bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis
Authors: Stuart Sarah F. , Bezawork-Geleta Ayenachew , Areeb Zammam , Gomez Juliana , Tsui Vanessa , Zulkifli Ahmad , Paradiso Lucia , Jones Jordan , Nguyen Hong P. T. , Putoczki Tracy L. , Licciardi Paul V. , Kannourakis George , Morokoff Andrew P. , Achuthan Adrian A. , Luwor Rodney B.
Published: February 2023

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.
Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
Authors: Unnithan Afeesh Rajan , Rotherham Michael , Markides Hareklea , El Haj Alicia J.
Published: February 2023

This study reports results of a mechanical platform-based screening assay (MICA) to evaluate the remote activation of mechanosensitive ion channels. Here, we studied ERK pathway activation and the elevation in intracellular Ca2+ levels in response to the MICA application using the Luciferase assay and Fluo-8AM assay, respectively. Functionalised magnetic nanoparticles (MNPs) targeting membrane-bound integrins and mechanosensitive TREK1 ion channels were studied with HEK293 cell lines under MICA application. The study demonstrated that active targeting of mechanosensitive integrins via RGD (Arginylglycylaspartic acid) motifs or TREK1 (KCNK2, potassium channel subfamily K member 2) ion channels can stimulate the ERK pathway and intracellular calcium levels compared to non-MICA controls. This screening assay offers a powerful tool, which aligns with existing high-throughput drug screening platforms for use in the assessment of drugs that interact with ion channels and influence ion channel-modulated diseases.
Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy
Authors: Zaffran Stéphane , Kraoua Lilia , Jaouadi Hager
Published: February 2023

Calcium (Ca2+) is the major mediator of cardiac contractile function. It plays a key role in regulating excitation–contraction coupling and modulating the systolic and diastolic phases. Defective handling of intracellular Ca2+ can cause different types of cardiac dysfunction. Thus, the remodeling of Ca2+ handling has been proposed to be a part of the pathological mechanism leading to electrical and structural heart diseases. Indeed, to ensure appropriate electrical cardiac conduction and contraction, Ca2+ levels are regulated by several Ca2+-related proteins. This review focuses on the genetic etiology of cardiac diseases related to calcium mishandling. We will approach the subject by focalizing on two clinical entities: catecholaminergic polymorphic ventricular tachycardia (CPVT) as a cardiac channelopathy and hypertrophic cardiomyopathy (HCM) as a primary cardiomyopathy. Further, this review will illustrate the fact that despite the genetic and allelic heterogeneity of cardiac defects, calcium-handling perturbations are the common pathophysiological mechanism. The newly identified calcium-related genes and the genetic overlap between the associated heart diseases are also discussed in this review.
AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats
Authors: Zineldeen Doaa Hussein , Tahoon Nahid Mohamed , Sarhan Naglaa Ibrahim
Published: February 2023

Non-alcoholic fatty liver disease (NAFLD) is a global health problem characterized by altered lipid and redox homeostasis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. The AMP-dependent kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) has been shown to improve the outcome of NAFLD in the context of AMPK activation, yet the underlying molecular mechanism remains obscure. This study investigated the potential mechanism(s) of AICAR to attenuate NAFLD by exploring AICAR’s effects on the HGF/NF-κB/SNARK axis and downstream effectors as well as mitochondrial and ER derangements. High-fat diet (HFD)-fed male Wistar rats were given intraperitoneal AICAR at 0.7 mg/g body weight or left untreated for 8 weeks. In vitro steatosis was also examined. ELISA, Western blotting, immunohistochemistry and RT-PCR were used to explore AICAR’s effects. NAFLD was confirmed by steatosis score, dyslipidemia, altered glycemic, and redox status. HGF/NF-κB/SNARK was downregulated in HFD-fed rats receiving AICAR with improved hepatic steatosis and reduced inflammatory cytokines and oxidative stress. Aside from AMPK dominance, AICAR improved hepatic fatty acid oxidation and alleviated the ER stress response. In addition, it restored mitochondrial homeostasis by modulating Sirtuin 2 and mitochondrial quality gene expression. Our results provide a new mechanistic insight into the prophylactic role of AICAR in the prevention of NAFLD and its complications.
Structures of MPND Reveal the Molecular Recognition of Nucleosomes
Authors: Yang Meiting , Li Xiaorong , Tian Zizi , Ma Lulu , Ma Jun , Liu Yunlong , Shang Guohui , Liang Ailing , Wu Wei , Chen Zhongzhou
Published: February 2023

Adenine N6 methylation in DNA (6mA) is a well-known epigenetic modification in bacteria, phages, and eukaryotes. Recent research has identified the Mpr1/Pad1 N-terminal (MPN) domain-containing protein (MPND) as a sensor protein that may recognize DNA 6mA modification in eukaryotes. However, the structural details of MPND and the molecular mechanism of their interaction remain unknown. Herein, we report the first crystal structures of the apo–MPND and MPND–DNA complex at resolutions of 2.06 Å and 2.47 Å, respectively. In solution, the assemblies of both apo–MPND and MPND–DNA are dynamic. In addition, MPND was found to possess the ability to bind directly to histones, no matter the N-terminal restriction enzyme-adenine methylase-associated domain or the C-terminal MPN domain. Moreover, the DNA and the two acidic regions of MPND synergistically enhance the interaction between MPND and histones. Therefore, our findings provide the first structural information regarding the MPND–DNA complex and also provide evidence of MPND–nucleosome interactions, thereby laying the foundation for further studies on gene control and transcriptional regulation.
Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response
Authors: Washburn Rachel L. , Dufour Jannette M.
Published: February 2023

Sertoli cells within the testis are instrumental in providing an environment for spermatogenesis and protecting the developing germ cells from detrimental immune responses which could affect fertility. Though these immune responses consist of many immune processes, this review focuses on the understudied complement system. Complement consists of 50+ proteins including regulatory proteins, immune receptors, and a cascade of proteolytic cleavages resulting in target cell destruction. In the testis, Sertoli cells protect the germ cells from autoimmune destruction by creating an immunoregulatory environment. Most studies on Sertoli cells and complement have been conducted in transplantation models, which are effective in studying immune regulation during robust rejection responses. In grafts, Sertoli cells survive activated complement, have decreased deposition of complement fragments, and express many complement inhibitors. Moreover, the grafts have delayed infiltration of immune cells and contain increased infiltration of immunosuppressive regulatory T cells as compared to rejecting grafts. Additionally, anti-sperm antibodies and lymphocyte infiltration have been detected in up to 50% and 30% of infertile testes, respectively. This review seeks to provide an updated overview of the complement system, describe its relationship with immune cells, and explain how Sertoli cells may regulate complement in immunoprotection. Identifying the mechanism Sertoli cells use to protect themselves and germ cells against complement and immune destruction is relevant for male reproduction, autoimmunity, and transplantation.
Polymorphisms in Genes Encoding VDR, CALCR and Antioxidant Enzymes as Predictors of Bone Tissue Condition in Young, Healthy Men
Authors: Jówko Ewa , Długołęcka Barbara , Cieśliński Igor , Kotowska Jadwiga
Published: February 2023

The aim of the study was to assess significant predictors of bone mineral content (BMC) and bone mineral density (BMD) in a group of young, healthy men at the time of reaching peak bone mass. Regression analyses showed that age, BMI and practicing combat sports and team sports at a competitive level (trained vs. untrained group; TR vs. CON, respectively) were positive predictors of BMD/BMC values at various skeletal sites. In addition, genetic polymorphisms were among the predictors. In the whole population studied, at almost all measured skeletal sites, the SOD2 AG genotype proved to be a negative predictor of BMC, while the VDR FokI GG genotype was a negative predictor of BMD. In contrast, the CALCR AG genotype was a positive predictor of arm BMD. ANOVA analyses showed that, regarding SOD2 polymorphism, the TR group was responsible for the significant intergenotypic differences in BMC that were observed in the whole study population (i.e., lower BMC values of leg, trunk and whole body were observed in AG TR compared to AA TR). On the other hand, higher BMC at L1–L4 was observed in the SOD2 GG genotype of the TR group compared to in the same genotype of the CON group. For the FokI polymorphism, BMD at L1–L4 was higher in AG TR than in AG CON. In turn, the CALCR AA genotype in the TR group had higher arm BMD compared to the same genotype in the CON group. In conclusion, SOD2, VDR FokI and CALCR polymorphisms seem to affect the association of BMC/BMD values with training status. In general, at least within the VDR FokI and CALCR polymorphisms, less favorable genotypes in terms of BMD (i.e., FokI AG and CALCR AA) appear to be associated with a greater BMD response to sports training. This suggests that, in healthy men during the period of bone mass formation, sports training (combat and team sports) may attenuate the negative impact of genetic factors on bone tissue condition, possibly reducing the risk of osteoporosis in later age.
Effect of the Enhanced Production of Chlorophyll b on the Light Acclimation of Tomato
Authors: Khan Imran , Zada Ahmad , Jia Ting , Hu Xueyun
Published: February 2023

Tomato (Solanum lycopersicum Mill.) is one of the widely cultured vegetables under protected cultivation, in which insufficient light is one of the major factors that limit its growth, yield, and quality. Chlorophyll b (Chl b) is exclusively present in the light-harvesting complex (LHC) of photosystems, while its synthesis is strictly regulated in response to light conditions in order to control the antenna size. Chlorophyllide a oxygenase (CAO) is the sole enzyme that converts Chl a to Chl b for Chl b biosynthesis. Previous studies have shown that overexpressing CAO without the regulating domain (A domain) in Arabidopsis overproduced Chl b. However, the growth characteristics of the Chl b overproduced plants under different light environmental conditions are not well studied. Considering tomatoes are light-loving plants and sensitive to low light stress, this study aimed to uncover the growth character of tomatoes with enhanced production of Chl b. The A domain deleted Arabidopsis CAO fused with the FLAG tag (BCF) was overexpressed in tomatoes. The BCF overexpressed plants accumulated a significantly higher Chl b content, resulting in a significantly lower Chl a/b ratio than WT. Additionally, BCF plants possessed a lower maximal photochemical efficiency of photosystem II (Fv/Fm) and anthocyanin content than WT plants. The growth rate of BCF plants was significantly faster than WT plants under low-light (LL) conditions with light intensity at 50–70 µmol photons m−2 s−1, while BCF plants grew slower than WT plants under high-light (HL) conditions. Our results revealed that Chl b overproduced tomato plants could better adapt to LL conditions by absorbing more light for photosynthesis but adapt poorly to excess light conditions by accumulating more ROS and fewer anthocyanins. Enhanced production of Chl b is able to improve the growth rate of tomatoes that are grown under LL conditions, indicating the prospect of employing Chl b overproduced light-loving crops and ornamental plants for protected or indoor cultivation.
RNAseq Analysis of FABP4 Knockout Mouse Hippocampal Transcriptome Suggests a Role for WNT/β-Catenin in Preventing Obesity-Induced Cognitive Impairment
Authors: So Simon W. , Nixon Joshua P. , Bernlohr David A. , Butterick Tammy A.
Published: February 2023

Microglial fatty-acid binding protein 4 (FABP4) is a regulator of neuroinflammation. We hypothesized that the link between lipid metabolism and inflammation indicates a role for FABP4 in regulating high fat diet (HFD)-induced cognitive decline. We have previously shown that obese FABP4 knockout mice exhibit decreased neuroinflammation and cognitive decline. FABP4 knockout and wild type mice were fed 60% HFD for 12 weeks starting at 15 weeks old. Hippocampal tissue was dissected and RNA-seq was performed to measure differentially expressed transcripts. Reactome molecular pathway analysis was utilized to examine differentially expressed pathways. Results showed that HFD-fed FABP4 knockout mice have a hippocampal transcriptome consistent with neuroprotection, including associations with decreased proinflammatory signaling, ER stress, apoptosis, and cognitive decline. This is accompanied by an increase in transcripts upregulating neurogenesis, synaptic plasticity, long-term potentiation, and spatial working memory. Pathway analysis revealed that mice lacking FABP4 had changes in metabolic function that support reduction in oxidative stress and inflammation, and improved energy homeostasis and cognitive function. Analysis suggested a role for WNT/β-Catenin signaling in the protection against insulin resistance, alleviating neuroinflammation and cognitive decline. Collectively, our work shows that FABP4 represents a potential target in alleviating HFD-induced neuroinflammation and cognitive decline and suggests a role for WNT/β-Catenin in this protection.
Hormonal Gut–Brain Signaling for the Treatment of Obesity
Authors: Roh Eun , Choi Kyung Mook
Published: February 2023

The brain, particularly the hypothalamus and brainstem, monitors and integrates circulating metabolic signals, including gut hormones. Gut–brain communication is also mediated by the vagus nerve, which transmits various gut-derived signals. Recent advances in our understanding of molecular gut–brain communication promote the development of next-generation anti-obesity medications that can safely achieve substantial and lasting weight loss comparable to metabolic surgery. Herein, we comprehensively review the current knowledge about the central regulation of energy homeostasis, gut hormones involved in the regulation of food intake, and clinical data on how these hormones have been applied to the development of anti-obesity drugs. Insight into and understanding of the gut–brain axis may provide new therapeutic perspectives for the treatment of obesity and diabetes.
Gut Molecules in Cardiometabolic Diseases: The Mechanisms behind the Story
Authors: Inceu Andreea-Ioana , Neag Maria-Adriana , Craciun Anca-Elena , Buzoianu Anca-Dana
Published: February 2023

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases.
Eukaryotic Ribosomal Protein S5 of the 40S Subunit: Structure and Function
Authors: Qiu Lijuan , Chao Wen , Zhong Shan , Ren An-Jing
Published: February 2023

The ribosomal protein RPS5 is one of the prime proteins to combine with RNA and belongs to the conserved ribosomal protein family. It plays a substantial role in the process of translation and also has some non-ribosome functions. Despite the enormous studies on the relationship between the structure and function of prokaryotic RPS7, the structure and molecular details of the mechanism of eukaryotic RPS5 remain largely unexplored. This article focuses on the structure of RPS5 and its role in cells and diseases, especially the binding to 18S rRNA. The role of RPS5 in translation initiation and its potential use as targets for liver disease and cancer are discussed.
Emerging Roles of Salicylic Acid in Plant Saline Stress Tolerance
Authors: Yang Wei , Zhou Zhou , Chu Zhaohui
Published: February 2023

One of the most important phytohormones is salicylic acid (SA), which is essential for the regulation of plant growth, development, ripening, and defense responses. The role of SA in plant–pathogen interactions has attracted a lot of attention. Aside from defense responses, SA is also important in responding to abiotic stimuli. It has been proposed to have great potential for improving the stress resistance of major agricultural crops. On the other hand, SA utilization is dependent on the dosage of the applied SA, the technique of application, and the status of the plants (e.g., developmental stage and acclimation). Here, we reviewed the impact of SA on saline stress responses and the associated molecular pathways, as well as recent studies toward understanding the hubs and crosstalk between SA-induced tolerances to biotic and saline stress. We propose that elucidating the mechanism of the SA-specific response to various stresses, as well as SA-induced rhizosphere-specific microbiome modeling, may provide more insights and support in coping with plant saline stress.
Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism
Authors: Meléndez-Fernández O. Hecmarie , Liu Jennifer A. , Nelson Randy J.
Published: February 2023

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health.
Effects of the Entomopathogenic Fungus Mucor hiemalis BO-1 on the Physical Functions and Transcriptional Signatures of Bradysia odoriphaga Larvae
Authors: Zhu Guodong , Ding Wenjuan , Zhao Haipeng , Xue Ming , Chu Pengfei , Jiang Liwei
Published: February 2023

Mucor hiemalis BO-1 is an entomopathogenic fungus that infects Bradysia odoriphaga, a destructive root maggot. M. hiemalis BO-1 possesses stronger pathogenicity to the larvae than to other stages of B. odoriphaga, and provides satisfactory field control. However, the physiological response of B. odoriphaga larvae to infection and the infection mechanism of M. hiemalis are unknown. We detected some physiological indicators of diseased B. odoriphaga larvae infected by M. hiemalis BO-1. These included changes in consumption, nutrient contents, and digestive and antioxidant enzymes. We performed transcriptome analysis of diseased B. odoriphaga larvae, and found that M. hiemalis BO-1 showed acute toxicity to B. odoriphaga larvae and was as toxic as some chemical pesticides. The food consumption of diseased B. odoriphaga after inoculation with M. hiemalis spores decreased significantly, and there was a significant decrease in total protein, lipid, and carbohydrates in diseased larvae. Key digestive enzymes (protease, α-amylase, lipase, and cellulase) were significantly inhibited during infection. Peroxidase maintained high activity, and the activity of other antioxidant enzymes (catalase, superoxide dismutase, and glutathione S-transferases) first increased and then decreased. Combined with the transcriptional signatures of diseased B. odoriphaga larvae, M. hiemalis BO-1 infection resulted in decreased food consumption, reduced digestive enzyme activity, and altered energy metabolism and material accumulation. Infection was also accompanied by fluctuations in immune function, such as cytochrome P450 and the Toll pathway. Therefore, our results laid a basis for the further study of the interactions between M. hiemalis BO-1 and B. odoriphaga and promoted the genetic improvement of entomopathogenic fungi.
Pregnancy-Related Complications and Incidence of Atrial Fibrillation: A Systematic Review
Authors: Al Bahhawi Tariq , Aqeeli Abdulwahab , Harrison Stephanie L. , Lane Deirdre A. , Skjøth Flemming , Buchan Iain , Sharp Andrew , Auger Nathalie , Lip Gregory Y. H.
Published: February 2023

Pregnancy-related complications are associated with a higher risk of various incident cardiovascular diseases, but their specific potential relationship with incident atrial fibrillation (AF) is less clear. This systematic review summarises the available evidence from observational studies which have examined associations between pregnancy-related complications and the risk of AF. MEDLINE and EMBASE (Ovid) were searched for studies between 1990 to 10 February 2022. Pregnancy-related complications examined included hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, small-for-gestational-age and stillbirth. Study selection, data extraction and quality assessment were completed independently by two reviewers. Narrative synthesis was used to evaluate the results of the included studies. Nine observational studies were included, with eight eligible for narrative synthesis. Sample sizes ranged from 1839 to 2,359,386. Median follow-up ranged from 2 to 36 years. Six studies reported that pregnancy-related complications were associated with a significantly increased risk of incident AF. Hazard ratios (HRs) (95% confidence intervals) for the four studies that evaluated HDP ranged from 1.1 (0.8–1.6) to 1.9 (1.4–2.7). For the four studies that evaluated pre-eclampsia, HRs ranged from 1.2 (0.9–1.6) to 1.9 (1.7–2.2). Current evidence from observational studies suggests pregnancy-related complications are associated with a significantly higher risk of incident AF. However, only a small number of studies examining each pregnancy-related complication were identified, and considerable statistical heterogeneity was observed. Further large-scale prospective studies are required to confirm the association between pregnancy-related complications and incident AF.
Which Adverse Events and Which Drugs Are Implicated in Drug-Related Hospital Admissions? A Systematic Review and Meta-Analysis
Authors: Haerdtlein Annette , Debold Elisabeth , Rottenkolber Marietta , Boehmer Anna Maria , Pudritz Yvonne Marina , Shahid Faiza , Gensichen Jochen , Dreischulte Tobias
Published: February 2023

Adverse drug events (ADEs) and adverse drug reactions (ADRs) are leading causes of iatrogenic injury, which can result in emergency department (ED) visits or admissions to inpatient wards. The aim of this systematic review and meta-analysis was to provide up-to-date estimates of the prevalence of (preventable) drug-related ED visits and hospital admissions, as well as the type and prevalence of implicated ADRs/ADEs and drugs. A literature search of studies published between January 2012 and December 2021 was performed in PubMed, Medline, EMBASE, Cochrane Library, and Web of Science. Retrospective and prospective observational studies investigating acute admissions to EDs or inpatient wards due to ADRs or ADEs in the general population were included. Meta-analyses of prevalence rates were conducted using generalized linear mixed models (GLMM) with the random-effect method. Seventeen studies reporting ADRs and/or ADEs were eligible for inclusion. The prevalence rates of ADR- and ADE-related admissions to EDs or inpatient wards were estimated at 8.3% ([95% CI, 6.4–10.7%]) and 13.9% ([95% CI, 8.1–22.8%]), respectively, of which almost half (ADRs: 44.7% [95% CI: 28.1; 62.4]) and more than two thirds (ADEs: 71.0% [95% CI, 65.9–75.6%]) had been classified as at least possibly preventable. The ADR categories most frequently implicated in ADR-related admissions were gastrointestinal disorders, electrolyte disturbances, bleeding events, and renal and urinary disorders. Nervous system drugs were found to be the most commonly implicated drug groups, followed by cardiovascular and antithrombotic agents. Our findings demonstrate that ADR-related admissions to EDs and inpatient wards still represent a major and often preventable health care problem. In comparison to previous systematic reviews, cardiovascular and antithrombotic drugs remain common causes of drug-related admissions, while nervous system drugs appear to have become more commonly implicated. These developments may be considered in future efforts to improve medication safety in primary care.
Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson’s Disease
Authors: Santos-García Diego , Laguna Ariadna , Hernández-Vara Jorge , de Deus Fonticoba Teresa , Cores Bartolomé Carlos , Feal Painceiras Maria J. , Íñiguez-Alvarado Maria Cristina , García Díaz Iago , Jesús Silvia , Boungiorno Maria Teresa , Planellas Lluís , Cosgaya Marina , García Caldentey Juan , Caballol Nuria , Legarda Ines , Cabo Iria , López Manzanares Lydia , González Aramburu Isabel , Ávila Rivera Maria A. , Gómez Mayordomo Víctor , Nogueira Víctor , Puente Víctor , Dotor García-Soto Julio , Borrué Carmen , Solano Vila Berta , Álvarez Sauco María , Vela Lydia , Escalante Sonia , Cubo Esther , Carrillo Padilla Francisco , Castrillo Juan C. Martínez , Sánchez Alonso Pilar , Alonso Losada Maria G. , López Ariztegui Nuria , Gastón Itziar , Kulisevsky Jaime , Menéndez González Manuel , Seijo Manuel , Rúiz Martínez Javier , Valero Caridad , Kurtis Mónica , Ardura Jessica González , Alonso Redondo Ruben , Ordás Carlos , López Díaz Luis M. , McAfee Darrian , Martinez-Martin Pablo , Mir Pablo ,   on behalf of the COPPADIS Study Group
Published: February 2023

Background and objective: Sex plays a role in Parkinson’s disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
Blood Type A1 Mismatch Does Not Affect Heart Transplant Outcomes at One Year
Authors: Cao Louie , Kim Seongkyu , Klapper Ellen , Kobashigawa Jon A. , Kittleson Michelle M.
Published: February 2023

There are subtypes within blood type A, termed non-A1, that have reduced expression of A antigen on cell surfaces. This can result in the development of anti-A1 antibodies. There is limited information regarding the impact of this in heart transplant (HTx) recipients. We conducted a single-center cohort study of 142 Type A HTx recipients in which we compared outcomes of a match group (an A1/O heart into an A1 recipient or a non-A1/O heart into a non-A1 recipient) with a mismatch group (an A1 heart into a non-A1 recipient or a non-A1 heart into an A1 recipient). At one year post-transplant, there were no differences between the groups in survival, freedom from non-fatal major adverse cardiovascular events, freedom from any treated rejection, or freedom from cardiac allograft vasculopathy. There was an increased hospital length of stay in the mismatch group (13.5 vs. 17.1 days, p = 0.04). Our study showed that A1 mismatch was not associated with worse outcomes at one year post-HTx.
COVID-19 and Acute Ischemic Stroke Mortality and Clinical Outcomes among Hospitalized Patients in the United States: Insight from National Inpatient Sample
Authors: Davis Monique G. , Gangu Karthik , Suriya Sajid , Maringanti Babu Sriram , Chourasia Prabal , Bobba Aniesh , Tripathi Alok , Avula Sindhu Reddy , Shekhar Rahul , Sheikh Abu Baker
Published: February 2023

Coronavirus-19, primarily a respiratory virus, also affects the nervous system. Acute ischemic stroke (AIS) is a well-known complication among COVID-19 infections, but large-scale studies evaluating AIS outcomes related to COVID-19 infection remain limited. We used the National Inpatient Sample database to compare acute ischemic stroke patients with and without COVID-19. A total of 329,240 patients were included in the study: acute ischemic stroke with COVID-19 (n = 6665, 2.0%) and acute ischemic stroke without COVID-19 (n = 322,575, 98.0%). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation, vasopressor use, mechanical thrombectomy, thrombolysis, seizure, acute venous thromboembolism, acute myocardial infarction, cardiac arrest, septic shock, acute kidney injury requiring hemodialysis, length of stay, mean total hospitalization charge, and disposition. Acute ischemic stroke patients who were COVID-19-positive had significantly increased in-hospital mortality compared to acute ischemic stroke patients without COVID-19 (16.9% vs. 4.1%, aOR: 2.5 [95% CI 1.7–3.6], p < 0.001). This cohort also had significantly increased mechanical ventilation use, acute venous thromboembolism, acute myocardial infarction, cardiac arrest, septic shock, acute kidney injury, length of stay, and mean total hospitalization charge. Further research regarding vaccination and therapies will be vital in reducing worse outcomes in patients with acute ischemic stroke and COVID-19.
Routine Use of a Pocket-Sized Handheld Echoscopic Device Plus a Biomarker by Emergency Medicine Residents with an Early Screening Algorithm for Suspected Type A Acute Aortic Syndrome
Authors: Lian Rui , Zhang Tongzhe , Liu Juanjuan , Zhang Guochao , Hu Tianpeng , Li Guonan , Zhang Suqiao , Zhang Guoqiang
Published: February 2023

(1) Background: The early screening strategy for type A acute aortic syndrome (A-AAS) patients has always been challenging. (2) Methods: From September 2020–31 March 2022, 179 consecutive patients with suspected A-AAS were retrospectively reviewed. We assessed the diagnostic value of the use of handheld echocardiographic devices (PHHEs) by emergency medicine (EM) residents either alone or in combination with serum acidic calponin in this patient group. (3) Results: The direct sign of PHHE had a specificity (SP) of 97.7%. The sign of ascending aortic dilatation showed SE = 77.6%, SP = 68.5%, PPV = 48.1% and NPV = 89%. SE, SP, PPV and NPV of a positive PHHE direct sign were 55.6%, 100%, 100% and 71.4% in 19 hypotension/shock patients with suspected A-AAS, respectively. The area under curve (AUC) of acidic calponin combined with an ascending aorta diameter >40 mm was 0.927, with an SE and SP of 83.7% and 89.2%, respectively. These two combined indicators significantly improved the diagnostic efficiency of A-AAS compared with either of them alone (p = 0.017; standard error 0.016, Z value 2.39; p = 0.001, standard error 0.028, Z value 3.29). (4) Conclusion: EM resident-performed PHHE was highly indicative of A-AAS in patients presenting with shock or hypotension. An ascending aorta diameter > 40 mm combined with acidic calponin demonstrated acceptable diagnostic accuracy as a rapid first-line triage tool to identify patients with suspected A-AAS.
Bronchoscopic Endobronchial Valve Therapy for Persistent Air Leaks in COVID-19 Patients Requiring Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Ficial Barbara , Whebell Stephen , Taylor Daniel , Fernández-Garda Rita , Okiror Lawrence , Meadows Christopher I. S.
Published: February 2023

COVID-19 acute respiratory distress syndrome (ARDS) can be associated with extensive lung damage, pneumothorax, pneumomediastinum and, in severe cases, persistent air leaks (PALs) via bronchopleural fistulae (BPF). PALs can impede weaning from invasive ventilation or extracorporeal membrane oxygenation (ECMO). We present a series of patients requiring veno-venous ECMO for COVID-19 ARDS who underwent endobronchial valve (EBV) management of PAL. This is a single-centre retrospective observational study. Data were collated from electronic health records. Patients treated with EBV met the following criteria: ECMO for COVID-19 ARDS; the presence of BPF causing PAL; air leak refractory to conventional management preventing ECMO and ventilator weaning. Between March 2020 and March 2022, 10 out of 152 patients requiring ECMO for COVID-19 developed refractory PALs, which were successfully treated with bronchoscopic EBV placement. The mean age was 38.3 years, 60% were male, and half had no prior co-morbidities. The average duration of air leaks prior to EBV deployment was 18 days. EBV placement resulted in the immediate cessation of air leaks in all patients with no peri-procedural complications. Weaning of ECMO, successful ventilator recruitment and removal of pleural drains were subsequently possible. A total of 80% of patients survived to hospital discharge and follow-up. Two patients died from multi-organ failure unrelated to EBV use. This case series presents the feasibility of EBV placement in severe parenchymal lung disease with PAL in patients requiring ECMO for COVID-19 ARDS and its potential to expedite weaning from both ECMO and mechanical ventilation, recovery from respiratory failure and ICU/hospital discharge.
Successful Intubation Using a Cap-Assisted Colonoscope for Endoscopic Retrograde Cholangiopancreatography in Patients Undergoing Roux-en-Y Reconstruction
Authors: Lee Kyong Joo , Park Se Woo , Jang Hyun Joo , Park Da Hae , Kim Jung Hee , Jung Jang Han , Koh Dong Hee , Lee Jin
Published: February 2023

Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in patients undergoing Roux-en-Y (REY) reconstruction; although balloon-assisted enteroscopy is the first-line treatment, it is not always available considering equipment and expertise. We aimed to evaluate the feasibility of using a cap-assisted colonoscope as the primary approach for ERCP in REY reconstruction. We included 47 patients with REY who underwent ERCP using a cap-assisted colonoscope between January 2017 and February 2022. The primary outcome was intubation success for ERCP using a cap-assisted colonoscope during REY reconstruction. The secondary outcomes were cannulation success, procedure-related adverse events, and variables affecting successful intubation. Comparing side-to-side jejunojejunostomy (SS-JJ) and side-to-end jejunojejunostomy (SE-JJ) groups, the intubation success rate using a cap-assisted colonoscope in the SS-JJ group was higher than that in the SE-JJ group (34 of 38 (89.5%) vs. 1 of 9 (11.1%), p < 0.001). Successful intubation was achieved in 37 (97.4%) and 8 (88.9%) patients in the SS-JJ and SE-JJ groups, respectively, after applying the rescue technique using a balloon-assisted enteroscope for failed ERCP using only a colonoscope. No perforation occurred. Multivariable analysis showed that SS-JJ was a predictive factor for successful intubation (odds ratio [95% confidence interval] = 37.06 [3.91–925.56], p = 0.005). Usage of a cap-assisted colonoscope can be crucial for ERCP in patients undergoing REY reconstruction. Anatomically, SS-JJ can facilitate easy and accurate identification of the afferent limb and a highly successful ERCP using a cap-assisted colonoscope.
Single-Heuristic Reasoning: Is It Still Dual-Process?
Authors: Valerjev Pavle , Dujmović Marin
Published: February 2023

Traditionally, paradigms used to study conflict in reasoning (and metacognition during reasoning) pit heuristic processes against analytical processes. Findings indicate that the presence of conflict between processes prolongs reasoning and decreases accuracy and confidence. In this study, we aimed to explore reasoning and metacognition when only one type of heuristic process is exploited to cue multiple responses. In two experiments, a novel modification of the Base Rate neglect task was used to create versions in which one belief-based heuristic competes, or works in concert, with another of the same type to provide a response. Experiment 1 results reveal that the presence of conflict between cued responses does not affect meta-reasoning, which indicates that reasoning defaulted to a single process. An alternative explanation was that the effect of conflict was masked due to an imbalance in the strength of the dominant response between conflicting and congruent versions. Experiment 2 was designed to test hypotheses based on these competing explanations. Findings show that when the strength of a response was no longer masking the effect, the conflict did result in longer reasoning times and lower confidence. The study provides more robust evidence in favor of the dual-process account of reasoning, introduces a new methodological approach, and discusses how conflict may be modulated during reasoning.
Node Depth Adjustment Based Target Tracking in Sparse Underwater Sensor Networks
Authors: Zhang Zhenkai , Tian Shengkai , Yang Yi
Published: February 2023

Due to the limited energy in underwater sensor networks, underwater nodes need to be deployed sparsely. However, sparse USNs will lead to poor tracking coverage and detection capability. To solve these problems, the mobility of nodes in depth can be utilized to optimize the node topology to achieve data fusion more reliably and effectively. In this paper, for underwater target tracking, a node depth adjustment algorithm is proposed. Firstly, after introducing the sound velocity profile on acoustic signal transmission, the asynchronous particle filter algorithm based on delay estimation is improved, which makes the filter more suitable for an underwater environment. Secondly, the influence of node topology on the tracking accuracy is analyzed, and the optimization problem of node depth adjustment is constructed, in which the depth-related Fisher Information Matrix is designed as the optimization criterion. Thirdly, for scenarios in which the target depth is either known or unknown, the analytical method and the interior point method are employed to solve the problem, respectively, and the optimal depth adjustment strategies in corresponding scenarios are obtained. The simulation results show that the proposed algorithm can fully adjust the node depth and achieve a more accurate tracking performance.
Analysis of County-Scale Eco-Efficiency and Spatiotemporal Characteristics in China
Authors: Zhang Hui , Sun Yingqi , Fan Zhaoying , Long Zhi , Wan Shilong , Zhang Zilong , Chen Xingpeng
Published: February 2023

Eco-efficiency is a key indicator to measure the level of regional sustainable development. The county is the basic spatial unit of socio-economic activities and sustainable policy implementation in China. Hence, this paper conducts eco-efficiency analysis at the county scale in order to provide reference for the central and local governments to formulate differentiated eco-efficiency enhancement policies, further promote Chinese ecological sustainable development, and advance the construction of ecological civilization with high quality. Based on the Super-Slacks-Based Measure (SBM) model and the Malmquist index, the paper constructed an eco-efficiency measurement method and analyzed the variation characteristics, influencing factors, spatial pattern of eco-efficiency in Chinese counties from 2000 to 2020. The results showed that: (1) The eco-efficiency of the county unit was generally low in China and was roughly distributed in a pyramid. The county-level eco-efficiency had a spatial distribution pattern of being high in the west and low in the east, and high in the south and low in the north, with significant non-equilibrium. There was a positive correlation between eco-efficiency of neighboring counties in China. (2) The per-capita GDP has a significant positive correlation with eco-efficiency, while energy consumption, arable land area and eco-efficiency have a negative correlation. The redundancy rate of input indicators was high in Chinese counties. (3) During the study period, the eco-efficiency of most counties displayed a fluctuating growth trend. The growth was mainly driven by technological progress.
Could Biparametric MRI Replace Multiparametric MRI in the Management of Prostate Cancer?
Authors: Iacob Roxana , Stoicescu Emil-Robert , Cerbu Simona , Manolescu Diana-Luminiţa , Bardan Răzvan , Cumpănaş Alin
Published: February 2023

Prostate cancer (PCa) is a worldwide epidemiological problem, since it is one of the most prevalent types of neoplasia among men, and the third-leading cause of cancer-related deaths, after lung and colorectal tumors. Unfortunately, the early stages of PCa have a wide range of unspecific symptoms. For these reasons, early diagnosis and accurate evaluation of suspicious lesions are crucial. Multiparametric MRI (mpMRI) is currently the imaging modality of choice for diagnostic screening and local staging of PCa, but also has a leading role in guiding biopsies and in treatment biparametric MRI (bpMRI) could partially replace mpMRI due to its lack of adverse reactions caused by contrast agents, relatively lower costs, and shorter acquisition time. Further, 31 relevant articles regarding the advantages and disadvantages of the aforementioned imaging techniques were scanned. As a result, while bpMRI has comparable accuracy in detecting PCa, its roles in the other steps of PCa management are limited.
Predictors of Progression and Mortality in Patients with Chronic Hypersensitivity Pneumonitis: Retrospective Analysis of Registry of Fibrosing Interstitial Lung Diseases
Authors: Trushenko Natalia V. , Suvorova Olga A. , Pershina Ekaterina S. , Nekludova Galina V. , Chikina Svetlana Yu. , Levina Iuliia A. , Chernyaev Andrey L. , Samsonova Maria V. , Tyurin Igor E. , Mustafina Malika Kh. , Yaroshetskiy Andrey I. , Nadtochiy Nikita B. , Merzhoeva Zamira M. , Proshkina Anna A. , Avdeev Sergey N.
Published: February 2023

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) resulting from an immune-mediated response in susceptible and sensitized individuals to a large variety of inhaled antigens. Chronic HP with a fibrotic phenotype is characterized by disease progression and a dismal prognosis. The aim of this study was to identify predictors of progression and mortality in patients with chronic HP in real clinical practice. Materials and methods: This retrospective, multicenter, observational study used data from a registry of 1355 patients with fibrosing ILDs. The study included 292 patients diagnosed with chronic HP based on the conclusion of a multidisciplinary discussion (MDD). Results: The patients were divided into groups with progressive (92 (30.3%) patients) and nonprogressive pulmonary fibrosis (200 (69.7%) patients). The most significant predictors of adverse outcomes were a DLco < 50% predicted, an SpO2 at the end of a six-minute walk test (6-MWT) < 85%, and a GAP score ≥ 4 points. Conclusion: Pulmonary fibrosis and a progressive fibrotic phenotype are common in patients with chronic HP. Early detection of the predictors of an adverse prognosis of chronic HP is necessary for the timely initiation of antifibrotic therapy.