bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Essential Hypothetical Proteins of Pseudomonas aeruginosa PAO1 for Mining of Novel Therapeutics: An In Silico Approach
Authors: Rahman Atikur , Sarker Md. Takim , Islam Md Ashiqul , Hossain Mohammad Uzzal , Hasan Mahmudul , Susmi Tasmina Ferdous
Published: April 2023

As an omnipresent opportunistic bacterium, Pseudomonas aeruginosa PAO1 is responsible for acute and chronic infection in immunocompromised individuals. Currently, this bacterium is on WHO’s red list where new antibiotics are urgently required for the treatment. Finding essential genes and essential hypothetical proteins (EHP) can be crucial in identifying novel druggable targets and therapeutics. This study is aimed at characterizing these EHPs and analyzing subcellular and physiochemical properties, PPI network, nonhomologous analysis against humans, virulence factor and novel drug target prediction, and finally structural analysis of the identified target employing around 42 robust bioinformatics tools/databases, the output of which was evaluated using the ROC analysis. The study discovered 18 EHPs from 336 essential genes, with domain and functional annotation revealing that 50% of these proteins belong to the enzyme category. The majority are cytoplasmic and cytoplasmic membrane proteins, with half being stable proteins subjected to PPIs network analysis. The network contains 261 nodes and 269 edges for 9 proteins of interest, with 11 hubs containing at least three nodes each. Finally, a pipeline builder predicts 7 proteins with novel drug targets, 5 nonhomologous proteins against human proteome, human antitargets, and human gut flora, and 3 virulent proteins. Among these, homology modeling of NP_249450 and NP_251676 was done, and the Ramachandran plot analysis revealed that more than 94% of the residues were in the preferred region. By analyzing functional attributes and virulence characteristics, the findings of this study may facilitate the development of innovative antibacterial drug targets and drugs of Pseudomonas aeruginosa PAO1.
miR-31-5p as a Potential Circulating Biomarker and Tracer of Clinical Improvement for Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Dziadkowiak Edyta , Baczyńska Dagmara , Wieczorek Małgorzata , Olbromski Mateusz , Moreira Helena , Mrozowska Monika , Budrewicz Sławomir , Dzięgiel Piotr , Barg Ewa , Koszewicz Magdalena
Published: April 2023

Background. MicroRNAs are endogenous, small noncoding RNA molecules that play a pivotal role in the regulation of gene expression. MicroRNAs are involved in many biological processes such as proliferation, cell differentiation, neovascularization, and apoptosis. Studies on microRNA expression may contribute to a better understanding of the pathomechanism of chronic inflammatory demyelinating polyneuropathy (CIDP) and consequently enable the development of new therapeutic measures using antisense miRNAs (antagomirs). In this study, we evaluated the level of miR-31-5p in the serum of patients with CIDP and its correlation with the miR-31-5p level and clinical presentation and electrophysiological and biochemical parameters. Methods. The study group consisted of 48 patients, mean age

61.60
±
11.76

, who fulfilled the diagnostic criteria of a typical variant of CIDP. The expression of miR-31-5p in patient serum probes was investigated by droplet digital PCR. The results were correlated with neurophysiological findings and the patient’s clinical and biochemical parameters. Results. The mean copy number of miRNA-31 in 100 μl serum was

1288.64
±
2001.02

in the CIDP group of patients, while in the control group, it was

3743.09
±
4026.90

. There was a significant positive correlation (0.426) between IgIV treatment duration and miR-31-5p expression. Patients without IgIV treatment showed significantly lower levels of miR-31 compared to the treated group (

259.44
±
304.02

vs.

1559.48
±
2168.45

;

p
=
0.002

). The group of patients with

body
 
weight
>
80
 
kg

showed statistically significantly lower levels of miRNA-31-5p than the patients with lower body weight (

934.37
±
1739.66

vs.

1784.62
±
2271.62

, respectively;

p
=
0.014

). Similarly, the patients with elevated cerebrospinal fluid (CSF) protein levels had significantly higher miRNA-31-5p expression than those with normal protein levels (

1393.93
±
1932.27

vs.

987.38
±
2364.10

, respectively;

p
=
0.044

). Conclusion. The results may support the hypothesis that miR-31-5p is strongly involved in the autoimmune process in CIDP. The positive correlation between higher miR-31-5p levels and duration of IVIg treatment may be an additional factor explaining the efficacy of prolonged IVIg therapy in CIDP.
The Impact of Online Socialization on Adolescent Mental Health: The Mediating Role of Friendship Quality and Family Relationships
Authors: Zhang Xiaojie
Published: April 2023

In the age of advanced information networks, the importance of adolescent mental health has received increasing attention. While previous research has focused on the effects of friendship quality and online socialization behaviors on adolescent mental health, little is known about the mediating variables involved. This study is aimed at exploring the direct and mediating effects of online socialization on adolescent mental health, as well as the role of friendship quality and family relationships. A structural equation model was constructed based on questionnaire results from a sample of adolescents. The results indicated that active social networks promote healthy psychological development in adolescents, either directly or by enhancing friendship quality, but may reduce family relationships and suppress adolescent mental health. Passive social networks with a lack of communication, on the other hand, can negatively affect both friendship and family relationships, resulting in adverse emotions and detrimental effects on healthy development. Based on these findings, this study provides important insights for parents and educators to support the healthy psychological development of adolescents. Specifically, parents and educators should pay attention to adolescents’ online socialization behaviors and encourage healthy communication and interaction on social media. They should also promote strong and positive family relationships, which may mitigate the negative effects of passive social networks on adolescent mental health. This study adds to the theory of adolescent psychology research and offers practical recommendations for improving adolescent mental health.
The Effect of Different Fibers on Granite Residual Soil Reinforced with Alkaline Solution
Authors: Yuan Bingxiang , Liang Jianhong , Liang Jingkang , Chen Weijie , Zhang Baifa , Chen Wei , Chen Tianying
Published: April 2023

This study explores the reinforcement effect of different fibers in an alkaline solution on the mechanical properties of granite residual soil using the single variable method. The macroscopic mechanical properties of the reinforced samples were studied using the unconfined lateral compressive strength test and the drop-weight load test, while the microscopic properties were characterized using techniques such as SME and XRD. The results indicated that the greatest reinforcing effect was attained when the ratio of SiO2/Na2O in the alkaline solution was 0.5 mol with the compressive strength of 4402.85 kPa. At the time, the reinforcing effect of glass fiber in an alkaline solution on granite residual soil was superior to that of basalt fiber. The inclusion of glass fibers and an alkaline solution of 0.5 mol SiO2/Na2O into the granite residual soil exhibited the best capacity for reinforcing, with the maximum impact load and compression reaching 120 kN and 12.1 mm, respectively. The findings of SME analysis revealed that GRS included a significant amount of kaolinite, which, when decomposed in an alkaline solution, generated a gel substance that bound the fibers and soil together and filled the pores between them, thereby enhancing the sample’s compactness. XRD results demonstrated the formation of gel and a small amount of geopolymer in the soil under the alkaline solution of 0.5 mol SiO2/Na2O, which tighten the binding between soil particles and fibers and increase the overall strength.
Observer‐Based Finite‐Time Sliding‐Mode Control of Robotic Manipulator with Flexible Joint Using Partial States
Authors: Wang Yang , Guan Yan , Li Huanyun
Published: April 2023

This paper addresses the control problem of the flexible joint manipulator (FJM) with unmeasurable system states and mismatched uncertainties. First, the control system is transformed as a matched uncertain system with unmeasurable states based on differentiation method. Then, the uncertainties and unmeasurable states are estimated by designing a fixed‐time observer (FTO). Based on the integral sliding‐mode control (SMC), the bi‐limit homogeneity technique and the estimation of FTO, a finite‐time SMC is proposed for FJM. Compared with the existing finite‐time SMC method for FJM, the most attractive feature of the proposed method is that not only the finite‐time convergence is guaranteed but also the two angular velocity sensors for rotation angles of link and motor are simplified. Moreover, the proposed SMC can suppress the mismatched and matched uncertainties by using chattering‐free control input. The fixed‐time stability of FTO and finite‐time stability of proposed controller are proved. Finally, the efficiency of proposed scheme is shown by the numerical simulation.
Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis
Authors: Schepers Emily J. , Glaser Kathryn , Zwolshen Harrison M. , Hartman Stephen J. , Bondoc Alexander J.
Published: April 2023

Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma (HCC). GPC3 undergoes extensive posttranslational modification (PTM) including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the PTM of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial–mesenchymal transition, and drug development. Through review of current literature, this article provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of PTM on GPC3 function at the molecular, cellular, and disease level.
The Association of Neighborhood Characteristics and Frailty in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study
Authors: Schwartz Lindsay F. , Dhaduk Rikeenkumar , Howell Carrie R. , Brinkman Tara M. , Ehrhardt Matthew J. , Delaney Angela , Srivastava Deo Kumar , Lanctot Jennifer Q. , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. , Henderson Tara O.
Published: April 2023

Background:

Childhood cancer survivors experience reduced physiologic reserve, or frailty, earlier and more frequently than peers. In other populations, frailty is impacted by one's neighborhood. This study's purpose was to evaluate associations between neighborhood characteristics and frailty in childhood cancer survivors.

Methods:

Participants in the St. Jude Lifetime Cohort Study with geocoded residential addresses were analyzed. Pre-frailty/Frailty was defined as having 1–2/≥3 of sarcopenia, muscle weakness, poor endurance, slow walking speed, and exhaustion from direct assessments. Neighborhood characteristics [e.g., access to exercise opportunities and healthy food, neighborhood socioeconomic status (nSES), and rurality/urbanicity] were determined using publicly available geospatial data. Nested multivariable logistic regression models identified associations between neighborhood characteristics and pre-frailty/frailty, adjusting for chronic health conditions, individual health behaviors and socio-demographics, and high-risk cancer treatment exposures.

Results:

For our cohort (N = 3,806, 46.79% female, 81.40% white, mean age 33.63±9.91 years), compared with non-frail survivors (n = 2,573; 67.6%), pre-frail (n = 900; 23.6%) and frail survivors (n = 333; 8.7%) were more likely to live in neighborhoods with decreased exercise opportunities (frail OR: 1.62, 1.26–2.09), reduced healthy food access (pre-frail OR: 1.28, 1.08–1.51; frail OR: 1.36, 1.06–1.75), and lower nSES (pre-frail OR: 1.31, 1.12–1.52; frail OR: 1.64, 1.30–2.07). Participants had 8% increased odds (95% confidence interval, 2%–14%) of being pre-frail/frail if they lived in “resource poor” neighborhoods as opposed to “resource rich” neighborhoods after adjusting for other pre-frailty/frailty risk factors.

Conclusions:

The neighborhood a childhood cancer survivor resides in as an adult is associated with pre-frailty/frailty.

Impact:

This study provides valuable information for creating interventions using neighborhood-level factors to mitigate frailty and improve health outcomes in survivors.

See related commentary by Bhandari and Armenian, p. 997
Triple-Negative Breast Cancer-Derived Extracellular Vesicles Promote a Hepatic Premetastatic Niche via a Cascade of Microenvironment Remodeling
Authors: Heo Woohang , Lee Woochan , Cheun Jong Ho , Lee Eun-Shin , Li Songbin , Kim Hoe suk , Son Hye-Youn , Kim Ju Hee , Woo Yeon Duk , Chung Doo Hyun , Yun Jihui , Jung Ji Gwang , Lee Han-Byoel , Han Wonshik , Kim Hong-Kyu , Kim Jong-Il , Moon Hyeong-Gon
Published: April 2023

Patients with triple-negative breast cancer (TNBC) often develop metastases in visceral organs including the liver, but the detailed molecular mechanisms of TNBC liver metastasis is not clearly understood. In this study, we tried to dissect the process of premetastatic niche formation in the liver by using patient-derived xenograft (PDX) models of TNBC with different metastatic propensity. RNA sequencing of TNBC PDX models that successfully metastasized to liver showed upregulation of the Cx3cr1 gene in the liver microenvironment. In syngeneic breast cancer models, the Cx3cr1 upregulation in liver preceded the development of cancer cell metastasis and was the result of recruitment of CX3CR1-expressing macrophages. The recruitment was induced by the CX3CL1 production from the liver endothelial cells and this CX3CL1–CX3CR1 signaling in the premetastatic niche resulted in upregulation of MMP9 that promoted macrophage migration and cancer cell invasion. In addition, our data suggest that the extracellular vesicles derived from the breast cancer cells induced the TNFα expression in liver, which leads to the CX3CL1 upregulation. Lastly, the plasma CX3CL1 levels in 155 patients with breast cancer were significantly associated with development of liver metastasis.

Implications:

Our data provides previously unknown cascades regarding the molecular education of premetastatic niche in liver for TNBC.
Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses
Authors: Diwanji Rohan , O'Brien Neil A. , Choi Jiyoung E. , Nguyen Beverly , Laszewski Tyler , Grauel Angelo L. , Yan Zheng , Xu Xin , Wu Jincheng , Ruddy David A. , Piquet Michelle , Pelletier Marc R. , Savchenko Alexander , Charette LaSalette , Rodrik-Outmezguine Vanessa , Baum Jason , Millholland John M. , Wong Connie C. , Martin Anne-Marie , Dranoff Glenn , Pruteanu-Malinici Iulian , Cremasco Viviana , Sabatos-Peyton Catherine , Jayaraman Pushpa
Published: April 2023

High levels of IL1β can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL1β could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL1β blockade induced by the mAbs canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti–programmed cell death protein 1 (anti–PD-1), anti-VEGFα, and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL1β blockade enhanced the effectiveness of docetaxel and anti–PD-1. Accompanying these effects, blockade of IL1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAF) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL1β inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL1β blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL1β inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages, and lines of treatment.
Influence of Adipose Tissue Distribution, Sarcopenia, and Nutritional Status on Clinical Outcomes After CD19 CAR T-cell Therapy
Authors: Rejeski Kai , Cordas dos Santos David M. , Parker Nathan H. , Bücklein Veit L. , Winkelmann Michael , Jhaveri Khushali S. , Liu Lian , Trinkner Paul , Günther Sophie , Karschnia Philipp , Blumenberg Viktoria , Schmidt Christian , Kunz Wolfgang G. , von Bergwelt-Baildon Michael , Jain Michael D. , Theurich Sebastian , Subklewe Marion
Published: April 2023

Although CD19-directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) has proven clinical efficacy for multiple refractory B-cell malignancies, over 50% of patients ultimately relapse. Recent evidence has underlined the critical role of the host in determining treatment responses. In this retrospective observational study of 106 patients with relapsed/refractory large B-cell lymphoma receiving standard-of-care CD19.CAR-T, we analyzed the impact of immunometabolic host features and detailed body composition measurements on post–CAR T clinical outcomes. We extracted muscle and adipose tissue distributions from prelymphodepletion CT images and assessed laboratory-based immuno-nutritional scores. Early responders displayed increased total abdominal adipose tissue deposits (TAT: 336 mm3 vs. 266 mm3, P = 0.008) and favorable immuno-nutritional scores compared to nonresponding patients. On univariate Cox regression analysis, visceral fat distribution, sarcopenia, and nutritional indices significantly impacted both progression-free (PFS) and overall survival (OS). Patients with a low skeletal muscle index (SMI; e.g.<34.5), a sarcopenia indicator, exhibited poor clinical outcomes (mOS 3.0 months vs. 17.6 months, log-rank P = 0.0026). Prognostically adverse immuno-nutritional scores were linked to inferior survival [low PNI: HROS, 6.31; 95% confidence interval (CI), 3.35–11.90; P < 0.001]. In a multivariable analysis adjusting for baseline Eastern Cooperative Oncology Group performance status, C-reactive protein, and lactate dehydrogenase, increased TAT was independently associated with improved clinical outcomes (adjusted HROS, 0.27; 95% CI, 0.08–0.90; P = 0.03). We noted particularly favorable treatment outcomes in patients with both increased abdominal fat and muscle mass (TAThigh/SMIhigh: 1-year PFS 50%, 1-year OS 83%). These real-world data provide evidence for a role of body composition and immuno-nutritional status in the context of CD19.CAR-T and suggest that the obesity paradox may extend to modern T cell–based immunotherapies.

See related Spotlight by Nawas and Scordo, p. 704
Mechanical Insufflation-Exsufflation: The Rest of the Story
Authors: Bach John R. , Choi Won Ah
Published: April 2023

Mechanical insufflation-exsufflation has been reported to decrease pneumonia rates by about 90% for patients with Duchenne muscular dystrophy now living into their 40s and 50s without tracheotomy tubes. It greatly reduces respiratory complications and hospitalization rates to less than one per 10 patient-years for advanced spinal muscular atrophy type 1, through 25–30 years of age. It is most successful from the point at which small children become able to cooperate with it, generally from 3 to 5 years of age. However, since the 1950s, successful use to extubate and decannulate ventilator “unweanable” patients with little to no measurable vital capacity without resorting to tracheostomy has always been at pressures of 50–60 cm H2O via oronasal interfaces and at 60–70 cm H2O via airway tubes when present. It must usually also be used in conjunction with up to continuous noninvasive positive pressure ventilatory support. Centers that use these effectively have eliminated need to resort to tracheotomies for people with muscular dystrophies and spinal muscular atrophies, including unmedicated patients with spinal muscular atrophy type 1. Barotrauma has been rare despite dependence on it and noninvasive ventilatory support. Despite this, noninvasive respiratory management continues to be widely underutilized.
Identification of the Genetic Influence of SARS-CoV-2 Infections on IgA Nephropathy Based on Bioinformatics Method
Authors: Deng Xiaoqi , Luo Yu , Guan Tianjun , Guo Xiaodan
Published: April 2023

Introduction: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. It was initially detected in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. Compared to healthy individuals, patients with IgA nephropathy (IgAN) are at a higher risk of SARS-CoV-2 infection. However, the potential mechanisms remain unclear. This study explores the underlying molecular mechanisms and therapeutic agents for the management of IgAN and COVID-19 using the bioinformatics and system biology way. Methods: We first downloaded GSE73953 and GSE164805 from the Gene Expression Omnibus (GEO) database to obtain common differentially expressed genes (DEGs). Then, we performed the functional enrichment analysis, pathway analysis, protein-protein interaction (PPI) analysis, gene regulatory networks analysis, and potential drug analysis on these common DEGs. Results: We acquired 312 common DEGs from the IgAN and COVID-19 datasets and used various bioinformatics tools and statistical analyses to construct the PPI network to extract hub genes. Besides, we performed gene ontology (GO) and pathway analyses to reveal the common correlation between IgAN and COVID-19. Finally, on the basis of common DEGs, we determined the interactions between DEGs-miRNAs, the transcription factor-genes (TFs-genes), protein-drug, and gene-disease networks. Conclusion: We successfully identified hub genes that may act as biomarkers of COVID-19 and IgAN and also screened out some potential drugs to provide new ideas for COVID-19 and IgAN treatment.
Strategies to Improve Long-Term Outcomes for Patients with Chronic Kidney Disease in China
Authors: Liu Jing , Shi Yunying , Diao Yongshu , Zeng Xiaoxi , Fu Ping
Published: April 2023

Background: Chronic kidney disease (CKD) is an incurable disease requiring lifelong management. China has a high prevalence of CKD, which disproportionately affects older adults and those with chronic risk factors for CKD development. The rising prevalence of CKD in China places a substantial burden on the general population and the healthcare system. Summary: In China, there are currently many unmet needs for patients with CKD and high-risk individuals, resulting from a lack of education and support to reduce risk factors, delayed diagnoses, limited knowledge of CKD among primary-care physicians, and poor access to treatments among some patient populations. An integrated, nationwide approach is required to improve the current situation of CKD management in China. There are currently several national healthcare frameworks in place that focus on new major health policies to prevent disease and encourage people to adopt healthier lifestyles, and while they do not directly target CKD, they may have a positive indirect impact. We explore the unmet needs for patients with CKD in China and discuss the potential strategies that may be required to overcome them. Such strategies include improving physician and patient education, establishing a targeted screening programme, supporting patients to improve self-management behaviours, accelerating the creation of medical consortia and medical satellite centres, and migrating from hospital- to community-based management. In addition to policy-driven strategies, development of novel therapies will be key to providing new solutions for the long-term management of CKD. Key Messages: An integrated, nationwide approach is required, incorporating policy-driven changes to the clinical management of CKD, as well as the development of novel CKD treatments.
Integrative Post-Genome-Wide Association Study Analyses Relevant to Psychiatric Disorders: Imputing Transcriptome and Proteome Signals
Authors: Gedik Huseyin , Peterson Roseann E. , Riley Brien P. , Vladimirov Vladimir I. , Bacanu Silviu-Alin
Published: April 2023

Background: The genome-wide association study (GWAS) is a common tool to identify genetic variants associated with complex traits, including psychiatric disorders (PDs). However, post-GWAS analyses are needed to extend the statistical inference to biologically relevant entities, e.g., genes, proteins, and pathways. To achieve this goal, researchers developed methods that incorporate biologically relevant intermediate molecular phenotypes, such as gene expression and protein abundance, which are posited to mediate the variant-trait association. Transcriptome-wide association study (TWAS) and proteome-wide association study (PWAS) are commonly used methods to test the association between these molecular mediators and the trait. Summary: In this review, we discuss the most recent developments in TWAS and PWAS. These methods integrate existing “omic” information with the GWAS summary statistics for trait(s) of interest. Specifically, they impute transcript/protein data and test the association between imputed gene expression/protein level with phenotype of interest by using (i) GWAS summary statistics and (ii) reference transcriptomic/proteomic/genomic datasets. TWAS and PWAS are suitable as analysis tools for (i) primary association scan and (ii) fine-mapping to identify potentially causal genes for PDs. Key Messages: As post-GWAS analyses, TWAS and PWAS have the potential to highlight causal genes for PDs. These prioritized genes could indicate targets for the development of novel drug therapies. For researchers attempting such analyses, we recommend Mendelian randomization tools that use GWAS statistics for both trait and reference datasets, e.g., summary Mendelian randomization (SMR). We base our recommendation on (i) being able to use the same tool for both TWAS and PWAS, (ii) not requiring the pre-computed weights (and thus easier to update for larger reference datasets), and (iii) most larger transcriptome reference datasets are publicly available and easy to transform into a compatible format for SMR analysis.
Feasibility of Patient-Managed ECG Recordings to Detect the Time of Atrial Fibrillation Recurrence after Electrical Cardioversion: Results from the PRE-ELECTRIC Study
Authors: Andersen Elizabeth Lyster , Solberg Magnar Gangås , Walle-Hansen Marte Meyer , Enger Steve , Onarheim Sophia , Olufsen Mona , Berge Trygve , Christophersen Ingrid Elisabeth , Ulimoen Sara Reinvik , Tveit Arnljot
Published: April 2023

Background: Electrical cardioversion (ECV) is a common procedure to terminate persistent atrial fibrillation (AF). The recurrence rate is high, and the patients often fail to recognize AF recurrence. Objectives: The aim of the study was to evaluate the feasibility of patient-managed electrocardiography (ECG) to detect the time to AF recurrence after ECV. Methods: PRE-ELECTRIC (predictors for recurrence of atrial fibrillation after electrical cardioversion) is a prospective, observational study. Patients ≥18 years of age scheduled for ECV of persistent AF at Bærum Hospital were eligible for inclusion in the study. Time to recurrence of AF was detected by thumb ECG, recorded twice daily and whenever experiencing symptoms. The observation period was 28 days. We defined adherence as the observed number of days with ECG recordings divided by the expected number of days with ECG recordings. Study personnel contacted the participants by phone to assess their awareness of AF recurrence after a recurrence was detected in the thumb ECG. Results: The study enrolled 200 patients scheduled for ECV of persistent AF at Bærum Hospital between 2018 and 2022. The mean age was 66.2 ± 9.3 years, and 21.0% (42/200) were women. The most frequent comorbidities were hypertension (n = 94, 47.0%) and heart failure (n = 51, 25.5%). A total of 164 participants underwent ECV of AF. The procedure was initially successful in 90.9%, of which 50.3% had a recurrence of AF within 4 weeks. The median time to recurrence was 5 days. Among the cardioverted participants, 123 (75.0%) had no missing days of thumb ECG recording during the observation period, and 97.0% had ≤3 missing days. More than a third (37.3%) of the participants with AF recurrence were unaware of the recurrence at the time of contact. Women were older and more symptomatic than men but had similar outcomes after ECV. Conclusions: Recurrence of AF after ECV was common. Using patient-managed thumb ECG was a feasible method to detect AF recurrence following ECV. Further studies are needed to investigate whether patient-managed ECG after ECV can optimize AF treatment.
Avances y perspectivas de la inmunoterapia perioperatoria en el cáncer de pulmón no-microcítico
Authors: Peng Yurong , Li Zhuo , Fu Yucheng , Pan Yue , Zeng Yue , Liu Junqi , Xiao Chaoyue , Zhang Yingzhe , Su Yahui , Li Guoqing , Wu Fang
Published: April 2023

]El cáncer de pulmón es una de las principales causas de muerte por neoplasias. La mortalidad del cáncer de pulmón ha disminuido en la última década, lo que se atribuye en parte a la mejoría de los tratamientos. La cirugía curativa es el tratamiento habitual para pacientes con cáncer pulmonar en estadio inicial, pero no todas las intervenciones quirúrgicas tienen buen pronóstico. La quimioterapia adyuvante y neoadyuvante se utiliza para mejorar el pronóstico de los pacientes con cáncer de pulmón resecable. La inmunoterapia, tratamiento que marcó una época, ha mejorado los efectos curativos, el pronóstico y la tolerabilidad en comparación con la quimioterapia citotóxica tradicional, ofreciendo nuevas esperanzas a pacientes con cáncer de pulmón no-microcítico (CPNM). Ensayos clínicos relacionados con la inmunoterapia han registrado resul­tados clínicos alentadores en la exploración de los distintos tipos de inmunoterapia perioperatoria, incluida la monoterapia neoadyu­vante con inhibidores de puntos de control inmunitarios (ICI), la inmunoterapia combinada neoadyuvante (quimioinmunoterapia, inmunoterapia más terapia antiangiogénica, inmunoterapia más radioterapia o quimiorradioterapia concurrente), la inmunoterapia adyuvante y la inmunoterapia combinada adyuvante y neoadyuvante. Estudios de fase III como IMpower 010 y CheckMate 816 reportaron beneficios en la supervivencia de la inmunoterapia perioperatoria para pacientes operables. Esta revisión resume varios estudios clínicos actualizados y analiza la eficacia y viabilidad de diferentes terapias neoadyuvantes, así como biomarcadores para identificar los tipos óptimos de inmunoterapia perioperatoria para el CPNM.
Improvements in Glucose Regulation in Children and Young People with Cystic Fibrosis-Related Diabetes following Initiation of Elexacaftor/Tezacaftor/Ivacaftor
Authors: Park Julie , Walsh Anna , Kerr Sue , Woodland Clare , Southward Suzanne , Deakin Mark , Senniappan Senthil , Thursfield Rebecca
Published: April 2023

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are increasingly used in children and young people with cystic fibrosis (CF). Data in adults show there may be an impact on glycaemic control in those with CF-related diabetes (CFRD). Paediatric data are rare. Case Series/Presentation: Children aged >12 years with CFRD, who were eligible for elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were commenced on treatment. Glucose monitoring via the FreeStyle Libre system was commenced prior to, immediately after, and several months after commencing ELX/TEZ/IVA. Glycaemic control, shown by time in range (3–10 mmol/L), percentage of time spent hypoglycaemic (<3 mmol/L), and percentage of time spent hyperglycaemic (>10 mmol/L) on Insulin doses were recorded. Following ELX/TEZ/IVA, four of seven children stopped insulin, two required substantially reduced doses of insulin, one showed no response. Glycaemic control remained similar on lower doses or no insulin. Hypoglycaemia was detected in those not requiring insulin. Conclusion: ELX/TEZ/IVA has a positive impact on glycaemic control and insulin requirements in children with CFRD. Close monitoring is required when commencing treatment. Children with CFRD need counselling regarding possible reductions in insulin requirement and re-education regarding symptoms, signs, and management of hypoglycaemia.
Sex Differences in Cocaine Sensitization Vary by Mouse Strain
Authors: Chapp Andrew D , Nwakama Chinonso A , Thomas Mark J , Meisel Robert L , Mermelstein Paul G.
Published: April 2023

Introduction: Preclinical literature, frequently utilizing rats, suggests females display a more rapid advancement of substance abuse and a greater risk of relapse following drug abstinence. In clinical populations, it is less clear as to what extent biological sex is a defining variable in the acquisition and maintenance of substance use. Even without considering environmental experiences, genetic factors are presumed to critically influence the vulnerability to addiction. Genetically diverse mouse models provide a robust tool to examine the interactions between genetic background and sex differences in substance abuse. Methods: We explored mouse strain variability in male versus female behavioral sensitization to cocaine. Locomotor sensitization was observed following 5 consecutive days of subcutaneous cocaine across three genetically different mice strains: C57BL/6J, B6129SF2/J, and Diversity Outbred (DO/J). Results: Sex differences in cocaine locomotor sensitization were dependent on mouse strain. Specifically, we observed opposing sex differences in locomotor sensitization, with male C57BL/6J and female B6129SF2/J mice displaying heightened activity compared to their opposite sex counterparts. Conversely, no sex differences were observed in the DO/J mice. Acute cocaine administration resulted in locomotor differences across strains in male, but not female, mice. The magnitude of sensitization (or lack thereof) also varied by genetic background. Conclusions: While sex differences in drug addiction may be observed, these effects can be mitigated, or even reversed, depending on genetic background. The clinical implications are that in the absence of understanding the genetic variables underlying vulnerability to addiction, sex provides little information regarding the predisposition of an individual to drug abuse.
Identidades e grupos étnicos do Litoral Norte do Rio Grande do Sul no Festival Tafona da Canção Nativa
Authors: Silveira Pedro Leandro Scarparo , Marques Olavo Ramalho
Published: April 2023

Os Festivais Nativistas, no contexto do Movimento Nativista Gaúcho, consistem em concursos de músicas que visam fomentar a criação e produção cultural de cunho regional. Estes eventos, através das canções julgadas, classificadas e premiadas, celebram identidades e ensejam disputas entre grupos sociais em busca de visibilidade, delimitando fronteiras simbólicas, vivificando mitos de origem e tradições inventadas. O presente artigo apresenta  uma análise de algumas canções da “Tafona da Canção Nativa de Osório”, de aspectos de seus regulamentos, de textos e depoimentos de pessoas envolvidas no festival ao longo de seus 31 anos de existência. A Tafona revela-se um festival sui-generis, já que, para além da “Linha Campeira”, destinada a canções que celebram essa dimensão hegemônica da identidade gaúcha, abre espaço para a premiação de canções que versam sobre "temática litorânea”, uma vez que a cidade de Osório está inserida no Litoral Norte do Rio Grande do Sul.
Role of Resilience in the Psychological Recovery of Women With Acute Myocardial Infarction
Authors: Arabadjian Milla , Duberstein Zoe T. , Sperber Sarah H. , Kaur Kiranjot , Kalinowski Jolaade , Xia Yuhe , Hausvater Anaïs , O'Hare Olivia , Smilowitz Nathaniel R. , Dickson Victoria Vaughan , Zhong Hua , Berger Jeffrey S. , Hochman Judith S. , Reynolds Harmony R. , Spruill Tanya M.
Published: April 2023

Background

Psychological well‐being is important among individuals with myocardial infarction (MI) given the clear links between stress, depression, and adverse cardiovascular outcomes. Stress and depressive disorders are more prevalent in women than men after MI. Resilience may protect against stress and depressive disorders after a traumatic event. Longitudinal data are lacking in populations post MI. We examined the role of resilience in the psychological recovery of women post MI, over time.

Methods and Results

We analyzed a sample from a longitudinal observational multicenter study (United States, Canada) of women post MI, between 2016 and 2020. Perceived stress (Perceived Stress Scale‐4 [PSS‐4]) and depressive symptoms (Patient Health Questionnaire‐2 [PHQ‐2]) were assessed at baseline (time of MI) and 2 months post MI. Demographics, clinical characteristics, and resilience (Brief Resilience Scale [BRS]) were collected at baseline. Low and normal/high resilience groups were established as per published cutoffs (BRS scores <3 or ≥3). Mixed‐effects modeling was used to examine associations between resilience and psychological recovery over 2 months. The sample included 449 women, mean (SD) age, 62.2 (13.2) years, of whom 61.1% identified as non‐Hispanic White, 18.5% as non‐Hispanic Black, and 15.4% as Hispanic/Latina. Twenty‐three percent had low resilience. The low resilience group had significantly higher PSS‐4 and PHQ‐2 scores than the normal/high resilience group at all time points. In adjusted models, both groups showed a decrease in PSS‐4 scores over time.

Conclusions

In a diverse cohort of women post MI, higher resilience is associated with better psychological recovery over time. Future work should focus on developing strategies to strengthen resilience and improve psychological well‐being for women with MI.

Registration

URL:
https://clinicaltrials.gov/ct2/show/NCT02905357
; Unique identifier: NCT02905357.
Revised Definition of Pulmonary Hypertension and Approach to Management: A Clinical Primer
Authors: Maron Bradley A.
Published: April 2023

The definition of pulmonary hypertension (PH) has changed recently based, in part, on contemporary outcome data and to focus on early disease detection. Now, PH includes patients with mean pulmonary artery pressure >20 mm Hg measured by right heart catheterization. In contrast to the classical era, pulmonary vascular resistance >2.0 Wood units is also used for diagnosis and prognostication. These lowered thresholds aim to identify patients early in the disease course, which is important because delay to diagnosis of PH is common and linked to elevated morbidity and shortened lifespan. This clinical primer highlights key changes in diagnosis and approach to PH management, focusing on concepts that are likely to be encountered frequently in general practice. Specifically, this includes hemodynamic assessment of at‐risk patients, pharmacotherapeutic management of pulmonary arterial hypertension, approach to PH in patients with heart failure with preserved ejection fraction, and newly established indications for early referral to PH centers to prompt comanagement of patients with pulmonary vascular disease experts.
Morphological and multigene phylogenetic analyses reveal two new nematode-trapping fungi (Arthrobotrys, Orbiliaceae) from Yunnan, China
Authors: YANG YAO-QUAN , ZHANG FA , LI ZHENG-QIANG , ZHOU FA-PING , YANG XIAO-YAN , XIAO WEN
Published: April 2023

During the investigation of nematode-trapping fungi in Yunnan Province, four strains were isolated from the soil collected in Nujiang City, Yunnan Province, China and were identified as two new Arthrobotrys (Orbiliaceae) species based on morphology and multigene (ITS, EF1-α, and RPB2) phylogenetic analysis. Arthrobotrys gongshanensis is characterized by conidiophores producing 1–5 short denticles near the apex, bearing a single conidium on each denticle and obovoid to fusiform, 1–4-septate conidia. Arthrobotrys luzhangensis is characteristics by its obovoid to fusiform, 1–4-septate macroconidia, and clavate or obovoid, aseptate microconidia. These two new species both capture nematodes using adhesive networks. The multigene phylogenetic analyses further confirmed the taxonomic positions of these two new species within Arthrobotrys. This paper described them with illustrations and compared them with similar taxa.
Quantitation of trace protein in lactose for injection using SensiNanoOrange fluorescence assay
Authors: Sun Jiabei , Li Chan , Zhang Mengyu , Gan Yaling , Liang Xing-Jie , Xu Jing
Published: April 2023

Lactose is an important pharmaceutical excipient in the drug industry. Residual protein in lactose derived from cow milk can cause acute allergic reactions in some patients, especially when lactose-containing drugs are administered via the intravenous route. The aim of this study was
to develop an accurate and reliable method for quantitating trace amount of residual protein in lactose using simple instrumentation. In this work, we developed a new method called SensiNanoOrange that is based on the NanoOrange protein quantitation assay. 1. Compared with the original NanoOrange
method, the sample volume was increased from ≤4% to 90% in the final test solution. 2. Using the SensiNanoOrange method, the sensitivity of the test was significantly improved. In this work, an LOQ of 0.6 μg/mL in sample solution was achieved, which is 4.2 times lower than the
value reported in the original NanoOrange protocol. The calibration curve was linear from 0.5 to 5 μg/mL. 3. The accuracy and precision of the method for quantitation of protein in lactose solution were confirmed. The results showed that for the accuracy test, all recovery values
ranged from 81.45 to 100.85% with RSD ≤ 11.33% in each group. The RSD for the precision test was less than 10.08%. 4. The SensiNanoOrange method was used to indicate that treatment by activated carbon can remarkably reduce the protein content in lactose solution. Our data suggested that
this method is not only highly suitable for the characterization of lactose used for injections in the pharmaceutical industry but also may be useful for other biochemical and clinical applications.
Inhibitory effect of obatoclax mesylate-Loaded nanoparticles on lung cancer through Bcl-2 pathway
Authors: Gao Fei , Lan Hualin , Jiao Longbing , Zuo Tiantian , Sun Nan , Hu Zebin , Huang Jie
Published: April 2023

Lung cancer is a common tumor with poor survival, despite great advancements in etiology and treatments for lung cancer in recent years. Nanoparticles (NPs) are highlighted as a promising tool for drug treatment to improve patients’ outcomes. Obatoclax mesylate (OM) is a current
experimental drug for treatment of cancers, and modified OM is expected to more effectively control progression of diseases. Our study assessed the efficacy of combined NPs and OM on tumors. After synthesis of OM-NPs and examination of their characteristics, we treated lung cancer cells with
synthesized OM-NPs and OM, respectively. Besides, animal model of lung cancer was established to explore the impact of modified OM on tumor growth. Cytotoxicity of the NPs and their inhibitory effect on tumor cells was assessed. Administration of OM-NPs effectively downregulated Bcl-2 and
Bcl-xl, upregulated Bax, Cyto-c, cleavage of Caspase-9, Caspase-3 and poly ADP-ribose polymerase (PARP.) modified with NPs, the OM exerted greater inhibitory effect on lung cancer cell proliferation, and significantly induced apoptosis, prolonged circulation time for NPs and improved targeted
ability. The OM-NPs prepared in this study effectively reduced lung cancer cells proliferation and inhibited tumor growth. These findings indicate the potential of NPs on targeted therapy.
LINC01232 Facilitates the Proliferation of Esophageal Squamous Cell Carcinoma by Sponging miR-708-5p to Upregulate Upstream Stimulatory Factor 1
Authors: Chen Jian , Meng Jingjing , Zhao Yongsheng , Zhang Lin , Jia Ke
Published: April 2023

LncRNAs are vital regulators in human diseases. LINC01232 is found to be upregulated in esophageal squamous cell carcinoma (ESCC). This study aims to uncover the biological functions of LINC01232 in the development of ESCC and the underlying mechanism. Expression pattern of LINC01232
and its influence on the prognosis in ESCC were determined by analyzing the dataset downloaded from TCGA. LINC01232 levels in ESCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of LINC01232 on proliferative and apoptotic
abilities in ESCC were examined by Cell Counting Kit (CCK-8) assay, colony formation assay and flow cytometry, respectively. The interaction in the LINC01232/miR-708-5p/USF1 axis was tested by dual-luciferase reporter assay. By analyzing ESCC profiling downloaded from TCGA, LINC01232 was found
to be upregulated in ESCC tissues, while its level was unrelated to overall survival and disease-free survival in ESCC patients. LINC01232 was further confirmed to be highly expressed in ESCC tissues and cell lines we collected. Knockdown of LINC01232 inhibited proliferative ability and induced
apoptosis in ESCC cells. LINC01232 competed with USF1 to bind miR-708-5p, and thereafter regulated the development of ESCC. LINC01232/miR-708-5p/USF1 axis is responsible for facilitating the proliferative ability in ESCC, thereby aggravating the malignant development of ESCC.
Short-Term Vagus Nerve Stimulation Improves Cardiac Function and Mitigates Myocardial Remodeling in Heart Failure Rats with Preserved Ejection Fraction
Authors: Luo Jiaying , Liu Qi , Bai Yunke , Gou Jingwen , Tian Fangjing , Zhang Yuhong
Published: April 2023

Standard therapies for heart failure with preserved ejection fraction (HFpEF) remain controversial. Vagus nerve stimulation (VNS) can downregulate extracellular matrix (ECM) expression and improve the prognosis of patients with heart failure. In order to verify whether the positive
effect of VNS on HFpEF is feasible, HFpEF model constructed by Dahl salt-sensitive rats were subjected to VNS. Thirty male Dahl salt-sensitive rats were fed a high-salt diet (inducing HFpEF) and ten were fed a low-salt diet (controls) from the age of 7 weeks old. Roughly 12 weeks later, rats
with HFpEF were randomly assigned to VNS (HF-VNS group, n = 13) and sham stimulation (HF-SS group, n = 13). Age-matched controls also underwent sham stimulation (control-SS group, n = 10). Cardiac function, myocardial hypertrophy, and fibrosis were evaluated after 72 h
of treatment. Heart rate and systolic blood pressure decreased in rats receiving VNS compared with untreated counterparts. In addition, both systolic and diastolic cardiac function improved concurrently. The concentration of serum brain natriuretic peptide (BNP) concentration and the mRNA
and protein expression of ECM proteins in serum and tissues, including collagen type I and III, connective tissue growth factor (CTGF), and transforming growth factor-β1 (TGF-β1) in serum and in tissue (mRNA and protein expression), were remarkably
downregulated by VNS. VNS improved cardiac function and mitigated myocardial remodeling in Dahl salt-sensitive rats with HFpEF, which exhibited a good clinical application prospect.