bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights of Chinese herbal medicine for mitochondrial dysfunction in chronic cerebral hypoperfusion induced cognitive impairment: Existed evidences and potential directions
Authors: Wang Yefei , Wang Ying , Li Shixin , Jin Huihui , Duan Jiayu , Lu Xiyue , Qin Yinglin , Song Jiale , Li Xiaoshan , Jin Xianglan
Published: February 2023

Chronic cerebral hypoperfusion (CCH) is one of the main pathophysiological markers of cognitive impairment in central nervous system diseases. Mitochondria are cores of energy generation and information process. Mitochondrial dysfunction is the key upstream factors of CCH induced neurovascular pathology. Increasing studies explored the molecular mechanisms of mitochondrial dysfunction and self-repair for effective targets to improve CCH-related cognitive impairment. The clinical efficacy of Chinese herbal medicine in the treatment of CCH induced cognitive impairment is definite. Existed evidences from pharmacological studies have further proved that, Chinese herbal medicine could improve mitochondrial dysfunction and neurovascular pathology after CCH by preventing calcium overload, reducing oxidative stress damage, enhancing antioxidant capacity, inhibiting mitochondria-related apoptosis pathway, promoting mitochondrial biogenesis and preventing excessive activation of mitophagy. Besides, CCH mediated mitochondrial dysfunction is one of the fundamental causes for neurodegeneration pathology aggravation. Chinese herbal medicine also has great potential therapeutic value in combating neurodegenerative diseases by targeting mitochondrial dysfunction.
Physiological and transcriptomic responses to cold waves of the most cold-tolerant mangrove, Kandelia obovata
Authors: He Shanshan , Wang Xianxian , Du Zhiyu , Liang Pingping , Zhong Yifan , Wang Lin , Zhang Yuan-Ye , Shen Yingjia
Published: February 2023

Mangrove forests inhabit tropical or subtropical intertidal zones and have remarkable abilities in coastline protection. Kandelia obovata is considered the most cold-tolerant mangrove species and has been widely transplanted to the north subtropical zone of China for ecological restoration. However, the physiological and molecular mechanisms of K. obovata under colder climate was still unclear. Here, we manipulated the typical climate of cold waves in the north subtropical zone with cycles of cold/recovery and analyzed the physiological and transcriptomic responses of seedlings. We found that both physiological traits and gene expression profiles differed between the first and later cold waves, indicating K. obovata seedlings were acclimated by the first cold experience and prepared for latter cold waves. 1,135 cold acclimation-related genes (CARGs) were revealed, related to calcium signaling, cell wall modification, and post-translational modifications of ubiquitination pathways. We identified the roles of CBFs and CBF-independent transcription factors (ZATs and CZF1s) in regulating the expression of CARGs, suggesting both CBF-dependent and CBF- independent pathways functioned in the cold acclimation of K. obovata. Finally, we proposed a molecular mechanism of K. obovata cold acclimation with several key CARGs and transcriptional factors involved. Our experiments reveal strategies of K. obovata coping with cold environments and provide prospects for mangrove rehabilitation and management.
Improving phosphorus acquisition efficiency through modification of root growth responses to phosphate starvation in legumes
Authors: Chen Zhijian , Wang Linjie , Cardoso Juan Andres , Zhu Shengnan , Liu Guodao , Rao Idupulapati M. , Lin Yan
Published: February 2023

Phosphorus (P) is one of the essential macronutrients for plant growth and development, and it is an integral part of the major organic components, including nucleic acids, proteins and phospholipids. Although total P is abundant in most soils, a large amount of P is not easily absorbed by plants. Inorganic phosphate (Pi) is the plant-available P, which is generally immobile and of low availability in soils. Hence, Pi starvation is a major constraint limiting plant growth and productivity. Enhancing plant P efficiency can be achieved by improving P acquisition efficiency (PAE) through modification of morpho-physiological and biochemical alteration in root traits that enable greater acquisition of external Pi from soils. Major advances have been made to dissect the mechanisms underlying plant adaptation to P deficiency, especially for legumes, which are considered important dietary sources for humans and livestock. This review aims to describe how legume root growth responds to Pi starvation, such as changes in the growth of primary root, lateral roots, root hairs and cluster roots. In particular, it summarizes the various strategies of legumes to confront P deficiency by regulating root traits that contribute towards improving PAE. Within these complex responses, a large number of Pi starvation-induced (PSI) genes and regulators involved in the developmental and biochemical alteration of root traits are highlighted. The involvement of key functional genes and regulators in remodeling root traits provides new opportunities for developing legume varieties with maximum PAE needed for regenerative agriculture.
The executive disruption model of tinnitus distress: Model validation in two independent datasets using factor score regression
Authors: Clarke Nathan A. , Akeroyd Michael A. , Henshaw Helen , Hall Deborah A. , Mohamad Wan Najibah Wan , Hoare Derek J.
Published: February 2023

This study presents the executive disruption model (EDM) of tinnitus distress and subsequently validates it statistically using two independent datasets (the Construction Dataset: n = 96 and the Validation Dataset: n = 200). The conceptual EDM was first operationalised as a structural causal model (construction phase). Then multiple regression was used to examine the effect of executive functioning on tinnitus-related distress (validation phase), adjusting for the additional contributions of hearing threshold and psychological distress. For both datasets, executive functioning negatively predicted tinnitus distress score by a similar amount (the Construction Dataset: β = −3.50, p = 0.13 and the Validation Dataset: β = −3.71, p = 0.02). Theoretical implications and applications of the EDM are subsequently discussed; these include the predictive nature of executive functioning in the development of distressing tinnitus, and the clinical utility of the EDM.
Time from injury and age interact in relationship with perceived quality of life outcomes following vocation-focused neuropsychological rehabilitation
Authors: Bloch Ayala , Shany-Ur Tal , Sharoni Limor , Bar-Lev Narkis , Salomon-Shushan Tali , Maril Sari , Druckman Eran , Hoofien Dan
Published: February 2023

At the group level, community-based neuropsychological rehabilitation interventions with a vocational focus are generally effective among individuals with brain injuries. However, individual participants vary significantly in the extent of their improvement, prompting attempts to elucidate individual, injury-related, and environmental factors affecting prognosis. In this study, we examined the relationships between one such factor – “time from injury” (the time between injury and intervention) – and two outcome measures: employment status and perceived quality of life (PQoL), in 157 brain injury survivors, before and after a holistic neuropsychological vocational rehabilitation program. We also examined whether relationships between the variables were moderated by age at onset of treatment and injury severity. In the entire sample, both the proportion of employed participants and average PQoL increased following program participation. Neither, time from injury, severity, nor age at onset of treatment predicted the increase in employment proportion, and severity was not a significant predictor of PQoL. However, an interactive effect indicated that when treatment was started at a younger age, longer time from injury predicted higher levels of PQoL, but when treatment was started at older ages, longer time from injury predicted lower levels of PQoL. When interpreted alongside existing literature, these results suggest that delaying vocational components of rehabilitation can be beneficial for younger participants, while the effectiveness of vocational rehabilitation can be maximized by starting as early as possible among older participants. Most importantly, regardless of age, it appears that vocational rehabilitation can be effective even when initiated many years after injury.
Latent classes of eating disorders and addictions by sex: Implication of alexithymia and stressful life events in youths
Authors: Macía Laura , Momeñe López Janire , Macía Patricia , Herrero Marta , Jauregui Paula , Iruarrizaga Iciar , Estévez Ana
Published: February 2023

Introduction

Eating disorders (EDs) and behavioural addictions show common psychological vulnerability factors such as alexithymia and stressful life events (SLE). This study aims, firstly, to explore the prevalence and latent profiles of participants based on their risk of suffering EDs, gambling disorder (GD), alcohol and/or drug abuse, and compulsive buying (CB) by sex. Secondly, it aimed to test whether alexithymia and having experienced SLE are associated with group membership.

Methods

The sample was predominantly drawn from university students and social networks. It was composed of 352 young adults between 18 and 35 years old, of whom 77.8% were women and 22.2% men.

Results

The results showed that the most prevalent disorders of the sample were alcohol, EDs, CB, drugs and GD, respectively. Moreover, latent class analyses were conducted based on the risk of suffering EDs or addictions by sex. Three main profiles were found: ‘Men with addictions’, ‘Healthy women’ and ‘Women with EDs’. Finally, differences in SLE and alexithymia levels were tested by latent classes. “Men with addictions” and “Women with EDs” had higher scores on alexithymia and SLE than the group of “Healthy women”. However, the group of “Women with EDs” (class 3) reported significantly higher levels of SLE and alexithymia than the other two groups.

Discussion and conclusion

In conclusion, we discuss the possibility that some vulnerability factors operate generally and transdiagnostically in EDs and addictive disorders. The identification of clinical phenotypes could complement and deepen prediction, prevention and treatment research in clinical settings. The need to take sex and gender differences into account is reinforced.
There is no rush to upgrade the tennis racket in young intermediate competitive players: The effects of scaling racket on serve biomechanics and performance
Authors: Touzard Pierre , Lecomte Chloé , Bideau Benoit , Kulpa Richard , Fourel Loïc , Fadier Maxime , Cantin Nicolas , Martin Caroline
Published: February 2023

Introduction

Scaling the equipment of young athletes is justified by the constraints-led approach introduced in motor learning. The aim of the present study is to analyze the effect of racket scaling on the serve biomechanics and performance parameters for young tennis players (between 8 and 11 years-old).

Methods

Nine young intermediate competitive tennis players (age: 9.9 ± 1.0 years) performed maximal effort flat serves with three different rackets (scaled 23 inches, scaled 25 inches and full-size 27 inches) in a randomized order. A radar measured ball speed while shoulder and elbow kinetics and upper and lower limb kinematics were calculated with a 20-camera optical motion capture system. Repeated measures ANOVAs were used to analyze the effect of the three rackets on ball speed, percentage of serve in, serve kinematics and kinetics.

Results

No significant differences in ball speed, maximal racket head velocity and percentage of serve in were observed between the three rackets. The lowest maximal upper limb kinetics and the highest upper limb maximal angular velocities were obtained with the scaled 23 inches racket.

Discussion

Using scaled rackets has the advantage to decrease shoulder and elbow loadings without reducing serve performance. Consequently, the present results incite tennis coaches and parents to not upgrade too soon the size of the racket in young intermediate tennis players to avoid overuse injury risks in the long term. Our results showed that the full-size 27 inches racket induced higher lower limb kinematics. As a consequence, occasionally serving with a fullsize racket can be a sparingly interesting intervention to help young tennis players to intuitively and immediately increase their leg drive action, allowing a more functional representation of the elite junior serve.
Development of a theoretical construct for teacher expertise in the Chinese context and identification of its components: A mixed-methods study
Authors: Cai Yonghong , Li Yanli , Tang Runjia
Published: February 2023

Introduction

Teacher expertise is a vital element of teaching quality. Examining what constitutes teacher expertise has important implications for the theoretical development and practical application of teacher expertise. The present study was conducted to develop a theoretical construct for teacher expertise in the Chinese context, identify its components, and verify the validity of this construct.

Methods

This study adopted an exploratory sequential mixed-methods design. To develop a construct for teacher expertise and identify its components, critical incident interviews were conducted with 102 primary and secondary school teachers. Grounded theory analysis was applied to code 621 stories from critical incident interviews. To verify the construct validity and discriminant validity, a survey of 1,041 teachers was conducted in 21 primary schools and 20 secondary schools in Hebei and Shanxi provinces. Confirmative factor analysis, Kruskal-Wallis test, and Mann-Whitney test were used to evaluate the validity of the construct.

Results

Knowledge structure, teaching ability, and professional development agency constituted the construct for teacher expertise. This construct had good construct validity and discriminant validity. Knowledge structure could not identify expertise. Teaching ability and professional development agency could differentiate between expert and non-expert teachers.

Discussion

Teacher expertise is a complex, multidimensional, and adaptive construct. The construct can be used as a valid and reliable instrument to identify and develop teacher expertise. Moreover, this study expands on prior studies and complements recent theoretical models describing teacher expertise.
Expectations do not need to be accurate to be maintained: Valence and need for cognitive closure predict expectation update vs. persistence
Authors: Henss Larissa , Pinquart Martin
Published: February 2023

Expectations about us and our environment serve to successfully anticipate the future, make accurate predictions, and guide behavior and decisions. However, when expectations are not accurate, individuals need to resolve or minimize incongruence. Coping is especially important when expectations affect important domains such as students’ academic self-concept. Whether expectations are adjusted after expectation violation (accommodation), maintained by denying the discrepancy (immunization), or whether individuals modify behavior to minimize the likelihood of future expectation violations (assimilation) depends on situational and dispositional predictors. In our experiment, we examined valence of expectation violation (positive vs. negative) as a situational predictor together with need for cognitive closure (NCC) as a dispositional predictor with N = 297 participants in a word riddle study. MANCOVA revealed that students tended to assimilate and accommodate more strongly after worse-than-expected achievement, and also NCC promoted both stronger accommodation and assimilation. NCC interacted with the valence of expectation violation: individuals with high NCC reported more assimilation and accommodation only after worse-than-expected achievement. The results replicate and extend previous findings: individuals do not always strive to have the most accurate expectations possible. Instead, both affective (valence) and cognitive (NCC) predictors appear to affect which coping strategy is preferred by the individual.
Effect of developmental stress on the in vivo neuronal circuits related to excitation–inhibition balance and mood in adulthood
Authors: Oh Se Jong , Lee Namhun , Nam Kyung Rok , Kang Kyung Jun , Lee Kyo Chul , Lee Yong Jin , Seok Jeong-Ho , Choi Jae Yong
Published: February 2023

Introduction

Traumatic events in early life have a deleterious effect on the development of normal brain developments, which may be a cause of various psychiatric disorders in adulthood. Most prior studies focused on molecular biological aspects, and research on functional changes in neural circuits is still limited. We aimed to elucidate the effect of early life stress on in vivo excitation–inhibition and serotonergic neurotransmission in the adulthood using non-invasive functional molecular imaging (positron emission tomography, PET).

Methods

To compare the effect of stress intensity, early life stress animal models were divided into single trauma (MS) and double trauma groups (MRS). MS was derived from maternal separation, whereas MRS was derived from maternal separation and restraint stress after birth. And to evaluate the stress vulnerability on the sex, we used male and female rats.

Results

The MRS group showed greater weight loss and more severe depressive/anxiety-like behaviors than the MS and control groups. Corticosterone levels in MRS showed a greater extent of decline than in the MS group; however, there was no significant difference in the change of T3 and T4 between MS and MRS. In the PET, the stress exposure groups showed lower brain uptake for GABAergic, glutamatergic, and serotonergic systems compared with the control group. The excitatory/inhibitory balance, which was derived by dividing glutamate brain uptake into GABAergic uptake, increased as stress intensity increased. Neuronal degeneration in the stress exposure groups was confirmed by immunohistochemistry. In the sex comparison, female showed the greater changes of body weight, corticosterone level, depressive/anxiety-like behavior, and neurotransmission systems than those in male.

Conclusion

Taken together, we demonstrated that developmental stress induces dysfunction of neurotransmission in vivo, and that females are more vulnerable to stress than males.
Long-term care insurance and multidimensional poverty of middle-aged and elderly: Evidence from China
Authors: Li Wenxiu , Ke Jin , Sun Fei
Published: February 2023

Introduction

This paper examined the impact of public long-term care insurance (LTCI) pilots in China on the multidimensional poverty status of middle-aged and older adults.

Methods

Using panel data from the China Health and Retirement Longitudinal Survey, we utilized LTCI pilots conducted in different cities from 2012 to 2018 and assessed the impact of LTCI using a difference-in-differences strategy.

Results

We found that the implementation of LTCI reduces the multidimensional poverty of middle-aged and older adults and their likelihood of future multidimensional poverty. LTCI coverage was also associated with a reduction in the likelihood that middle-aged and older adults in need of care fall into income poverty, living consumption poverty, health poverty, and social participation poverty.

Discussion

From a policy perspective, the findings of this paper suggest that the establishment of an LTCI system can improve the poverty of middle-aged and older adults in several ways, which has important implications for the development of LTCI systems in China and other developing countries.
A study on the content of integrity policies and research integrity management in Chinese universities
Authors: Cao Yuan , Jiang Yuwei , Zhao Yong
Published: February 2023

Background

This study outlines a comprehensive analysis of the primary characteristics of managing research integrity (RI) in domestic colleges and universities in China. RI education in China consists primarily of soft advocacy, with no hard requirements or continuous and systematic support. Together with other stakeholders, such as funders and publishers, higher education institutions (e.g., colleges and universities) are one of the vital actors that have a lot of influence on RI promotion and implementation among researchers. However, the literature on the regulation of RI policies in China's universities is limited.

Methods

We investigate the top 50 colleges and universities in the 2021 Best Chinese Universities Ranking. Their guidance and policy documents on RI were collected via their official websites. By integrating the use of scientometrics analysis, including descriptive statistical analysis, inductive content analysis, and quantitative analysis, we examine whether and how these higher education institutions respond to national policies in a timely manner, especially in terms of their frequency of updates, topic clustering analysis, terms clustering analysis, content aggregation. To further understand the composition mechanism and the main working systems of university RI management organizations, we conducted in-depth research on the organizational functions, meeting system, staff composition mechanism, and scientific research misconduct acceptance and investigation mechanisms.

Results

The regulations on the treatment of RI in China's universities have, in response to the government's call to establish their own management policies and working mechanisms, maintained a zero-tolerance stance on research misconduct. The sampled universities listed the definition and principles of misconduct practices, investigation procedures, and sanctions of research misconduct in their own policy documents. Some of them listed inappropriate research practices All 50 sampled universities have formed relevant organizations responsible for RI management, they all provide the detailed regulations of the committees. Yet, there is still a need to further define Questionable Research Practice, foster higher standards for integrity in research and, establish and improve an efficient, authoritative, well-restrained and supervision working mechanism for organizations responsible for RI treatment.
Eco-physiological response of secondary metabolites of teas: Review of quality attributes of herbal tea
Authors: Ramphinwa Maanea Lonia , Mchau Godwin Richard Ainamensa , Mashau Mpho Edward , Madala Ntakadzeni Edwin , Chimonyo Vimbayi Grace Petrova , Modi Thembinkosi Albert , Mabhaudhi Tafadzwanashe , Thibane Vuyisile Samuel , Mudau Fhatuwani Nixwell
Published: February 2023

Herbal tea is a rich source of secondary metabolites which are reputed to have medicinal and nutritional efficacy. These secondary metabolites are influenced by the abiotic and biotic stresses that improve the production of herbal teas in terms of biomass production, accumulation and partitioning of assimilates of compounds. In this study, various examples of herbal teas have been shown to respond differently to secondary metabolites affected by environmental factors. Thus, the meta-analysis of this study confirms that different herbal teas' response to environmental factors depends on the type of species, cultivar, and the degree of shade that the plant is exposed. It is also evident that the metabolic processes are also known to optimize the production of secondary metabolites which can thus be achieved by manipulating agronomic practices on herbal teas. The different phenolic compound in herbal teas possesses the antioxidant, antimicrobial, antiatherosclerosis, anti-inflammatory, antimutagenic, antitumor, antidiabetic and antiviral activities that are important in managing chronic diseases associated with lifestyle. It can be precluded that more studies should be conducted to establish interactive responses of biotic and abiotic environmental factors on quality attributes of herbal teas.
Comparative Analysis of the Methods for Fiber Bragg Structures Spectrum Modeling
Authors: Agliullin Timur , Anfinogentov Vladimir , Morozov Oleg , Sakhabutdinov Airat , Valeev Bulat , Niyazgulyeva Ayna , Garovov Yagmyrguly
Published: February 2023

The work is dedicated to a comparative analysis of the following methods for fiber Bragg grating (FBG) spectral response modeling. The Layer Sweep (LS) method, which is similar to the common layer peeling algorithm, is based on the reflectance and transmittance determination for the plane waves propagating through layered structures, which results in the solution of a system of linear equations for the transmittance and reflectance of each layer using the sweep method. Another considered method is based on the determination of transfer matrices (TM) for the FBG as a whole. Firstly, a homogeneous FBG was modeled using both methods, and the resulting reflectance spectra were compared to the one obtained via a specialized commercial software package. Secondly, modeling results of a π-phase-shifted FBG were presented and discussed. For both FBG models, the influence of the partition interval of the LS method on the simulated spectrum was studied. Based on the analysis of the simulation data, additional required modeling conditions for phase-shifted FBGs were established, which enhanced the modeling performance of the LS method.
Antioxidant Thymoquinone and Its Potential in the Treatment of Neurological Diseases
Authors: Isaev Nickolay K. , Genrikhs Elizaveta E. , Stelmashook Elena V.
Published: February 2023

Oxidative stress is one of the main pathogenic factors of neuron damage in neurodegenerative processes; this makes it an important therapeutic target to which the action of neuroprotectors should be directed. One of these drugs is thymoquinone. According to modern data, this substance has a wide range of pharmacological activity, including neuroprotective, which was demonstrated in experimental modeling of various neurodegenerative diseases and pathological conditions of the brain. The neuroprotective effect of thymoquinone is largely due to its antioxidant ability. Currently available data show that thymoquinone is an effective means to reduce the negative consequences of acute and chronic forms of cerebral pathology, leading to the normalization of the content of antioxidant enzymes and preventing an increase in the level of lipid peroxidation products. Antioxidant properties make this substance a promising basis for the development of prototypes of therapeutic agents aimed at the treatment of a number of degenerative diseases of the central nervous system.
Personalized Biomarkers and Neuropsychological Status Can Predict Post-Stroke Fatigue
Authors: Zhang Hanwen , Liu Guidong , Zhang Li , Wei Wenshi
Published: February 2023

Post-stroke fatigue (PSF) is a common complication of stroke that has a negative impact on prognosis and recovery. We aimed to investigate the relationship between PSF and demographics, mood disorders, sleep disorders, and other clinical characteristics of patients with stroke. In this exploratory cross-sectional study, we collected data on sociodemographic characteristics, biological indicators, and imaging features and evaluated patients using neuropsychological scales. Patients were assessed using the Fatigue Severity Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Pittsburgh Sleep Quality Index. Magnetic resonance imaging scans were primarily used to evaluate infarctions and white matter lesions. The correlation between the PSF of patients with stroke and clinical indicators was obtained by logistic regression analysis and power analysis. We observed an independent association between fatigue severity and female sex (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.14–3.94), depressive state (OR, 1.50; 95% CI, 1.01–1.73), and sleep disorders (OR, 1.58; 95% CI, 1.01–1.98). High levels of blood glucose, serum uric acid, and homocysteine and low levels of serum triiodothyronine were strongly associated with poor functional outcomes in patients with stroke. Further studies are needed to elucidate how specific structural lesions and anxiety symptoms are related to early PSF.
Derivation and Validation of a New Visceral Adiposity Index for Predicting Short-Term Mortality of Patients with Acute Ischemic Stroke in a Chinese Population
Authors: Chang Yuhong , Zhang Lulu , Li Yidan , Wang Dapeng , Fang Qi , Tang Xiang
Published: February 2023

The visceral adiposity index (VAI) is related to the occurrence of various cardiometabolic diseases, atherosclerosis, and stroke. However, few studies have analyzed the impact on the short-term prognosis of stroke. We assessed the effect of VAI on short-term prognoses in patients with acute ischemic stroke through a retrospective cohort study of 225 patients with acute stroke who were admitted to the neurological intensive care unit of our hospital. We collected metabolic indicators (blood pressure, fasting glucose, lipids), National Institutes of Health Stroke Scale (NIHSS) scores, symptomatic intracranial hemorrhage, and other disease evaluation indicators on 197 patients who were screened for inclusion. VAI was calculated by using baseline data (sex, height, weight, waist circumference (WC)). We assessed functional recovery according to modified Rankin scale scores after 90 days. The receiver operating characteristic (ROC) curve was used to calculate the VAI cutoff value that affects short-term outcomes. A nomogram that can predict the risk of short-term mortality in patients with acute ischemic stroke was drawn. In total, 28 patients died within 90 days. Those patients had higher VAI (p = 0.000), higher triglyceride (TG) (p = 0.020) and NIHSS scores (p = 0.000), and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.000) than patients who survived. VAI had higher predictive value of short-term mortality than did body mass index (BMI), body fat mass index (BFMI), and WC. VAI and NIHSS scores were independent risk factors for the short-term mortality of patients with stroke. Patients with a VAI > 2.355 had a higher risk of short-term mortality. VAI has a predictive value higher than that of traditional metabolic indicators such as BMI, BFMI, and WC. The nomogram, composed of NIHSS, VAI, HDL-C, and TG, may predict the short-term mortality of cerebral infarction patients.
Correlation between “Snake-Eyes” Sign and Role of Surgery with a Focus on Postoperative Outcome: A Systematic Review
Authors: Scalia Gianluca , Costanzo Roberta , Brunasso Lara , Garufi Giada , Bonosi Lapo , Ricciardo Giuseppe , Graziano Francesca , Nicoletti Giovanni Federico , Cardali Salvatore Massimiliano , Iacopino Domenico Gerardo , Maugeri Rosario , Umana Giuseppe Emmanuele
Published: February 2023

(1) Background: The “snake-eyes” sign represents a unique finding characterized by bilateral hyperintense symmetric, circular, or ovoid foci on T2-weighted MRI sequences in the anterior horn cells of the spinal cord. There are conflicting opinions as some authors affirm that it does not affect the prognosis of cervical myelopathy while other papers emphasize the opposite, stating how the “snake-eyes” sign constitutes an irreversible lesion and a predictor of poor prognosis. This systematic review evaluates the correlation between the “snake-eyes” sign and the prognosis of cervical myelopathy after surgery including anterior and/or posterior approaches; (2) Methods: A systematic literature review was conducted following the PRISMA statement and a total of seven papers were included; (3) Results: A total of 419 patients were evaluated, with a mean age of 55.72 ± 14.38 years. After surgery, 26.01% of patients experienced a significant clinical improvement, while in 61.81%, there was no significant improvement. In particular, 144 of 196 patients (73.5%) treated through an anterior approach and 114 of 223 (51.1%) that underwent a posterior approach, did not present a significant improvement. Furthermore, in 12.17% of patients, the postoperative outcome was not reported, leading to a high risk of bias in the assessment of the prognostic significance of the “snake-eyes” appearance; (4) Conclusions: The “snake-eyes” sign is usually considered as an unfavorable predictive marker for myelopathic surgical patients, but the pathophysiology is still unclear, and the results have not yet reached unified levels of evidence.
A Novel Molecular Analysis Approach in Colorectal Cancer Suggests New Treatment Opportunities
Authors: López-Camacho Elena , Prado-Vázquez Guillermo , Martínez-Pérez Daniel , Ferrer-Gómez María , Llorente-Armijo Sara , López-Vacas Rocío , Díaz-Almirón Mariana , Gámez-Pozo Angelo , Vara Juan Ángel Fresno , Feliu Jaime , Trilla-Fuertes Lucía
Published: February 2023

Colorectal cancer (CRC) is a molecular and clinically heterogeneous disease. In 2015, the Colorectal Cancer Subtyping Consortium classified CRC into four consensus molecular subtypes (CMS), but these CMS have had little impact on clinical practice. The purpose of this study is to deepen the molecular characterization of CRC. A novel approach, based on probabilistic graphical models (PGM) and sparse k-means–consensus cluster layer analyses, was applied in order to functionally characterize CRC tumors. First, PGM was used to functionally characterize CRC, and then sparse k-means–consensus cluster was used to explore layers of biological information and establish classifications. To this aim, gene expression and clinical data of 805 CRC samples from three databases were analyzed. Three different layers based on biological features were identified: adhesion, immune, and molecular. The adhesion layer divided patients into high and low adhesion groups, with prognostic value. The immune layer divided patients into immune-high and immune-low groups, according to the expression of immune-related genes. The molecular layer established four molecular groups related to stem cells, metabolism, the Wnt signaling pathway, and extracellular functions. Immune-high patients, with higher expression of immune-related genes and genes involved in the viral mimicry response, may benefit from immunotherapy and viral mimicry-related therapies. Additionally, several possible therapeutic targets have been identified in each molecular group. Therefore, this improved CRC classification could be useful in searching for new therapeutic targets and specific therapeutic strategies in CRC disease.
A New Optimized Version of a Colorectal Cancer-Targeted Immunotoxin Based on a Non-Immunogenic Variant of the Ribotoxin α-Sarcin
Authors: Narbona Javier , Gordo Rubén G. , Tomé-Amat Jaime , Lacadena Javier
Published: February 2023

Due to its incidence and mortality, cancer remains one of the main risks to human health and lifespans. In order to overcome this worldwide disease, immunotherapy and the therapeutic use of immunotoxins have arisen as promising approaches. However, the immunogenicity of foreign proteins limits the dose of immunotoxins administered, thereby leading to a decrease in its therapeutic benefit. In this study, we designed two different variants of non-immunogenic immunotoxins (IMTXA33αSDI and IMTXA33furαSDI) based on a deimmunized variant of the ribotoxin α-sarcin. The inclusion of a furin cleavage site in IMTXA33furαSDI would allow a more efficient release of the toxic domain to the cytosol. Both immunotoxins were produced and purified in the yeast Pichia pastoris and later functionally characterized (both in vitro and in vivo), and immunogenicity assays were carried out. The results showed that both immunotoxins were functionally active and less immunogenic than the wild-type immunotoxin. In addition, IMTXA33furαSDI showed a more efficient antitumor effect (both in vitro and in vivo) due to the inclusion of the furin linker. These results constituted a step forward in the optimization of immunotoxins with low immunogenicity and enhanced antitumor activity, which can lead to potential better outcomes in cancer treatment.
Rare Neuronal, Glial and Glioneuronal Tumours in Adults
Authors: Crainic Nicolas , Furtner Julia , Pallud Johan , Bielle Franck , Lombardi Giuseppe , Rudà Roberta , Idbaih Ahmed
Published: February 2023

Rare glial, neuronal and glioneuronal tumours in adults form a heterogeneous group of rare, primary central nervous system tumours. These tumours, with a glial and/or neuronal component, are challenging in terms of diagnosis and therapeutic management. The novel classification of primary brain tumours published by the WHO in 2021 has significantly improved the diagnostic criteria of these entities. Indeed, diagnostic criteria are nowadays multimodal, including histological, immunohistochemical and molecular (i.e., genetic and methylomic). These integrated parameters have allowed the specification of already known tumours but also the identification of novel tumours for a better diagnosis.
Evaluating the Risk of Inguinal Lymph Node Metastases before Surgery Using the Morphonode Predictive Model: A Prospective Diagnostic Study in Vulvar Cancer Patients
Authors: Fragomeni Simona Maria , Moro Francesca , Palluzzi Fernando , Mascilini Floriana , Rufini Vittoria , Collarino Angela , Inzani Frediano , Giacò Luciano , Scambia Giovanni , Testa Antonia Carla , Garganese Giorgia
Published: February 2023

Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients.
Resistance to Antibody-Drug Conjugates Targeting HER2 in Breast Cancer: Molecular Landscape and Future Challenges
Authors: Guidi Lorenzo , Pellizzari Gloria , Tarantino Paolo , Valenza Carmine , Curigliano Giuseppe
Published: February 2023

The treatment of HER2-positive metastatic breast cancer (mBC) with Trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd), two antibody-drug conjugates (ADCs) targeting HER2, is burdened by progression of disease related to the acquisition of mechanisms of resistance. Resistance to T-DM1 is caused by the decrease of HER2 expression, the alteration of intracellular trafficking, the impairment of lysosome functions, the drug expulsion through efflux pumps and the activation of alternative signal pathways. Instead, the decrease of HER2 expression and SLX4 loss of function mutations represent the first evidences of mechanisms of resistance to T-DXd, according to the results of DAISY trial. Several strategies are under evaluation to overcome resistances to anti-HER2 ADCs and improve clinical outcomes in patients progressing on these agents: combinations with tyrosine kinase inhibitors, statins, immune checkpoint inhibitors and synthetic DNA-damaging agents are emerging as promising approaches. Furthermore, novel anti-HER2 ADCs with innovative structures and mechanisms of action are in development, in the attempt to further improve the activity and tolerability of currently available agents.
Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer
Authors: Kabel Jonas , Henriksen Tenna Vesterman , Demuth Christina , Frydendahl Amanda , Rasmussen Mads Heilskov , Nors Jesper , Birkbak Nicolai J. , Madsen Anders Husted , Løve Uffe S. , Andersen Per Vadgaard , Kolbro Thomas , Monti Alessio , Thorlacius-Ussing Ole , Gögenur Mikail , Kildsig Jeppe , Schlesinger Nis Hallundbæk , Bondeven Peter , Iversen Lene Hjerrild , Gotschalck Kåre Andersson , Andersen Claus Lindbjerg
Published: February 2023

Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12–2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22–5.03) and Stage II (OR = 1.76, 95%CI: 1.11–2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44–1.53) patients. Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.
‘Unfinished’ Morphogenesis Hides Different Speciation Pathways in Charophytes: Evidence from the 190-Year-Old Original Material of Chara denudata (Charales, Charophyceae)
Authors: Romanov Roman , Barinova Sophia , Nikulin Vyacheslav , Gontcharov Andrey
Published: February 2023

Several Chara L. species have ‘unfinished’ morphogenesis that is recognizable because of their imperfect stem and branchlet cortication compared to the perfectly corticated species. Chara denudata A. Braun, described from South Africa, is one of these species, assumed for a long time to be conspecific with C. dissoluta A. Braun ex Leonhardi, as described from Central Europe. An attempt to resolve this long-lasting uncertainty in the framework of integrative taxonomy is implemented here. The restudy of the original material of both species showed similarities but did not identify a hiatus in their morphological traits, which represents evidence for their placement in the subsection Chara R.D. Wood according to morphology. Bifid adaxial bract cells, a trait rarely encountered among charophytes, were found for the first time in C. dissoluta. According to the rbcL and matK sequences, C. denudata was unexpectedly placed within the section Grovesia R.D. Wood, far from the clusters of the section Chara with C. dissoluta. This is in obvious disagreement with the position of C. denudata according to morphology. Both species were distinct according to their biology, habitat preference, and distribution and were accepted as distinct species. Therefore, the ‘unfinished’ morphogenesis resulting in morphological similarity hides different speciation pathways in charophytes.
Endoscopic Ultrasound-Guided Gallbladder Drainage versus Percutaneous Gallbladder Drainage for Acute Cholecystitis: A Systematic Review and Meta-Analysis
Authors: Boregowda Umesha , Chen Millie , Saligram Shreyas
Published: February 2023

Background: Percutaneous transhepatic gallbladder drainage (PT-GBD) has been the treatment of choice for acute cholecystitis patients who are not suitable for surgery. The effectiveness of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) as an alternative to PT-GBD is not clear. In this meta-analysis, we have compared their efficacy and adverse events. Methods: We adhered to the PRISMA statement to conduct this meta-analysis. Online databases were searched for studies that compared EUS-GBD and PT-GBD for acute cholecystitis. The primary outcomes of interest were technical success, clinical success, and adverse events. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the random-effects model. Results: A total of 396 articles were screened, and 11 eligible studies were identified. There were 1136 patients, of which 57.5% were male, 477 (mean age 73.33 ± 11.28 years) underwent EUS-GBD, and 698 (mean age 73.77 ± 8.7 years) underwent PT-GBD. EUS-GBD had significantly better technical success (OR 0.40; 95% CI 0.17–0.94; p = 0.04), fewer adverse events (OR 0.35; 95% CI 0.21–0.61; p = 0.00), and lower reintervention rates (OR 0.18; 95% CI 0.05–0.57; p = 0.00) than PT-GBD. No difference in clinical success (OR 1.34; 95% CI 0.65–2.79; p = 0.42), readmission rate (OR 0.34; 95% CI 0.08–1.54; p = 0.16), or mortality rate (OR 0.73; 95% CI 0.30–1.80; p = 0.50) was noted. There was low heterogeneity (I2 = 0) among the studies. Egger’s test showed no significant publication bias (p = 0.595). Conclusion: EUS-GBD can be a safe and effective alternative to PT-GBD for treating acute cholecystitis in non-surgical patients and has fewer adverse events and a lower reintervention rate than PT-GBD.
Heterostructure of Metal Oxides Integrated on a GCE for Estimation of H2O2 Capacity in Milk and Fruit Juice Samples
Authors: Silwana Bongiwe , Matoetoe Mangaka
Published: February 2023

High levels of H2O2 in food can lead to oxidative stress. Which has been linked to a number of neurological diseases. Hence, its detection in beverages is essential. However, a complicated structure of the reaction medium of H2O2 makes the detection procedure very difficult. For this reason, sensitive strategic methods are required. In this study, quantification of H2O2 in milk and apple juice has been obtained via the electrochemical sensing platform based on GCE/SiO-CeONPs. Scanning Electron Microscopy (SEM), Cyclic voltammetry(CV), and electron impedance spectroscopy(EIS) were employed to characterize the composite. The kinetics investigation of the sensor with H2O2 revealed an a quasi-reversible one -electron adsorption process. Under optimized conditions, the Differential Pulse Voltammetry (DPV) in 0.1 M Phosphate buffer (PB) pH 5.5 of the H2O2 displayed a peak at 0.13 V vs. Ag/AgCl with the detection limits of 0.0004 µM, linearity range of 0.01–0.08 µM. The observed LOD values of this method for real samples were calculated to be 0.006 µM and 0.007 µM with LOQ of 0.02 µM for milk and apple juice, respectively. The recovery of the analyte was from 92 to 99%. Furthermore, due to good selectivity and stability, the benefit of this sensor is its applicability in multiple fields.