bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic hypoxia leads to cognitive impairment by promoting HIF-2 alpha -mediated alpha-synuclein hyperphosphorylation
Authors: Li Gaifen , Liu Jia , Guo Mengyuan , Gu Yakun , Guan Yuying , Shao Qianqian , Ma Wei , Ji Xunming
Published: March 2022

Background: Cognitive impairment is involved in various central nervous system diseases. Hypoxia is a critical common factor that induces cognitive impairment, but its specific molecular mechanism remains unclear. Understanding the mechanism of cognitive impairment induced by hypoxia will provide potential molecular targets for the intervention of cognitive disorders.Methods: We used hypoxic chambers to establish a chronic hypoxic model in mice. Cognitive impairment, hippocampal neurodegeneration, and alpha-synuclein (α-syn) pathology were assessed in these mice. The α-syn knockout mice or mice administered a competing peptide targeting serine 129 (ser129) were used to investigate the role and molecular mechanism of α-syn pathology in chronic hypoxia-induced cognitive impairment. Finally, we investigated the protective role of intermittent hypoxia preconditioning in chronic hypoxia-induced α-syn pathology and cognitive impairment.Results: Chronic hypoxia resulted in α-syn hyperphosphorylation at ser129 and protein aggregation, hippocampal neurodegeneration, and irreversible cognitive deficits. The latter could be reversed by α-syn knockdown or an administered short peptide competing at α-syn ser129. These results suggest that α-syn hyperphosphorylation at ser129 mediates hippocampal degeneration and cognitive impairment following chronic hypoxia. Furthermore, we found that chronic hypoxia enhanced ceramide catabolism by inducing hypoxia-inducible factor (HIF)-2α and HIF-2α-dependent transcriptional activation of alkaline ceramidase 2 (Acer2). Thus, the enzymatic activity of protein phosphatase 2A (PP2A), a specific phosphatase for α-syn, is inhibited, leading to sustained induction of α-syn hyperphosphorylation and aggregation. Finally, we found that enhancing hypoxia tolerance through intermittent hypoxic preconditioning protected against subsequent chronic hypoxia-induced hippocampal neurodegeneration and cognitive impairment by preventing α-syn pathology. Conclusion: These results proved the critical role of α-syn pathology in hypoxia-afforded cognitive impairment and revealed a novel mechanism underlying hypoxic-specific induction of cognitive impairment. The findings bear implications in developing novel therapeutic interventions for hypoxia-related cognitive disorders.
Soluble TREM2 induces microglia dysfunction and brain damage while cleavage-reduced TREM2 shows sustained microglia activation with enhanced remyelination in the cuprizone model
Authors: Beckmann Nicolau , Neuhaus Anna , Zurbruegg Stefan , Joller Stefanie , Feuerbach Dominik , Doelemeyer Arno , Schweizer Tatjana , Rudin Stefan , Neumann Ulf , Berth Ramon , Frieauff Wilfried , Gasparini Fabrizio , Shimshek Derya R.
Published: March 2022

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface immunoreceptor expressed on microglia, osteoclasts and monocytes/macrophages. In humans, homozygous loss-of-function mutation carriers exhibit bone cysts and fractures with an early-onset frontal lobe syndrome and progressive presenile dementia known as Nasu-Hakola. Neuropathological findings include myelin/neuronal loss and neuroinflammation. Heterozygous loss-of-function mutation in TREM2 has been associated with several neurodegenerative diseases like Alzheimer`s disease and Frontotemporal Dementia. We investigated the involvement of soluble and cleavage-reduced TREM2 on central myelination processes by using different gene-modified animals expressing (cleavage-reduced (TREM2-IPD), soluble-only (TREM2-sol), knock-out (TREM2-KO) TREM2and wildtype (WT) mice in the cuprizone model.. In the acute cuprizone model all genotypes showed demyelination detected by T2-weighted signal intensity increase in Magnetic resonance imaging (MRI), most prominent in the external capsule (EC) and less in the corpus callosum. In the 4-week recovery phase a partial signal reduction in WT and TREM2-IPD was observed, while in TREM2-sol and TREM2-KO showed an increase in MRI signal in the EC. In TREM2-IPD histology revealed no recovery of neuroinflammation as well as of the lysosomal marker LAMP-1, which was also evidenced in enhanced cytokine/chemokine levels. This persistent microgliosis and astrocytosis was also observed in TREM2-sol, to a lesser extent in TREM2-KO during recovery with both homeostatic (TMEM119) as well as activated (LAMP-1) microglia markers increased. An increase in cytokines/chemokines was not evident. This was accompanied, specifically in the EC with no myelin recovery, appearance of myelin debris and axonal pathology, while oligodendrocytes recovered. In the chronic cuprizone model TREM2-IPD displayed sustained microgliosis and enhanced remyelination in the recovery phase. Taken together, our data suggest that sustained microglia activation leads to increased remyelination, whereas microglia without membrane-functional or complete loss of TREM2 results in a dysfunctional phenotype with improper myelin debris removal, lack of remyelination and axonal pathology.
Development of an intrinsic health risk prediction model for camera-based monitoring of older adults living alone
Authors: Youm Sekyoung , Kim Minji , Hong Songiee
Published: March 2022

Due to the recent COVID-19 pandemic, drastic changes in the social service system for the care and safety of vulnerable social groups are urgently required in South Korea. It is interesting whether welfare technology can temporarily replace or supplement traditional care services, originally performed by trained human resources and further can be applied in a closed and non-contact living space. Therefore, efforts are being made to converge various intelligent information technologies such as artificial intelligence, robots, and IoT in care services. Considering the limitations of the "National Emergency Notification System,” which was first implemented for older adults living alone in Korea, we performed to establish a monitoring system that can measure health-threatening behaviors, social isolation, and self-neglect of older adults living alone using RGB video data and the latest deep learning methodologies. We would like to suggest future applicability of welfare technology, which can aid in active health care management instead of just simple monitoring. Such a welfare technology can provide a new alternative form of social service to increasing aging population in single-person households and to overcome changes in elder care environment
Hysteroscopic resection of type 3 fibroids improve pregnancy outcomes in infertile women: a case-control study
Authors: Han Ying , Yao Ruqiang , Zhang Yinfeng , Yang Zexin , Luo Haining , Wang XinYan , Du Aijun , Zhang Yunshan , Zhu Yingjun
Published: March 2022

Background: Evaluate the effect of hysteroscopic resection of type 3 fibroids on pregnancy outcomes in infertile women.Methods: Patients who underwent IVF-ICSI in our unit were divided into type 3 fibroids group and hysteroscopic myomectomy group according to whether or not they underwent ultrasound-guided hysteroscopic myomectomy. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroids group and hysteroscopic myomectomy group, random sampling was carried out in patients between 25 to 47 years to determine a control group. The outcomes measured included average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate.Results: A total 386 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. Average transfer times to live birth were significantly higher in the type 3 fibroids group than the other two groups. The frequency of cumulative live births in the type 3 fibroids group was significantly lower than control group. Compared with the control group, hysteroscopic myomectomy patients had no statistically significant differences in the rates of cumulative clinical pregnancy rate and cumulative live birth rate.Conclusions: Type 3 fibroids reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids, to improve pregnancy outcomes in infertile women.
3M MicrofoamTM Surgical Tape Prevents Nasal Pressure Injury Associated with Nasotracheal Intubation. A Randomized Double-Blind Trial
Authors: HASHIMOTO Mayumi , SATO(BOKU) Aiji , SENTO Yoshiki , KAMIMURA Yuji , KAKO Eisuke , OKUDA Masahiro , TACHI Naoko , OKUMURA Yoko , KURODA Izumi , HOSHIJIMA Hiroshi , ITO Hidekazu , SOBUE Kazuya
Published: March 2022

BACKGROUND
ː 3M Microfoam™ Surgical Tape (3ST: 3M Japan Limited) is a surgical tape used for pressure wound control of medical equipment and has characteristics of being cushioned and fitting to any body part. Herein, we investigated whether 3ST prevents nasotracheal intubation (NTI)-associated nasal pressure injury.
METHODS
ː We conducted a prospective, randomized double-blind study, enrolling 63 patients aged 20–70 years, who were subjected to general anesthesia with NTI and divided into two groups; those treated with 3ST (group S; n = 31) and control (group C; n = 31). After NTI and before securing the nasotracheal tube a 35 × 25 mm 3ST was used to protect the nasal wing in group S, and the nasotracheal tube was fixed in place after NTI without protection in group C. The primary outcome was the presence or absence of nasal pressure injury after extubation. Chi-Square test was used to assess the association between the two categorical variables.
RESULTS
ː Nasal pressure injury was observed in 7 and 19 patients from groups S and C, respectively, representing a significant difference between the two groups (24.1% vs. 67.8%, P = 0.001). None of the patients developed ulcers.
CONCLUSIONS
ː 3ST prevents NTI-associated nasal pressure injury.
A New Experimental Model of Krypton Laser-Induced Choroidal Neovascularization in Tree Shrew
Authors: LIU Xiao-Chen , WU Min
Published: March 2022

Purpose
This study was designed to establish a new choroidal neovascularization (CNV) model on tree shrew, and evaluate whether it is an ideal experimental animal model for CNV-related research.
Methods
60 tree shrews (60 eyes) were divided into one normal group and five experimental groups. Krypton laser photocoagulation was applied for CNV induction on tree shrew. Fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and flash visual evoked potential (F-VEP) were examined at 3, 7, 14, 21, and 28 days after laser. The pathological performance was observed by pathological section. The expression of multiple angiogenesis-related factors during CNV formation were checked by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
According to FFA and ICGA findings, success rate of CNV modeling on tree shrew was 70%. OCT showed the formation of typical CNV lesions on tree shrew. F-VEP indicated characteristic decrease of N1-P1 wave amplitude after CNV development. Pathological examination showed thin-walled new blood vessels emerging from choroid. The significant increased/decreased expression of angiogenesis-related factors were detected by qRT-PCR.
Conclusions
Krypton laser photocoagulation can successfully induce the CNV model on tree shrew with high success rate. The tree shrew CNV model could be widely accessible to CNV-related research.
Effectiveness of a Health Technician-delivered Brief Intervention for alcohol A Bayesian reanalysis of a clinical trial
Authors: Barticevic Nicolas Antonio , Poblete Fernando , Bradshaw Laura , Bendtsen Marcus
Published: March 2022

Objective:
To reanalyze a clinical trial on the effectiveness of a Brief Intervention (BI) delivered by non-professionals to reduce risky alcohol drinking. Our previous null-hypothesis test of the effects of the BI yielded a ‘non-significant’ p-value, yet remained uninformative. Here we use the Bayesian paradigm which allows for expressing the probability of different effect sizes to better inform public policy decisions.
Results:
The posterior probability of the odds of risky drinking at follow-up favored a marked effect of the BI, with 96% of the probability mass being less than OR = 1, and 84% being less than OR = 0.8. Our findings show that there is a high probability that the BI delivered by health technicians lowered risky alcohol use. The posterior distributions of the BI’s effects are presented to help contextualize the evidence for policy making in Chile.
Radiomic phenotype of epicardial adipose tissue in the prognosis of atrial fibrillation recurrence after catheter ablation in patients with isolated atrial fibrillation.
Authors: Ilyushenkova Julia , Sazonova Svetlana , Popov Evgeny , Zavadovsky Konstantin , Batalov Roman , Archakov Evgeny , Moskovskih Tatyana , Popov Sergey , Minin Stanislav , Romanov Alexander
Published: March 2022

BackgroundTo estimate the utility of pre-procedural CT-radiomic analysis of epicardial adipose tissue (EAT), and to identify patients at risk for isolated atrial fibrillation (AF) recurrence after catheter ablation (CA).MethodsThe study population (63 patients) consisted of study group (Group 1) and comparative group (Group 2). 43 patients with isolated AF referred for CA. Before CA, all of them underwent multidetector computed tomography coronary angiography. Segmentation and subsequent radiomic analysis of EAT were performed on calcium scoring series of 3D DICOM images using by 3D-Slicer. ResultsEpicardial adipose tissue in patients with isolated AF had a distinct radiomic phenotype. Thus, 45 of 93 calculated radiomic parameters of EAT, as well as EAT volume and attenuation, were significantly different between patients with isolated AF (Group 1) and persons without any arrhythmia (Group 2). Moreover, 17 radiomic parameters were significantly different in subgroups with and without AF recurrence (Group 1a and Group 1b). Multivariate regression analysis demonstrated that among all radiomic parameters only Gray Level Non-Uniformity Normalized (GLSZM) was an independent predictor of AF recurrence (OR 0.10027, 95%CI 1.0009-1.0044, p=0.002). ROC-curve analysis data showed that GLSZM >1227.4 indicates high probability of AF recurrence during 12 months (sensitivity 89.4 %, specificity 70.8 %, AUC: 0.809; p=0.001).ConclusionThe radiomic parameter GLSZM is associated with late AF recurrence after CA in patients with isolated AF. In current study GLSZM was a stronger predictor of isolated AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation.
Lower fiber consumption in women with Polycystic Ovary Syndrome: A Meta-analysis of observational studies
Authors: Leung Wing-Ting , Tang Zhi-Jing , Feng Yuan-Yuan , Guan Hai-Yun , Huang Zeng-Shu , Zhang Wei
Published: March 2022

Polycystic ovary syndrome is a common endocrine disorder of reproductive women which is associated with metabolic abnormalities and gut microbiota dysbiosis. The deficiency of dietary fiber, a crucial nutrient in daily diet, is also associated with a wide range of metabolic and reproductive abnormalities, and an altered gut microbial ecosystem. This study is a meta-analysis to summarize the available evidence on dietary fiber intake level in PCOS patients. Databases of PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were searched for observational studies and 13 studies were finally included. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) of daily dietary fiber intake and total energy intake were calculated using random-effect model. The pooled result (12 studies) on absolute dietary fiber intake showed that while there was no significant difference in the total energy intake [− 0.17 (− 0.44, − 0.009), P = 0.208], the dietary fiber intake was significantly lower in PCOS women than those of controls [− 0.32 (− 0.50, − 0.14), P < 0.001]. However, significant heterogeneity was detected across the studies (I2 = 65.6%, P = 0.001). Meta-regression suggested that geographic region and dietary assessment method may confer borderline significance of influence on the heterogeneity. The pooled result (2 studies) on dietary fiber intake which adjusted for total energy intake, however, showed no significant difference [−2.11 (− 4.77, 0.56), P = 0.122]. In subgroup analyses based on absolute dietary fiber intake, a lower dietary fiber intake in PCOS was observed in the studies which conducted in Asia, or studies which adopted food diary or records or food recall as dietary assessment method, or studies which had a case-control study design, or used Rotterdam criteria for PCOS definition. The difference of SMD was still significant in adult subgroup or in studies matched or unmatched for age.
Prevalence, awareness and control of type 2 diabetes mellitus and risk factors in Chinese elderly population
Authors: Liu Qing , Yan Yaqiong , Wu Tingting , Zhang Miao , Li Changfeng , Li Fang
Published: March 2022

Background: Type 2 diabetes mellitus is an expanding global public health issue, especially in developing countries. This study aimed to investigate the prevalence, awareness and control rate of type 2 diabetes mellitus, and assess its risk factors in elderly Chinese individuals.Methods: The health screening data of 376,702 individuals aged ≥65 years in Wuhan, China, were collected to analyse the prevalence, awareness, and control rates of diabetes. Indices, including fasting plasma glucose and other biochemical indicators, were measured for all participants using standard methods at the central laboratory. Multilevel logistic regression analysis was performed to assess the key determinants of the prevalence, awareness, and control rates of diabetes.Results: The prevalence, awareness, and control rates of diabetes in the Chinese individuals aged ≥65 years were 18.80%, 77.14%, and 41.33%, respectively. There were statistically significant differences in the prevalence, awareness, and control rates by gender. Factors associated with diabetes prevalence were age, body mass index (BMI), and central obesity; while those associated with awareness and control were gender, education level, marital status, physical activity, alcohol consumption, BMI, and central obesity.Conclusions: Diabetes is an important public health problem in the elderly in China. The awareness and control rates have improved, but overall remained poor. Therefore, effective measures to raise awareness and control the rates of diabetes should be undertaken to circumvent the growing disease burden in elderly Chinese people.
Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism
Authors: Liu Jichun , Liu Yuanyuan , Zhang Feilong , Cong F , Ling Yang , Fang Ping , Xie Xiangrong , Wang Xianghai , Yang Hao , Wei Youquan , Wang Jinfeng
Published: March 2022

Background: Intermediate-risk APE patients usually defined as hemodynamically stable, comprehending a great therapeutic dilemma , since some can deteriorate and eventually require reperfusion therapy .To evaluate the predictive values of short-term prognosis for intermediate-risk acute pulmonary embolism (APE) patients based on clinical data. Methods: A retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography (CTPA) was analyzed in the present study. Adverse clinical events outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. APE patients were stratified into two groups based on their adverse outcomes (n = 25) and controls (n = 49). Then, the clinical data of the two groups were compared. The receiver operating characteristic (ROC) curve was employed to explore the predictive value of white blood cell (WBC) counts and the ratio of right to left ventricular short-axis (RV/LV). Results: Brain natriuretic peptide, WBC count, and the RV/LV were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (TWI) in V1-V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2＜90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241-23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145-48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702-89.032; p = 0.013) ,TWI in V1-V3 (OR 5.617, 95% CI 1.228-25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035-1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curves indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p＜0.01). Moreover, an RV/LV > 1.165 was predictive for adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p＜0.01). A WBC count > 9.05 was predictive for adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively.Conclusion: Overall, a SaO2＜90%, RV/LV ratio, Syncope, TWI in V1-V3, and WBC counts could independently predict adverse outcomes in intermediate-risk APE patients.
Analysing the Component Changes and Microbial Community Structures in Huangjiu undergoing Rancidification
Authors: 胡 健 , Liu Shuangping , Liu Caixia , Huang Yuanyuan , Mao Jian
Published: March 2022

In an effort to develop rapid tests to grade the quality of rancidification characteristics during the traditional pottery jar storage process of Huangjiu, the microbial community structures and associated compositional variation at different stages of the rancidification were analyzed. A comparative analysis of component variations between rancidification and normal Huangjiu samples was carried out by HPLC. Microbial pollution induced rancidification by affecting alcohol strength, acidity, amino acid nitrogen, and conductivity indexes. Moreover, microelements, such as organic acids, amino acids, and bioamine also changed significantly. According to the PacBio RS II analysis of J-10 and J-13, J-10 contained 10 bacteria genera, 3 fungi genera, and 1 unclassified binuclear subkingdom fungus, at a significantly higher relative abundance compared to that of J-13 (p-value<0.01). The relative abundance of only 1 bacterium genus and 1 fungus genus in J-10 was significantly lower compared to those in J-13 (p-value<0.01). This indicated that microbial community structures vary in Huangjiu depending on the rancidification time. Increasing rancidification time caused the relative abundance of microbial community structure to also increase. Collectively, this study can serve as a reference point for researchers and industry partners interested in discussing the influence of rancidification on the quality, health safety, and industrialized development of Huangjiu.
Parasocial Relationships and Repeated Viewing of YouTube and TV Channels: A Mediated Moderated Framework
Authors: Hasan Asif , Rahman Eisha , Khan Amna , Abbas Mariyam
Published: March 2022

With the increasing penetration of the internet and modern entertainment-related technologies, there is a shift and surge in media usage behavior. Owing to the gravity of this issue, the researchers probed the predictors of audiences' repeated usage of certain media, i.e., TV and YouTube channels. Moreover, they explored the mediating influence of parasocial relationships on the relationship between media addiction and repeated usage. They also studied the moderation of emotional engagement on the relationship between media addiction and parasocial relationships. The nature of this study is cross-sectional and descriptive. A total of 400 participants were approached via convenience sampling and were requested to fill the questionnaires. However, the researchers received only 325 complete responses. Therefore, the data analysis via the PLS-SEM approach was performed on 325 responses. This assessment was done on the measurement model as well as the structural model. The results of the study revealed that TV channel addiction among the respondents tends to result in parasocial relationships. Moreover, the moderation of parasocial relationships and mediation of emotional engagement were also found to be significant in the case of TV channels. On the contrary, the results did not reveal a significant relationship between YouTube channel addiction and parasocial relationships. Additionally, the moderation of parasocial relationships and mediation of emotional engagement were also not found significant. A more detailed result is presented in the corresponding sections, and future directions are also provided.
Circulating redox status in sheep infected with dermatophytes: a field study
Authors: Saleh Mostafa A. , Rateb M. H. , Abd-Allah Elham A. , Mohamed Ghada A.E.
Published: March 2022

Dermatophytosis is a zoonotic mycotic infection of the skin caused by dermatophytes. The present study aimed to evaluate the oxidative stress (OS) and redox status in blood of sheep clinically infected with the dermatophyte, Trichophyton verrucosum. According to clinical and mycological investigations, 48 juvenile male Balady sheep were selected in their natural habitat and divided into four groups depending on lesions size: mild (MID), moderate (MOD), severe T. verrucosum infection (SEV) and healthy control groups. Compared to the controls, plasma superoxide anion increased (P < 0.05) in both MOD and SEV but total peroxides (TPx) gradually increased (P < 0.05) in MID followed by MOD and SEV. Superoxide dismutase and total antioxidant capacity (TAC) were higher (P < 0.05) in MID and lower (P < 0.05) in MOD and SEV than in controls, but SEV showed lower TAC than MOD. Malondialdehyde (MDA, a lipid peroxide marker) increased (P < 0.05) in SEV than in controls but protein carbonyl (PC, protein peroxidation marker) was augmented (P < 0.05) as lesions progressed from mild to severe. oxidative stress index (TPx/TAC ratio) progressively increased (P < 0.05) in MOD and SEV. The correlation of PC was positive with TPx and negative with TAC (P < 0.01). In conclusion, sheep infection with T. verrucosum is characterized by increased TPx and decreased TAC in plasma depending on the lesion area. The redox status is shifted towards the oxidizing state especially in MOD and SEV cases resulting in a condition of OS, which may contribute to the pathogenesis of the disease.
An Enhanced Harris Hawk Optimization Algorithm for Parameter Estimation of Single, Double and Triple Diode Photovoltaic Models
Authors: Ramadan Abdelhady , Kamel Salah , Korashy Ahmed , Almalaq Abdulaziz , Domínguez-García Jose Luis
Published: March 2022

Due to the rapid development of photovoltaic (PV) system and spreading of its application, the accuracy of modelling of solar cells, as the main and basic element of PV systems, is gaining relevance. In this paper, an Enhanced Harris Hawk Optimization Algorithm (EHHO) is proposed and applied for estimating the required parameters of different PV models in an effective and accurate way. Harris Hawk Algorithm (HHO) is based on Hawks ways in hunting and catching their brays. The HHO utilizes two phases including exploration and exploitation. The main purpose of proposed enhancement is to improve the second phase of HHO. This enhancement is performed on the exploration phase by fluctuating towards or outwards the best optimal solution using sine and cosine functions. Both conventional and proposed algorithms are applied for single, double and triple diode PV models. In order to test the applicability and robustness of proposed algorithm, it is applied for estimating the parameters of different real PV systems and compared with other recent optimization algorithms. The results show that the proposed EHHO is more accurate than conventional HHO and other algorithms.
GluR2 may drive neuroinflammation and cognitive impairments following peripherally repeated lipopolysaccharide exposures
Authors: He Xue , Gao Yuzhu , Yin Xiaoyu , Wu Xinmiao , Ji Muhuo , Shen Jinchun
Published: March 2022

Neuroinflammation has been demonstrated to play a key role in the pathogenesis of many neurological and neuropsychiatric diseases. Lipopolysaccharides (LPS), an element of the cell envelope of gram-negative bacteria, could activate the innate immune system to induce neuroinflammation and eventually lead to cognitive impairments. Accumulating evidence has suggested the presence of glutamate receptors (GluRs) on glial cells can induce glial activation. Therefore, we hypothesized that repeated lipopolysaccharide exposures could increase GluR levels and mediate microglia activation, eventually contributing to synaptic plasticity and cognitive impairments. In the present study, C57/BL6 mice were subjected to repeated LPS exposures to establish the animal model of neuroinflammation. The levels of GluRs, inflammatory cytokines, ionized calcium binding adaptor molecule 1 (Iba1), postsynaptic density protein 95 (PSD-95), synaptophysin 38 (SVP38), NMDA receptor 2A (GluN2A), and GluN2B were determined in the hippocampi. The dendritic spine density was evaluated in the CA1 of the hippocampi. Our results showed that repeated LPS exposures induced cognitive impairments, increased the levels of GluR1 and GluR2 and induced microglia activation, which were accompanied by significantly decreased GluN2B expression and dendritic spine density in the hippocampi. However, AMPAR antagonist CFM-2 administration reversed these abnormalities. In addition, microglia inhibitor minocycline also reversed these abnormalities, downregulated GluR2 but not GluR1 expresssion. In conclusion, our study demonstrated that GluR2 may be an important contributor to microglia mediated-neuroinflammation, leading to synaptic plasticity and cognitive impairments induced by repeated LPS exposures.
Decline in Carbon Decomposition from Litter After Snow Removal is Driven by a Decreased Release of Carbohydrates
Authors: Zhu Jingjing , Wu Qiuxia , Wu Fuzhong , Yue Kai , Ni Xiangyin
Published: March 2022

Purpose
Winter snow cover is a key control over soil biogeochemical cycles in cold biomes but has decreased with climate warming, particularly in high-latitude and high-altitude areas. Previous studies have found a decline in carbon (C) release from decomposing litter without snow cover, yet partitioning of what C fractions in response to snow removal remains not fully understood.
Methods
Here we incubated fir and birch litter in microcosms over two years of decomposition in an alpine forest to assess the release of various C fractions with and without snow cover using 13C nuclear magnetic resonance (NMR).
Results
We found that 51% and 61% of total C were lost from fir and birch litter, respectively, after two years of decomposition, and 59% and 60% of these C were decomposed during winter time. More C was lost from both fir and birch litter under snow cover, and the decomposition rate of birch litter C was decreased by 50% after snow removal. However, only O-alkyl C (particularly carbohydrate C) release was reduced with snow removal, and the release of other C fractions (i.e., alkyl C, aromatic C and carbonyl C) did not change significantly after removing snow cover. Reduction in O-alkyl C release from fir and birch litter was in accordance with the declines in soil dissolved organic C, invertase activity and microbial respiration rate under removed snow plots.
Conclusion
We conclude that a reduction in winter snow cover regulates early decomposition of plant litter by controlling the rapid release of more labile C fractions in seasonally snow-covered ecosystems.
Ferroptosis Contributes to Hypoxic-Ischemic Brain Injury in Neonatal Rats: Role of the SIRT1/Nrf2/GPx4 Signaling Pathway
Authors: Li Chang , Wu Zi-Yi , Xue Hang , Gao Qiu-Shi , Zhang Ya-Han , Wang Chang-Ming , Zhao Ping
Published: March 2022

Aims
Hypoxic-ischemic brain injury (HIBI) often results in cognitive impairments. Herein, we investigated the roles of ferroptosis in HIBI and the underlying signaling pathways.
Methods
The ferrostatin-1(Fer-1) or resveratrol (Res) treatments were administered intracerebroventricularly 30 min before HIBI in 7-day-old rats. Glutathione peroxidase 4 (GPx4) expression, malondialdehyde (MDA) concentration, iron content, mitochondrial morphology and the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured after HIBI modeling. Additionally, the weight ratio of left/right hemispheres and brain morphology were determined and Nissl staining was conducted to reflect brain damage. The Morris water maze test was used to assess cognitive function.
Results
At 24 h after HIBI, GPx4 expression was decreased and MDA concentration and iron content were increased in the hippocampi. HIBI led to mitochondrial atrophy, brain atrophy/damage, and resultant learning and memory impairments, which were alleviated by inhibiting ferroptosis using Fer-1. Furthermore, the upregulation of SIRT1 expression by Res treatment increased the expression of Nrf2 and GPx4, which in turn attenuated ferroptosis, reducing brain atrophy/damage and improving learning and memory abilities.
Conclusion
Our results demonstrated the occurrence of ferroptosis during HIBI via the SIRT1/Nrf2/GPx4 signaling pathway. Thus, this pathway represents a potential therapeutic target for the inhibition of ferroptosis and amelioration of HIBI-induced cognitive impairments.
Relationships between physical activity, healthy eating and cortical thickness in children and young adults
Authors: Angelo Brendan C , DeFendis Alexis , Yau Anita , Alves Jasmin M. , Thompson Paul M. , Xiang Anny H , Page Kathleen A. , Luo Shan
Published: March 2022

Prior neuroimaging studies have shown associations between healthy lifestyle factors and cortical thickness measurements; however, results on the direction of the association between cortical thickness, a measure of gray matter width, and healthy lifestyle factors have been inconsistent. While the majority of studies were performed in older adults within specific weight status categories, little has been reported in younger populations with a range of adiposity, including groups with healthy-weight, overweight and obesity. Here we investigated relationships between indices of physical activity (PA) and healthy eating with cortical thickness in children and young adults and examined whether these relationships differed by weight status and age groups. Study participants included 119 young adults and 159 children. We hypothesized that greater levels of PA and/or healthy eating index (HEI) composite scores would be positively associated with cortical thickness across age groups, and that this association would differ in overweight or obese groups versus normal weight groups. Overall PA (minutes/day) was assessed using 24-hour PA recalls. HEI was calculated to assess diet quality. A structural MRI was performed, and FreeSurfer 6.0 was used to assess cortical thickness in 68 regions of interest (ROI). Mixed effects modeling was performed to investigate associations of PA or HEI with cortical thickness. FDR corrections were applied for multiple ROIs. PA was positively associated with cortical thickness in the caudal middle frontal cortex (FDR adjusted p = 0.042) and cuneus cortex (FDR adjusted p = 0.017), after controlling for sex, age group and weight status. When stratified by age, in young adults, higher time spent in PA was associated with greater cortical thickness in the frontal, temporal, parietal and occipital cortex, after adjusting for sex and weight group (FDR adjusted ps < 0.05). No significant associations between PA and cortical thickness were observed in children. No significant associations between HEI and cortical thickness were observed. These results indicate that higher time spent in PA is associated with greater cortical thickness, a relationship that appears to be stronger during young adulthood and may be related to more favorable brain health outcomes.
Pan-Cancer Analysis of Kinesin Family Member 2C (KIF2C) in Human Tumors
Authors: Zhang Bixi , Li Yanchun , Gong Siming , Duan Yingjuan , Xu Meihua , Xu Canxia , Wu Hao
Published: March 2022

Kinesin family member 2C (KIF2C) is the best-characterized member of the kinesin-13 family and is involved in accurately fine-tuned dynamics of mitotic spindles. As KIF2C is involved in both spindle formation and regulation of DNA double-strand breaks, precise regulation of KIF2C is essential to prevent malignant transformation associated with gains and losses of DNA content. In the present study, we initially reviewed The Cancer Genome Atlas database and observed that KIF2C is abundantly expressed in most tumor types. We then analyzed the gene alteration profile, protein expression, prognosis, and immune reactivities of KIF2C in more than 10,000 samples from several well-established databases. In addition, we conducted a gene enrichment set analysis to investigate the potential mechanisms underlying the role of KIF2C in tumorigenesis. Pan-cancer analysis of KIF2C demonstrated significant statistical correlations between KIF2C expression and clinical prognosis, oncogenic signature gene sets, myeloid-derived suppressor cell infiltration, ImmunoScore, immune checkpoints, microsatellite instability, and tumor mutational burden across multiple tumors. The findings of this study provide important insight for understanding the role and mechanisms of KIF2C in tumorigenesis and immunotherapy and its clinical progression in a variety of cancers.
On Mann Implicit Composite Subgradient Extragradient Methods for General Systems of Variational Inequalities with Hierarchical Variational Inequality Constraints
Authors: Shehu Yekini , Ceng Lu-Chuan , Yao Jen-Chih
Published: March 2022

In a real Hilbert space, let the VIP, GSVI, HVI and CFPP denote a variational inequality problem, a general system of variational inequalities, a hierarchical variational inequality and a common fixed-point problem of a countable family of uniformly Lipschitzian pseudocontractive mappings and an asymptotically nonexpansive mapping, respectively. We design two Mann implicit composite subgradient extragradient algorithms with line-search process for finding a common solution of the CFPP, GSVI and VIP. The suggested algorithms are based on the Mann implicit iteration method, subgradient extragradient method with line-search process, and viscosity approximation method. Under mild assumptions, we prove the strong convergence of the suggested algorithms to a common solution of the CFPP, GSVI and VIP, which solves a certain HVI defined on their common solutions set.
Ross operation in pediatric population: impact of surgical timing and the native pulmonary diameter on the outcome.
Authors: Varrica Alessandro , Giamberti Alessandro , Rito Mauro Lo , Reali Matteo , Hafdhullah Mahmood , Satriano Angela , Saracino Antonio , Micheletti Angelo , Frigiola Alessandro
Published: March 2022

Background: Aortic valve replacement early in life maybe inevitable at times. Ross operation until present-day remains the favorite surgical option in pediatrics with irreparable aortic valve disease. Nonetheless the necessity for re-operation was always its principal limitation due to aortic valve failure or homograft degeneration. We hereby present our 25 years of experience in pediatric population.Methods: From August 1994 until June 2018, a total of 157 children below 18 years underwent a Ross operation. This retrospective review aims at assessing long-term outcome likewise risk factors for re-operation after Ross procedure.Results: Median age was 10.9 years, of which 7 were infants, 79 children and 71 adolescents. Median follow-up was 14 years. Hospital mortality was 0.6%. Freedom from autograft re-operation for children was 96.7% and 94.1% at 10 and 20 years respectively, whereas for adolescents it was 92.6% and 74.9% at 10 and 20 years. For children freedom from homograft re-operation was 92.5%, 83.5% and 56.2% at 10, 15, and 20 years respectively. While for adolescents, it was 96.8%, 91.8%, and 86.7% at 10, 15, and 20 years. Homograft size (p=0.008) and childhood (p=0.05) were risk factors for homograft re-operation. Pulmonary valve diameter >24 mm (p=0.044) and adolescence (p=0.032) were risk factors for autograft re-operation.Conclusions: Our experience demonstrated excellent early and late survival. Whilst children have preferential outcomes concerning autograft re-operation, those who received a smaller homograft had higher incidences of right-sided re-intervention compared to adolescents. Pulmonary diameter >24mm at surgery was an indicator for future autograft failure.
A ferroptosis-related signature for predicting prognosis and immunotherapy response in cervical squamous carcinoma
Authors: Yang Yuling , Fu Xing , Yang Yiping
Published: March 2022

Background: Ferroptosis is an iron-dependent form of programmed cell death that plays a vital role in tumorigenesis and progression. However, the prognostic value of ferroptosis related genes (FRGs) in cervical squamous carcinoma (CSC) remains unknown. Method: Differentially expressed FRGs (DE-FRGs) were identified via the GEO2R online tool. Univariate and LASSO cox regression analyses were used to develop a ferroptosis-related signature. Kaplan-Meier curves, receiver operating characteristics (ROC), and Cox regression analyses were applied to explore the prognostic performance of signature. GSEA analysis was used to identify tumor hallmarks. The immune inflation and Immunophenoscore (IPS) analysis were used to predict immune response. Result: A total of 22 differentially expressed FRGs were screened between CSC and normal tissue. Based on the DE-FRGs, CSC patients were classified into three subtypes, with significant immune status and survival differences. The ferroptosis-related signature was developed based on 5-FRGs by LASSO cox regression analysis. The area under the curve (AUC) for predicting 1-, 3-, and 5-year overall survival (OS) was 0.755, 0.701, and 0.697 in the TCGA, and 0.790, 0.756, and 0.701 in the GSE52903, respectively. Kaplan-Meier curves indicate a poor prognosis for the high risk group. The riskscore was an independent prognostic factor. The term of hypoxia, epithelial mesenchymal transition，mtorc1signal，myc-targets were enriched in high risk group. The infiltration of T-cell CD8+, Myeloid dendritic cell resting，and Mast cell resting was higher in the low-risk group. IPS analysis suggests that patients with low risk score may be suitable for immunotherapy. We found a lower risk score correlated with the immunotherapy response (PR/CR) group than in the non-response (PD/SD) group by datasets of GSE78220 and IMvigor210. Surprisingly, the AUCs for predicting immune response were 0.728 and 0.628, respectively, which were better than PD-1 and PDL-1.Conclusion：We constructed a ferroptosis-related signature that can accurately predict prognosis and correlates with immune infiltration and immunotherapy.
Influence of glutathione-S-transferase polymorphisms on the metabolism of the potent aromatase inhibitor, exemestane
Authors: Teslenko Irina , Trudeau Julia , Luo Shaman , Watson Christy J.W. , Chen Gang , Truica Cristina I. , Lazarus Philip
Published: March 2022

Background:Exemestane (EXE) is used to treat post-menopausal women diagnosed with estrogen receptor positive (ER+) breast cancer. A major mode of metabolism of EXE and its active metabolite, 17β-dihydroexemestane (17β-DHE), is via glutathionylation by glutathione-S-transferase (GST) enzymes. The goal of the present study was to investigate the effects of genetic variation in EXE-metabolizing GST enzymes on overall EXE metabolism.Methods:Seventy-five normal human liver tissue bank specimens, and plasma and urine from 68 ER+ breast cancer patients receiving EXE, were included in this study. Samples were genotyped for GSTA1 and GSTM1 by real-time PCR. The EXE-GS and DHE-GS conjugation rates in human liver specimens and levels of EXE-cys, DHE-cys and DHE-Gluc in plasma and urine were determined by UPLC/MS.Results:Ex vivo assays examining human liver revealed the GSTA1 *B/*B genotype was associated with significant decreases in EXE-GS (26%, p=0.034) and DHE-GS (15%, p=0.014) formation. In the plasma of 68 ER+ breast cancer patients treated with EXE, the GSTA1 *B*B genotype was associated with significant decreases in both EXE-cys (29%, p=0.0056) and DHE-cys (34%, p=0.032). A near-significant (ptrend=0.060) trend was observed for urinary EXE-cys levels from the same patients. In contrast, plasma and urinary DHE-Gluc levels were significantly increased (36%, p=0.00097; and 52%, p=0.0089, respectively) in patients with the GSTA1 *B*B genotype. No significant correlations were observed between GSTM1 genotype and EXE metabolite levels.Conclusions:These data suggest that the GSTA1*B allele is associated with interindividual variability in EXE metabolism and may play a role in overall response to EXE.Trial registration: retrospectively registered
Comprehensive immunovirological and environmental screening reveals risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks
Authors: Cuypers Lize , Keyaerts Els , Hong Samuel , Gorissen Sarah , Menezes Soraya Maria , Starick Marick , Elslande Jan Van , Weemaes Matthias , Wawina-Bokalanga Tony , Vanmechelen Bert , Holm Bram Van , Bloemen Mandy , Dogne Jean-Michel , Dufrasne François , Durkin Keith , Ruelle Jean , De Mendonca Ricardo ,   COVID-19 Genomics Belgium Consortium, Wollants Elke , Vermeersch Pieter , Bouloffe Caroline , Djiena Achille , Broucke Caroline , Catry Boudewijn , Lagrou Katrien , Ranst Marc Van , Neyts Johan , Baele Guy , Maes Piet , André Emmanuel , Dellicour Simon , Weyenbergh Johan Van
Published: March 2022

COVID-19 vaccination has resulted in excellent protection against fatal disease, including in the elderly. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases) by combining SARS-CoV-2 aerosol monitoring, whole-genome phylogenetic analysis, and immunovirological profiling by digital nCounter transcriptomics. Phylogenetic investigations indicated each outbreak stemmed from a single introduction event, though with different variants (Delta, Gamma, and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 days after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 signatures and reanalysis of single-cell RNAseq data highlights the unique immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy including environmental sampling, immunomonitoring, and early antiviral therapy should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.