bluuebunny/crossref_metadata_2025 huggingface dataset:
The spatial analysis of green economy indicators of OECD countries
Authors: Çay Atalay Ayşe , Akan Yusuf
Published: October 2023

The present study aims to examine the effect of the geographical location relationship between economic growth and environmental pollution. For this purpose, the spatial relationship between the variable CO2 emission and the variables energy consumption (ENC), real GDP per capita (GDP), urbanization rate (URB), and trade liberalization (DAE) was investigated by using the data of 37 OECD countries for the period of 1990–2015. The geographical location relationship was determined by using LISA (Local Indicators of Spatial Association) analysis, which is one of the spatial autocorrelation analysis methods. Spatial distribution maps were prepared. Considering the years determined according to Moran I index results, a gradually increasing positive autocorrelation was found for CO2 and ENC variables and a low increasing positive correlation for DAE and GDP variables. For the variable URB, a low increasing positive autocorrelation was found for the year 1990 and a high increasing positive autocorrelation for the year 2015. Then, using the LISA clustering maps, the relationships between the countries were clustered as low, high, and non-related. As a result of this study, given the spatial analysis results, the effect of energy consumption on the carbon emission was found to be positive in general. Increases in trade liberalization increased carbon emissions in some countries and decreased it in some others. On the other hand, increases in the urbanization rate decreased carbon emissions in some countries and had a positive effect in some others. The trade openness index was found to have a generally negative effect on the carbon emission. Within the scope of this study, Spatial Regression Analysis was conducted separately for the years 1990 and 2015. In this analysis, CO2 is the dependent variable, whereas ENC, GDP, URB, and DAE are independent variables. Given the results of spatial regression analysis, it was found that ENC, GDP, and DAE variables have a positive relationship with the CO2 variable. It was determined that there was no significant relationship between URB and CO2. Considering the results achieved, it could be possible to observe the increasing and decreasing effects of variables, which were examined here, on the CO2 emissions.
Global root trait underrepresentation in Paleotropical communities: a qualitative analysis
Authors: Lee Ming Yang , Andersen Kelly M.
Published: October 2023

Many ecosystem processes revolve around plant roots and the rhizosphere, but root trait knowledge has generally lagged behind aboveground plant traits from leaves and stems. In particular, root trait representation of Paleotropical species and tropical communities in modern trait databases remains poor, constraining our understanding of belowground processes in these regions. Therefore, we sought to examine the current state of root trait representation and associated topics in the Paleotropics to identify gaps and biases in the existing literature. Using an exhaustive literature scan, we compiled a list of publications that contained various belowground trait information. Subsequently, we utilized a statistical topic modeling method to analyze abstracts of publications in order to identify topics studied alongside root trait documentation. Finally, we consolidated trends in root trait coverage and topics across five geographical regions and four time periods to illustrate shifts in literature and knowledge of ecological processes revolving around roots. Root trait representation was heavily biased toward root biomass but other aspects of root systems such as physiology, architecture and anatomical traits remain underrepresented. We categorized 23 unique topics around root trait literature across eight categories: ecosystem productivity and biomass stocks, plant functional traits, resource availability, ecosystem processes and dynamics, mycorrhizal colonization, edaphic processes, seedling experiments, and global change and variation. Traits and topic coverage were unequally distributed across the Paletropics and exhibited a notable shift in focus from resource limitation and mycorrhizae research to root trait variation at large spatial and temporal scales over the last 50 years of root trait literature. Given these trends and the heterogenous effects global change exerts on the tropics at a regional scale, we provided several recommendations to facilitate inter-study comparisons of traits to advance the field’s understanding of belowground ecosystem processes in pantropical communities.
Psychiatric mental health nurse practitioner student knowledge and perceptions of pharmacogenetic testing
Authors: Kaltenrieder Corrina M. , White Michelle Marie , Cheek Dennis J.
Published: October 2023

Psychotropic medications are typically prescribed in a trial-and-error fashion, and some providers are beginning to utilize pharmacogenetic testing (PGx) as a supplemental prescribing tool in treatment decision making. PGx testing shows potential in enhancing provider insights into personalized prescribing for patients by examining genetic information related to drug metabolism. Literature points to providers’ lack of knowledge in PGx interpretation as a main barrier, including psychiatric mental health nurse practitioners (PMHNPs). The aim of this study was to measure a difference, if any, in the knowledge and perceptions of PGx after implementation using a pre-post design. This study implemented an educational intervention on graduate nursing students (n = 15). Data were collected by using a pre- and post-interventional questionnaire. Results demonstrated a significant difference in findings related to students’ knowledge (p < 0.001), students’ skills related to pharmacogenetics, (p < 0.001), as well as students’ perceived ability to implement pharmacogenetics into their practice, (p = 0.028). The authors propose that the knowledge gained from the study demonstrates the importance of introducing PGx education into the PMHNP curricula and to prepare future PMHNPs to confidently utilize PGx in their clinical practice.
An optimized cocktail of small molecule inhibitors promotes the maturation of dendritic cells in GM-CSF mouse bone marrow culture
Authors: Matsuba Shintaro , Ura Hiroki , Saito Fumiji , Ogasawara Chie , Shimodaira Shigetaka , Niida Yo , Onai Nobuyuki
Published: October 2023

Dendritic cells (DCs) are the most potent antigen-presenting cells, playing an essential role in the pathogen and tumor recognition, and anti-tumor immunity, and linking both the innate and adaptive immunity. The monocyte-derived DCs generated by ex vivo culture, have been used for cancer immunotherapy to eliminate tumor; however, the clinical efficacies are not sufficient, and further improvement is essential. In this study, we established a method to generate DCs using small molecule compounds for cancer immunotherapy. We observed an increase in the percentage of CD11c+I-A/I-Ehigh cells, representing DCs, by adding four small molecular inhibitors: Y27632, PD0325901, PD173074, and PD98059 (abbreviated as YPPP), in mouse bone marrow (BM) culture with granulocyte-macrophage colony stimulating factor (GM-CSF). BM-derived DCs cultured with YPPP (YPPP-DCs) showed high responsiveness to lipopolysaccharide stimulation, resulting in increased interleukin (IL) -12 production and enhanced proliferation activity when co-cultured with naïve T cells compared with the vehicle control. RNA-seq analysis revealed an upregulation of peroxisome proliferator - activated receptor (PPAR) γ associated genes increased in YPPP-DCs. In tumor models treated with anti-programmed death (PD) -1 therapies, mice injected intratumorally with YPPP-DCs as a DCs vaccine exhibited reduced tumor growth and increased survival. These findings suggested that our method would be useful for the induction of DCs that efficiently activate effector T cells for cancer immunotherapy.
A bibliometric analysis: Ca2+ fluxes and inflammatory phenotyping by flow cytometry in peripheral blood mononuclear cells
Authors: Brun Camille , Chalet Lucie , Moulin Florentin , Bochaton Thomas , Ducreux Sylvie , Paillard Melanie , Crola Da Silva Claire
Published: October 2023

Background

The immune system, composed of organs, tissues, cells, and proteins, is the key to protecting the body from external biological attacks and inflammation. The latter occurs in several pathologies, such as cancers, type 1 diabetes, and human immunodeficiency virus infection. Immunophenotyping by flow cytometry is the method of choice for diagnosing these pathologies. Under inflammatory conditions, the peripheral blood mononuclear cells (PBMCs) are partially activated and generate intracellular pathways involving Ca2+-dependent signaling cascades leading to transcription factor expression. Ca2+ signaling is typically studied by microscopy in cell lines but can present some limitations to explore human PBMCs, where flow cytometry can be a good alternative.

Objective

In this review, we dived into the research field of inflammation and Ca2+ signaling in PBMCs. We aimed to investigate the structure and evolution of this field in a physio-pathological context, and then we focused our review on flow cytometry analysis of Ca2+ fluxes in PBMCs.

Methods

From 1984 to 2022, 3865 articles on inflammation and Ca2+ signaling in PBMCs were published, according to The Clarivate Web of Science (WOS) database used in this review. A bibliometric study was designed for this collection and consisted of a co-citation and bibliographic coupling analysis.

Results

The co-citation analysis was performed on 133 articles: 4 clusters highlighted the global context of Ca2+ homeostasis, including chemical probe development, identification of the leading players in Ca2+ signaling, and the link with chemokine production in immune cell function. Next, the bibliographic coupling analysis combined 998 articles in 8 clusters. This analysis outlined the mechanisms of PBMC activation, from signal integration to cellular response. Further explorations of the bibliographic coupling network, focusing on flow cytometry, revealed 21 articles measuring cytosolic Ca2+ in PBMCs, with only 5 since 2016. This final query showed that Ca2+ signaling analysis in human PBMCs using flow cytometry is still underdeveloped and investigates mainly the cytosolic Ca2+ compartment.

Conclusion

Our review uncovers remaining knowledge gaps of intracellular players involved in Ca2+ signaling in PBMCs, such as reticulum and mitochondria, and presents flow cytometry as a solid option to supplement gold-standard microscopy studies.
Optimal temperature for the long-term culture of adult porcine islets for xenotransplantation
Authors: Sakata Naoaki , Yoshimatsu Gumpei , Kawakami Ryo , Aoyagi Chikao , Kodama Shohta
Published: October 2023

Porcine islet xenotransplantation represents a promising therapy for severe diabetes mellitus. Long-term culture of porcine islets is a crucial challenge to permit the on-demand provision of islets. We aimed to identify the optimal temperature for the long-term culture of adult porcine islets for xenotransplantation. We evaluated the factors potentially influencing successful 28-day culture of islets at 24°C and 37°C, and found that culture at 37°C contributed to the stability of the morphology of the islets, the proliferation of islet cells, and the recovery of endocrine function, indicated by the expression of genes involved in pancreatic development, hormone production, and glucose-stimulated insulin secretion. These advantages may be provided by islet-derived CD146-positive stellate cells. The efficacy of xenotransplantation using islets cultured for a long time at 37°C was similar to that of overnight-cultured islets. In conclusion, 37°C might be a suitable temperature for the long-term culture of porcine islets, but further modifications will be required for successful xenotransplantation in a clinical setting.
Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach
Authors: Agogo George O. , Verani Jennifer R. , Otieno Nancy A. , Nyawanda Bryan O. , Widdowson Marc-Alain , Chaves Sandra S.
Published: October 2023

Introduction

Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW).

Methods

We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA.

Results

Calibration improved the precision of LMP (correlation coefficient, ρ from 0.48 to 0.57) and FH-based GA (ρ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from −0.159 to −0.205) by calibrating FH-based GA and by more than twofold (from −0.158 to −0.471) by calibrating LMP-based GA.

Conclusion

Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available.
Different responses of abundant and rare bacterial composition to groundwater depth and reduced nitrogen application in summer maize field
Authors: Bai Fangfang , Guo Wei , Li Ping , Qiao Dongmei , Du Zhenjie , Qi Xuebin
Published: October 2023

Introduction

It is well known that reduced nitrogen application and groundwater depth can change soil microbial communities, but the associated difference in the response of abundant and rare bacterial composition to these local environmental changes remains unclear.

Methods

In this study a lysimeter experiment was carried out to examine the impact of reduced nitrogen and groundwater depth on the composition of abundant and rare bacteria.

Results and discussion

Our results demonstrated that the summer maize field soil species composition of rare bacterial sub-communities was significantly regulated by reduced nitrogen application, groundwater depth change and their interactions. However, only reduced nitrogen application had a significant influence on the species composition of abundant bacterial sub-communities. The structural equation model (SEM) indicated that reduced nitrogen application and groundwater depth change also could indirectly regulate the species composition of abundant and rare bacteria by altering soil attributes. The changes in soil pH and TSN had the most significant effects on the community composition of abundant and rare bacteria, respectively. More importantly, rare bacterial sub-communities were more sensitive to the changes in nitrogen input, groundwater depth and soil factors. Collectively, our study first demonstrated that abundant and rare microbial sub-communities responded differently to reduced nitrogen application and groundwater depth change. This study highlights that summer maize farmland production management should take nitrogen input and groundwater depth into consideration to maintain the compositional stability of soil rare microbial sub-communities.
Teicoplanin associated gene tcaA inactivation increases persister cell formation in Staphylococcus aureus
Authors: Habib Gul , Gul Haji , Ahmad Prevez , Hayat Azam , Rehman Mujaddad Ur , Mohamed Moussa Ihab , Elansary Hosam O.
Published: October 2023

Staphylococcus aureus is part of normal human flora and is widely associated with hospital-acquired bacteremia. S. aureus has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant S. aureus (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. S. aureus has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the S. aureus glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in S. aureus persister cells formation, and ΔtcaA dependent persisters’ ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of glyS and sgtB. The RNA-seq data revealed a significant decrease in tcaA (p = 0.008) and tcaB (p = 0.04) expression while tcaR was not significantly altered. We knocked down tcaA, tcaB, and tcaR using CRISPR-dCas9 and the results showed that when tcaA was suppressed by dCas9, a significant increase was witnessed in persister cells while tcaB suppression did not induce persistence. The results were further evaluated by creating a tcaA mutant that showed ΔtcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that tcaA is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in S. aureus.
Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis
Authors: Zeng Huiqiong , Zhou Kaixia , Zhuang Yu , Li Aidong , Luo Baiwei , Zhang Ye
Published: October 2023

Purpose

Studies have shown a close relationship between gut microbiota (GM) and Alzheimer’s disease (AD). However, the causal relationship between them remains unclear.

Methods

We conducted a genome-wide association study (GWAS) using publicly available summary statistics data for GM and AD. We extracted independent genetic loci significantly associated with GM relative abundances as instrumental variables based on predefined thresholds (p < 1*e−5). The inverse variance-weighted (IVW) method was primarily used for causal relationship assessment. Additional analyses, including MR-Egger, weighted median, simple mode, and weighted mode, were performed as supplementary analyses.

Results

IVW analysis revealed significant correlations between certain microbial taxa and the risk of AD. Higher abundances of Actinobacteria at the class level, phylum. Actinobacteria, class. Deltaproteobacteria, order. Desulfovibrionales, genus. Oscillospira, and genus. Ruminococcaceae UCG004 (p < 0.048) was found to be positively associated with an elevated risk of AD. However, within the genus-level taxa, Ruminococcus1 (p = 0.030) demonstrated a protective effect on lowering the risk of AD. In addition, to ensure the robustness of the findings, we employed Cochrane’s Q test and leave-one-out analysis for quality assessment, while the stability and reliability of the results were validated through MR-Egger intercept test, MR-PRESSO global test, and sensitivity analysis.

Conclusion

This study provided a comprehensive analysis of the causal relationship between 211 GM taxa and AD. It discerned distinct GM taxa linked to the susceptibility of AD, thereby providing novel perspectives on the genetic mechanisms governing AD via the GM. Additionally, these discoveries held promise as valuable biomarkers, enabling the identification of potential therapeutic targets and guiding forthcoming AD investigations.
Reduction of Kcnt1 is therapeutic in mouse models of SCN1A and SCN8A epilepsy
Authors: Hill Sophie F. , Jafar-Nejad Paymaan , Rigo Frank , Meisler Miriam H.
Published: October 2023

Developmental and epileptic encephalopathies (DEEs) are severe seizure disorders with inadequate treatment options. Gain- or loss-of-function mutations of neuronal ion channel genes, including potassium channels and voltage-gated sodium channels, are common causes of DEE. We previously demonstrated that reduced expression of the sodium channel gene Scn8a is therapeutic in mouse models of sodium and potassium channel mutations. In the current study, we tested whether reducing expression of the potassium channel gene Kcnt1 would be therapeutic in mice with mutation of the sodium channel genes Scn1a or Scn8a. A Kcnt1 antisense oligonucleotide (ASO) prolonged survival of both Scn1a and Scn8a mutant mice, suggesting a modulatory effect for KCNT1 on the balance between excitation and inhibition. The cation channel blocker quinidine was not effective in prolonging survival of the Scn8a mutant. Our results implicate KCNT1 as a therapeutic target for treatment of SCN1A and SCN8A epilepsy.
High-throughput autoantibody screening identifies differentially abundant autoantibodies in autism spectrum disorder
Authors: Mesleh Areej , Ehtewish Hanan , Lennard Katie , Abdesselem Houari B. , Al-Shaban Fouad , Decock Julie , Alajez Nehad M. , Arredouani Abdelilah , Emara Mohamed M. , Albagha Omar , Stanton Lawrence W. , Abdulla Sara A. , Blackburnand Jonathan M. , El-Agnaf Omar M. A.
Published: October 2023

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by defects in two core domains, social/communication skills and restricted/repetitive behaviors or interests. There is no approved biomarker for ASD diagnosis, and the current diagnostic method is based on clinical manifestation, which tends to vary vastly between the affected individuals due to the heterogeneous nature of ASD. There is emerging evidence that supports the implication of the immune system in ASD, specifically autoimmunity; however, the role of autoantibodies in ASD children is not yet fully understood.

Materials and methods

In this study, we screened serum samples from 93 cases with ASD and 28 healthy controls utilizing high-throughput KoRectly Expressed (KREX) i-Ome protein-array technology. Our goal was to identify autoantibodies with differential expressions in ASD and to gain insights into the biological significance of these autoantibodies in the context of ASD pathogenesis.

Result

Our autoantibody expression analysis identified 29 differential autoantibodies in ASD, 4 of which were upregulated and 25 downregulated. Subsequently, gene ontology (GO) and network analysis showed that the proteins of these autoantibodies are expressed in the brain and involved in axonal guidance, chromatin binding, and multiple metabolic pathways. Correlation analysis revealed that these autoantibodies negatively correlate with the age of ASD subjects.

Conclusion

This study explored autoantibody reactivity against self-antigens in ASD individuals' serum using a high-throughput assay. The identified autoantibodies were reactive against proteins involved in axonal guidance, synaptic function, amino acid metabolism, fatty acid metabolism, and chromatin binding.
The outcome of acute leukemia patients with SET-NUP214 fusion after allogeneic stem cell transplantation
Authors: Shen Yuyan , Yang Donglin , Zhang Rongli , Chen Xin , Ma Qiaoling , Wei Jialin , Zhai Weihua , Pang Aiming , He Yi , Jiang Erlie , Feng Sizhou
Published: October 2023

SET-NUP214 fusion gene, also known as TAF-1-CAN and SET-CAN, is observed in acute myeloid leukemia (AML) and T-cell lymphoblastic leukemia (T-ALL). SET-NUP214 fusion in T-cell lymphoblastic leukemia is associated with chemotherapy resistance, but the prognosis of patients with AML with SET-NUP214 has rarely been reported. In the present study, we retrospectively analyzed all patients with acute leukemia including AML and T-ALL patients with SET-NUP214 fusion who underwent allogeneic stem cell transplantation (alloHSCT) in our center from July 2017 to November 2022. Of the total 11 patients, 5 patients were diagnosed with AML and 6 patients were diagnosed with T-ALL de novo. All patients received myeloablative regimens in CR1, and there were three (60%) AML patients who relapsed post-alloHSCT and three T-ALL (50%) patients who relapsed post-alloHSCT. Only one patient with AML who relapsed post-alloHSCT responded to subsequent chemotherapy plus donor lymphocyte infusion and survived the last follow-up. The estimated 1-year overall survival and 3-year overall survival for all these 11 patients were 69.3% and 38.5%, respectively. The estimated 1-year leukemia-free survival and 3-year leukemia-free survival for all patients were 69.3% and 38.5%, respectively. The research shows a high incidence of relapse for patients with acute leukemia with the SET-NUP214 fusion gene, even after alloHSCT. More clinical trials or research with larger samples are urgently needed for this group of patients.
A model for personalized diagnostics for non-specific low back pain: the role of the myofascial unit
Authors: Sikdar Siddhartha , Srbely John , Shah Jay , Assefa Yonathan , Stecco Antonio , DeStefano Secili , Imamura Marta , Gerber Lynn H.
Published: October 2023

Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear specific cause or pathology. Current guidelines for clinical evaluation are based on ruling out underlying serious medical conditions, but not on addressing underlying potential contributors to pain. Although efforts have been made to identify subgroups within this population based on response to treatment, a comprehensive framework to guide assessment is still lacking. In this paper, we propose a model for a personalized mechanism-based assessment based on the available evidence that seeks to identify the underlying pathologies that may initiate and perpetuate central sensitization associated with chronic non-specific low back pain (nsLBP). We propose that central sensitization can have downstream effects on the “myofascial unit”, defined as an integrated anatomical and functional structure that includes muscle fibers, fascia (including endomysium, perimysium and epimysium) and its associated innervations (free nerve endings, muscle spindles), lymphatics, and blood vessels. The tissue-level abnormalities can be perpetuated through a vicious cycle of neurogenic inflammation, impaired fascial gliding, and interstitial inflammatory stasis that manifest as the clinical findings for nsLBP. We postulate that our proposed model offers biological plausibility for the complex spectrum of clinical findings, including tissue-level abnormalities, biomechanical dysfunction and postural asymmetry, ecological and psychosocial factors, associated with nsLBP. The model suggests a multi-domain evaluation that is personalized, feasible and helps rule out specific causes for back pain guiding clinically relevant management. It may also provide a roadmap for future research to elucidate mechanisms underlying this ubiquitous and complex problem.
Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching
Authors: Wei An-Hua , Zeng Lu , Wang Lu , Gui Lin , Zhang Wen-Ting , Gong Xue-Peng , Li Juan , Liu Dong
Published: October 2023

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety.

Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded.

Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565).

Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.
Tree-rings analysis to reconstruct atmospheric mercury contamination at a historical mining site
Authors: Baroni Davide , Ancora Stefania , Franzaring Jürgen , Loppi Stefano , Monaci Fabrizio
Published: October 2023

Mercury (Hg) is a global environmental concern due to its toxicity (especially high in methylated form) and the long-range distribution of its gaseous elemental form (GEM). Hg-contaminated areas, such as abandoned mining sites, pose intrinsic difficulties for their management and heavy monitoring costs. In these environments, plant-based solutions may play a key role in the ecosystem quality assessment and support remediation strategies, combining reliability and cost-effectiveness. In this study, we adopted a biomonitoring approach by using tree rings of four different species collected in the proximity of the mining-metallurgical area of Abbadia San Salvatore, central Italy, a major former Hg mining district whose reclamation is currently in progress. Our dendrochemical analysis was aimed at identifying the historical changes of local atmospheric Hg contamination and at singling out, for the first time in the study area, other potentially toxic elements (PTEs) associated with the past mining activity. Collected cores dated back to early as 1940 and provided the temporal patterns of atmospheric Hg emission vs the produced liquid quantities, so reconstructing the historical impact of the mining site on nearby terrestrial ecosystems and resident human population. Current GEM contamination was found about twenty times lower than that of the fully operational mine periods. From a first survey on other PTEs, thallium (Tl) and lead (Pb) appeared to be potentially associated with the mining activity, thus suggesting new working assumptions for further dendrochemical analyses and for the inclusion of Pb in human biomonitoring surveys of the Mt. Amiata area, actually not present in the control list. The results prompt a more thorough assessment by tracking for a longer time span a critical site that is an ideal open-field lab to study the ecophysiology of different tree species in relation to environmental behavior of PTEs for better-assessing wildlife and human exposures.
Identification of psychological constructs for a positive psychology intervention to assist with the adjustment to closed loop technology among adolescents living with type 1 diabetes
Authors: Kruger Sylvia , Deacon Elmari , van Rensburg Esmé , Segal David
Published: October 2023

Aim

Adolescents have been identified as the group who struggle most with successful adjustment to closed loop technology. This study aims to identify the psychological constructs that should form part of a positive psychology intervention to assist with the adjustment to closed loop technology among adolescents living with type 1 diabetes.

Method

Qualitative document analysis was employed to integrate findings from two documents: a published ongoing intervention study and a recent phenomenological study by the authors. Reflexive thematic analysis was used to identify themes from the documents.

Findings

The following themes were identified as important psychological constructs that aid adjustment: the importance of knowledge and education; the process of positive adjustment to closed loop technology; a positive outlook; and building a relationship with diabetes.

Conclusion

Interventions are needed to assist adolescents in their adjustment to closed loop technology. The psychological constructs identified served as a starting point in designing an effective, evidence-based intervention grounded in data and theory. Knowledge and education, responsibility, identity, positive affect, gratitude, support, and trust are psychological constructs that need to be included in an intervention program.
Changes in insight throughout the natural four-year course of obsessive-compulsive disorder and its association with OCD severity and quality of life
Authors: Wolf Nadja , du Mortier Johanna A. M. , van Oppen Patricia , Hoogendoorn Adriaan W. , van Balkom Anton J. L. M. , Visser Henny A. D.
Published: October 2023

Objective

Patients with obsessive-compulsive disorder (OCD) and poor insight show higher symptom severity, lower quality of life (QoL), and a reduced treatment response compared to patients with good insight. Little is known about changes in insight. This study explored the course of insight and its association with OCD severity and QoL among 253 patients with OCD participating in the prospective naturalistic Netherlands Obsessive Compulsive Disorder Association (NOCDA) Study.

Results

In 70% of the participants with available insight data, the level of insight changed during the four-year course. Insight was most variable in participants with poor insight. Improvement of insight scores was statistically significantly associated with improvement of Y-BOCS scores (r = 0.19), but not with changes in QoL scores. Change in insight in the first 2 years was not statistically significantly predictive of OCD severity or QoL at four-year follow-up.

Conclusion

These findings suggest that patients’ levels of insight may change during the natural four-year course of OCD and that improvement in the level of insight have a positive association with improvement in OCD severity.
Turbulent dipolarization regions in the Earth’s magnetotail: ion fluxes and magnetic field changes
Authors: Kozak Liudmyla , Kronberg Elena A. , Petrenko Bohdan , Blöcker Aljona , Akhmetshyn Roman , Ballai Istvan , Fedun Viktor
Published: October 2023

In this work, we consider the dynamics of ion fluxes and magnetic field changes in turbulent regions of magnetotail dipolarizations. The data from the Cluster-II mission (magnetic field measurements from fluxgate magnetometers and energetic charged particle observations from RAPID spectrometers) were used for the analysis. We study individual events and investigate statistically the changes of charged particle fluxes during magnetic field dipolarizations observed during 2001–2015. Received changes in the spectral index indicate that CNO+ ions undergo stronger acceleration during dipolarization than protons and helium ions. Before dipolarization front monotonic growth the ions flux is observed (the maximum of flux is observed at 1–1,5 min after the start of dipolarization) in the range of ∼ 92–374 keV for proton; in the energy range ∼ 138–235 keV for He+ and in the energy range of 414–638 keV for CNO+ ions. Flux increase before arriving dipolarization front may result from the reflection of plasma sheet ions at the dipolarization front and the result of the resonant interactions of ions with low-frequency electromagnetic waves.
Effect of Morinda citrifolia fruit powder on physiological and productive performance of Cavia porcellus
Authors: Paredes-López Daniel Marco , Robles-Huaynate Rizal Alcides , Beteta-Blas Xiomara , Aldava-Pardave Uriel
Published: October 2023

The breeding of guinea pig is part of the pluriactivity for millions of farming families in rural areas from the Peruvian Andean and Amazonian regions and other South American Andean countries. Rearing these specie plays an important source of employment, income, and nutrition for millions of rural families on these countries. The search of natural products for enhancing animal wellbeing, health, and production and thereby of guinea pigs is being searched nowadays. The aim of this study was to determine the effect of the ripe fruit powder of Morinda citrifolia on the physiological and productive performance parameters of reared guinea pigs under humid tropical conditions and to find a new use of noni fruit and to improve the guinea pig as an agrifood product. For this purpose, forty-eight male Peru breed guinea pigs sixty days old, were used and distributed into four treatments with diets containing 0, 2, 4 and 8% of the noni ripe fruit powder, with four replicates and 3 guinea pigs each. Erythrocytes, hematocrit, hemoglobin profiles, hematological indices MCV (mean cell volume), MCHC (mean corpuscular hemoglobin concentration), MCH (mean corpuscular hemoglobin) and blood metabolites profiles: TP (total protein), ALB (albumin), GLO (globulin), TC (total cholesterol) were determined. The productive performance indices: DWG (daily weight gain), DCFI (daily concentrated feed intake), TFIFM (total feed intake of fresh matter) and TFIDM (total feed intake of dry matter), FRCFM (feed rate conversion for fresh mater) and FRCDM (feed rate conversion for dry matter) were evaluated. The guinea pigs were evaluated at 60, 75 and 90 days old. The interaction between noni fruit powder and the age of guinea pigs produced an increase in the erythrocyte, hematocrit, MCH and MCHC levels at 75 days old, (p < 0.05). The final weight and the daily weight gain increased, while the feed rate conversion for fresh and dry matter decreased, as the level of noni fruit powder in the diet increased until 4% (p < 0.05). Thus, the level of noni ripe fruit powder in the guinea pigs' diets had a positive effect on the erythrocyte, leucocytes, hematocrit, MCH, MCHC levels, the final weight, the daily weight gain, and the feed rate conversion of fresh and dry matter.
Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes
Authors: Hussein Mohamed Ali , Munirathinam Gnanasekar
Published: October 2023

Prostate cancer (PCa) constitutes a significant cause of mortality, with over 37,000 new deaths each year [...]
Histone and DNA Methylation as Epigenetic Regulators of DNA Damage Repair in Gastric Cancer and Emerging Therapeutic Opportunities
Authors: De Marco Katia , Sanese Paola , Simone Cristiano , Grossi Valentina
Published: October 2023

Gastric cancer (GC), one of the most common malignancies worldwide, is a heterogeneous disease developing from the accumulation of genetic and epigenetic changes. One of the most critical epigenetic alterations in GC is DNA and histone methylation, which affects multiple processes in the cell nucleus, including gene expression and DNA damage repair (DDR). Indeed, the aberrant expression of histone methyltransferases and demethylases influences chromatin accessibility to the DNA repair machinery; moreover, overexpression of DNA methyltransferases results in promoter hypermethylation, which can suppress the transcription of genes involved in DNA repair. Several DDR mechanisms have been recognized so far, with homologous recombination (HR) being the main pathway involved in the repair of double-strand breaks. An increasing number of defective HR genes are emerging in GC, resulting in the identification of important determinants of therapeutic response to DDR inhibitors. This review describes how both histone and DNA methylation affect DDR in the context of GC and discusses how alterations in DDR can help identify new molecular targets to devise more effective therapeutic strategies for GC, with a particular focus on HR-deficient tumors.
Targeting the Heterogeneous Tumour-Associated Macrophages in Hepatocellular Carcinoma
Authors: Agirre-Lizaso Aloña , Huici-Izagirre Maider , Urretabizkaia-Garmendia Josu , Rodrigues Pedro M. , Banales Jesus M. , Perugorria Maria J.
Published: October 2023

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that comprises a complex tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are one of the most abundant immune cells present in the TME, and play a key role both in the development and in the progression of HCC. Thus, TAM-based immunotherapy has been presented as a promising strategy to complement the currently available therapies for HCC treatment. Among the novel approaches focusing on TAMs, reprogramming their functional state has emerged as a promising option for targeting TAMs as an immunotherapy in combination with the currently available treatment options. Nevertheless, a further understanding of the immunobiology of TAMs is still required. This review synthesizes current insights into the heterogeneous nature of TAMs in HCC and describes the mechanisms behind their pro-tumoural polarization focusing the attention on their interaction with HCC cells. Furthermore, this review underscores the potential involvement of TAMs’ reprogramming in HCC therapy and highlights the urgency of advancing our understanding of these cells within the dynamic landscape of HCC.
89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study
Authors: Linders D. G. J. , Deken M. M. , van Dam M. A. , Wasser M. N. J. M. , Voormolen E. M. C. , Kroep J. R. , van Dongen G. A. M. S. , Vugts D. , Oosterkamp H. M. , Straver M. E. , van de Velde C. J. H. , Cohen D. , Dibbets-Schneider P. , van Velden F. H. P. , Pereira Arias-Bouda L. M. , Vahrmeijer A. L. , Liefers G. J. , de Geus-Oei L. F. , Hilling D. E.
Published: October 2023

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.
A Systematic Review of Economic Evaluations of Insulin for the Management of Type 2 Diabetes
Authors: Gkrinia Elvira Meni Maria , Faour Andrea Katrin , Belančić Andrej , Bazile Jacques , Marland Emma , Vitezić Dinko
Published: October 2023

Diabetes is a chronic, metabolic disease characterized by hyperglycemia, which occurs as a result of inadequate production or utilization of insulin. Type 2 diabetes (T2D) is the most common type of diabetes with estimates projecting a prevalence of more than 1 billion people living with T2DM by 2050. Hence, it was decided to conduct a systematic literature review of health economic evaluations of insulin, the most common medication used for the treatment of the disease, to inform policy. Pharmacoeconomic analyses, written in English and published after 2016, were considered for inclusion. PubMed/Medline, Global Health, Embase and Health Management Consortium were searched separately between 5 July 2023 and 17 July 2023. Grey literature articles were searched on ISPOR and the Cost-Effectiveness Analysis Registry during the same period. After the exclusion criteria were applied, 21 studies were included. Using the BMJ checklist, a quality appraisal was performed on all included studies. Data extraction was performed manually. Regarding evidence synthesis, data were heterogenous and are presented based on study type. The results showed a variety of treatment combinations being available for the treatment of diabetes, with insulin degludec/DegLira and semaglutide being cost-effective despite their high cost, due to the effectiveness of managing the disease. Research around the cost-effectiveness or cost-utility of insulin has potential to progress further, to ensure informed policy-making in the future.
A Methodological Approach of Predicting the Performance of Thermoelectric Generators with Temperature-Dependent Properties and Convection Heat Losses
Authors: Sanin-Villa Daniel , Monsalve-Cifuentes Oscar D.
Published: October 2023

Thermoelectric generators are devices that transform thermal energy into electric energy. These devices play an influential role in our constantly developing civilization due to their energy conversion capabilities and advantages over other conventional methods. The material properties and thermoelectric phenomena are paramount to the design process of such devices. The design process must have a complex tool to model all the thermoelectric phenomena, such as, for example, the commercial numerical code of Ansys Mechanical. However, these numerical tools can be methodologically and computationally demanding. Thus, this study aims to develop a methodology through which to characterize thermoelectric generators by using a simplified one-dimensional numerical model that considers temperature-dependent N- and P-type material properties and convective heat losses. The proposed model’s results are compared and validated to a single thermoelectric leg and a complete thermoelectric commercial module, both modeled in Ansys Thermal-Electric. These results consider the different values for electric and thermal loads as current densities, electric resistivities, and heat transfer coefficients. The main result of this study is the correct prediction of the output voltage and output power given by the one-dimensional proposed model, which was validated against a comprehensive model and the commercial thermoelectric module’s information. Therefore, the proposed methodology of this study provides a deeper understanding of the thermoelectric energy conversion process, and it can guide the design and optimization of thermoelectric generators for practical applications.