bluuebunny/crossref_metadata_2025 huggingface dataset:
Let's connect nature with hypothesis‐based experimentation and explore life in context
Authors: Negin Boaz , Aharoni Asaph
Published: November 2022

In a recent paper in Nature, Edith Heard from the European Molecular Biology Laboratory (EMBL) suggested that molecular biologists should ‘reconnect with nature’ by diversifying sampling locations. Although this approach has its own benefits, we suggest that advanced methods should rather be used to take hypothesis‐based experiments to nature, thereby supplying a much‐needed context for experimentation under controlled conditions. Following the CRISPR (clustered regularly interspaced short palindromic repeats) revolution, this approach has become accessible to many research groups. For the past several years we have developed the groundwork and initiated such experimentation. This included the assembly of a mobile laboratory on a four‐wheel drive truck and examining genome‐edited metabolic mutants in wild tree tobacco (Nicotiana glauca), grown in nature. Our findings included both targeted answers to focused questions, but also surprising results that could only be reached while working in natural settings.
HDAC19 recruits ERF4 to the MYB5a promoter and diminishes anthocyanin accumulation during grape ripening
Authors: Jia Haifeng , Zuo Qianqian , Sadeghnezhad Ehsan , Zheng Ting , Chen Xueqin , Dong Tianyu , Fang JinggGui
Published: November 2022

DNA acetylation alters the expression of responsive genes during plant development. In grapes (Vitis vinifera), however, little is known about this regulatory mechanism. In the present study, ‘Kyoho’ grapes treated with trichostatin A (TSA, a deacetylase inhibitor) were used for transcriptome sequencing and quantitative proteomics analysis. We observed that acetylation was associated with anthocyanin accumulation and gene expression. Acetylation positively regulated phenylalanine metabolism and flavonoid biosynthesis pathways. Using omics analysis, we detected an increase in the levels of the AP2/EREBP transcription factor family after TSA treatment, indicating its association with acetylation–deacetylation dynamics in grapes. Furthermore, ethylene response factor 4 (ERF4) physically interacted with VvHDAC19, a histone deacetylase, which synergistically reduced the expression of target genes involved in anthocyanin biosynthesis owing to the binding of VvERF4 to the GCC‐box cis‐regulatory element in the VvMYB5a promoter. VvHDAC19 and VvERF4 also controlled anthocyanin biosynthesis and accumulation by regulating acetylation levels of histones H3 and H4. Therefore, alterations in histone modification can significantly regulate the expression of genes involved in anthocyanin biosynthesis and affect grape ripening.
The epidemiology of transfusion‐related acute lung injury: A scoping review and analysis
Authors: White Sandra K. , Schmidt Robert L. , Walker Brandon S. , Metcalf Ryan A.
Published: November 2022

Background

The purpose of this scoping review was to identify available sources of evidence on the epidemiology of transfusion‐related acute lung injury (TRALI) and whether meta‐analysis on the incidence of TRALI is feasible. TRALI is a serious complication and the second leading cause of death related to blood transfusion. Estimates of the incidence of TRALI would provide a useful benchmark for research to reduce TRALI.

Study Design and Methods

We searched the Medline, EMBASE, and PubMed databases for publications related to the incidence of TRALI and hemovigilance. We included all studies irrespective of language or country. Both full‐text articles and conference abstracts were included. Participants of the studies must all have received a blood transfusion. Reviews and case studies were excluded.

Results

We identified 427 articles or abstracts to include for review. More than half were abstracts, and the majority were published after 2010. Reported TRALI definitions varied, but only 27.2% of studies reported any definition for TRALI. TRALI rates were reported using different denominators, such as per blood unit (54.1%), patient (34.4%), and transfusion episode (14.8%). Study populations and contexts were mostly general (75.6% and 80.3%, respectively). There was also variation in study design with most being observational (90.6%) and only 13.1% of all studies used modern donor restriction policies.

Discussion

There was substantial variation in reporting in studies on TRALI incidence. Meta‐analysis of TRALI rates may be feasible in specific circumstances where reporting is clear. Future studies should clearly report key items, such as a TRALI definition.
Intervenciones para reducir el consumo de alcohol en jóvenes universitarios
Authors: Martin del Campo Navarro Alicia Sarahy , Medina Quevedo Pablo , Calixto Olalde Gloria
Published: November 2022

Introducción: el consumo nocivo y excesivo de alcohol en los jóvenes ha sido reconocido como un comportamiento de riesgo significativo, por tanto, reducir el consumo y los problemas asociados es una prioridad entre los investigadores, educadores y profesionales de la salud que trabajan con esta población. Objetivo: examinar la evidencia actual sobre las intervenciones para reducir el consumo de alcohol de jóvenes universitarios. Método: se utilizó la metodología propuesta por Toronto y Remington. Para la evaluación y selección de los artículos cuantitativos se empleó el Instrumento de Criterios de Elegibilidad para la Selección de los Artículos de Investigación (ICrESAI) y para la evaluación de los ensayos clínicos aleatorizados se empleó la lista de verificación Estándares Consolidados de Informes de Ensayos (Consort). Resultados: se encontraron trece artículos, diez de ellos ensayos clínicos aleatorizados, dos cuantitativos longitudinales y un ensayo factorial. Conclusión: se encontró una gran variedad de diseños y propuestas de intervención, dentro de las cuales se demostró que las intervenciones breves entregadas de manera digital, tanto en la web, como en teléfonos inteligentes, son efectivas para reducir el consumo de riesgo de alcohol entre los jóvenes.
Earth-abundant photocatalyst for H
2
generation from NH
3
with light-emitting diode illumination
Authors: Yuan Yigao , Zhou Linan , Robatjazi Hossein , Bao Junwei Lucas , Zhou Jingyi , Bayles Aaron , Yuan Lin , Lou Minghe , Lou Minhan , Khatiwada Suman , Carter Emily A. , Nordlander Peter , Halas Naomi J.
Published: November 2022

Catalysts based on platinum group metals have been a major focus of the chemical industry for decades. We show that plasmonic photocatalysis can transform a thermally unreactive, earth-abundant transition metal into a catalytically active site under illumination. Fe active sites in a Cu-Fe antenna-reactor complex achieve efficiencies very similar to Ru for the photocatalytic decomposition of ammonia under ultrafast pulsed illumination. When illuminated with light-emitting diodes rather than lasers, the photocatalytic efficiencies remain comparable, even when the scale of reaction increases by nearly three orders of magnitude. This result demonstrates the potential for highly efficient, electrically driven production of hydrogen from an ammonia carrier with earth-abundant transition metals.
Zygotic genome activation by the totipotency pioneer factor Nr5a2
Authors: Gassler Johanna , Kobayashi Wataru , Gáspár Imre , Ruangroengkulrith Siwat , Mohanan Adarsh , Gómez Hernández Laura , Kravchenko Pavel , Kümmecke Maximilian , Lalic Aleksandar , Rifel Nikita , Ashburn Robert John , Zaczek Maciej , Vallot Antoine , Cuenca Rico Laura , Ladstätter Sabrina , Tachibana Kikuë
Published: November 2022

Life begins with a switch in genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA). Despite its importance, the essential regulators of ZGA remain largely unknown in mammals. On the basis of de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse two-cell embryos. Nr5a2 is required for progression beyond the two-cell stage. It binds to its motif within
SINE B1/Alu
retrotransposable elements found in cis-regulatory regions of ZGA genes. Chemical inhibition suggests that 72% of ZGA genes are regulated by Nr5a2 and potentially other orphan nuclear receptors. Nr5a2 promotes chromatin accessibility during ZGA and binds nucleosomal DNA in vitro. We conclude that Nr5a2 is an essential pioneer factor that regulates ZGA.
Rethinking premedical education
Authors: Gladysz John A.
Published: November 2022

The world needs more physicians. Increasing their numbers alone won’t solve the many problems associated with improving health care. But it doesn’t help to have a dearth of doctors, who were generally in short supply before COVID-19 struck. The pandemic has only exacerbated doctor shortages everywhere. This doesn’t bode well for a world that must prepare for future pandemics and for populations that are both growing and aging. Better health outcomes require more physicians. So, where are the bottlenecks?
Will viral interference hold off the tripledemic?
Authors: Cohen Jon
Published: November 2022

As multiple respiratory viruses surge, some researchers predict they will block one another
How to regrow a forest? Scientists aren’t sure
Authors: Pennisi Elizabeth
Published: November 2022

Reforestation has become a global priority but evidence on what works is still scant
AI learns the art of Diplomacy
Authors: Hutson Matthew
Published: November 2022

Meta’s algorithm tackles both language and strategy in a classic board game that involves negotiation
NASA mulls end for long-lived climate sentinels
Authors: Voosen Paul
Published: November 2022

Drifting satellites could still yield insights into wildfires and storms, researchers argue
Case of myocarditis secondary to severePlasmodium falciparuminfection
Authors: Langdon Angharad , Abdlaziz Ihab , Rhodes Kim , Clarke Jayson
Published: November 2022

Malaria remains one of the most prevalent infectious diseases globally. Despite targets set out by the WHO in 2015, there has been a rise in the number of cases since 2019 as an indirect effect of the COVID-19 pandemic.

Cardiac complications are very rarely witnessed with severe malaria. Of the cardiac sequelae, myocarditis is one of the most frequently observed with a handful of case reports in the literature. We report a case of a man in his 50s who developed myocarditis while being managed for severePlasmodium falciparummalaria in an intensive care unit in the UK and review the literature relevant to this case. This is the second reported case of this condition in the UK.
Case of organising pneumonia in HIV infection
Authors: Yamauchi Momoko , Kanie Nobuhiro , Takahashi Kensuke , Katoh Shungo
Published: November 2022

A man in his 50s presented to his doctor with a fever, sore throat, cough, dysgeusia and dyspnoea of several days’ duration. Tests for HIV antigen, HIV antibody and HIV PCR were positive. He was referred to our hospital for initiation of antiretroviral therapy and bronchoscopy to clarify the cause of an abnormal lung shadow on chest CT. He was diagnosed with organising pneumonia, with concurrent HIV infection. His pulmonary lesions were remitted spontaneously, and he was administered a fixed-dose combination of tenofovir (50 mg), emtricitabine (200 mg) and bictegravir (25 mg) for HIV. This is a rare report of organising pneumonia with HIV infection. Physicians need to consider organising pneumonia when lung opacity is observed in a patient with HIV infection.
Petrous apex’s dural arteriovenous fistula (DAVF) mimicking a pineal region tumour: a rare cause of Hakim triad
Authors: Guarrera Brando , Cavasin Nicola , Rossetto Marta , Magrini Salima
Published: November 2022

A dural arteriovenous fistula (DAVF) is a dural-based shunt between meningeal arteries and meningeal veins, sinuses and/or cortical veins; they have been classified and named according to the location and the flow pattern. Petrous apex DAVFs are located where the petrosal vein penetrates the dura mater into the superior petrosal sinus; there are only few cases reported in the literature, they can show an aggressive behaviour (subarachnoid haemorrhage, severe brainstem oedema) with a high mortality rate. The described case is, to the best of our knowledge, the first case of a DAVF presenting with symptoms mimicking idiopathic normal pressure hydrocephalus. After worsening of gait impairment, memory loss and urinary incontinence an urgent CT of the brain showed hydrocephalus and a hyperdense mass in the pineal region mimicking a pineal tumour; an emergent digital subtraction angiogram showed a left petrous apex Borden type III DAVF. A transvenous embolisation was performed obtaining a complete obliteration.
Metastatic spread of serous ovarian carcinoma to the bilateral breasts: a rare presentation
Authors: Musa Arif , Joiner Michael , Dzul Stephen , Miller Steven Raymond
Published: November 2022

A woman presented with a mass in her right breast. She had previously been treated with carboplatin, paclitaxel and bevacizumab for serous ovarian carcinoma diagnosed 5 years previously and was currently on maintenance olaparib. A right breast mammogram demonstrated periareolar skin thickening and the physical examination revealed an erythematous, non-blanching cutaneous lesion. A punch biopsy revealed high-grade serous carcinoma of ovarian origin, positive for PAX-8, WT-1 and p53. Positron emission tomogram-CT scan showed diffusely increased fluorodeoxyglucose uptake in the right breast. She was treated with external beam radiation therapy to the right breast and regional lymphatics and received 5200 cGy in 20 fractions to the right breast and supraclavicular region with good response. Two weeks after completing radiation therapy, she presented with a new lesion inferior to her left areola, concerning for metastasis to the contralateral breast. Subsequent biopsy of the left breast identified metastatic serous ovarian carcinoma for which she received an additional 5200 cGy in 20 fractions to the breast.
Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis
Authors: Mallardo Domenico , Giannarelli Diana , Vitale Maria Grazia , Galati Domenico , Trillò Giusy , Esposito Assunta , Isgrò Maria Antonietta , D'Angelo Grazia , Festino Lucia , Vanella Vito , Trojaniello Claudia , White Andrew , De Cristofaro Teresa , Bailey Michael , Pignata Sandro , Caracò Corrado , Petrillo Antonella , Muto Paolo , Maiolino Piera , Budillon Alfredo , Warren Sarah , Cavalcanti Ernesta , Ascierto Paolo Antonio
Published: November 2022

Background

Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes.

Methods

In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient’s genetic profile plays a role in this association.

Results

We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival. Moreover, patients who achieved a clinical or partial response tended to have higher levels of nivolumab than those who reached stable disease or had disease progression. However, the difference was not statistically significant. In particular, patients who reached a clinical response had a significantly higher concentration of nivolumab and presented a distinct genetic signature, with more marked activation of ICOS and other genes involved in effector T-cells mediated proinflammatory pathways.

Conclusions

In conclusion, these preliminary results show that in patients with MM, nivolumab concentration correlates with clinical outcomes and is associated with an increased expression of ICOS and other genes involved in the activation of T effectors cells.
Ion-pairing assemblies of self-associating pyrrole-based anion-responsive π-electronic molecules
Authors: Haketa Yohei , Nishiyama Kenta , Maeda Hiromitsu
Published: November 2022

Dipyrrolylbenzenes bearing a tethered carboxylate unit with a countercation have been synthesized as components of anion-binding self-assemblies via hydrogen bonding between the anionic moieties and pyrrole NH units. The 1D-chain self-assembled structures, as negatively charged supramolecular polymers, provide solid-state ion-pairing assemblies, whose assembly modes depend on the coexisting cations.
Effect of Sr-Doping on Structural and Magnetic Properties of La1−xSrxMnO3 Nanoparticles
Authors: Kaur Yashpreet , Chudasama Bhupendra
Published: November 2022

Polycrystalline La[Formula: see text]SrxMnO3 ([Formula: see text]–0.4) lanthanum strontium manganese oxide (LSMO), nanoparticles exhibit interesting size-dependent structural and magnetic properties. LSMO nanoparticles have attracted considerable attention in recent years because of their tunable magnetic properties like intrinsic and extrinsic colossal magnetoresistance, single domain superparamagnetic structure with near room temperature Curie point ([Formula: see text]). They find interesting applications in catalysis, biomedicine and data storage. Properties of LSMO nanoparticles are strongly correlated to extent of Sr-doping at La-site, their particle size and the extent to which different crystallographic phases (rhombohedral/orthorhombic) appear. A major aim of this study is to understand the effect of Sr-doping on the structural and magnetic properties of LSMO nanoparticles synthesized via the sol–gel auto combustion route. Structural and magnetic properties were investigated by powder X-ray diffraction coupled with Rietveld refinement and vibrating sample magnetometer, respectively. Rietveld refinement of diffractograms revealed that irrespective of Sr-doping, LSMO nanoparticles were crystallized in rhombohedral ([Formula: see text]) and orthorhombic (Pbnm) mixed phases. The rhombohedral phase appears to be the dominant crystallographic phase. VSM study revealed that irrespective of Sr-doping LSMO nanoparticles exhibit soft ferromagnetic behavior. With the increase in Sr-doping, saturation magnetization ([Formula: see text]) of LSMO nanoparticles increases, while their Curie temperature remains constant at [Formula: see text][Formula: see text]K. To establish the correlation between structural and magnetic properties of LSMO nanoparticles, [Formula: see text]–[Formula: see text] curves were fitted with modified Langevin function. It was observed that with an increase in Sr-doping, magnetic domain size, polydispersity and saturation magnetization increase. This increase is attributed to the corresponding increase in the rhombohedral phase fraction of LSMO nanoparticles. Thus, through Sr-doping, the magnetic properties of LSMO nanoparticles can be tuned by controlling their crystallographic phase fractions.
A Comparative Study of Speaker Role Identification in Air Traffic Communication Using Deep Learning Approaches
Authors: Guo Dongyue , Zhang Jianwei , Yang Bo , Lin Yi
Published: November 2022

Automatic spoken instruction understanding (SIU) of the controller-pilot conversations in the air traffic control (ATC) requires not only recognizing the words and semantics of the speech but also determining the role of the speaker. However, few of the published works on the automatic understanding systems in air traffic communication focus on speaker role identification (SRI). In this article, we formulate the SRI task of controller-pilot communication as a binary classification problem. Furthermore, the text-based, speech-based, and speech-and-text-based multi-modal methods are proposed to achieve a comprehensive comparison of the SRI task. To ablate the impacts of the comparative approaches, various advanced neural network architectures are applied to optimize the implementation of text-based and speech-based methods. Most importantly, a multi-modal speaker role identification network (MMSRINet) is designed to achieve the SRI task by considering both the speech and textual modality features. To aggregate modality features, the modal fusion module is proposed to fuse and squeeze acoustic and textual representations by modal attention mechanism and self-attention pooling layer, respectively. Finally, the comparative approaches are validated on the ATCSpeech corpus collected from a real-world ATC environment. The experimental results demonstrate that all the comparative approaches worked for the SRI task, and the proposed MMSRINet shows competitive performance and robustness compared with the other methods on both seen and unseen data, achieving 98.56% and 98.08% accuracy, respectively.
Weighted Grand Herz-Type Spaces and Its Applications
Authors: Yu Xia , Liu Zongguang
Published: November 2022

In this paper, we introduce the weighted grand Herz spaces and weighted grand Herz-type Hardy spaces. The decompositional characterizations of these spaces are established. As its applications, the boundedness of some sublinear operators are established.
Quantifying Health State Utilities for Permanent Dentition: A Cross-Sectional Study
Authors: Alharthi Yazeed , Alasmari Osama , Almuaiqly Hamad , Alhumaidi Saif , Alemam Amjad , Elkwatehy Wahdan , Bukhari Omair M.
Published: November 2022

Introduction. Health utility represents individual preference strengths regarding health-related outcomes as a numerical value, with higher utility values of a health state achieved by a service or treatment strategy suggesting that it is more worthwhile to implement and allocate resources to this service. This study aimed to find and compare the utilities of permanent teeth-related health state outcomes. Materials and Methods. Two groups, one of the dentists (50) and another of dental patients (50), responded to a standard gamble questionnaire to determine the utilities of four hypothetical alternatives of dental health state as follows: (1) carious posterior tooth with pain, (2) carious posterior tooth without pain, (3) filled posterior tooth with a temporary restoration, and (4) filled posterior tooth with a permanent restoration. Values were calculated and compared between the two groups using the unpaired Student’s t-test, and another comparison between gender groups was performed using a one-way analysis of variance. Results. There were significant differences between dentists and patients regarding health states 2, 3, and 4 (p = 0.011, 0.026, and 0.008, respectively). However, there were no significant differences between men and women regarding all health statuses. Nonetheless, there were significant differences between male dentists and male patients for health statuses 1 and 3 (p = 0.047 and p = 0.036), respectively. Conclusion. The oral health-related quality of life and its relation to economic dentistry is essential aspects of our modern practice. In the present study, there was a statistically significant difference in the utility value reported by dentists and patients. However, more research is needed in this area.
NS1619 Alleviate Brain-Derived Extracellular Vesicle-Induced Brain Injury by Regulating BKca Channel and Nrf2/HO-1/NF-ĸB Pathway
Authors: Gao Yalong , Zhang Hejun , Li Xiaotian , Li Lei , Li Fanjian , Li Tuo , Peng Ruilong , Wang Cong , Wang Jiwei , Liu Xiao , Zhang Shu , Zhang Jianning
Published: November 2022

Brain induced extracellular vesicle (BDEV) elevates after traumatic brain injury (TBI) and contributes to secondary brain injury. However, the role of BDEV in TBI remains unclear. In this study, we determined the mechanisms of BDEV in brain injury and explored whether neuroprotective drug BKca channel opener NS1619 may attenuate BDEV-induced brain injury. We injected BDEV and lactadherin, respectively, to mimic the up and downregulation of BDEV after TBI and illustrated the role of BDEV in vivo. In vitro, the membrane potential and calcium concentration of HT-22, bEnd3, and BV-2 were measured by fluorescent staining. The effects of BDEV and NS1619 on HT-22 were evaluated by CCK-8, LDH release assay, Na+/k+-ATPase activity, JC-1 staining, DHE staining, and 4-HNE staining, respectively. The role of BDEV and NS1619 on the Nrf2/HO-1/p65 pathway was also evaluated in HT-22. Finally, we administrated TBI mice with NS1619 to clarify the role of NS1619 against BDEV in vivo. Our results suggested that BDEV aggravated and lactadherin mitigated TBI-induced EB leakage, brain edema, neuronal degeneration, apoptosis, ROS level, microgliosis, MMP-9 activity, and NF-κB activation. In vitro, BDEV-caused depolarized membrane potential and calcium overload were significantly attenuated by NS1619 in HT-22, bEnd3, and BV-2. BDEV markedly decreased cell viability, Na+/k+-ATPase activity, and caused mitochondrial dysregulation, oxidative stress, and NF-ĸB activation. NS1619 pretreatment alleviated above process and enhanced antioxidant system Nrf2/HO-1 in HT-22. Finally, NS1619 administration significantly inhibited neuroinflammation response and improved TBI outcome after TBI. NS1619 treatment also reduced 4-HNE content and NF-ĸB activation and enhanced Nrf2/HO-1 pathway. Our data showed that BDEV aggravated brain injury by perturbing cell membrane potential, calcium homeostasis, oxidative stress, and neuroinflammation. The BKca channel opener NS1619 attenuated BDEV-induced pathological process in vitro and in vivo by modulating the BKca channel and Nrf2/HO-1/NF-ĸB pathway.
MSC Senescence-Related Genes Are Associated with Myeloma Prognosis and Lipid Metabolism-Mediated Resistance to Proteasome Inhibitors
Authors: Cao Yang-Jia , Zheng Yan-Hua , Li Qing , Zheng Jin , Ma Li-Tian , Zhao Can-Jun , Li Tian
Published: November 2022

Background. Complex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM. Methods. In this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed genes in both senescent MSCs and MM tumour cells were considered relevant damaged genes. GO and KEGG analyses were applied for functional evaluation. A PPI network was constructed to identify hub genes. Subsequently, we studied the damaged genes that affected the prognosis of MM. Least absolute shrinkage and selection operator (lasso) regression was used to identify the most important features, and a risk model was created. The reliability of the risk model was evaluated with the other 3 GEO validation cohorts. In addition, ROC analysis was used to evaluate the novel risk model. An analysis of immune checkpoint-related genes, tumour immune dysfunction and exclusion (TIDE), and immunophenotypic scoring (IPS) were performed to assess the immune status of risk groups. pRRophetic was utilized to predict the sensitivity to administration of chemotherapeutic agents. Results. We identified that MAPK, PI3K, and p53 signalling pathways were activated in both senescent MSCs and tumour cells, and we also located hub genes. In addition, we constructed a 14-gene prognostic risk model, which was analysed with the ROC and validated in different datasets. Further analysis revealed significant differences in predicted risk values across the International Staging System (ISS) stage, sex, and 1q21 copy number. A high-risk group with higher immunogenicity was predicted to have low proteasome inhibitor sensitivity and respond poorly to immunotherapy. Lipid metabolism pathways were found to be significantly different between high-risk and low-risk groups. A nomogram was created by combining clinical data, and the optimization model was further improved. Finally, real-time qPCR was used to validate two bortezomib-resistant myeloma cell lines, and the test confirmed that 10 genes were detected to be expressed in resistant cell lines with the same trend as in the high-risk cohort compared to nonresistant cells. Conclusion. Fourteen genes related to ageing in BM-MSCs were associated with the prognosis of MM, and by combining this genotypic information with clinical factors, a promising clinical prognostic model was established.
A Novel Inflammatory Response-Related Gene Signature Predicts Immune Status and Prognosis of Breast Cancer
Authors: Zhao Ruijun , Xie Chaoyu , Gong Yu , Wei Songzhi , Yuan Mei , Gan Jinfeng , Chen Wenyan
Published: November 2022

Purpose. Breast cancer is the most common type of cancer and the leading cause of cancer-related death in women worldwide. In this study, we aimed to construct an inflammatory response-related gene model for predicting the immune status and prognosis of breast cancer patients. Methods. We obtained the inflammatory response-related genes from the Molecular Signatures Database. Furthermore, we used univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) regression analysis, and multivariate Cox regression to construct an inflammatory response-related gene signature (IRGS) model based on dataset obtained from The Cancer Genome Atlas (TCGA). Patients were consequently categorized into high-risk and low-risk groups. Kaplan–Meier analysis was used to compare the overall survival (OS) of high-risk and low-risk groups. Following that, we validated the model using a dataset (GSE96058) acquired from Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox analyses were used to determine the independent prognostic value of the IRGS in the TCGA and GSE96058 cohorts. A nomogram was constructed to predict the OS in the TCGA cohort. Further, we used Gene Set Enrichment Analysis (GSEA), CIBERSORT, and single-sample Gene Set Enrichment Analysis (ssGSEA) to evaluate the associations of IRGS with immune-associated pathways and immune infiltration. Finally, the relationship between the expression of the signature genes and drug sensitivity was conducted using Pearson correlation analysis. Results. We established an IRGS to stratify breast cancer patients into the low-risk and high-risk groups. In both the training and validation sets, patients in the high-risk group had significantly shorter OS than those in the low-risk group. The risk score was significantly correlated with the clinical characteristics and could be used as a tool to predict the prognosis of breast cancer. Moreover, we found that the IRGS risk score was an independent predictor of OS in breast cancer patients, and a nomogram model based on IRGS risk score and other clinical factors could effectively predict the prognosis of breast cancer patients. Furthermore, the IRGS risk score was correlated with immune characteristics and was inversely associated with the abundance of immune cell infiltration. Patients with a low IRGS risk score had higher expression levels of immune checkpoint genes, suggesting that IRGS can be used as a potential indicator for immunotherapy. Finally, we found that the expression levels of prognostic genes were significantly correlated with tumor cell sensitivity to chemotherapeutic drugs. Conclusion. Overall, these findings suggest that the IRGS can be used to predict the prognosis and immune status of breast cancer patients and provide new therapeutic targets for the treatment of these patients.
Role of Serum Amyloid A as a Biomarker for Predicting the Severity and Prognosis of COVID-19
Authors: Abbas Amal A. , Alghamdi Asma , Mezghani Sonia , Ben Ayed Mourad , Alamori Ahmed M. , Alghamdi Ghazi A. , Bajhmom Wail , Wajeeh Hanan , Almutairi Salma S. , Radwan Wafaa M.
Published: November 2022

Objective. To detect biomarkers that can be used to predict COVID-19 severity to identify patients with high probability of disease progression and poor prognosis. Methods. Of the 102 patients with confirmed COVID-19 who were admitted to King Fahd General Hospital, Jeddah City, Saudi Arabia, from July 1, 2021 to August 5, 2021, 50 were included in this cross-sectional study to investigate the influence of serum amyloid A (SAA) on disease severity and survival outcomes of COVID-19 patients. Dynamic shifts in SAA, C-reactive protein (CRP), white blood cell (WBC), lymphocytes, neutrophils, biochemical markers, and disease progression were examined. At admission, and at three, five, and seven days after treatment, at least four data samples were collected from all patients, and they underwent clinical status assessments. Results. Critically ill patients showed higher SAA and CRP levels and WBC and neutrophil counts and significantly lower lymphocyte and eosinophil counts compared to the moderately/severely ill patients, especially with regard to disease progression. Similarly, nonsurvivors had higher SAA levels than survivors. The moderately/severely ill patients and the survivors had significantly higher dynamic changes in SAA compared to the critically ill patients and nonsurvivors, respectively, with differences clearly noticed on the fifth and seventh day of treatment. ROC curve analysis revealed that the combination of SAA and CRP was valuable in evaluating the disease progression and prognosis of COVID-19 patients at different time points; however, a combination of SAA and lymphocyte counts was more sensitive for disease severity prediction on admission. The most sensitive parameters for predicting survival on admission were the combination of SAA/WBC and SAA/neutrophil count. Conclusions. The study findings indicate that SAA can be used as a sensitive indicator to assess the degree of disease severity and survival outcomes of COVID-19 patients.
Cordycepin Inhibits the Growth of Hepatocellular Carcinoma by Regulating the Pathway of Aerobic Glycolysis
Authors: Chen Ya , Jiang Yuan , Huang Xinyu , Chen Lin , Yang Hao , Zhao Jian , Liang Beibei
Published: November 2022

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with a high incidence and mortality rate. Glucose metabolism reprogramming is a major characteristic of tumor cells. Increasing evidence indicates that aerobic glycolysis is associated with tumor growth and insensitivity to chemotherapy. Cordycepin inhibits the growth of HCC cells, but the mechanism is yet to be elucidated. Herein, in vitro and in vivo methods were utilized to investigate the cordycepin-inhibited growth of HCC by regulating the metabolic pathway of aerobic glycolysis. In vitro analyses using colony formation and flow cytometry revealed that cordycepin inhibits HCC cells’ proliferation and promotes apoptosis. In addition, cordycepin reduced the production of lactic acid and pyruvate, reduced the uptake of glucose, and decreased the extracellular acidification in HCC cells. Specifically, cordycepin inhibited the expression of HK2, LDHA, and PKM2 in aerobic glycolysis via the AMPK-Akt pathway. Taken together, these findings revealed that cordycepin reduces the tumor energy supply and decreases lactic acid production, thereby inhibiting the growth of HCC cells by regulating the metabolic pathway of aerobic glycolysis. These findings might provide novel insights into the mechanisms underlying cordycepin-mediated inhibition of tumor growth as well as a new treatment for HCC.
Adaptive Control of the Atmospheric Plasma Spray Process for Functionally Graded Thermal Barrier Coatings
Authors: Guduri Balachandar , Batra Romesh C.
Published: November 2022

Functionally graded coatings (FGCs) have a material composition continuously varying through the thickness but uniform in the surface parallel to the coated substrate. When used as a thermal barrier on a metallic substrate, the coating composition varies from an almost pure metal near the substrate to a pure ceramic adjacent to the outer surface exposed to a hot environment. Challenging issues in producing high quality FGCs in the presence of external disturbances with an atmospheric plasma spray process (APSP) include controlling the mean temperature, the mean axial velocity, and the positions of the constituent material particles when they arrive at the substrate to be coated. The unavoidable disturbances include fluctuations in the arc voltage and clogging of the powder in the delivery system. For a two-constituent coating, this work proposes using three modified robust model reference adaptive controllers based on the σ-modified laws and low frequency learning. One controller adjusts the current and flow rates of argon and hydrogen into the torch. The other two controllers adjust the distance of the two powder injector ports from the plasma jet axis and the average injection velocity of each powder. It is shown through numerical experiments that the three controllers implemented in an APSP consistently produce high-quality FGCs.
Modulation of the p38 MAPK Pathway by Anisomycin Promotes Ferroptosis of Hepatocellular Carcinoma through Phosphorylation of H3S10
Authors: Chen Wei , Yang Wenjing , Zhang Chunyan , Liu Te , Zhu Jie , Wang Hao , Li Tong , Jin Anli , Ding Lin , Xian Jingrong , Tian Tongtong , Pan Baishen , Guo Wei , Wang Beili
Published: November 2022

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Ferroptosis is emerging as an effective target for tumor treatment as it has been shown to potentiate cell death in some malignancies. However, it remains unclear whether histone phosphorylation events, an epigenetic mechanism that regulates transcriptional expression, are involved in ferroptosis. Our study found that supplementation with anisomycin, an agonist of p38 mitogen-activated protein kinase (MAPK), induced ferroptosis in HCC cells, and the phosphorylation of histone H3 on serine 10 (p-H3S10) was participated in anisomycin-induced ferroptosis. To investigate the anticancer effects of anisomycin-activated p38 MAPK in HCC, we analyzed cell viability, colony formation, cell death, and cell migration in Hep3B and HCCLM3 cells. The results showed that anisomycin could significantly suppress HCC cell colony formation and migration and induce HCC cell death. The hallmarks of ferroptosis, such as abnormal accumulation of iron and elevated levels of lipid peroxidation and malondialdehyde, were detected to confirm the ability of anisomycin to promote ferroptosis. Furthermore, coincubation with SB203580, an inhibitor of activated p38 MAPK, partially rescued anisomycin-induced ferroptosis. And the levels of p-p38 MAPK and p-H3S10 were successively increased by anisomycin treatment. The relationship between p-H3S10 and ferroptosis was revealed by ChIP sequencing. The reverse transcription PCR and immunofluorescence results showed that NCOA4 was upregulated both in mRNA and protein levels after anisomycin treatment. And by C11-BODIPY staining, we found that anisomycin-induced lipid reactive oxygen species was reduced after NCOA4 knockdown. In conclusion, the anisomycin-activated p38 MAPK promoted ferroptosis of HCC cells through H3S10 phosphorylation.
On Refinements of Multidimensional Inequalities of Hardy‐Type via Superquadratic and Subquadratic Functions
Authors: Zakarya M. , AlNemer Ghada , Abd El-Hamid H. A. , Butush Roqia , Rezk H. M.
Published: November 2022

By utilizing the peculiarities of superquadratic and subquadratic functions, we give the extensions for multidimensional inequalities of Hardy‐type with general kernel. We use some algebraic inequalities such as the Minkowski inequality, the refined Jensen inequality, and the Bernoulli inequality to prove the essential results in this paper. The performance of the superquadratic functions is reliable and effective to obtain new dynamic inequalities on time scales. By utilizing special kernels, we also acquire numerous examples and implementations of the related inequalities.
Ameliorative and Renoprotective Effect of Electrical Stimulation on Blood Sugar, Blood Urea Nitrogen (BUN), Creatinine Levels, and the Islets of Langerhans Weight in Diabetic Mice
Authors: Suhariningsih Suhariningsih , Glory S. , Khaleyla F. , Kusumawati H. N. , Septriana M. , Susilo Y. , Yaqubi A. K. , Astuti S. D. , Syahrom A.
Published: November 2022

Diabetes mellitus (DM) is a chronic metabolic disease or disorder characterized by high blood sugar levels as well as impaired carbohydrate, lipid, and protein metabolism due to insulin function insufficiency. Insulin deficiency can be caused by impaired or deficient insulin production by Langerhans beta cells in the pancreas or by a lack of responsiveness of the body's cells to insulin. This study aims to the effects of electrostimulation on the ameliorative (improves disease manifestations) or renoprotective (protects the kidneys) in a diabetic rat model using noninvasive (electrical stimulation with the magnetic and nonmagnetic electrode) and invasive (using needles) methods. This study used 25 female rats, with a normal control group (KN), a diabetes control group (KD), a needle treatment group (A), an electro-stimulator treatment group with a magnetic electrode (M), and an ES group with a nonmagnetic electrode (ES) (L). The electro-stimulator used AES-05 with a magnetic field strength of 90 mT at two acupoints, Pishu (BL20) and Shenshu (BL23). The treatment was administered 12 times in one month with a therapy time of 6.6 minutes per session. Body weight and blood sugar levels were compared before and after the treatment. After treatment, the diameter of the islets of Langerhans, as well as levels of creatinine and blood urea nitrogen (BUN), was measured. Furthermore, statistical analysis was performed (α = 0.05). The results of this study showed that electrical stimulation treatments with needle-invasive, noninvasive magnetic electrodes, and nonmagnetic electrodes significantly reduced diabetic rats’ blood glucose levels before and after the treatment. The analysis of the diameter of the islets of Langerhans revealed a significant difference between the treatment groups. The analysis of creatinine levels revealed a significant difference between groups, but creatinine levels in the group with the magnetic electrode (0.58 ± 0.17 mg/dL) were not significantly different from the control group (0.58 ± 0.07 mg/dL). The BUN test results revealed a significant difference compared with the diabetic control group, but no significant difference with the magnetic electrode treatment group. Conclusion. Based on the results, the most effective therapy for diabetes is a noninvasive method with magnetic (M) electrodes.
Growth Hormone Response to L-Arginine Alone and Combined with Different Doses of Growth Hormone-Releasing Hormone: A Systematic Review and Meta-Analysis
Authors: Goli Parvin , Yazdi Maryam , Heidari-Beni Motahar , Kelishadi Roya
Published: November 2022

Background. Arginine (ARG) can modulate growth hormone (GH) release by suppressing its endogenous inhibitory regulator, somatostatin. ARG also induces the release of the GH-releasing hormone (GHRH). This study aims to review the effects of L-arginine supplementation alone and combined with GHRH in different doses on GH secretion. Methods. In this systematic review and meta-analysis, an electronic literature search was conducted on Medline database (PubMed), Scopus, and Web of Science databases. All eligible studies were randomized clinical trials that reported the effects of ARG supplementation alone or with GHRH on GH levels. Mean difference (MD) and 95% confidence intervals (CI) were computed as the effect size. Results. Meta-analyses showed significant effects of ARG alone on GH release (MD = 10.07, 95% CI: 7.87, 12.28). Moreover, the response of GH was greater with ARG in combination with GHRH (MD = 24.96, 95% CI: 17.51, 32.42). There was no significant difference between the patients and healthy individuals and between oral and injection use of ARG. The systematic review revealed the important role of ARG in combination with other amino acids on GH secretion in patients with GH deficiency. Conclusion. This study revealed that in GH-deficient individuals, high doses of ARG supplementation in combination with GHRH and/or other amino acids might have potential therapeutic effects on increasing GH concentrations. These findings propose that ARG supplementation can be considered as a potential stimulator in management of GH deficiency.
Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles
Authors: Xu Jia , Yang Ming , Shao Ai-zhong , Pan Hui-wen , Fan Yi-xuan , Chen Ke-ping
Published: November 2022

Esophageal squamous cell carcinoma (ESCC) is one of the subtypes of esophageal cancer with Chinese characteristics, and its five‐year survival rate is less than 20%. Early diagnosis is beneficial to improving the survival rate of ESCC significantly. Quantitative Real‐Time Polymerase Chain Reaction is a high‐throughput technique that can quantify tumor‐related genes for early diagnosis. Its accuracy largely depends on the stability of the reference gene. There is no systematic scientific basis to demonstrate which reference gene expression is stable in ESCC and no consensus on the selection of internal reference. Therefore, this research used four software programs (The comparative delta-Ct method, GeNorm, NormFinder, and BestKeeper) to evaluate the expression stability of eight candidate reference genes commonly used in other tumor tissues and generated a comprehensive analysis by RefFinder. Randomly selected transcriptome sequencing analysis confirmed the SPP1 gene is closely related to ESCC. It was found that the expression trend of SPP1 obtained by RPS18 and PPIA as internal reference genes were the same as that of sequencing. The results show that RPS18 and PPIA are stable reference genes, and PPIA + RPS18 are a suitable reference gene combination. This is a reference gene report that combines transcriptome sequencing analysis and only focuses on ESCC, which makes the quantification more precise, systematic, and standardized, and promotes gene regulation research and the early diagnosis of ESCC in the future.
La enseñanza de español a inmigrantes: el caso de la comunidad haitiana en Rosario (Argentina) desde una perspectiva de integración regional
Authors: Rubio Scola Virginia Irene , Tramallino Carolina Paola
Published: November 2022

Este artículo aborda la enseñanza de español como lengua segunda y extranjera (ELSE) para la inclusión ciudadana de inmigrantes haitianos que residen en la ciudad de Rosario, Argentina. Para ello, se analizó la situación sociolingüística del grupo migrante y sus dificultades comunicativas. El objetivo de esta iniciativa, enmarcada en un proyecto que vincula extensión e investigación, es fomentar la conciencia intercultural y plurilingüe de las comunidades inmigrantes y los ciudadanos. Por lo tanto, en primer lugar, se reseñan propuestas de ELSE para migrantes y refugiados llevadas a cabo en Argentina y Chile. A continuación, a partir del análisis de manuales de ELSE que circulan en Argentina, identificamos la necesidad de elaborar una propuesta específica para estudiantes migrantes o refugiados. Así, se exponen las características requeridas para la conformación de un material didáctico situado. Las conclusiones muestran la necesidad de incorporar una perspectiva plurilingüe e intercultural crítica, tanto en los contenidos como en las propuestas de actividades didácticas.