bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the coupling and coordination relationship between the digital economy and green development: evidence from Guangdong province in China
Authors: Zhong Xiaojun , Cao Zhiyi , Peng Bo , Cheong Tsun Se
Published: November 2023

The digital economy city and green development of China are important engines with important backgrounds. This paper takes 21 prefecture-level cities in Guangdong Province as the research object. By constructing the index system of the digital economy and green development, this paper discusses the external spatial pattern and internal temporal evolution characteristics of the coordinated development of the digital economy and green development from the two perspectives of intercity and inner city. The results show that: 1) From the perspective of intercity, there is a large gap between the development level of the digital economy and the green development level of all cities, only Guangzhou and Shenzhen have the digital economy development level ahead of the green development level. The coupling level of the two systems presents an unbalanced pattern of “centre-edge,” and “Guangzhou-Foshan-Shenzhen-Dongguan” becomes the core pole of the coupling development of the two systems in the province. The coordinated horizontal cascade distribution of the two systems is obvious, showing a spatial pattern of decreasing step by step from the first circle to the third circle. 2) From the perspective of inner city, the digital economy level and green development level of all cities showed an upward trend from 2013 to 2019. The coupling level shows a two-stage development trend: the stable development stage from 2013 to 2016, and he accelerated development stage from 2016 to 2019, and the internal interaction of the two systems is deepening. The coordination level of all cities improved significantly in 7 years, and in 2019, 21 cities all reached the level of moderate coordination or high coordination. Based on above research conclusions, in order to promote the positive interaction between digital economy and green development, this paper proposes to optimize resource allocation based on regional differences, and adhere to innovation-driven policy proposals to activate the potential of green development.
The human genome as the common heritage of humanity
Authors: Kabata Faith , Thaldar Donrich
Published: November 2023

While debate on the international regulation of human genomic research remains unsettled, the Universal Declaration on the Human Genome and Human Rights, 1997 qualifies the human genome as “heritage of humankind” in a symbolic sense. Using document analysis this article assesses whether, how and to what extent the common heritage framework is relevant in regulation of human genomic research. The article traces the history of the Human Genome Project to reveal the international community’s race against privatization of the human genome and its resulting qualification as the common heritage of humanity. Further, it reviews the archival records of UNESCO’s International Bioethics Committee to discover the rationale for qualifying the human genome as common heritage of humankind. The article finds that the common heritage of mankind framework remains relevant to the application of the human genome at the collective level. However, the framework is at odds with the individual dimension of the human genome based on individual personality rights. The article thus argues that the right to benefit from scientific progress and its applications offers an alternative international regulatory framework for human genomic research.
Combination of linkage and association mapping with genomic prediction to infer QTL regions associated with gray leaf spot and northern corn leaf blight resistance in tropical maize
Authors: Omondi Dennis O. , Dida Mathews M. , Berger Dave K. , Beyene Yoseph , Nsibo David L. , Juma Collins , Mahabaleswara Suresh L. , Gowda Manje
Published: November 2023

Among the diseases threatening maize production in Africa are gray leaf spot (GLS) caused by Cercospora zeina and northern corn leaf blight (NCLB) caused by Exserohilum turcicum. The two pathogens, which have high genetic diversity, reduce the photosynthesizing ability of susceptible genotypes and, hence, reduce the grain yield. To identify population-based quantitative trait loci (QTLs) for GLS and NCLB resistance, a biparental population of 230 lines derived from the tropical maize parents CML511 and CML546 and an association mapping panel of 239 tropical and sub-tropical inbred lines were phenotyped across multi-environments in western Kenya. Based on 1,264 high-quality polymorphic single-nucleotide polymorphisms (SNPs) in the biparental population, we identified 10 and 18 QTLs, which explained 64.2% and 64.9% of the total phenotypic variance for GLS and NCLB resistance, respectively. A major QTL for GLS, qGLS1_186 accounted for 15.2% of the phenotypic variance, while qNCLB3_50 explained the most phenotypic variance at 8.8% for NCLB resistance. Association mapping with 230,743 markers revealed 11 and 16 SNPs significantly associated with GLS and NCLB resistance, respectively. Several of the SNPs detected in the association panel were co-localized with QTLs identified in the biparental population, suggesting some consistent genomic regions across genetic backgrounds. These would be more relevant to use in field breeding to improve resistance to both diseases. Genomic prediction models trained on the biparental population data yielded average prediction accuracies of 0.66–0.75 for the disease traits when validated in the same population. Applying these prediction models to the association panel produced accuracies of 0.49 and 0.75 for GLS and NCLB, respectively. This research conducted in maize fields relevant to farmers in western Kenya has combined linkage and association mapping to identify new QTLs and confirm previous QTLs for GLS and NCLB resistance. Overall, our findings imply that genetic gain can be improved in maize breeding for resistance to multiple diseases including GLS and NCLB by using genomic selection.
Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes
Authors: Kalaitsidou Milena , Moon Owen R. , Sykorova Martina , Bao Leyuan , Qu Yun , Sukumaran Sujita , Valentine Michael , Zhou Xingliang , Pandey Veethika , Foos Kay , Medvedev Sergey , Powell Jr Daniel J. , Udyavar Akshata , Gschweng Eric , Rodriguez Ruben , Dudley Mark E. , Hawkins Robert E. , Kueberuwa Gray , Bridgeman John S.
Published: November 2023

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation.
The impact of the comorbid seizure/epilepsy on the health related quality of life in people with multiple sclerosis: an international multicentric study
Authors: Drulovic Jelena , Pekmezovic Tatjana , Tamas Olivera , Adamec Ivan , Aleksic Dejan , Andabaka Marko , Basic Kes Vanja , Butkovic Soldo Silva , Cukic Mirjana , Despinic Livija , Dincic Evica , Djelilovic Vranic Jasminka , Grgic Sanja , Habek Mario , Hristova Sonya Ivanova , Ivanovic Jovana , Jovanovic Aleksa , Jovicevic Vanja , Krbot Skoric Magdalena , Kuzmanovski Igor , Maric Gorica , Mesaros Sarlota , Milanov Ivan Gospodinov , Miletic Drakulic Svetlana , Sinanovic Osman , Skarpa Prpic Ingrid , Sremec Josip , Tadic Daliborka , Toncev Gordana , Sokic Dragoslav
Published: November 2023

Introduction

The health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS.

Methods

We conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients.

Results

The study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy.

Discussion

Our results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy.
Detection of anti-SARS-CoV-2 salivary antibodies in vaccinated adults
Authors: Castro Vitória Tavares , Chardin Hélène , Amorim dos Santos Juliana , Barra Gustavo Barcelos , Castilho Grazielle Rodrigues , Souza Paula Monteiro , Magalhães Pérola de Oliveira , Acevedo Ana Carolina , Guerra Eliete Neves Silva
Published: November 2023

Since the introduction of efficient anti-SARS-CoV-2 vaccines, the detection of antibodies becomes useful for immunological monitoring and COVID-19 control. Therefore, this longitudinal study aimed to evaluate the detection of SARS-CoV-2 antibodies in the serum and saliva of COVID-19-vaccinated adults. The study included 13 not vaccinated and 35 vaccinated participants with two doses of CoronaVac (Sinovac/Butantan) vaccine who subsequently received BNT162b2 (Pfizer-BioNTech) vaccine as a booster dose. Vaccinated participants donated saliva and serum in three different time points. Enzyme-linked immunosorbent assay was used for antibody detection. In our results, the serum neutralizing antibodies (NAb) were detected in 34/35 samples after second dose and in 35/35 samples one and five months after the booster dose. In saliva, NAb were detected in 30/35 samples after second dose and in 35/35 of samples one and five months after the booster dose. IgA was detected in 19/34 saliva samples after second dose, in 18/35 one month after the booster and in 30/35 five months after. IgG in saliva was detected in 1/34 samples after second dose, 33/35 samples one month after the booster dose and in 20/35 five months after. A strong correlation was found between IgG and neutralizing activity in saliva, and salivary IgA would be a sign of recent exposure to the virus. In conclusion, saliva can be suitable for monitoring antibodies anti-SARS-CoV-2 after vaccination. Heterologous vaccination contributed to increase anti-SARS-CoV-2 antibodies in the Brazilian health context. Complementary studies with large groups are mandatory to conclude the interest in following mucosal immunity.
Verification and Modeling of the Maritime Channel for Maritime Communications and Navigation Networks
Authors: Raulefs Ronald , Bellido-Manganell Miguel A. , Dammann Armin , Walter Michael , Wang Wei
Published: November 2023

This paper presents a geometric stochastic channel model designed for analyzing maritime communication and navigation services between moving ships using the C-band or sub-6 GHz spectrum, which aligns with the focus of emerging 5G networks on land. The channel model is validated through channel measurements conducted both on the sea and land. A software tool has been developed to integrate and analyze these measurements, which is included with this publication. The main challenge in developing the channel model for maritime services lies in the dynamic nature of the sea surface, leading to constantly changing reflection conditions due to varying reflectors and scatterers on the water. Additionally, the motion conditions of the transmitter and receiver on ships change in all three dimensions, depending on the sea state. To address these complexities, data from several measurement campaigns in diverse areas were collected. The analysis involved examining the propagation conditions over the sea with variations in sea surface roughness, antenna heights, and used bandwidths. Moreover, additional propagation conditions over nearby land were also taken into account. The study demonstrates that the changing antenna height on the ship, influenced by sea conditions, significantly affects the reflection and scattering conditions. The research aims to develop reliable, high-data rate, and broadband marine communication systems. Therefore, a measurement bandwidth of 120MHz was employed to derive the propagation model. This model not only offers absolute timing information but can also be used for time-based ranging or positioning systems. The proposed geometric stochastic channel model provides valuable insights into the complex maritime communication and navigation environment. By accounting for the continuously evolving sea surface and its impact on antenna height, the model offers a robust framework for studying and optimizing marine communication systems. The availability of a software tool integrating real-world measurements further enhances the usability and practicality of the channel model for future maritime communication research and deployment.
Foreign body aspiration and mucormycosis: a case report
Authors: Mehdinezhad Hamed , Mohseni Ahangar Reza , Golparvar Azizi Mohammad , Ghasemian Mohammad , Yari Zahra , Jafarian Elham , Tavakoli Pirzaman Ali
Published: November 2023

Over the course of the Coronavirus disease 2019 (COVID-19) pandemic, numerous complications have been documented. In this report, we have detailed an unexpected complication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in a 73-year-old female patient who was simultaneously afflicted with mucormycosis and another unanticipated problem. Due to the lack of recovery of the patient after receiving mucormycosis treatment and continued fever, cough and hemoptysis, bronchoscopy was performed for her. During bronchoscopy, we encountered a foreign body that was the cause of the patient’s fever, cough, and hemoptysis. Rigid bronchoscopy was performed and the foreign body was removed from the left main bronchus. The lack of a favorable treatment response after administering antifungal therapy suggested that the presence of a foreign body could potentially act as an underlying nidus, thus influencing the suboptimal therapeutic outcome. Mucormycosis is usually characterized by distinct radiological patterns. However, this case did not present predictable imaging findings, further complicating the diagnostic process associated with this invasive fungal infection.
In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor
Authors: Dindi Uma Maheswara Rao , Sadiq Suhadha Parveen , Al-Ghamdi Sameer , Alrudian Naif Abdurhman , Dayel Salman Bin , Abuderman Abdulwahab Ali , Shahid Mohammad , Ramesh Thiyagarajan , Vilwanathan Ravikumar
Published: November 2023

Introduction

Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development.

Materials and methods

Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes.

Results and discussion

We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.
Bioremediation of contaminated soil and groundwater by in situ biostimulation
Authors: Romantschuk Martin , Lahti-Leikas Katariina , Kontro Merja , Galitskaya Polina , Talvenmäki Harri , Simpanen Suvi , Allen John A. , Sinkkonen Aki
Published: November 2023

Bioremediation by in situ biostimulation is an attractive alternative to excavation of contaminated soil. Many in situ remediation methods have been tested with some success; however, due to highly variable results in realistic field conditions, they have not been implemented as widely as they might deserve. To ensure success, methods should be validated under site-analogous conditions before full scale use, which requires expertise and local knowledge by the implementers. The focus here is on indigenous microbial degraders and evaluation of their performance. Identifying and removing biodegradation bottlenecks for degradation of organic pollutants is essential. Limiting factors commonly include: lack of oxygen or alternative electron acceptors, low temperature, and lack of essential nutrients. Additional factors: the bioavailability of the contaminating compound, pH, distribution of the contaminant, and soil structure and moisture, and in some cases, lack of degradation potential which may be amended with bioaugmentation. Methods to remove these bottlenecks are discussed. Implementers should also be prepared to combine methods or use them in sequence. Chemical/physical means may be used to enhance biostimulation. The review also suggests tools for assessing sustainability, life cycle assessment, and risk assessment. To help entrepreneurs, decision makers, and methods developers in the future, we suggest founding a database for otherwise seldom reported unsuccessful interventions, as well as the potential for artificial intelligence (AI) to assist in site evaluation and decision-making.
Unraveling the salt tolerance of Phi29 DNA polymerase using compartmentalized self-replication and microfluidics platform
Authors: Sun Yaping , Ko Danny Hsu , Gao Jie , Fu Kang , Gao Yaping , Zhang Qiwen , Baldi Salem , Hong Tao , Ivanov Igor , He Yun , Tian Hui
Published: November 2023

In Phi29-α–hemolysin (α-HL) nanopore sequencing systems, a strong electrochemical signal is dependent on a high concentration of salt. However, high salt concentrations adversely affect polymerase activity. Sequencing by synthesis (SBS) requires the use of phi29 polymerase without exonuclease activity to prevent the degradation of modified nucleotide tags; however, the lack of exonuclease activity also affects polymerase processivity. This study aimed to optimize phi29 polymerase for improved salt tolerance and processivity while maintaining its lack of exonuclease activity to meet the requirements of nanopore sequencing. Using salt tolerance compartmentalized self-replication (stCSR) and a microfluidic platform, we obtained 11 mutant sites with enhanced salt tolerance attributes. Sequencing and biochemical analyses revealed that the substitution of conserved amino acids such as G197D, Y369E, T372N, and I378R plays a critical role in maintaining the processivity of exonuclease-deficient phi29 polymerase under high salt conditions. Furthermore, Y369E and T372N have been identified as important determinants of DNA polymerase binding affinity. This study provides insights into optimizing polymerase processability under high-salt conditions for real-time polymerase nanopore sequencing, paving the way for improved performance and applications in nanopore sequencing technologies.
The potential role of gut microbiota outer membrane vesicles in colorectal cancer
Authors: Meng Ran , Zeng Minmin , Ji Ying , Huang Xinxiang , Xu Min
Published: November 2023

Colorectal cancer (CRC) is a common malignant digestive tract tumor in colorectal regions. Considerable evidence now shows that the gut microbiota have essential roles in CRC occurrence and development. Most Gram-negative bacteria release outer membrane vesicles (OMVs) via outer membrane blistering, which contain specific cargoes which interact with host cells via intercellular communications, host immune regulation, and gut microbiota homeostasis. Studies have also shown that OMVs selectively cluster near tumor cells, thus cancer treatment strategies based on OMVs have attracted considerable research attention. However, little is known about the possible impact of gut microbiota OMVs in CRC pathophysiology. Therefore, in this review, we summarize the research progress on molecular composition and function of OMV, and review the microbial dysbiosis in CRC. We then focus on the potential role of gut microbiota OMVs in CRC. Finally, we examine the clinical potential of OMVs in CRC treatment, and their main advantages and challenges in tumor therapy.
Trichoderma koningiopsis Tk905: an efficient biocontrol, induced resistance agent against banana Fusarium wilt disease and a potential plant-growth-promoting fungus
Authors: Luo Mei , Chen Yue , Huang Qiurong , Huang Zhenxin , Song Handa , Dong Zhangyong
Published: November 2023

Fusarium oxysporum f. sp. cubense tropical race 4 (FocTR4) is a devastating phytopathogen responsible for significant losses in banana production worldwide. Trichoderma and other biocontrol agents (BCAs) have been used as suitable disease control methods for banana Fusarium wilt. In this study, the endophytic T. koningiopsis Tk905 strain was isolated from the roots of dendrobe plants and identified utilizing morphological and molecular analyses. Antifungal activity tests revealed that Tk905 effectively inhibited mycelial growth with inhibition rates ranging from 26.52 to 75.34%. Additionally, Tk905 covered the pathogen mycelia, and spores were observed on or around the pathogen hyphae. The average root and shoot fresh weights and plant height, of Tk905-inoculated plants were significantly higher than those of the untreated plants. Furthermore, Tk905 treatment significantly increased the activity of antioxidant enzymes, such as catalase (CAT), phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD), suggesting that Tk905 may enhance plant defence systems by activating their antioxidant mechanisms. Most importantly, Tk905-treated plants inoculated by three methods exhibited significantly lower disease incidence and severity than untreated plants. The protective effects of Tk905 against FocTR4 infection were not only observed in the early stages of infection but persisted throughout the experiment, suggesting that T. koningiopsis Tk905 can provide long-lasting protection against Fusarium wilt.
Diagnosis of Alzheimer’s disease via resting-state EEG: integration of spectrum, complexity, and synchronization signal features
Authors: Zheng Xiaowei , Wang Bozhi , Liu Hao , Wu Wencan , Sun Jiamin , Fang Wei , Jiang Rundong , Hu Yajie , Jin Cheng , Wei Xin , Chen Steve Shyh-Ching
Published: November 2023

Background

Alzheimer’s disease (AD) is the most common neurogenerative disorder, making up 70% of total dementia cases with a prevalence of more than 55 million people. Electroencephalogram (EEG) has become a suitable, accurate, and highly sensitive biomarker for the identification and diagnosis of AD.

Methods

In this study, a public database of EEG resting state-closed eye recordings containing 36 AD subjects and 29 normal subjects was used. And then, three types of signal features of resting-state EEG, i.e., spectrum, complexity, and synchronization, were performed by applying various signal processing and statistical methods, to obtain a total of 18 features for each signal epoch. Next, the supervised machine learning classification algorithms of decision trees, random forests, and support vector machine (SVM) were compared in categorizing processed EEG signal features of AD and normal cases with leave-one-person-out cross-validation.

Results

The results showed that compared to normal cases, the major change in EEG characteristics in AD cases was an EEG slowing, a reduced complexity, and a decrease in synchrony. The proposed methodology achieved a relatively high classification accuracy of 95.65, 95.86, and 88.54% between AD and normal cases for decision trees, random forests, and SVM, respectively, showing that the integration of spectrum, complexity, and synchronization features for EEG signals can enhance the performance of identifying AD and normal subjects.

Conclusion

This study recommended the integration of EEG features of spectrum, complexity, and synchronization for aiding the diagnosis of AD.
Treatment efficacy of repositioning maneuvers in multiple canal benign paroxysmal positional vertigo: a systematic review and meta-analysis
Authors: Alfarghal Mohamad , Singh Niraj Kumar , Algarni Mohammed Abdullah , Jagadish Nirmala , Raveendran Rajesh Kumar
Published: November 2023

Introduction

Benign paroxysmal positional vertigo (BPPV) involving the posterior canal is more common than other canals; however, simultaneous involvement of multiple canals can be seen up to 20% of all BPPV cases. The diagnosis and management of multiple canal BPPV can be quite challenging due to the complexity of findings. Therefore, this systematic review and meta-analysis aimed at unveiling the most effective repositioning strategy for the treatment of multiple canal BPPV.

Methods

A literature search through PubMed, Scopus, and Web of Science databases was conducted using search terms such as BPPV, multiple canals, bilateral BPPV, repositioning maneuvers etc. After duplicate removal, the retained articles underwent various stages of elimination by two independent reviewers, and a third reviewer resolved the discrepancy between them.

Results

A total of 22 articles were included in the systematic review. These publications documented 5,196 patients diagnosed with BPPV, of which 513 had multiple canal BPPV. Of 295 individuals with multiple canal BPPV, 58.9% were effectively treated in 1 session, whereas 18.3 and 4.4% achieved a symptom-free state after two and three sessions, respectively. Failure of treatment using repositioning maneuvers was found in 18.4%.

Possible implications

This study offers insight into the real world of BPPV management in single and multiple canal BPPV. It is evident that repositioning maneuvers provide rapid and long-lasting relief of BPPV in most single canal BPPV patients; however, multiple canal BPPV often requires repeated treatment, and the risk of recurrence is higher in this variety than the single canal BPPV.
Novel approaches targeting ferroptosis in treatment of glioma
Authors: Zhao Jing , Zang Fengling , Huo Xiaoya , Zheng Shengzhe
Published: November 2023

Glioma is a malignant brain tumor with a high mortality rate; hence novel treatment approaches are being explored to improve patient outcomes. Ferroptosis, a newly described form of regulated cell death, is emerging as a potential therapeutic target in glioma. Ferroptosis is characterized by the accumulation of lipid peroxides due to a loss of intracellular antioxidant systems represented by the depletion of glutathione and decreased activity of glutathione peroxidase 4 (GPX4). Since glioma cells have a high demand for iron and lipid metabolism, modulation of ferroptosis may represent a promising therapeutic approach for this malignancy. Recent studies indicate that ferroptosis inducers like erastin and RSL3 display potent anticancer activity in a glioma model. In addition, therapeutic strategies, including GPX4 targeting, lipid metabolism modulation, inhibition of amino acid transporters, and ferroptosis targeting natural compounds, have shown positive results in preclinical studies. This review will provide an overview of the functions of ferroptosis in glioma and its potential as a suitable target for glioma therapy.
Prominent elevation of extracellular matrix molecules in intracerebral hemorrhage
Authors: Li Hongmin , Ghorbani Samira , Zhang Ruiyi , Ebacher Vincent , Stephenson Erin L. , Keough Michael B. , Yong V. Wee , Xue Mengzhou
Published: November 2023

Background

Intracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurological conditions, the deposition of extracellular matrix (ECM) molecules is a prominent obstacle for regenerative processes and an enhancer of neuroinflammation. Whether ECM molecules alter in composition after ICH, and which ECM members may inhibit repair, remain largely unknown in hemorrhagic stroke.

Methods

The collagenase-induced ICH mouse model and an autopsied human ICH specimen were investigated for expression of ECM members by immunofluorescence microscopy. Confocal image z-stacks were analyzed with Imaris 3D to assess the association of immune cells and ECM molecules. Sections from a mouse model of multiple sclerosis were used as disease and staining controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs).

Results

Among the lectican chondroitin sulfate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in murine ICH. Fibrinogen, fibronectin and heparan sulfate proteoglycan (HSPG) were also elevated after murine ICH while thrombospondin and tenascin-C was not. Confocal microscopy with Imaris 3D rendering co-localized neurocan, fibrinogen, fibronectin and HSPG molecules to Iba1+ microglia/macrophages or GFAP+ astrocytes. Marked differentiation from the multiple sclerosis model was observed, the latter with high versican-V1 and negligible neurocan. In culture, purified neurocan inhibited adhesion and process outgrowth of OPCs, which are early steps in myelination in vivo. The prominent expression of neurocan in murine ICH was corroborated in human ICH sections.

Conclusion

ICH caused distinct alterations in ECM molecules. Among CSPG members, neurocan was selectively upregulated in both murine and human ICH. In tissue culture, neurocan impeded the properties of oligodendrocyte lineage cells. Alterations to the ECM in ICH may adversely affect reparative outcomes after stroke.
Analysis of the risk factors of radiation pneumonitis in patients after radiotherapy for esophageal squamous cell carcinoma
Authors: Sun Lu , Wang Yan , Zhu Lihua , Chen Jun , Chen Zhifu , Qiu Zhiyuan , Wu Chaoyang
Published: November 2023

Objective

To predict the risk factors of radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy.

Methods

From January 2015 to October 2021, 477 ESCC patients were enrolled and were assessed retrospectively. All these patients received radiotherapy for primary lesions or mediastinal metastatic lymph nodes. Clinical efficacy and adverse events (AEs) were observed. Univariate analysis identified clinical and dosimetric factors associated with the development of RP, and multivariate logistic regression analysis identified independent potential risk factors associated with the development of RP. Nomograms were constructed to predict RP based on the results of multivariate logistic regression analysis.

Results

Among the 477 ESCC patients, the incidence of RP was 22.2%, and the incidence of grade 4 or higher RP was 1.5%. Univariate analysis indicated that chronic obstructive pulmonary disease (COPD), pulmonary infection, leucopenia, PTV volume, V5, V20, V30 and MLD affected the occurrence of RP. The multivariate logistic regression analysis indicated that COPD (OR:1.821, 95%CI:1.111-2.985; P=0.017), pulmonary infection (OR:2.528, 95%CI:1.530-4.177; P<0.001), higher V20 (OR: 1.129, 95% CI:1.006-1.266; P=0.029) were significant independent predictors of RP in ESCC patients. COPD, pulmonary infection, V20 have been integrated for the RP nomogram. The rate of RP was significantly reduced in the V20<21.45% group. Further analysis indicated that the old age, diabetes, higher V20, and higher MLD were risk factors for grade 4 or higher RP. The area under the curve (AUC) value for V20 was 0.73 (95% CI, 0.567-0.893, P < 0.05).

Conclusion

We have determined the risk factors of RP and grade 4 or higher RP in ESCC patients after radiotherapy. MLD, V20, COPD were independent factors for RP. It was necessary to take measures to reduce or avoid the occurrence of RP for patients with these risk factors at the early stage.
m6A regulates breast cancer proliferation and migration through stage-dependent changes in Epithelial to Mesenchymal Transition gene expression
Authors: Dorgham Mohammed G. , Elliott Brittany A. , Holley Christopher L. , Mansfield Kyle D.
Published: November 2023

While many factors have been implicated in breast cancer progression, effective treatments are still lacking. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy and metastasis. For example, the mRNA modification N6-methyladenosine (m6A) is involved in numerous post-transcriptional regulation processes and has been implicated in many cancer types, including breast cancer. Despite intense study, even within a single type of cancer, there is little consensus, and often conflicting results, as to the role of m6A, suggesting other factors must influence the process. The goal of this study was to determine if the effects of m6A manipulation on proliferation and migration differed based on the stage of disease progression. Using the MCF10 model of breast cancer, we reduced m6A levels by targeting METTL3, the main cellular m6A RNA methyltransferase. Knocking down Mettl3 at different stages of breast cancer progression indeed shows unique effects at each stage. The early-stage breast cancer line showed a more proliferative phenotype with the knockdown of Mettl3 while the transformed breast cancer line showed a more migratory phenotype. Interestingly, the metastasized breast cancer cell line showed almost no effect on phenotype with the knockdown of Mettl3. Furthermore, transcriptome wide analysis revealed EMT as the probable pathway influencing the phenotypic changes. The results of this study may begin to address the controversy of m6A’s role in cancer and suggest that m6A may have a dynamic role in cancer that depends on the stage of progression.
Pediatric pituitary neuroendocrine tumors–a 13-year experience in a tertiary center
Authors: Li Xiaoxu , Deng Kan , Zhang Yi , Feng Ming , Xing Bing , Lian Wei , Yao Yong
Published: November 2023

Introduction

Pediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified.

Methods

We conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor.

Results

232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery.

Conclusion

Pediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.
Evolutionary reversion in tumorigenesis
Authors: Nagahata Yosuke , Kawamoto Hiroshi
Published: November 2023

Cells forming malignant tumors are distinguished from those forming normal tissues based on several features: accelerated/dysregulated cell division, disruption of physiologic apoptosis, maturation/differentiation arrest, loss of polarity, and invasive potential. Among them, accelerated cell division and differentiation arrest make tumor cells similar to stem/progenitor cells, and this is why tumorigenesis is often regarded as developmental reversion. Here, in addition to developmental reversion, we propose another insight into tumorigenesis from a phylogeny viewpoint. Based on the finding that tumor cells also share some features with unicellular organisms, we propose that tumorigenesis can be regarded as “evolutionary reversion”. Recent advances in sequencing technologies and the ability to identify gene homologous have made it possible to perform comprehensive cross-species transcriptome comparisons and, in our recent study, we found that leukemic cells resulting from a polycomb dysfunction transcriptionally resemble unicellular organisms. Analyzing tumorigenesis from the viewpoint of phylogeny should reveal new aspects of tumorigenesis in the near future, and contribute to overcoming malignant tumors by developing new therapies.
The impact of partnered pharmacist medication charting in the emergency department on the use of potentially inappropriate medications in older people
Authors: Atey Tesfay Mehari , Peterson Gregory M. , Salahudeen Mohammed S. , Wimmer Barbara C.
Published: November 2023

Introduction: A process redesign, partnered pharmacist medication charting (PPMC), was recently piloted in the emergency department (ED) of a tertiary hospital. The PPMC model was intended to improve medication safety and interdisciplinary collaboration by having pharmacists work closely with medical officers to review and chart medications for patients. This study, therefore, aimed to evaluate the impact of PPMC on potentially inappropriate medication (PIM) use.

Methods: A pragmatic concurrent controlled study compared a PPMC group to both early best-possible medication history (BPMH) and usual care groups. In the PPMC group, pharmacists initially documented the BPMH and collaborated with medical officers to co-develop treatment plans and chart medications in ED. The early BPMH group included early BPMH documentation by pharmacists, followed by traditional medication charting by medical officers in ED. The usual care group followed the traditional charting approach by medical officers, without a pharmacist-collected BPMH or collaborative discussion in ED. Included were older people (≥65 years) presenting to the ED with at least one regular medication with subsequent admission to an acute medical unit. PIM outcomes (use of at least one PIM, PIMs per patient and PIMs per medication prescribed) were assessed at ED presentation, ED departure and hospital discharge using Beers criteria.

Results: Use of at least one PIM on ED departure was significantly lower for the PPMC group than for the comparison groups (χ2, p = 0.040). However, PIM outcomes at hospital discharge were not statistically different between groups. PIM outcomes on ED departure or hospital discharge did not differ from baseline within the comparison groups.

Discussion: In conclusion, PIM use on leaving ED, but not at hospital discharge, was reduced with PPMC. Close interprofessional collaboration, as in ED, needs to continue on the wards.
Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells
Authors: Noguchi Soma , Kajimoto Taketoshi , Kumamoto Takuya , Shingai Masashi , Narasaki Soshi , Urabe Tomoaki , Imamura Serika , Harada Kana , Hide Izumi , Tanaka Sigeru , Yanase Yuhki , Nakamura Shun-Ichi , Tsutsumi Yasuo M. , Sakai Norio
Published: November 2023

Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation.

Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process.

Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different.

Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol.
Computer-aided drug design for virtual-screening and active-predicting of main protease (Mpro) inhibitors against SARS-CoV-2
Authors: Dai Renhui , Gao Hongwei , Su Ruiling
Published: November 2023

Introduction: SARS-CoV-2 is a novel coronavirus with highly contagious and has posed a significant threat to global public health. The main protease (Mpro) is a promising target for antiviral drugs against SARS-CoV-2.

Methods: In this study, we have used pharmacophore-based drug design technology to identify potential compounds from drug databases as Mpro inhibitors.

Results: The procedure involves pharmacophore modeling, validation, and pharmacophore-based virtual screening, which identifies 257 compounds with promising inhibitory activity.

Discussion: Molecular docking and non-bonding interactions between the targeted protein Mpro and compounds showed that ENA482732 was the best compound. These results provided a theoretical foundation for future studies of Mpro inhibitors against SARS-CoV-2.
Spending time in the forest or the field: qualitative semi-structured interviews in a randomized controlled cross-over trial with highly sensitive persons
Authors: Oomen-Welke Katja , Hilbich Tina , Schlachter Evelyn , Müller Alexander , Anton Andreas , Huber Roman
Published: November 2023

Introduction

The effects of spending time in forests have been subject to investigations in various countries around the world. Qualitative comparisons have been rarely done so far.

Methods

Sixteen healthy highly sensitive persons (SV12 score ≥ 18) aged between 18 and 70 years were randomly assigned to groups spending 1 h in the forest and in the field at intervals of one week. Semi-structured interviews were conducted after each intervention and analyzed using a mixed-methods approach of content analysis and grounded theory.

Results

Both natural environments induced feelings of inner calmness, inner cleansing, joy, freedom, connectedness, strengthening qualities, and heightened body awareness. The forest environment additionally offered emotional shelter, and showed advantages in promoting inner strength and self-concentration.

Discussion

People with previous negative experiences in the forest may feel safer in fields because of the wider view and better overview. Important preconditions are enough time and the absence of a judgmental authority. The two environments induced in part different but also similar emotions which might be useful to promote psychological well-being differentially.