bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecosystem Services of Ecosystem Approach to Mariculture: Providing an Unprecedented Opportunity for the Reform of China’s Sustainable Aquaculture
Authors: Zhou Xijie , Fang Jinghui , Shi Siyuan , Yang Ling , Xie Bin , Huang Lingfeng
Published: July 2022

China is the biggest provider of mariculture products, and the industry is still growing rapidly. Increasing scientific evidence indicates that mariculture may provide valuable ecosystem goods and services in China. Here, we performed a systematic literature review of studies with the aim of understanding the ecosystem services of mariculture and a comprehensive review of ecosystem approaches that may improve mariculture ecosystem services and goods in China. We highlight four ecosystem services functions in China, including food supply, nutrient extraction, carbon sequestration, and biodiversity conservation. Given the further reform of China’s mariculture, we outlined several ecosystem approaches including integrated multi-trophic aquaculture (IMTA), carrying capacity assessment and monitoring, marine spatial planning, and waste treatment and recirculating mariculture system. We conclude that the ecosystem services of the ecosystem approach to mariculture provide an unprecedented opportunity for the reform of China’s sustainable aquaculture. Finally, a synthesis of sustainable development of mariculture, along with the five recommendations for future mariculture development in China, is outlined.
Heterogeneous Interfaces of Magnetic CIP and Binary Dielectric Carbon-Based Material Toward High-Efficiency Microwave Attenuation
Authors: Song Yongzhi , Bi Song , Hou Genliang , Li Hao , Liu Zhaohui
Published: July 2022

Carbon-based materials, as lightweight absorbers, have been widely applied in varied fields to counteract the adverse effects of electromagnetic waves. Nevertheless, there remain challenges in coping with the impairment of microwave absorption performance caused by the excessively high permittivity of carbon materials. Herein, carbonyl iron powder (CIP) was added to graphene oxide/carbon black (RGO-CB) composites to adjust the permittivity improving impedance matching and electromagnetic absorption properties. In this work, the RGO provides a three-dimensional structure net, which introduces circularly and variously electromagnetic loss interfaces within the RGO-CB/CIP composites. Owing to the unique architecture and synergy of the three components, the as-prepared absorber exhibits good impedance matching and gratifying microwave absorption properties. It was found that the 1:1 mixture of RGO-CB and CIP in the composite had superb impedance matching at the thicknesses of 2.6 and 2.7 mm to achieve complete X-band microwave absorption. Such excellent performance benefits from the multiple polarization provided by the heterogeneous interfaces and the ideal impedance match attributed to the tunable permeability and permittivity of this work.
Do Relapses Follow ANCA Rises? A Systematic Review and Meta-Analysis on the Value of Serial ANCA Level Evaluation
Authors: Al-Soudi Aram , Vegting Yosta , Klarenbeek Paul L. , Hilhorst Marc L.
Published: July 2022

Objectives

ANCA-vasculitis (AAV) patients frequently suffer from relapses and risk subsequent organ damage. There is much debate on the value of serial ANCA level evaluation to monitor disease activity. We aimed to evaluate the association between ANCA rises and disease relapses at (I) moment of the rise, (II) within 6 months or (III) within a year from the rise.

Methods

3 databases (MEDLINE, EMBASE, COCHRANE) were searched from 1993 through September 2021. We included studies that reported relapse incidence within 12 months after an ANCA rise measured by antigen-specific immunoassays in peripheral blood of AAV patients in remission. Quality assessment was performed using QUADAS-2. Finally, a meta-analysis was carried out to estimate average OR using a random effects model.

Results

Twenty unique studies were included. The methodological quality was limited due to risk of selection bias. An ANCA rise often preceded a disease relapse within 6 months (OR 3.65, 95% CI 1.66–8.03) and less often within 12 months (OR 2.88, 95% CI 1.21–6.88), while it was not indicative of a concurrent relapse (OR 0.13, 95% CI 0.03–0.53). Once a relapse is diagnosed, ANCA is significantly more often present than not (OR 10.80, 95% CI 3.82–30.55). As expected based on clinical, technical and methodological variability between studies, there was substantial heterogeneity across studies in all analyses (I2 = 70–87%).

Conclusion

In previously ANCA-positive patients, the ANCA test is often positive upon clinical suspicion of a disease relapse. Patients with a rise in ANCA are at risk of encountering disease relapses in the upcoming 6 or 12 months.
Widefield Optical Coherence Tomography in Pediatric Retina: A Case Series of Intraoperative Applications Using a Prototype Handheld Device
Authors: Nguyen Thanh-Tin P. , Ni Shuibin , Liang Guangru , Khan Shanjida , Wei Xiang , Skalet Alison , Ostmo Susan , Chiang Michael F. , Jia Yali , Huang David , Jian Yifan , Campbell J. Peter
Published: July 2022

Optical coherence tomography (OCT) has changed the standard of care for diagnosis and management of macular diseases in adults. Current commercially available OCT systems, including handheld OCT for pediatric use, have a relatively narrow field of view (FOV), which has limited the potential application of OCT to retinal diseases with primarily peripheral pathology, including many of the most common pediatric retinal conditions. More broadly, diagnosis of all types of retinal detachment (exudative, tractional, and rhegmatogenous) may be improved with OCT-based assessment of retinal breaks, identification of proliferative vitreoretinopathy (PVR) membranes, and the pattern of subretinal fluid. Intraocular tumors both benign and malignant often occur outside of the central macula and may be associated with exudation, subretinal and intraretinal fluid, and vitreoretinal traction. The development of wider field OCT systems thus has the potential to improve the diagnosis and management of myriad diseases in both adult and pediatric retina. In this paper, we present a case series of pediatric patients with complex vitreoretinal pathology undergoing examinations under anesthesia (EUA) using a portable widefield (WF) swept-source (SS)-OCT device.
Identifying Novel Clusters of Patients With Prolonged Mechanical Ventilation Using Trajectories of Rapid Shallow Breathing Index
Authors: Yang Tsung-Ming , Chen Lin , Lin Chieh-Mo , Lin Hui-Ling , Fang Tien-Pei , Ge Huiqing , Cai Huabo , Hong Yucai , Zhang Zhongheng
Published: July 2022

Objective

Patients with prolonged mechanical ventilation (PMV) are comprised of a heterogeneous population, creating great challenges for clinical management and study design. The study aimed to identify subclusters of PMV patients based on trajectories of rapid shallow breathing index (RSBI), and to develop a machine learning model to predict the cluster membership based on baseline variables.

Methods

This was a retrospective cohort study conducted in respiratory care center (RCC) at a tertiary academic medical center. The RCC referral criteria were patients with mechanical ventilation for at least 21 days with stable hemodynamic and oxygenation status. Patients admitted to the RCC from April 2009 to December 2020 were screened. Two-step clustering through linear regression modeling and k-means was employed to find clusters of the trajectories of RSBI. The number of clusters was chosen by statistical metrics and domain expertise. A gradient boosting machine (GBM) was trained, exploiting variables on RCC admission, to predict cluster membership.

Results

A total of 1371 subjects were included in the study. Four clusters were identified: cluster A showed persistently high RSBI; cluster B was characterized by a constant low RSBI over time; Cluster C was characterized by increasing RSBI; and cluster D showed a declining RSBI. Cluster A showed the highest mortality rate (72%), followed by cluster D (63%), C (62%) and B (61%; p = 0.005 for comparison between 4 clusters). GBM was able to predict cluster membership with an accuracy of > 0.95 in ten-fold cross validation. Highly ranked variables for the prediction of clusters included thyroid-stimulating hormone (TSH), cortisol, platelet, free thyroxine (T4) and serum magnesium.

Conclusions

Patients with PMV are composed of a heterogeneous population that can be classified into four clusters by using trajectories of RSBI. These clusters can be easily predicted with baseline clinical variables.
Imaging Characteristics of Neovascular and Atrophic Pachychoroidal Spectrum Diseases
Authors: Hua Rui , Zhang Meixia
Published: July 2022

Background

This study qualitatively and quantitatively compared imaging characteristics between neovascular and atrophic pachychoroid spectrum disease (PSD) by optical coherence tomography (OCT), and OCT angiography (OCTA).

Methods

The subtypes of PSD were identified by multi-modality imaging approaches. Subfoveal choroidal thickness (SFCT), choroidal vascular index (CVI), and vascular density of choroidal neovascularization (CNV) were measured.

Results

The CVI and SFCT of 174 PSD eyes were 67.6% ± 5.48% and 362.2 ± 131.88 μm, respectively. After adjustment for age, linear regression indicated that SFCT was positively associated with CVI (p < 0.001), and patched hyper-reflective lesions in choriocapillaris layers (p = 0.009). Compared with neovascular PSD eyes, atrophic PSD eyes had similar patient age (57.1 ± 16.72 years, p = 0.639), SFCT (332.0 ± 111.00 μm, p = 0.51), and CVI (67.6% ± 3.94%, p = 0.527). There were no differences between polypoidal choroidal vasculopathy (PCV) eyes with aneurysmal polypoidal lesions and PCV eyes with tangled polypoidal lesions in terms of age, CVI, SFCT, vascular density, or the occurrence of double layer signs (DLSs, all p > 0.05). Logistic regression indicated that age (p = 0.003), SFCT (p = 0.003), patched hyper-reflective lesions in choriocapillaris layers (p = 0.009), and DLSs (p < 0.001) were predictive factors for CNV progression in PSD eyes (all p < 0.05).

Conclusions

Our study highlighted the similarities in SFCT and CVI between neovascular and atrophic PSD, both of which were late stage lesions. Besides, age, SFCT, patched hyper-reflective lesions in choriocapillaris layers, and DLSs were risk factors for CNV in PSD. Our results showed that atrophic PSD is an important change in the late stage of PSD disease, which is helpful for in-depth understanding of the pathological mechanism of PSD and corresponding intervention.
Anti-SARS-CoV-2 Revaccination Success in Kidney Transplant Recipients With No Initial Humoral Response Is Linked to Primary Vaccine Type
Authors: Stumpf Julian , Schwöbel Jörg , Karger Claudia , Schirutschke Holger , Mauer René , Klimova Anna , Tonn Torsten , Hugo Christian
Published: July 2022

Background

While anti-SARS-CoV-2 vaccination success in kidney transplant recipients (KTR) after two doses and 1273-mRNA was associated with higher seroconversion rates compared to BNT162b2-mRNA in our “DIA-Vacc Study” (NCT04799808), it remains unclear whether this may also be the case in non-responding KTR after a third vaccination dose.

Materials and Methods

Non-responding KTR (after two mRNA vaccinations) were investigated 4.5–6 months after study enrollment at first vaccination. One hundred sixty-six of 193 received a third vaccination between 3.5 and 5 months after the initial study enrollment and were always investigated 4 weeks later, exploring humoral immune response (ELISA) and specific cellular responses (interferon-γ release assay). Sixty-seven of 193 measurements in KTR were done immediately before the third vaccination or in KTR without further vaccination at 4.5–6 months.

Results

Of 193 KTR with no initial immune response 4 weeks after the second vaccination, 106/87 were immunized twice with 1273-mRNA/BNT162b2-mRNA, respectively. Additional mRNA booster vaccination led to positive seroconversion rates of 30–50%, while 16% of the initial non-responders demonstrated a delayed seroconversion without any booster vaccination. Using logistic regression analysis, a positive IgG response after the third vaccination was 23% more likely if the primary vaccine type was 1273-mRNA compared to BNT162b2-mRNA (OR = 4.420, 95% CI [1.208–16.173], p = 0.025). Primary vaccine type, a weak anti-SpikeS1 IgG response 4 weeks after second vaccination (3.2–35.2 BAU/ml, p < 0.001) and a lack of MMF/MPA as part of the immunosuppressive treatment (trend, p = 0.06) but no other variables studied correlated with seroconversion success.

Conclusion

This observational study adds important evidence toward using 1273-mRNA as the primary mRNA vaccine type for immunosuppressed KTR.
Ultrasound-Guided Erector Spinae Plane Block in Thoracolumbar Spinal Surgery: A Systematic Review and Meta-Analysis
Authors: Viderman Dmitriy , Aubakirova Mina , Umbetzhanov Yerlan , Kulkaeva Gulnara , Shalekenov S. B. , Abdildin Yerkin G.
Published: July 2022

Introduction

Neurosurgical spinal surgeries such as micro- discectomy and complex fusion surgeries remain the leading causes of disability-adjusted life-year. Major spinal surgeries often result in severe postprocedural pain due to massive dissection of the underlying tissues. While opioids offer effective pain control, they frequently lead to side effects, such as post-operative nausea and vomiting, pruritus, constipation, and respiratory depression. ESPB was successfully used in spinal surgery as a component of a multimodal analgesic regimen and it eliminated the requirements for opioids. The primary purpose of this systematic review and meta-analysis was to compare post-operative opioid consumption between ESPB and placebo.

Methods

To conduct this systematic review, we used the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)” guidelines. We conducted a search for relevant articles available in the following databases: Google Scholar, PubMed, and the Cochrane Library published up to March 2022.

Results

The total morphine consumption within 24 h after surgery was lower in the ESPB group, the mean difference (in mg of morphine) with 95% CI is −9.27 (−11.63, −6.91). The pain intensity (0–10) at rest measured 24 h after surgery was lower in the ESPB group, the MD with 95% CI is −0.47 (−0.77, −0.17). The pain intensity during movement measured 24 h after surgery was lower in the ESPB group, the MD with 95% CI is −0.73 (−1.00, −0.47). Post-operative nausea and vomiting were significantly lower in the ESPB group, the risk ratio with 95% CI is 0.32 (0.19, 0.53).

Conclusion

Ultrasound-guided ESPB was superior to placebo in reducing post-operative opioid consumption, pain intensity, post-operative nausea and vomiting, and prolonging the time to first rescue analgesia. There were no ESPB-related serious complications reported.
Effect of Dietary Methylsulfonylmethane Supplementation on Growth Performance, Hair Quality, Fecal Microbiota, and Metabolome in Ragdoll Kittens
Authors: Guo Dan , Zhang Limeng , Zhang Lingna , Han Sufang , Yang Kang , Lin Xinye , Wen Chaoyu , Tong Aorigeile , Zhang Meiyu , Yin Yulong , Deng Baichuan
Published: July 2022

Methylsulfonylmethane (MSM) is a natural sulfur-containing organic substance that has many biological functions, such as antioxidant, anti-inflammatory, skin nourishing, and hair growth-promoting effects. This study was conducted to determine the effect of MSM supplementation on growth performance, antioxidant capacity, and hair quality in kittens. A total of 21 Ragdoll kittens were assigned to three diets by initial body weight and gender: basal diet supplemented with 0%, 0.2%, and 0.4% MSM (CON, LMSM, and HMSM groups) for 65 days. During the whole period, the food intake of kittens in the MSM-treated groups tended to be higher (P < 0.10) compared with the CON group, and the average daily gain (ADG) had no significant difference when compared to the kittens in the CON group (P > 0.05). Antioxidant capacity had no significant difference (P > 0.05) among the groups. The scale thickness of hair tended to be smaller in the LMSM group compared to the CON group (P < 0.10) and decreased significantly (P < 0.05) over time from d 0 to d 65 in the LMSM group, indicating the improvement of hair quality. Besides, supplementation with LMSM increased bacterial diversity. Kittens fed MSM had no significant differences in fecal genus at the end of the study. No significant differences in fecal short-chain fatty acids were observed among groups. Fecal metabolomics analysis further revealed that MSM hardly affected the metabolites. Overall, dietary supplementation with 0.2% MSM can improve the hair quality of kittens. Furthermore, 0.2∼0.4% of MSM had no detrimental effects on serum biochemistry, growth performance, gut microbiota, and metabolome, which supports the safety inclusion of MSM to a certain degree in feline diets. To the best of our knowledge, this is the first study to investigate the effects of MSM supplementation in cats.
Identification of Sponge-Associated Bacteria From the Coast of Kuwait and Their Potential Biotechnological Applications
Authors: Abbas Shahad , Mahmoud Huda
Published: July 2022

Sponges are among the most ancient animals harboring complex microbial communities with potential applications in biotechnology. The Arabian Gulf is a thermally stressed enclosed body of water located in an arid region where sponges and their halobionts are understudied. This study combined 16S rRNA next-generation gene amplicon sequencing and cultivation techniques to explore the abundance and diversity of sponge-associated bacteria. Culture-independent techniques showed the associations of more than 25 bacterial phyla with Amphimedon sp., Chondrilla australiensis, Haliclona sp., and Niphates spp. Regarding cultivable bacteria, 315 bacterial isolates associated with the sponge Haliclona sp. were cultivated; these isolates were affiliated with the phyla Proteobacteria and Firmicutes and were distributed among six bacterial genera. Selected strains of Bacillus, Ferrimonas, Pseudovibrio, Shewanella, Spongiobacter, and Vibrio were tested for antimicrobial activity against indicator microorganisms and protease enzyme production. Seven Bacillus strains exhibited weak to moderate growth inhibition against Bacillus subtilis, Staphylococcus aureus, and Candida albicans. Furthermore, 29 different strains of Bacillus, Ferrimonas, Shewanella, and Vibrio exhibited different degrees of positive protease activity. In addition, cultivated strains of Bacillus, Shewanella, Pseudovibrio, and Vibrio were tested for their biomineralization abilities. Herein we report for the first time the isolation of biomineralizing bacteria from sponge tissue where eleven bacterial isolates produced different shapes of calcium carbonate crystals on agar. Our observations shed light on the diversity and biotechnological potentials of sponges-associated bacteria inhabiting one of the world’s hottest seas.
Early Transcriptional Response to Monensin in Sensitive and Resistant Strains of Eimeria tenella
Authors: Zhang Hongtao , Zhang Lei , Si Hongbin , Liu Xianyong , Suo Xun , Hu Dandan
Published: July 2022

Eimeria parasites are the causative agents of coccidiosis, a common parasitic disease in poultry and livestock that causes significant economic losses to the animal husbandry industry. Ionophore coccidiostats, such as monensin and salinomycin, are widely used for prophylaxis of coccidiosis in poultry. Unfortunately, widespread drug resistance has compromised their efficacy. As a result, there is an increasing need to understand the targets and resistance mechanisms to anticoccidials. However, how Eimeria parasite genes respond to ionophores remains unclear. In this study, resistance to monensin was induced in E. tenella through serial generations of selection. Both sensitive and resistant E. tenella sporozoites were treated with 5 μg/ml monensin for 0, 2, and 4 h, respectively. Gene transcription profiles were then compared by high-throughput sequencing. The results showed that protein translation-related genes were significantly downregulated after drug induction. A total of 1,848 DEGs were detected in the sensitive strain after 2 h of exposure, whereas only 31 were detected in the resistant strain. Among these DEGs in the sensitive strain, genes associated with protein degradation were significantly upregulated, supporting the autophagy-like parasite killing theory. Then, 4 h of exposure resulted in additional 626 and 621 DEGs for sensitive and resistant strains, respectively. This result implies that the gene transcription in sensitive strain is more susceptible to monensin treatment. Our results provide gene expression landscapes of E. tenella following monensin treatment. These data will contribute to a better understanding of the mechanism of drug resistance to polyether ionophores in coccidia.
Innovative Approach for a Classic Target: Fragment Screening on Trypanothione Reductase Reveals New Opportunities for Drug Design
Authors: Fiorillo Annarita , Colotti Gianni , Exertier Cécile , Liuzzi Anastasia , Seghetti Francesca , Salerno Alessandra , Caciolla Jessica , Ilari Andrea
Published: July 2022

Trypanothione reductase (TR) is a key factor in the redox homeostasis of trypanosomatid parasites, critical for survival in the hostile oxidative environment generated by the host to fight infection. TR is considered an attractive target for the development of new trypanocidal agents as it is essential for parasite survival but has no close homolog in humans. However, the high efficiency and turnover of TR challenging targets since only potent inhibitors, with nanomolar IC50, can significantly affect parasite redox state and viability. To aid the design of effective compounds targeting TR, we performed a fragment-based crystal screening at the Diamond Light Source XChem facility using a library optimized for follow-up synthesis steps. The experiment, allowing for testing over 300 compounds, resulted in the identification of 12 new ligands binding five different sites. Interestingly, the screening revealed the existence of an allosteric pocket close to the NADPH binding site, named the “doorstop pocket” since ligands binding at this site interfere with TR activity by hampering the “opening movement” needed to allow cofactor binding. The second remarkable site, known as the Z-site, identified by the screening, is located within the large trypanothione cavity but corresponds to a region not yet exploited for inhibition. The fragments binding to this site are close to each other and have some remarkable features making them ideal for follow-up optimization as a piperazine moiety in three out of five fragments.
A Novel Multifunctional 5,6-Dimethoxy-Indanone-Chalcone-Carbamate Hybrids Alleviates Cognitive Decline in Alzheimer’s Disease by Dual Inhibition of Acetylcholinesterase and Inflammation
Authors: Liu Chan , Sang Zhipei , Pan Hong , Wu Qin , Qiu Yu , Shi Jingshan
Published: July 2022

Backgrounds

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease. The treatment of AD through multiple pathological targets may generate therapeutic efficacy better. The multifunctional molecules that simultaneously hit several pathological targets have been of great interest in the intervention of AD.

Methods

Here, we combined the chalcone scaffold with carbamate moiety and 5,6-dimethoxy-indanone moiety to generate a novel multi-target-directed ligand (MTDL) molecule (E)-3-((5,6-dimethoxy-1-oxo-1,3-dihydro-2H-inden-2-ylidene)-methyl)phenylethyl(methyl) carbamate (named AP5). In silico approaches were used to virtually predict the binding interaction of AP5 with AChE, the drug-likeness, and BBB penetrance, and later validated by evaluation of pharmacokinetics (PK) in vivo by LC-MS/MS. Moreover, studies were conducted to examine the potential of AP5 for inhibiting AChE and AChE-induced amyloid-β (Aβ) aggregation, attenuating neuroinflammation, and providing neuroprotection in the APP/PS1 model of AD.

Results

We found that AP5 can simultaneously bind to the peripheral and catalytic sites of AChE by molecular docking. AP5 exhibited desirable pharmacokinetic (PK) characteristics including oral bioavailability (67.2%), >10% brain penetrance, and favorable drug-likeness. AP5 inhibited AChE activity and AChE-induced Aβ aggregation in vivo and in vitro. Further, AP5 lowered Aβ plaque deposition and insoluble Aβ levels in APP/PS1 mice. Moreover, AP5 exerted anti-inflammatory responses by switching microglia to a disease-associated microglia (DAM) phenotype and preventing A1 astrocytes formation. The phagocytic activity of microglial cells to Aβ was recovered upon AP5 treatment. Importantly, chronic AP5 treatment significantly prevented neuronal and synaptic damage and memory deficits in AD mice.

Conclusion

Together, our work demonstrated that AP5 inhibited the AChE activity, decreased Aβ plaque deposition by interfering Aβ aggregation and promoting microglial Aβ phagocytosis, and suppressed inflammation, thereby rescuing neuronal and synaptic damage and relieving cognitive decline. Thus, AP5 can be a new promising candidate for the treatment of AD.
Nicotine Facilitates Facial Stimulation-Evoked Mossy Fiber-Granule Cell Long-Term Potentiation in vivo in Mice
Authors: Cao Li-Xin , Bing Yan-Hua , Xu Yin-Hua , Zhang Guang-Jian , Chu Chun-Ping , Hong Lan , Qiu De-Lai
Published: July 2022

Nicotine is a psychoactive component of tobacco that plays critical roles in the regulation of neuronal circuit function and neuroplasticity and contributes to the improvement of working memory performance and motor learning function via nicotinic acetylcholine receptors (nAChRs). Under in vivo conditions, nicotine enhances facial stimulation-evoked mossy fiber-granule cell (MF-GrC) synaptic transmission, which suggests that nicotine regulates MF-GrC synaptic plasticity in the mouse cerebellar cortex. In this study, we investigated the effects of nicotine on facial stimulation-induced long-term potentiation (LTP) of MF-GrC synaptic transmission in urethane-anesthetized mice. Our results showed that facial stimulation at 20 Hz induced an MF-GrC LTP in the mouse cerebellar granular layer that was significantly enhanced by the application of nicotine (1 μM). Blockade of α4β2 nAChRs, but not α7 nAChRs, during delivery of 20 Hz facial stimulation prevented the nicotine-induced facilitation of MF-GrC LTP. Notably, the facial stimulation-induced MF-GrC LTP was abolished by an N-methyl-D-aspartate (NMDA) receptor antagonist, but it was restored by additional application of nicotine during delivery of 20 Hz facial stimulation. Furthermore, antagonism of α4β2 nAChRs, but not α7 nAChRs, during delivery of 20 Hz facial stimulation prevented nicotine-induced MF-GrC LTP. Moreover, inhibition of nitric oxide synthase (NOS) abolished the facial stimulation-induced MF-GrC LTP, as well as the effect of nicotine on it. Our results indicated that 20 Hz facial stimulation induced MF-GrC LTP via an NMDA receptor/nitric oxide (NO) cascade, but MF-GrC LTP was enhanced by nicotine through the α4β2 AChR/NO signaling pathway. These results suggest that nicotine-induced facilitation of MF-GrC LTP may play a critical role in the improvement of working memory performance and motor learning function.
Distinct Encoding of Reward and Aversion by Peptidergic BNST Inputs to the VTA
Authors: Soden Marta E. , Yee Joshua X. , Cuevas Beatriz , Rastani Ariana , Elum Jordan , Zweifel Larry S.
Published: July 2022

Neuropeptides play an important role in modulating mesolimbic system function. However, while synaptic inputs to the ventral tegmental area (VTA) have been extensively mapped, the sources of many neuropeptides are not well resolved. Here, we mapped the anatomical locations of three neuropeptide inputs to the VTA: neurotensin (NTS), corticotrophin releasing factor (CRF), and neurokinin B (NkB). Among numerous labeled inputs we identified the bed nucleus of the stria terminalis (BNST) as a major source of all three peptides, containing similar numbers of NTS, CRF, and NkB VTA projection neurons. Approximately 50% of BNST to VTA inputs co-expressed two or more of the peptides examined. Consistent with this expression pattern, analysis of calcium dynamics in the terminals of these inputs in the VTA revealed both common and distinct patterns of activation during appetitive and aversive conditioning. These data demonstrate additional diversification of the mesolimbic dopamine system through partially overlapping neuropeptidergic inputs.
Predicting 30-Day Readmission for Stroke Using Machine Learning Algorithms: A Prospective Cohort Study
Authors: Chen Yu-Ching , Chung Jo-Hsuan , Yeh Yu-Jo , Lou Shi-Jer , Lin Hsiu-Fen , Lin Ching-Huang , Hsien Hong-Hsi , Hung Kuo-Wei , Yeh Shu-Chuan Jennifer , Shi Hon-Yi
Published: July 2022

Background

Machine learning algorithms for predicting 30-day stroke readmission are rarely discussed. The aims of this study were to identify significant predictors of 30-day readmission after stroke and to compare prediction accuracy and area under the receiver operating characteristic (AUROC) curve in five models: artificial neural network (ANN), K nearest neighbor (KNN), random forest (RF), support vector machine (SVM), naive Bayes classifier (NBC), and Cox regression (COX) models.

Methods

The subjects of this prospective cohort study were 1,476 patients with a history of admission for stroke to one of six hospitals between March, 2014, and September, 2019. A training dataset (n = 1,033) was used for model development, and a testing dataset (n = 443) was used for internal validation. Another 167 patients with stroke recruited from October, to December, 2019, were enrolled in the dataset for external validation. A feature importance analysis was also performed to identify the significance of the selected input variables.

Results

For predicting 30-day readmission after stroke, the ANN model had significantly (P < 0.001) higher performance indices compared to the other models. According to the ANN model results, the best predictor of 30-day readmission was PAC followed by nasogastric tube insertion and stroke type (P < 0.05). Using a machine learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients.

Conclusion

Using a machine-learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. For stroke patients who are candidates for PAC rehabilitation, these predictors have practical applications in educating patients in the expected course of recovery and health outcomes.
Case Report: Cognitive Assessment Before an Amnesic Seizure in Transient Epileptic Amnesia Syndrome
Authors: Bouyer Coline , de Toffol Bertrand
Published: July 2022

A patient with transient epileptic amnesia syndrome presented a clinically observable amnesic seizure immediately after a neuropsychological assessment. An hour and a half before the onset of the seizure, the patient progressively developed an isolated alteration of episodic memory. These data question the ictal/interictal distinction in this syndrome as well as the speed of propagation of an epileptic activity.
Functional and Prognostic Assessment in Comatose Patients: A Study Using Somatosensory Evoked Potentials
Authors: Arciniegas-Villanueva Andrea Victoria , Fernández-Diaz Eva María , Gonzalez-Garcìa Emilio , Sancho-Pelluz Javier , Mansilla-Lozano David , Segura Tomás
Published: July 2022

Aim

The functional prognosis of patients after coma following either cardiac arrest (CA) or acute structural brain injury (ABI) is often uncertain. These patients are associated with high mortality and disability. N20 and N70 somatosensory evoked potentials (SSEP) are used to predict prognosis. We evaluated the utility of SSEP (N20–N70) as an early indicator of long-term prognosis in these patients.

Methods

This was a retrospective cohort study of patients (n = 120) admitted to the intensive care unit (ICU) with a diagnosis of coma after CA (n = 60) or ABI (n = 60). An SSEP study was performed, including N20 and N70 at 24–72 h, after coma onset. Functional recovery was assessed 6–12 months later using the modified Glasgow scale (mGS). The study was approved by our local research ethics committee.

Results

In the CA and ABI groups, the absence of N20 (36% of CA patients and 41% of ABI patients; specificity = 100%) or N70 (68% of CA patients and 78% of ABI patients) was a strong indicator of poor outcome. Conversely, the presence of N70 was an indicator of a good outcome (AC: specificity = 84.2%, sensitivity = 92.7%; ABI: specificity = 64.2% sensitivity = 91.3%).

Conclusion

Somatosensory evoked potentials are useful early prognostic markers with high specificity (N20) and sensitivity (N70). Moreover, N70 has additional potential value for improving the prediction of good long-term functional outcomes.

Clinical Trial Registration:

[https://clinicaltrials.gov/], identifier [2018/01/001].
Codon Usage Bias Correlates With Gene Length in Neurodegeneration Associated Genes
Authors: Khandia Rekha , Saeed Mohd. , Alharbi Ahmed M. , Ashraf Ghulam Md. , Greig Nigel H. , Kamal Mohammad Amjad
Published: July 2022

Codon usage analysis is a crucial part of molecular characterization and is used to determine the factors affecting the evolution of a gene. The length of a gene is an important parameter that affects the characteristics of the gene, such as codon usage, compositional parameters, and sometimes, its functions. In the present study, we investigated the association of various parameters related to codon usage with the length of genes. Gene expression is affected by nucleotide disproportion. In sixty genes related to neurodegenerative disorders, the G nucleotide was the most abundant and the T nucleotide was the least. The nucleotide T exhibited a significant association with the length of the gene at both the overall compositional level and the first and second codon positions. Codon usage bias (CUB) of these genes was affected by pyrimidine and keto skews. Gene length was found to be significantly correlated with codon bias in neurodegeneration associated genes. In gene segments with lengths below 1,200 bp and above 2,400 bp, CUB was positively associated with length. Relative synonymous CUB, which is another measure of CUB, showed that codons TTA, GTT, GTC, TCA, GGT, and GGA exhibited a positive association with length, whereas codons GTA, AGC, CGT, CGA, and GGG showed a negative association. GC-ending codons were preferred over AT-ending codons. Overall analysis indicated that the association between CUB and length varies depending on the segment size; however, CUB of 1,200–2,000 bp gene segments appeared not affected by gene length. In synopsis, analysis suggests that length of the genes correlates with various imperative molecular signatures including A/T nucleotide disproportion and codon choices. In the present study we additionally evaluated various molecular features and their correlation with different indices of codon usage, like the Codon Adaptation Index (CAI) and Relative Dynonymous Codon Usage (RSCU) of codons. We also considered the impact of gene fragment size on different molecular features in genes related to neurodegeneration. This analysis will aid our understanding of and in potentially modulating gene expression in cases of defective gene functioning in clinical settings.
Pattern of Recurrence After Platinum-Containing Definitive Therapy and Efficacy of Salvage Treatment for Recurrence in Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Wakasugi Tetsuro , Nguyen Thi Nga , Takeuchi Shoko , Ohkubo Jun-ichi , Suzuki Hideaki
Published: July 2022

Background

In first-line systemic therapy for unresectable recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), regimens are generally selected by time-to-relapse with 6 months cutoff after platinum (Pt)-containing definitive therapy, Pt-refractory or Pt-sensitive recurrence, but clinical characteristics between Pt-refractory and Pt-sensitive recurrence of R/M SCCHN has not been fully investigated. This study aimed to evaluate pattern of recurrence and efficacy for salvage treatment for recurrence after Pt-containing definitive therapy for R/M SCCHN in a real-world setting.

Methods

We retrospectively reviewed 150 patients treated with Pt-containing definitive therapy and analyzed the pattern of recurrence and efficacy of salvage therapy for 63 patients with R/M SCCHN.

Results

Pt-refractory recurrence, Pt-sensitive recurrence, second primary cancer (SPC), and no relapse occurred in 23.3%, 18.7%, 14.7%, and 43.3% of patients, respectively. In the cases with distant metastatic recurrence, symptomatic recurrence was significantly more common in the Pt-refractory recurrence, while asymptomatic recurrence was significantly more common in the Pt-sensitive recurrence. The timing of detection of SPC was after 2 years in 59.0% of cases after the completion of definitive therapy and 63.6% of SPC were asymptomatic. There was a significant difference in ΔNLR2 (NLR after definitive therapy minus NLR at detection recurrence; p = 0.028) and in prognosis after the detection of recurrence for the overall population (p = 0.021), and for salvage treatment group (p = 0.023), and systemic therapy group (p = 0.003) between Pt-refractory and Pt-sensitive groups.

Conclusions and Significance

Our analysis revealed the recurrence pattern after Pt-containing definitive therapy and showed the validity of dividing patients into Pt-refractory and Pt-sensitive recurrence with different prognosis in salvage therapy, especially systemic therapy.
Mutator-Derived lncRNA Landscape: A Novel Insight Into the Genomic Instability of Prostate Cancer
Authors: Tang Liansha , Li Wanjiang , Xu Hang , Zheng Xiaonan , Qiu Shi , He Wenbo , Wei Qiang , Ai Jianzhong , Yang Lu , Liu Jiyan
Published: July 2022

Background

Increasing evidence has emerged to reveal the correlation between genomic instability and long non-coding RNAs (lncRNAs). The genomic instability-derived lncRNA landscape of prostate cancer (PCa) and its critical clinical implications remain to be understood.

Methods

Patients diagnosed with PCa were recruited from The Cancer Genome Atlas (TCGA) program. Genomic instability-associated lncRNAs were identified by a mutator hypothesis-originated calculative approach. A signature (GILncSig) was derived from genomic instability-associated lncRNAs to classify PCa patients into high-risk and low-risk groups. The biochemical recurrence (BCR) model of a genomic instability-derived lncRNA signature (GILncSig) was established by Cox regression and stratified analysis in the train set. Then its prognostic value and association with clinical features were verified by Kaplan–Meier (K-M) analysis and receiver operating characteristic (ROC) curve in the test set and the total patient set. The regulatory network of transcription factors (TFs) and lncRNAs was established to evaluate TF–lncRNA interactions.

Results

A total of 95 genomic instability-associated lncRNAs of PCa were identified. We constructed the GILncSig based on 10 lncRNAs with independent prognostic value. GILncSig separated patients into the high-risk (n = 121) group and the low-risk (n = 121) group in the train set. Patients with high GILncSig score suffered from more frequent BCR than those with low GILncSig score. The results were further validated in the test set, the whole TCGA cohort, and different subgroups stratified by age and Gleason score (GS). A high GILncSig risk score was significantly associated with a high mutation burden and a low critical gene expression (PTEN and CDK12) in PCa. The predictive performance of our BCR model based on GILncSig outperformed other existing BCR models of PCa based on lncRNAs. The GILncSig also showed a remarkable ability to predict BCR in the subgroup of patients with TP53 mutation or wild type. Transcription factors, such as FOXA1, JUND, and SRF, were found to participate in the regulation of lncRNAs with prognostic value.

Conclusion

In summary, we developed a prognostic signature of BCR based on genomic instability-associated lncRNAs for PCa, which may provide new insights into the epigenetic mechanism of BCR.
Clinical Study of Anlotinib as Third-Line or Above Therapy in Patients With Advanced or Metastatic Gastric Cancer: A Multicenter Retrospective Study
Authors: Nie Caiyun , He Yunduan , Lv Huifang , Gao Ming , Gao Xiaohui , Chen Beibei , Xu Weifeng , Wang Jianzheng , Liu Yingjun , Zhao Jing , Chen Xiaobing
Published: July 2022

Background

The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with advanced or metastatic gastric cancer.

Methods

Patients with advanced or metastatic gastric cancer who have failed from second-line treatment and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2019 to January 2021 in 3 institutions across China were retrospectively analyzed. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

Results

43 patients with advanced or metastatic gastric cancer who have failed prior treatment received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 4 patients achieved PR, 21 patients had SD and 18 patients had PD. The overall ORR and DCR were 9.3% (4/43) and 58.1% (25/43), respectively. Median PFS and OS were 3.0 months (95% CI=2.5-3.5) and 6.0 months (95% CI=4.4-7.6), respectively. The incidence of Grade 3-4 adverse events(AEs) was 34.9%. Subgroup analysis suggested that the ORR of anlotinib combination therapy was superior than anlotinib monotherapy, but with similar PFS and OS. The clinical benefit of anlotinib was not associated with previously anti-angiogenesis therapy with apatinib.

Conclusions

Anlotinib monotherapy or combination therapy provide a feasible third-line or above therapeutic strategy in patients with advanced or metastatic gastric cancer a median PFS of 3.0 months and median OS of 6.0 months was obtained with well tolerated toxicity.
β-Hydroxyisovaleryl-Shikonin Exerts an Antitumor Effect on Pancreatic Cancer Through the PI3K/AKT Signaling Pathway
Authors: Zeng Yu , Zhang Haifeng , Zhu Minghui , Pu Qingfan , Li Jinhai , Hu Xiao
Published: July 2022

Pancreatic cancer (PC) is marked with a low survival rate and lack of recognized effective treatment strategy. We investigated the antitumor effect of β-hydroxyisovaleryl-shikonin (β-HIVS) on PC and the associated working mechanism. Cell toxicity was determined using Cell Counting Kit-8 (CCK-8) assay. Acridine Orange/Ethidium Bromide (AO/EB) double-fluorescent staining assay accompanied by flow cytometry was utilized to estimate cell apoptosis. Cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were all evaluated using flow cytometry. Transwell and wound healing assays were performed to evaluate cell migration and invasion. Protein expression was analyzed by Western blots. A xenograft mouse model was employed to determine the antitumor effect of β-HIVS in vivo. PC cell viability gradually decreased with increasing β-HIVS while apoptosis was enhanced together with cell-cycle blockage in the G0–G1 phases. β-HIVS induced mitochondrial dysfunction, ROS production, and DNA damage and inhibited the invasive and migratory ability of PC cells. We further confirmed the suppression of EMT and PI3K/AKT pathways as underlying mechanisms. The mouse model treated with the increasing dose of β-HIVS displayed decreased tumor growth rate, along with increased apoptosis. Thus, β-HIVS exerts antitumor effects on PC through inducing apoptosis, ROS production, decreasing mitochondrial membrane potential, and suppressing signal pathways, such as PI3K/AKT. In summary, β-HIVS might be a promising strategy for PC treatment.
RAD21 Confers Poor Prognosis and Affects Ovarian Cancer Sensitivity to Poly(ADP-Ribose)Polymerase Inhibitors Through DNA Damage Repair
Authors: Gou Rui , Li Xiao , Dong Hui , Hu Yuexin , Liu Ouxuan , Liu Juanjuan , Lin Bei
Published: July 2022

Background

Poly(ADP-ribose)polymerase (PARP) inhibitors are a class of molecular-targeted cancer drugs. Synthetic lethality is a phenomenon that renders homologous recombination repair defective cells more sensitive to PARP inhibitors. As a component of the cohesin complex, RAD21 regulates DNA damage repair. However, the biological roles of RAD21 in ovarian cancer and their underlying mechanisms remain unclear.

Methods

An immunohistochemical assay was used to validate the expression of RAD21 in ovarian cancer and its correlation with prognosis. The effects of RAD21 were evaluated through Cell Counting Kit-8 (CCK8), wound-healing, and invasion assays in vitro and the tumor growth in vivo. Furthermore, CCK8 assay and immunofluorescence assay were used to detect the effect of RAD21 on cell sensitivity to PARP inhibitors and their mechanism. The pathway changes were detected by Western blotting.

Results

RAD21 was markedly upregulated in ovarian cancer samples. High RAD21 expression was correlated with poor differentiation and poor prognosis in patients with ovarian cancer. Functionally, RAD21 overexpression promoted cancer cell proliferation, migration, and invasion. Moreover, RAD21 knockdown increased the sensitivity of ovarian cancer cells to three kinds of PARP inhibitors by affecting DNA damage repair. In vivo experiments indicated that RAD21 promoted tumor growth. Mechanistically, the overexpression of RAD21 led to increased phosphorylation levels of Akt and mTOR. Blocking the Akt/mTOR signaling pathway reversed RAD21 overexpression-induced cancer progression and drug resistance.

Conclusions

RAD21 can serve as a valuable prognostic marker for ovarian cancer and has the potential as a therapeutic target that can expand the utility of PARP inhibitors.