bluuebunny/crossref_metadata_2025 huggingface dataset:
One-year outcomes of wide antral cryoballoon ablation guided by high-density mapping vs. conventional cryoballoon ablation for atrial fibrillation: a propensity score–matched study
Authors: Chen Sanbao , Wang Zulu , Xuan Fengqi , Liang Ming , Jin Zhiqing , Ding Jian , Sun Mingyu , Zhang Ping , Han Yaling
Published: February 2024

Background

Pulmonary vein isolation with wide antral ablation leads to better clinical outcomes for the treatment of atrial fibrillation, but the isolation lesion is invisible in conventional cryoballoon ablation. In this study, we aim to investigate the efficacy of the wide pulmonary vein isolation technique that includes the intervenous carina region, guided by high-density mapping, compared with pulmonary vein isolation alone without the mapping system.

Methods

We conducted a propensity score–matched comparison of 74 patients who underwent a wide cryoballoon ablation guided by high-density mapping (mapping group) and 74 controls who underwent conventional cryoballoon ablation in the same period (no-mapping group). The primary outcome was a clinical recurrence of documented atrial arrhythmias for >30 s during the 1-year follow-up.

Results

Of 74 patients in the mapping group, residual local potential in the pulmonary vein antrum was found in 30 (40.5%) patients, and additional cryothermal applications were performed to achieve a wide pulmonary vein isolation. Compared with the no-mapping group, the use of the mapping system in the mapping group was associated with a longer fluoroscopic time (26.97 ± 8.07 min vs. 23.76 ± 8.36 min, P = 0.023) and greater fluoroscopic exposure [339 (IQR181–586) mGy vs. 224 (IQR133–409) mGy, P = 0.012]. However, no significant differences between the two groups were found in terms of procedural duration and left atrial dwell time (104.10 ± 18.76 min vs. 102.45 ± 21.01 min, P = 0.619; 83.52 ± 17.01 min vs. 79.59 ± 17.96 min, P = 0.177). The rate of 12-month freedom from clinical atrial arrhythmia recurrence was 85.1% in the mapping group and 70.3% in the no-mapping group (log-rank P = 0.029).

Conclusion

Voltage and pulmonary vein potential mapping after cryoballoon pulmonary vein isolation can identify residual potential in the pulmonary vein antrum, and additional cryoablation guided by mapping leads to improved freedom from atrial arrhythmias compared with conventional pulmonary vein isolation without the mapping system.

Clinical Trial Registration Number

ChiCTR2200064383.
Right ventricular outflow tract stenting for late presenter unrepaired Fallot physiology: a single-center experience
Authors: Prakoso Radityo , Kurniawati Yovi , Siagian Sisca Natalia , Sembiring Aditya Agita , Sakti Damba Dwisepto Aulia , Mendel Brian , Pratiwi Indah , Lelya Olfi , Lilyasari Oktavia
Published: February 2024

Objectives

The purpose of this study was to assess the clinical outcome after right ventricular outflow tract (RVOT) stenting in late presenter patient with unrepaired Fallot physiology.

Background

In younger patients, RVOT stenting is an alternative to mBTT shunt; however, there have been few reports of this palliative technique in late presenter population, including adults.

Methods

This was a single-center, retrospective study of nonrandomized, palliated Fallot patients. Clinical outcomes such as left ventricular ejection fraction and saturation were measured in 32 individuals following RVOT stenting in adults (n = 10) and children (n = 22). The Statistical Package for Social Science (SPSS) 26.0 software was used to analyze the statistical data.

Results

During the procedure, the average stent diameter and length were 8.84 ± 1.64 mm and 35.46 ± 11.23 mm, respectively. Adult patients received slightly longer stents than pediatric patients (43.60 ± 11.64 mm vs. 31.77 ± 9.07 mm). Overall, patients' saturation increased from 58.56 ± 19.03% to 91.03 ± 8.98% (p < 0.001), as did their left ventricular ejection fraction (LVEF) from 64.00 ± 18.21% to 75.09 ± 12.98% (p = 0.001). Three patients improved their LVEF from 31 to 55%, 31 to 67%, and 26 to 50%. The median length of stay was 8 (2–35) days, with an ICU stay of 2 (0–30) days. The median time from RVOT stent palliation to total repair was 3 months (range: 1 month–12 months).

Conclusions

RVOT stenting is a safe and effective method for increasing saturation and ejection fraction not only in newborn infants but also in late presenters, including adults with unrepaired Fallot physiology.
Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology
Authors: Huang Shan , Cai Shuangming , Ling Lin , Zhang Wenni , Xiao Huanshun , Yu Danfeng , Zhong Xuan , Tao Pei , Luo Yiping
Published: February 2024

Introduction

Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method.

Methods

After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The “ClusterProfiler” R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes.

Results

We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1β (IL-1β) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below −5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2.

Conclusions

GROA, IL-1β, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.
Causal relationship between gut microbiota and polycystic ovary syndrome: a literature review and Mendelian randomization study
Authors: Sun Junwei , Wang Mingyu , Kan Zhisheng
Published: February 2024

Introduction

Numerous studies have suggested an association between gut microbiota and polycystic ovarian syndrome (PCOS). However, the causal relationship between these two factors remains unclear.

Methods

A review of observational studies was conducted to compare changes in gut microbiota between PCOS patients and controls. The analysis focused on four levels of classification, namely, phylum, family, genus, and species/genus subgroups. To further investigate the causal relationship, Mendelian randomization (MR) was employed using genome-wide association study (GWAS) data on gut microbiota from the MiBioGen consortium, as well as GWAS data from a large meta-analysis of PCOS. Additionally, a reverse MR was performed, and the results were verified through sensitivity analyses.

Results

The present review included 18 observational studies that met the inclusion and exclusion criteria. The abundance of 64 gut microbiota taxa significantly differed between PCOS patients and controls. Using the MR method, eight bacteria were identified as causally associated with PCOS. The protective effects of the genus Sellimonas on PCOS remained significant after applying Bonferroni correction. No significant heterogeneity or horizontal pleiotropy was found in the instrumental variables (IVs). Reverse MR analyses did not reveal a significant causal effect of PCOS on gut microbiota.

Conclusion

The differences in gut microbiota between PCOS patients and controls vary across observational studies. However, MR analyses identified specific gut microbiota taxa that are causally related to PCOS. Future studies should investigate the gut microbiota that showed significant results in the MR analyses, as well as the underlying mechanisms of this causal relationship and its potential clinical significance.
Construction of a monthly dynamic sediment delivery ratio model at the hillslope scale: a case study from a hilly loess region
Authors: Xu Zan , Zhang Shanghong , Hu Xujian , Zhou Yang
Published: February 2024

Introduction: Soil loss is a worldwide environmental problem, and sediment transport is one of its important components. In recent years, a hillslope sediment delivery ratio (SDR) model based on an index of connectivity has been widely used to describe the variation in sediment transport characteristics. However, the hillslope SDR model only considers the structural characteristics of the watershed and ignores the dynamic mechanism of sediment transport, which leads to poor dynamic applicability over short timescales and makes it difficult to reflect changes of sediment yield.

Methods: Therefore, we here propose a monthly dynamic SDR model that integrates the hillslope structural connectivity and sediment transport threshold of rainfall event based on the main influencing factors of sediment delivery. We then combine the dynamic SDR model with an empirical erosion model to simulate the hillslope sediment yield in the Mahuyu watershed, and verify the applicability of the coupled model using the Heimutouchuan watershed.

Results: The results show that the coupled model can effectively simulate the hillslope sediment yields of the Mahuyu and Heimutouchuan watersheds. The contribution of the rainfall transport threshold factor to sediment delivery and yield is essentially in dynamic stability at the multi-year timescale, but increases the heterogeneity of both inter-month distributions and the spatial distribution of hillslope sediment yield.

Discussion: The dynamic SDR model, which considers the rainfall thresholds of transport and re-transport, can effectively improve the simulation accuracy of low and high sediment yield values on hillslopes. Our results can provide a reference for understanding sediment transport processes on hillslopes and optimizing soil and water conservation measures in watersheds.
Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity
Authors: Li Wei , Pucka Andrew Q. , Debats Candice , Reyes Brandon A. , Syed Fahim , O’Brien Andrew R.W. , Mehta Rakesh , Manchanda Naveen , Jacob Seethal A. , Hardesty Brandon M. , Greist Anne , Harte Steven E. , Harris Richard E. , Yu Qigui , Wang Ying
Published: February 2024

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients’ well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.

Clinical Trial Registration

ClinicalTrials.gov, Identifier: NCT05045820.
Hematopoietic stem cell transplantation in children with chronic granulomatous disease: the Spanish experience
Authors: Alonso García Laura , Bueno Sánchez David , Fernández Navarro Jose Maria , Regueiro Garcia Alexandra , Blanquer Blanquer Miguel , Benitez Carabante Maria Isabel , Mozo del Castillo Yasmina , Fuster Soler Jose Luis , Uria Oficialdegui Maria Luz , Sisinni Luisa , Perez Martinez Antonio , Diaz de Heredia Rubio Cristina
Published: February 2024

Introduction

Hematopoietic stem cell transplantation (HCT) can cure chronic granulomatous disease (CGD). However, transplant-associated morbidity or mortality may occur, and it is still controversial which patients benefit from this procedure. The aim of this retrospective study was to evaluate the outcome of pediatric patients who received HCT in one of the Spanish pediatric transplant units.

Results

Thirty children with a median age of 6.9 years (range 0.6–12.7) were evaluated: 8 patients received a transplant from a sibling donor (MSD), 21 received a transplant from an unrelated donor (UD), and 1 received a haploidentical transplant. The majority of the patients received reduced-intensity conditioning regimens based on either busulfan plus fludarabine or treosulfan. Relevant post-HCT complications were as follows: i) graft failure (GF), with a global incidence of 28.26% (CI: 15.15–48.88), 11.1% in patients with MSD (1.64–56.70) and 37.08% in unrelated donors (19.33–63.17); and ii) chronic graft-versus-host disease (GVHD), with an incidence of 20.5% (8.9–43.2), 11.1% in patients with MSD (1.64–56.70) and 26.7% in unrelated donors (10.42–58.44). Post-HCT infections were usually manageable, but two episodes of pulmonary aspergillosis were diagnosed in the context of graft rejection. The 2-year OS was 77.3% (55.92–89.23). There were no statistically significant differences among donor types.

Discussion

HCT in patients with CGD is a complex procedure with significant morbidity and mortality, especially in patients who receive grafts from unrelated donors. These factors need to be considered in the decision-making process and when discussing conditioning and GVHD prophylaxis.
Low-dose oral immunotherapy in immunoglobulin E-mediated food allergies
Authors: Ma Dongxia , Zhu Rongfei
Published: February 2024

Nowadays, the management of food allergies has increasingly moved from conventional oral immunotherapy (OIT) to low-dose OIT or low-dose OIT utilizing hypoallergenic foods. This shift is largely because the latter appears to induce oral tolerance with fewer adverse effects than the former. However, the mechanisms underpinning such differences remain unclear. To better understand these mechanisms, we conducted a comparative study scrutinizing the mechanisms of OIT, especially those of low-dose desensitization. We also summarized articles on low-dose OIT and low-dose OIT using hypoallergenic foods. We examined the efficacy, safety, and immunological parameters of low-dose OIT and those of low-dose OIT with hypoallergenic foods with the aim of shedding some light on low-dose OIT and its therapeutic application in inducing oral tolerance for individuals with food allergies.
Infrapatellar fat pad adipose tissue-derived macrophages display a predominant CD11c+CD206+ phenotype and express genotypes attributable to key features of OA pathogenesis
Authors: Hengtrakool Patchanika , Leearamwat Nitigorn , Sengprasert Panjana , Wongphoom Jutamas , Chaichana Thiamjit , Taweevisit Mana , Ngarmukos Srihatach , Tanavalee Aree , Palaga Tanapat , Reantragoon Rangsima
Published: February 2024

Objectives

In knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization.

Methods

Synovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed.

Results

Our findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs.

Conclusion

Our study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.
The management of a duodenal fistula involving the right hepatic duct: a rare case report
Authors: Ming Qiu , Jun Yang , Nai-wen Luo , Lei Cao , Yu-dong Fan , Shu-guang Wang
Published: February 2024

The formation of an internal fistula between the biliary system and the gastrointestinal tract is a rare condition with various etiologies, predominantly associated with recurrent chronic inflammation of the biliary system and tumors. Patients with this condition may lack specific clinical manifestations, presenting with symptoms such as abdominal pain, fever, jaundice, or may show no clinical signs at all. Common types of internal fistulas include cholecystoduodenal fistula, cholecystocolonic fistula, and choledochoduodenal fistula. Among these, the right hepaticoduodenal fistula is extremely rare and seldom reported in clinical literature. We herein report a case of right hepaticoduodenal fistula and analyze its mechanism, treatment principles, and preventive measures through a literature review.
Identification of lethal species in amanita section Phalloideae based on nucleotide signature and specific TaqMan-MGB probe and primer
Authors: Duan Renhe , Huang Jiahui , Zhang Donghan , Tian Enjing
Published: February 2024

Amanita section Phalloideae consists of lethal toxic mushroom species, causing many fatal poisoning incidents worldwide. Molecular techniques of nucleotide signatures and single nucleotide polymorphism (SNP) detection could be used to develop a specific method for identifying lethal section (sect.) Phalloideae species. A comparison of 38 sequenced and 228 validated sequences from sect. Phalloideae species showed a 17-base pair nucleotide signature and an SNP site between the lethal and non-lethal species. A specific minor groove binder probe was designed based on them. The results indicated that this method exhibited excellent specificity for the lethal subgroup, good detection in samples subjected to simulated gastric digestion (60 min boiling and 120 min digestion), and a 10 pg./μL detection limit. This method enables accurate detection of target species in samples under complex conditions and can provide evidence for poisoning incidents caused by lethal sect. Phalloideae species to assist in targeted treatment strategies.
Genome-wide transcriptome profiling reveals molecular response pathways of Trichoderma harzianum in response to salt stress
Authors: Yang Qihong , Mao Zhenchuan , Hao Yali , Zheng Shijie , Zhao Jianlong , Li Yan , Yang Yuhong , Xie Bingyan , Ling Jian , Li Yanlin
Published: February 2024

Trichoderma harzianum exhibits a strong biological control effect on many important plant pathogens, such as Fusarium oxysporum, Botrytis cinerea, and Meloidogyne. However, its biocontrol effectiveness is weakened or reduced under salt stress. The aim of this study was to investigate the molecular response of T. harzianum to salt stress at the whole-genome level. Here, we present a 44.47 Mb near-complete genome assembly of the T. harzianum qt40003 strain for the first time, which was assembled de novo with 7.59 Gb Nanopore sequencing long reads (~170-fold) and 5.2 Gb Illumina short reads (~116-fold). The assembled qt40003 genome contains 12 contigs, with a contig N50 of 4.81 Mb, in which four of the 12 contigs were entirely reconstructed in a single chromosome from telomere to telomere. The qt40003 genome contains 4.27 Mb of repeat sequences and 12,238 protein-coding genes with a BUSCO completeness of 97.5%, indicating the high accuracy and completeness of our gene annotations. Genome-wide transcriptomic analysis was used to investigate gene expression changes related to salt stress in qt40003 at 0, 2% (T2), and 4% (T4) sodium chloride concentrations. A total of 2,937 and 3,527 differentially expressed genes (DEGs) were obtained under T2 and T4 conditions, respectively. GO enrichment analysis showed that the T2-treatment DEGs were highly enriched in detoxification (p < 0.001), while the T4 DEGs were mainly enriched in cell components, mostly in cellular detoxification, cell surface, and cell wall. KEGG metabolic pathway analysis showed that 91 and 173 DEGs were significantly enriched in the T2 and T4 treatments, respectively (p < 0.01), mainly in the glutathione metabolism pathway. We further experimentally analyzed the differentially expressed glutathione transferase genes in the glutathione metabolic pathway, most of which were downregulated (13/15). In addition, we screened 13 genes related to active oxygen clearance, including six upregulated and seven downregulated genes, alongside five fungal hydrophobic proteins, of which two genes were highly expressed. Our study provides high-quality genome information for the use of T. harzianum for biological control and offers significant insights into the molecular responses of T. harzianum under salt-stress conditions.
Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy
Authors: Colina Alfredo S. , Shah Viren , Shah Ravi K. , Kozlik Tanya , Dash Ranjan K. , Terhune Scott , Zamora Anthony E.
Published: February 2024

Since the FDA’s approval of chimeric antigen receptor (CAR) T cells in 2017, significant improvements have been made in the design of chimeric antigen receptor constructs and in the manufacturing of CAR T cell therapies resulting in increased in vivo CAR T cell persistence and improved clinical outcome in certain hematological malignancies. Despite the remarkable clinical response seen in some patients, challenges remain in achieving durable long-term tumor-free survival, reducing therapy associated malignancies and toxicities, and expanding on the types of cancers that can be treated with this therapeutic modality. Careful analysis of the biological factors demarcating efficacious from suboptimal CAR T cell responses will be of paramount importance to address these shortcomings. With the ever-expanding toolbox of experimental approaches, single-cell technologies, and computational resources, there is renowned interest in discovering new ways to streamline the development and validation of new CAR T cell products. Better and more accurate prognostic and predictive models can be developed to help guide and inform clinical decision making by incorporating these approaches into translational and clinical workflows. In this review, we provide a brief overview of recent advancements in CAR T cell manufacturing and describe the strategies used to selectively expand specific phenotypic subsets. Additionally, we review experimental approaches to assess CAR T cell functionality and summarize current in silico methods which have the potential to improve CAR T cell manufacturing and predict clinical outcomes.
Revisiting the calpain hypothesis of learning and memory 40 years later
Authors: Baudry Michel , Bi Xiaoning
Published: February 2024

In 1984, Gary Lynch and Michel Baudry published in Science a novel biochemical hypothesis for learning and memory, in which they postulated that the calcium-dependent protease, calpain, played a critical role in regulating synaptic properties and the distribution of glutamate receptors, thereby participating in memory formation in hippocampus. Over the following 40 years, much work has been done to refine this hypothesis and to provide convincing arguments supporting what was viewed at the time as a simplistic view of synaptic biochemistry. We have now demonstrated that the two major calpain isoforms in the brain, calpain-1 and calpain-2, execute opposite functions in both synaptic plasticity/learning and memory and in neuroprotection/neurodegeneration. Thus, calpain-1 activation is required for triggering long-term potentiation (LTP) of synaptic transmission and learning of episodic memory, while calpain-2 activation limits the magnitude of LTP and the extent of learning. On the other hand, calpain-1 is neuroprotective while calpain-2 is neurodegenerative, and its prolonged activation following various types of brain insults leads to neurodegeneration. The signaling pathways responsible for these functions have been identified and involve local protein synthesis, cytoskeletal regulation, and regulation of glutamate receptors. Human families with mutations in calpain-1 have been reported to have impairment in motor and cognitive functions. Selective calpain-2 inhibitors have been synthesized and clinical studies to test their potential use to treat disorders associated with acute neuronal damage, such as traumatic brain injury, are being planned. This review will illustrate the long and difficult journey to validate a bold hypothesis.
Determination of glomerular filtration rate “en passant” after high doses of iohexol for computed tomography in intensive care medicine—a proof of concept
Authors: Dejaco Alexander , Dorn Christoph , Paal Michael , Gruber Michael , Graf Bernhard M. , Kees Martin G.
Published: February 2024

Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an “en passant” approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by high-performance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (−3.44 mL/min/1.73 m2) compared to estimations based on creatinine alone (−0.76 mL/min/1.73 m2), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73 m2) and higher Lin’s correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the “en passant” variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies.
Annona Muricata L. extract restores renal function, oxidative stress, immunohistochemical structure, and gene expression of TNF-α, IL-β1, and CYP2E1 in the kidney of DMBA-intoxicated rats
Authors: Zeweil Mohamed M. , Khafaga Asmaa F. , Mahmoud Sahar F. , Wasef Lamiaa , Saleh Hamida , Elrehim Attaa. M. Abd , Bassuoni Naglaa F. , Alwaili Maha Abdullah , Saeedi Nizar H. , Ghoneim Hanan A.
Published: February 2024

Introduction: 7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats.

Methods: Forty male albino rats were allocated into four equal groups (n = 10). The 1st group served as the control, the 2nd group (GRV) was gastro-gavaged with GRV (200 mg/kg b.wt), the 3rd group (DMBA) was treated with a single dose of DMBA (15 mg/kg body weight), and the 4th group (DMBA + GRV) was gastro-gavaged with a single dose of DMBA, followed by GRV (200 mg/kg b.wt). The GRV administration was continued for 8 weeks.

Results and Discussion: Results revealed a significant improvement in renal function, represented by a decrease in urea, creatinine, and uric acid (UA) in the DMBA + GRV group. The antioxidant potential of GRV was confirmed in the DMBA + GRV group by a significant decline in malondialdehyde (MDA) and a significant increase in catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), and reduced glutathione (GSH) compared to DMBA-intoxicated rats; however, it was not identical to the control. Additionally, the antiinflammatory role of GRV was suggested by a significant decline in mRNA expression of cytochrome P450, family 2, subfamily e, polypeptide 1 (CYP2E1), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) in the DMBA + GRV group. Moreover, GRV improved the histopathologic and immunohistochemical expression of TNF-α, CYP450, and IL1β in DMBA-intoxicated kidney tissue. Conclusively, GRV is a natural medicinal product that can alleviate the renal injury resulting from environmental exposure to DMBA. The reno-protective effects of GRV may involve its anti-inflammatory and/or antioxidant properties, which are based on the presence of phytochemical compounds such as acetogenins, alkaloids, and flavonoids.
Plant root associated chitinases: structures and functions
Authors: Shobade Samuel O. , Zabotina Olga A. , Nilsen-Hamilton Marit
Published: February 2024

Chitinases degrade chitin, a linear homopolymer of β-1,4-linked N-acetyl-D-glucosamine (GlcNAc) residues found in the cell walls of fungi and the exoskeletons of arthropods. They are secreted by the roots into the rhizosphere, a complex and dynamic environment where intense nutrient exchange occurs between plants and microbes. Here we modeled, expressed, purified, and characterized Zea mays and Oryza sativa root chitinases, and the chitinase of a symbiotic bacterium, Chitinophaga oryzae 1303 for their activities with chitin, di-, tri-, and tetra-saccharides and Aspergillus niger, with the goal of determining their role(s) in the rhizosphere and better understanding the molecular mechanisms underlying plant-microbe interactions. We show that Zea mays basic endochitinase (ZmChi19A) and Oryza sativa chitinase (OsChi19A) are from the GH19 chitinase family. The Chitinophaga oryzae 1303 chitinase (CspCh18A) belongs to the GH18 family. The three enzymes have similar apparent KM values of (20-40 µM) for the substrate 4-MU-GlcNAc3. They vary in their pH and temperature optima with OsChi19A activity optimal between pH 5–7 and 30–40°C while ZmChi19A and CspCh18A activities were optimal at pH 7-9 and 50–60°C. Modeling and site-directed mutation of ZmChi19A identified the catalytic cleft and the active residues E147 and E169 strategically positioned at ~8.6Å from each other in the folded protein. Cleavage of 4-MU-GlcNAc3 was unaffected by the absence of the CBD but diminished in the absence of the flexible C-terminal domain. However, unlike for the soluble substrate, the CBD and the newly identified flexible C-terminal domain were vital for inhibiting Aspergillus niger growth. The results are consistent with the involvement of the plant chitinases in defense against pathogens like fungi that have chitin exoskeletons. In summary, we have characterized the functional features and structural domains necessary for the activity of two plant root chitinases that are believed to be involved in plant defense and a bacterial chitinase that, along with the plant chitinases, may participate in nutrient recycling in the rhizosphere.
Women’s and men’s experiences with participative decision-making at workplace and organizational levels
Authors: Plückelmann Clara , Gustafsson Sendén Marie , Bernhard-Oettel Claudia , Leineweber Constanze , Sczesny Sabine
Published: February 2024

Introduction

The concept of participative decision-making (PDM) has been well established as a positive organizational factor, and has recently gained attention as a measure of gender inclusivity in the workplace. However, findings regarding gender differences in the experiences of PDM are inconclusive. This study hypothesized that women perceive themselves as less influential than men at the organizational level rather than at the workplace level. Furthermore, the study explored whether these assumed gender differences depend on the gender typicality of occupational positions and professions. We expected gender differences to be more pronounced for male-typed positions and professions (e.g., leadership, engineer) compared to non-male-typed occupational positions and professions (e.g., non-leadership, nurse).

Methods

Data on experiences with participative decision-making at the workplace and organizational levels were drawn from a large representative Swedish survey (N = 10,500; 60% women).

Results

Results showed that women experienced being less influential than men at the organizational level, whereas the experiences of women and men did not differ at the workplace level. The gender difference at the organizational level was not related to the gender typicality of position and profession.

Discussion

The findings highlight the importance of the inclusion of both women and men in strategic, large-scale decisions for achieving gender equality at work.
Psychometric properties of the Italian version of the Parent Experience of Assessment Scale
Authors: Aschieri Filippo , Brasili Sara , Cavallini Anna , Cera Giulia
Published: February 2024

This paper describes the psychometric properties of the Italian version of the Parent Experience of Assessment Scale. Overall, 185 participants took part in the study. Confirmatory factor analysis and structural equation modeling tested the scale structure and its relationship with clients’ satisfaction. Reliability and multivariate analysis of variance measured the factors’ consistency and the differences among different typologies of assessment. Results replicated the original five factors structure of the scale (Parent-Assessor Relationship and Collaboration; New Understanding of the Child; Child-Assessor Relationship; Systemic Awareness; Negative Feelings). Full scale and individual factors’ reliability ranged from high to excellent. Structural equation modeling showed that Parent-Assessor Relationship and Collaboration and New Understanding of the Child factors had the strongest direct effects on parents’ General Satisfaction, measured by the Client Satisfaction Questionnaire. A multivariate analysis of variance showed that the type of assessment, the children’s age and the way the scale was completed impacted on the outcomes of the QUEVA-G. Results suggest that the Italian version of the Parent Experience of Assessment Scale is a valid and reliable tool for assessing parents’ experience of their child’s assessment.
Extremism, knowledge, and overconfidence in the covid-19 restriction times
Authors: Hatori Tsuyoshi , Bhandary Netra Prakash
Published: February 2024

Public response to restriction policy against the novel coronavirus disease (COVID-19) can polarize into two extremes: one absolutely in favor of restrictions for the sake of human life and health, and other absolutely against the restrictions for the sake of human rights and daily life. This study examines psychological nature of extremism regarding individuals’ self-restraint from social behavior, which was and has been encouraged by the Japanese government as restriction measures, as well as possible measures to mitigate this extremism. We hypothesize that people with more extreme views on self-restraint tend to have less knowledge of this virus, and, nevertheless, tend to be more overconfident in the sense that they falsely believe they understand COVID-19 and the effects of self-restraint. It is also postulated that overconfidence can be reduced by asking them to explain how self-restraint works. To test these hypotheses, we conducted an online experiment on the Japanese adults (n = 500) to measure the extent of their knowledge of COVID-19 and to examine the effect of explanation task on their understanding regarding COVID-19 and extremism. The results indicate that the extreme attitudes were associated with insufficient knowledge about the symptoms, risks, and characteristics of COVID-19. Moreover, their extreme attitudes tended to moderate through this experimental study to an extent that they realized they did not understand COVID-19 including the effects of self-restraint. This suggests that people with extremism may have been overconfident in their own understanding of the COVID-19 restrictions.
Perceived stress of COVID-19 pandemic and problematic mobile phone use during quarantine conditions among Chinese adolescents: a mediated moderation model
Authors: Jiang Shuyang , Zhang Lifan
Published: February 2024

The relation between perceived general stress and problematic mobile phone use (PMPU) has been well established. With the outbreak of the coronavirus disease (COVID-19), the present study was designed to examine the association between perceived stress of COVID-19 as a kind of event-related stress and PMPU, and the mechanisms underlying this relation. Participants were 724 adolescents ranging from 12 to 16 years old (M = 13.28, SD = 1.05) who completed four online questionnaires addressing perceived stress of COVID-19, search for meaning in life, escapism motivation, and PMPU. The results revealed that escapism motivation mediated the relationship between perceived stress of COVID-19 and PMPU. In addition, search for meaning in life played a moderating role between perceived stress of COVID-19 and escapism motivation. These findings extend the literature by addressing how and under what conditions perceived stress of COVID-19 can contribute to PMPU. We discussed the implications for developing targeted intervention programs aimed at reducing PMPU among adolescents.
Gambling and virtual reality: unraveling the illusion of near-misses effect
Authors: Quaglieri Alessandro , Pizzo Alessandra , Cricenti Clarissa , Tagliaferri Ginevra , Frisari Francesca Valeria , Burrai Jessica , Mari Emanuela , Lausi Giulia , Giannini Anna Maria , Zivi Pierpaolo
Published: February 2024

Introduction

Studying gambling behavior is a crucial element in reducing the impact of problem gambling. Nevertheless, most current research is carried out in controlled laboratory settings rather than real-life situations, which raises concerns about how applicable the findings are in the broader context. Virtual reality (VR) has proven to be a valuable tool and has been utilized in various experimental scenarios. A limited number of studies have employed VR to investigate gambling behaviors, and few have explored them in an older adolescent context.

Methods

This study examined the behavioral and physiological effects of gambling behavior, including problem gambling, gaming addiction, and risk-taking decision-making in a sample of 36 high-school students aged between 18 to 20 years using an ad-hoc constructed VR scenario designed to simulate a slot-machine platform.

Results

The behavioral results highlighted that participants reporting more problem gambling were sensitive to near-misses: i.e., they bet more after near-misses than after losses. This result may reflect the false belief that gamblers, after near-misses, are closer to winning. Physiological data showed that participants exhibited heart rate deceleration during the anticipation of the outcome, which has been suggested to represent a marker of feedback anticipation processing and hyposensitivity to losses.

Discussion

Overall, this study provides evidence for a new VR tool to assess gambling behaviors and new insights into gambling-related behavioral and physiological factors. Implications for the treatment of problem gambling are discussed.
Challenges in adapting a stroke unit in a middle-income country: warning about costs and underfunding to achieve the Brazilian Ministry of Health’s benchmark
Authors: Ferreira Natalia Cristina , Luvizutto Gustavo José , Bazan Silméia Garcia Zanati , Bonome Luana Aparecida Miranda , Winckler Fernanda Cristina , dos Santos Daniel Fabiano Barbosa , Chiloff Cristiane Lara Mendes , Modolo Gabriel Pinheiro , de Freitas Carlos Clayton Macedo , Barretti Pasqual , Lange Marcos Christiano , Minicucci Marcos Ferreira , de Souza Juli Thomaz , Bazan Rodrigo
Published: February 2024

Background

Since the implementation of the stroke care line in Brazil, the relationship (adequacy) of costs spent during hospitalization with the Brazilian Ministry of Health indicators for a stroke unit have not yet been analyzed.

Aims

This study aimed to assess the adequacy of a comprehensive stroke center for key performance indicators and analyze the costs involved in hospitalization. We verified the association between stroke severity at admission and care costs during hospitalization.

Methods

A retrospective medical chart review of 451 patients was performed using semiautomatic electronic data from a single comprehensive stroke center in Brazil between July 2018 and January 2020. Clinical and resource utilization data were collected, and the mean acute treatment cost per person was calculated. The Kruskal–Wallis test with Dunn’s post-test was used to compare the total costs between stroke types and reperfusion therapies. A robust linear regression test was used to verify the association between stroke severity at hospital admission and the total hospitalization costs. Good adequacy rates were observed for several indicators.

Results

Data from 451 patients were analyzed. The stroke unit had good adaptation to key performance indicators, but some critical points needed revision and improvement to adapt to the requirements of the Ministry of Health. The average total cost of the patient’s stay was the USD 2,637.3, with the daily hospitalization, procedure, operating room, and materials/medication costs equating to USD 2,011.1, USD 220.7, USD 234.1, and USD 98.8, respectively. There was a positive association between the total cost and length of hospital stay (p < 0.001).

Conclusion

The stroke unit complied with most of the main performance indicators proposed by the Brazilian Ministry of Health. Underfunding of the costs involved in the hospitalization of patients was verified, and high costs were associated with the length of stay, stroke severity, and mechanical thrombectomy.
Does the population size of a city matter to its older adults’ self-rated health? Results of China data analysis
Authors: Pan Zehan , Dong Weizhen , Huang Zuyu
Published: February 2024

Clarifying the association between city population size and older adults’ health is vital in understanding the health disparity across different cities in China. Using a nationally representative dataset, this study employed Multilevel Mixed-effects Probit regression models and Sorting Analysis to elucidate this association, taking into account the sorting decisions made by older adults. The main results of the study include: (1) The association between city population size and the self-rated health of older adults shifts from a positive linear to an inverted U-shaped relationship once individual socioeconomic status is controlled for; the socioeconomic development of cities, intertwined with the growth of their populations, plays a pivotal role in yielding health benefits. (2) There is a sorting effect in older adults’ residential decisions; compared to cities with over 5 million residents, unobserved factors result in smaller cities hosting more less-healthy older adults, which may cause overestimation of health benefits in cities with greater population size. (3) The evolving socioeconomic and human-made environment resulting from urban population growth introduces health risks for migratory older adults but yields benefits for those with local resident status who are male, aged over 70, and have lower living standards and socioeconomic status. And (4) The sorting effects are more pronounced among older adults with greater resources supporting their mobility or those without permanent local resident status. Thus, policymakers should adapt planning and development strategies to consider the intricate relationship between city population size and the health of older adults.