucidated. Grasses have a unique two-locus system, in which two independent genetic loci (S and Z) control self-recognition. S and Z are thought to have arisen from an ancient duplication, common to all grasses. With new chromosome-scale genome data, we examined the genes present at S- and Z-loci, firstly in ryegrass (Lolium perenne), and subsequently in ~20 other grass species. We found that two DUF247 genes and a short unstructured protein (SP/ZP) were present at both S- and Z- in all SI species, while in self-compatible species these genes were often lost or mutated. Expression data suggested that DUF247 genes acted as the male components and SP/ZP were the female components. Consistent with their role in distinguishing self- from non-self, all genes were hypervariable, although key secondary structure features were conserved, including the predicted N-terminal cleavage site of SP/ZP. The evolutionary history of these genes was probed, revealing that specificity groups at the Z-locus arose before the advent of various grass subfamilies/species, while specificity groups at the S-locus arose after the split of Panicoideae, Chloridoideae, Oryzoideae and Pooideae. Finally, we propose a model explaining how the proteins encoded at the S and Z loci might function to specify self-incompatibility.
Status and prospects of genome-wide association studies in cotton
Authors: Yasir Muhammad , Kanwal Hafiza Hamrah , Hussain Quaid , Riaz Muhammad Waheed , Sajjad Muhammad , Rong Junkang , Jiang Yurong
Published: October 2022

Over the last two decades, the use of high-density SNP arrays and DNA sequencing have allowed scientists to uncover the majority of the genotypic space for various crops, including cotton. Genome-wide association study (GWAS) links the dots between a phenotype and its underlying genetics across the genomes of populations. It was first developed and applied in the field of human disease genetics. Many areas of crop research have incorporated GWAS in plants and considerable literature has been published in the recent decade. Here we will provide a comprehensive review of GWAS studies in cotton crop, which includes case studies on biotic resistance, abiotic tolerance, fiber yield and quality traits, current status, prospects, bottlenecks of GWAS and finally, thought-provoking question. This review will serve as a catalog of GWAS in cotton and suggest new frontiers of the cotton crop to be studied with this important tool.
The Chromosome-level genome of Aesculus wilsonii provides new insights into terpenoid biosynthesis and Aesculus evolution
Authors: Ye Lichun , Yang Lulu , Wang Bo , Chen Gang , Jiang Liping , Hu Zhigang , Shi Zhaohua , Liu Yifei , Chen Shilin
Published: October 2022

Aesculus L. (buckeye and horse chestnut) are woody plant species with important horticultural and medicinal values. Aesculus seeds are widely used as biomedicine and cosmetic ingredients due to their saponins. We report a chromosomal-scale genome of Aesculus wilsonii. Sequences amounting to a total of 579.01 Mb were assembled into 20 chromosomes. More than half of the genome (54.46%) were annotated as repetitive sequences, and 46,914 protein-coding genes were predicted. In addition to the widespread gamma event with core eudicots, a unique whole-genome duplication (WGD) event (17.69 Mya) occurred in Aesculus after buckeye differentiated from longan. Due to WGD events and tandem duplications, the related synthetic genes of triterpene saponins unique to Aesculus increased significantly. Combined with transcriptome characterization, the study preliminarily resolved the biosynthetic pathway of triterpenoid saponins like aescin in A. wilsonii genome. Analyses of the resequencing of 104 buckeye accessions revealed clear relationship between the geographic distribution and genetic differentiation of buckeye trees in China. We found that the buckeye species found in southern Shaanxi is A. wilsonii rather than A. chinensis. Population dynamics analysis further suggests that the population size and evolution of existing buckeye species have been influenced by climate fluctuations during the Pleistocene and recent domestication events. The genome of A. wilsonii and population genomics of Aesculus provide a resource for future research on Hippocastanaceae. These findings will contribute to the utilization and diversity protection of Aesculus.
Joint metabolome and transcriptome analysis of the effects of exogenous GA3 on endogenous hormones in sweet cherry and mining of potential regulatory genes
Authors: Chen Chaoqun , Chen Hongxu , Chen Yuanfei , Yang Wenlong , Li Mengyao , Sun Bo , Song Haiyan , Tang Wenjing , Zhang Yao , Gong Ronggao
Published: October 2022

Gibberellin (GA) is an important phytohormone that can participate in various developmental processes of plants. The study found that application of GA3 can induce parthenocarpy fruit and improve fruit set. However, the use of GA3 affects endogenous hormones in fruits, thereby affecting fruit quality. This study mainly investigates the effect of exogenous GA3 on endogenous hormones in sweet cherries. The anabolic pathways of each hormone were analyzed by metabolome and transcriptome to identify key metabolites and genes that affect endogenous hormones in response to exogenous GA3 application. Results showed that exogenous GA3 led to a significant increase in the content of abscisic acid (ABA) and GA and affected jasmonic acid (JA) and auxin (IAA). At the same time, the key structural genes affecting the synthesis of various hormones were preliminarily determined. Combined with transcription factor family analysis, WRKY genes were found to be more sensitive to the use of exogenous GA3, especially the genes belonging to Group III (PaWRKY16, PaWRKY21, PaWRKY38, PaWRKY52, and PaWRKY53). These transcription factors can combine with the promoters of NCED, YUCCA, and other genes to regulate the content of endogenous hormones. These findings lay the foundation for the preliminary determination of the mechanism of GA3’s effect on endogenous hormones in sweet cherry and the biological function of WRKY transcription factors.
AtGCS promoter-driven clustered regularly interspaced short palindromic repeats/Cas9 highly efficiently generates homozygous/biallelic mutations in the transformed roots by Agrobacterium rhizogenes–mediated transformation
Authors: Liu Shuang , Wang Xiuyuan , Li Qianqian , Peng Wentao , Zhang Zunmian , Chu Pengfei , Guo Shangjing , Fan Yinglun , Lyu Shanhua
Published: October 2022

Agrobacterium rhizogenes–mediated (ARM) transformation is an efficient and powerful tool to generate transgenic roots to study root-related biology. For loss-of-function studies, transgenic-root-induced indel mutations by CRISPR/Cas9 only with homozygous/biallelic mutagenesis can exhibit mutant phenotype(s) (excluding recessive traits). However, a low frequency of homozygous mutants was produced by a constitutive promoter to drive Cas9 expression. Here, we identified a highly efficient Arabidopsis thaliana gamma-glutamylcysteine synthetase promoter, termed AtGCSpro, with strong activity in the region where the root meristem will initiate and in the whole roots in broad eudicots species. AtGCSpro achieved higher homozygous/biallelic mutation efficiency than the most widely used CaMV 35S promoter in driving Cas9 expression in soybean, Lotus japonicus, and tomato roots. Using the pAtGCSpro-Cas9 system, the average homozygous/biallelic mutation frequency is 1.7-fold and 8.3-fold higher than the p2 × 35Spro-Cas9 system for single and two target site(s) in the genome, respectively. Our results demonstrate the advantage of the pAtGCSpro-Cas9 system used in ARM transformation, especially its great potential in diploids with multiple-copy genes targeted mutations and polyploid plants with multiplex genome editing. AtGCSpro is conservatively active in various eudicots species, suggesting that AtGCSpro might be applied in a wide range of dicots species.
How and when workplace ostracism influences employee deviant behavior: A self-determination theory perspective
Authors: Luo Jian , Li Shuang , Gong Lizhu , Zhang Xueying , Wang Siwei
Published: October 2022

Drawing on self-determination theory, this study examines the relationship between workplace ostracism and deviant behavior by focusing on the mediating role of basic psychological needs and the moderating role of perceived inclusive climate. Findings based on the analysis of 247 valid survey samples suggest that (1) workplace ostracism has a significant positive impact on employees’ deviant behavior; (2) basic psychological needs mediate the relationship between workplace ostracism and employees’ deviant behavior; and (3) employees’ perceived inclusive climate weakens the negative effect of workplace ostracism on basic psychological needs. This study develops new perspectives for workplace ostracism research, extends the factors that influence employees’ deviant behavior, and expands the boundary conditions of organizational difference in self-determination theory. Moreover, these empirical results provide important theoretical guidance to decrease employees’ deviant behavior in organizations.