bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal relationships between mitochondrial proteins and different pathological types of lung cancer: a bidirectional mendelian randomization study
Authors: Ji Tanao , Lv Yue , Liu Meiqun , Han Yujie , Yuan Baochang , Gu Jun
Published: March 2024

An increasing number of studies point to an association between mitochondrial proteins (MPs) and lung cancer (LC). However, the causal relationship between MPs and LC remains unclear. Consequently, our study employed a bidirectional Mendelian randomization (MR) analysis to explore the causal association between MPs and different pathological types of LC. A two-sample MR study was performed using the genome-wide association study (GWAS) data publicly available. We applied the primary inverse variance weighted (IVW) method along with additional MR methods to validate the causality between MPs and different pathological types of LC. To ensure the robustness of our findings, sensitivity analyses were employed. Moreover, we performed a bi-directional MR analysis to determine the direction of the causal association. We identified a total of seven MPs had significant causal relationships on overall LC, lung squamous cell carcinoma (LUSC), and small cell lung carcinoma (SCLC). We found two MPs had significant associations with overall LC, four MPs had significant associations with LUSC, and four MPs had significant associations with SCLC. Additionally, an MP was found to have a nominal relationship with LUSC. Moreover, no causality was found between MPs and lung adenocarcinoma (LUAD). Bidirectional MR showed no reverse effect between identified MPs and different pathological types of LC. In general, our findings of this MR study suggest causal associations of specific MPs with overall LC, LUSC, and SCLC. However, no such causality was found in LUAD.
Comparison of ddRADseq and EUChip60K SNP genotyping systems for population genetics and genomic selection in Eucalyptus dunnii (Maiden)
Authors: Aguirre Natalia Cristina , Villalba Pamela Victoria , García Martín Nahuel , Filippi Carla Valeria , Rivas Juan Gabriel , Martínez María Carolina , Acuña Cintia Vanesa , López Augusto J. , López Juan Adolfo , Pathauer Pablo , Palazzini Dino , Harrand Leonel , Oberschelp Javier , Marcó Martín Alberto , Cisneros Esteban Felipe , Carreras Rocío , Martins Alves Ana Maria , Rodrigues José Carlos , Hopp H. Esteban , Grattapaglia Dario , Cappa Eduardo Pablo , Paniego Norma Beatriz , Marcucci Poltri Susana Noemí
Published: March 2024

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.
Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus
Authors: Van Eyndhoven Laura C. , Chouri Eleni , Matos Catarina I. , Pandit Aridaman , Radstake Timothy R. D. J. , Broen Jasper C. A. , Singh Abhyudai , Tel Jurjen
Published: March 2024

Introduction

The innate immune system serves the crucial first line of defense against a wide variety of potential threats, during which the production of pro-inflammatory cytokines IFN-I and TNFα are key. This astonishing power to fight invaders, however, comes at the cost of risking IFN-I-related pathologies, such as observed during autoimmune diseases, during which IFN-I and TNFα response dynamics are dysregulated. Therefore, these response dynamics must be tightly regulated, and precisely matched with the potential threat. This regulation is currently far from understood.

Methods

Using droplet-based microfluidics and ODE modeling, we studied the fundamentals of single-cell decision-making upon TLR signaling in human primary immune cells (n = 23). Next, using biologicals used for treating autoimmune diseases [i.e., anti-TNFα, and JAK inhibitors], we unraveled the crosstalk between IFN-I and TNFα signaling dynamics. Finally, we studied primary immune cells isolated from SLE patients (n = 8) to provide insights into SLE pathophysiology.

Results

single-cell IFN-I and TNFα response dynamics display remarkable differences, yet both being highly heterogeneous. Blocking TNFα signaling increases the percentage of IFN-I-producing cells, while blocking IFN-I signaling decreases the percentage of TNFα-producing cells. Single-cell decision-making in SLE patients is dysregulated, pointing towards a dysregulated crosstalk between IFN-I and TNFα response dynamics.

Discussion

We provide a solid droplet-based microfluidic platform to study inherent immune secretory behaviors, substantiated by ODE modeling, which can challenge the conceptualization within and between different immune signaling systems. These insights will build towards an improved fundamental understanding on single-cell decision-making in health and disease.
Emerging research themes in maternal hypothyroidism: a bibliometric exploration
Authors: Chen Ailing , Luo Zouqing , Zhang Jinqiu , Cao Xiaohui
Published: March 2024

Background

Hypothyroidism, a prevalent endocrine disorder, carries significant implications for maternal and infant health, especially in the context of maternal hypothyroidism. Despite a gradual surge in recent research, achieving a comprehensive understanding of the current state, focal points, and developmental trends in this field remains challenging. Clarifying these aspects and advancing research could notably enhance maternal-infant health outcomes. Therefore, this study employs bibliometric methods to systematically scrutinize maternal hypothyroidism research, serving as a reference for further investigations.

Objective

Through bibliometric analysis, this study seeks to unveil key research focus areas, developmental trends, and primary contributors in Maternal Hypothyroidism. The findings offer insights and recommendations to inform future research endeavors in this domain.

Methods

Literature metrics analysis was performed on data retrieved and extracted from the Web of Science Core Collection database. The analysis examined the evolution and thematic trends of literature related to Maternal Hypothyroidism. Data were collected on October 28, 2023, and bibliometric analysis was performed using VOSviewer, CiteSpace, and the Bibliometrix software package, considering specific characteristics such as publication year, country/region, institution, authorship, journals, references, and keywords.

Results

Retrieved from 1,078 journals, 4,184 articles were authored by 18,037 contributors in 4,580 institutions across 113 countries/regions on six continents. Maternal Hypothyroidism research publications surged from 44 to 310 annually, a 604.54% growth from 1991 to 2022. The USA (940 articles, 45,233 citations), China Medical University (82 articles, 2,176 citations), and Teng, Weiping (52 articles, 1,347 citations) emerged as the most productive country, institution, and author, respectively. “Thyroid” topped with 233 publications, followed by “Journal of Clinical Endocrinology & Metabolism” (202) with the most citations (18,513). “Pregnancy” was the most cited keyword, with recent high-frequency keywords such as “outcome,” “gestational diabetes,” “iodine intake,” “preterm birth,” “guideline,” and “diagnosis” signaling emerging themes in Maternal Hypothyroidism.

Conclusions

This study unveils developmental trends, global collaboration patterns, foundational knowledge, and emerging frontiers in Maternal Hypothyroidism. Over 30 years, research has predominantly focused on aspects like diagnosis, treatment guidelines, thyroid function during pregnancy, and postpartum outcomes, with a central emphasis on the correlation between maternal and fetal health.
Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis
Authors: Ma Zhiqiang , An Pingyu , Hao Siyu , Huang Zhangxin , Yin Anqi , Li Yuzhen , Tian Jiangtian
Published: March 2024

Background

Psoriasis is an immune-mediated disorder influenced by environmental factors on a genetic basis. Despite advancements, challenges persist, including the diminishing efficacy of biologics and small-molecule targeted agents, alongside managing recurrence and psoriasis-related comorbidities. Unraveling the underlying pathogenesis and identifying valuable biomarkers remain pivotal for diagnosing and treating psoriasis.

Methods

We employed a series of bioinformatics (including single-cell sequencing data analysis and machine learning techniques) and statistical methods to integrate and analyze multi-level data. We observed the cellular changes in psoriatic skin tissues, screened the key genes Fatty acid binding protein 5 (FABP5) and The killer cell lectin-like receptor B1 (KLRB1), evaluated the efficacy of six widely prescribed drugs on psoriasis treatment in modulating the dendritic cell-associated pathway, and assessed their overall efficacy. Finally, RT-qPCR, immunohistochemistry, and immunofluorescence assays were used to validate.

Results

The regulatory influence of dendritic cells (DCs) on T cells through the CD70/CD27 signaling pathway may emerge as a significant facet of the inflammatory response in psoriasis. Notably, FABP5 and KLRB1 exhibited up-regulation and co-localization in psoriatic skin tissues and M5-induced HaCaT cells, serving as potential biomarkers influencing psoriasis development.

Conclusion

Our study analyzed the impact of DC-T cell crosstalk in psoriasis, elucidated the characterization of two biomarkers, FABP5 and KLRB1, in psoriasis, and highlighted the promise and value of tofacitinib in psoriasis therapy targeting DCs.
Fructose overconsumption-induced reprogramming of microglia metabolism and function
Authors: Ting Kenneth K. Y.
Published: March 2024

The overconsumption of dietary fructose has been proposed as a major culprit for the rise of many metabolic diseases in recent years, yet the relationship between a high fructose diet and neurological dysfunction remains to be explored. Although fructose metabolism mainly takes place in the liver and intestine, recent studies have shown that a hyperglycemic condition could induce fructose metabolism in the brain. Notably, microglia, which are tissue-resident macrophages (Mφs) that confer innate immunity in the brain, also express fructose transporters (GLUT5) and are capable of utilizing fructose as a carbon fuel. Together, these studies suggest the possibility that a high fructose diet can regulate the activation and inflammatory response of microglia by metabolic reprogramming, thereby altering the susceptibility of developing neurological dysfunction. In this review, the recent advances in the understanding of microglia metabolism and how it supports its functions will be summarized. The results from both in vivo and in vitro studies that have investigated the mechanistic link between fructose-induced metabolic reprogramming of microglia and its function will then be reviewed. Finally, areas of controversies and their associated implications, as well as directions that warrant future research will be highlighted.
Relationship between the microenvironment and survival in kidney transplantation: a bibliometric analysis from 2013 to 2023
Authors: Huang Chun-Lian , Fu Xin-Yu , Feng Yi , Li Xiao-Kang , Sun Yi , Mao Xin-Li , Li Shao-Wei
Published: March 2024

Background

Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation.

Methods

Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package “bibliometrix”. The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering.

Results

Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor β, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years.

Conclusion

This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.
Induction of islet autoimmunity to defective ribosomal product of the insulin gene as neoantigen after anti-cancer immunotherapy leading to autoimmune diabetes
Authors: van Tienhoven Rene , Jansen Diahann T. S. L. , Park Miso , Williams John C. , Larkin James , Quezada Sergio A. , Roep Bart O.
Published: March 2024

Introduction

The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells. T1D patient-derived INS-DRiP specific T cells can kill beta cells and are present in the insulitic lesion. T cells reactive to INS-DRiP epitopes are part of the normal T cell repertoire and are believed to be kept in check by immune regulation without causing autoimmunity.

Method

T cell autoreactivity was tested using a combinatorial HLA multimer technology measuring a range of epitopes of islet autoantigens and neoantigen INS-DRiP. INS-DRiP expression in human pancreas and insulinoma sections was tested by immunohistochemistry.

Results

Here we report the induction of islet autoimmunity to INS-DRiP and diabetes after ICI treatment and successful tumor remission. Following ICI treatment, T cells of the cancer patient were primed against INS-DRiP among other diabetogenic antigens, while there was no sign of autoimmunity to this neoantigen before ICI treatment. Next, we demonstrated the expression of INS-DRiP as neoantigen in both pancreatic islets and insulinoma by staining with a monoclonal antibody to INS-DRiP.

Discussion

These results bridge cancer and T1D as two sides of the same coin and point to neoantigen expression in normal islets and insulinoma that may serve as target of both islet autoimmunity and tumor-related autoimmunity.
Serum isolevuglandin IgG antibody concentrations are increased in patients with systemic lupus erythematosus and associated with lower 24-hour blood pressure
Authors: Phothisane Anastasiia , Oeser Annette M. , Shaik Shahensha , Wu Qiong , Posey Olivia , Davies Sean S. , Krishnan Jaya , Patrick David M. , Stein C. Michael , Ormseth Michelle J.
Published: March 2024

Objective

Hypertension is frequent in patients with systemic lupus erythematosus (SLE) and is a major contributor to increased cardiovascular risk. Isolevuglandins (IsoLGs) are downstream products of oxidative stress that drive hypertension and SLE disease activity in animal models. Antibodies to IsoLGs (anti-IsoLGs) are present in human SLE and associated with disease activity, but it is not known if concentrations are higher compared to control subjects or if they are associated with blood pressure (BP).

Methods

We measured serum anti-IsoLG IgG antibody concentrations by sandwich ELISA in 23 patients with SLE and 30 controls who had participated in a cross-sectional 24-hour ambulatory BP study. We examined the association between anti-IsoLG IgG antibodies and BP measurements in patients with SLE and controls by Spearman Rho (rs) and linear regression analysis.

Results

Serum anti-IsoLG IgG antibody concentrations were higher in patients with SLE than controls (P = 0.007) and inversely associated with BP in SLE but not controls. In patients with SLE antibody concentrations were inversely associated with office (rs = −0.418) and diurnal systolic BP (rs = −0.421); the relationship was stronger among patients not taking anti-hypertensives (office: rs = −0.740, diurnal systolic BP: rs = −0.802) and every 20% increase in antibody concentration was associated with 10 mmHg decrease in 24-hour systolic BP (P = 0.004).

Conclusion

Serum anti-IsoLG IgG antibody concentrations are higher in patients with SLE than controls and are inversely associated with 24-hour BP measurements. Since IsoLGs promote hypertension, it is possible that in SLE, IsoLG antibodies could help clear these hypertension-inducing antigens.
Consistent Symbiodiniaceae community assemblage in a mesophotic-specialist coral along the Saudi Arabian Red Sea
Authors: Vimercati Silvia , Terraneo Tullia I. , Castano Carolina Bocanegra , Barreca Federica , Hume Benjamin C. C. , Marchese Fabio , Ouhssain Mustapha , Steckbauer Alexandra , Chimienti Giovanni , Eweida Ameer A. , Voolstra Christian R. , Rodrigue Mattie , Pieribone Vincent , Purkis Sam J. , Qurban Mohammed , Jones Burt H. , Duarte Carlos M. , Benzoni Francesca
Published: March 2024

Introduction

The Red Sea is a narrow rift basin characterized by latitudinal environmental gradients which shape the diversity and distribution of reef-dwelling organisms. Studies on Symbiodiniaceae associated with select hard coral taxa present species- specific assemblages and concordant variation patterns from the North to southeast Red Sea coast at depths shallower than 30 m. At mesophotic depths, however, algal diversity studies are rare. Here, we characterize for the first-time host-associated algal communities of a mesophotic specialist coral species, Leptoseris cf. striatus, along the Saudi Arabian Red Sea coast.

Methods

We sampled 56 coral colonies spanning the eastern Red Sea coastline from the Northern Red Sea to the Farasan Banks in the South, and across two sampling periods, Fall 2020 and Spring 2022. We used Next Generation Sequencing of the ITS2 marker region in conjunction with SymPortal to denote algal assemblages.

Results and discussion

Our results show a relatively stable coral species-specific interaction with algae from the genus Cladocopium along the examined latitudinal gradient, with the appearance, in a smaller proportion, of presumed thermally tolerant algal taxa in the genera Symbiodinium and Durusdinium during the warmer season (Fall 2020). Contrary to shallow water corals, our results do not show a change in Symbiodiniaceae community composition from North to South in this mesophotic specialist species. However, our study highlights for the first time that symbiont communities are subject to change over time at mesophotic depth, which could represent an important phenomenon to address in future studies.
Bending performance of prefabricated ultra-thin UHPC unit plate reinforced orthotropic steel bridge decks
Authors: Zhou Xiang , Jiang Jinlong , Liu Le , Wang Shan , Deng Xilei , Li Yong , Zhang Zhongya
Published: March 2024

To address the challenges related to lengthy construction period, complex maintenance requirement, and the elevated risk of shrinkage cracking associated with cast-in-place UHPC reinforcement of orthotropic steel bridge decks. This paper proposes a novel solution that prefabricated ultra-high-performance concrete (UHPC) slab with epoxy bond connection is used as a reinforcement layer for orthotropic steel bridge decks. Four sets of bending tests on composite bridge deck were carried out to compare the flexural performance of composite bridge decks under different joint forms and loading patterns. The results indicate that the precast UHPC decks delaminated from the epoxy bonding layer without failure of the epoxy layer itself in all cases. The positive bending capacity of the jointless composite bridge deck is approximately 27.67 kN, while the negative bending capacity is around 16.58 kN. For the composite bridge deckwith epoxy adhesive joints (EA-J-Ln), the negative bending capacity is 2.54 kN, and the negative bending capacity of the joint area reinforced with carbon fiber cloth (EA-JC-Ln) is increased to 4.17 kN. Therefore, the use of carbon fiber cloth can significantly improve the bending resistance of the joints. Finally, numerical model of the composite deck based on Cohesive Zone Model (CZM) was established, validating the applicability of this simulation method in the novel composite bridge deck.
Baltic Sea coastal sediment-bound eukaryotes have increased year-round activities under predicted climate change related warming
Authors: Li Songjun , Nilsson Emelie , Seidel Laura , Ketzer Marcelo , Forsman Anders , Dopson Mark , Hylander Samuel
Published: March 2024

Climate change related warming is a serious environmental problem attributed to anthropogenic activities, causing ocean water temperatures to rise in the coastal marine ecosystem since the last century. This particularly affects benthic microbial communities, which are crucial for biogeochemical cycles. While bacterial communities have received considerable scientific attention, the benthic eukaryotic community response to climate change remains relatively overlooked. In this study, sediments were sampled from a heated (average 5°C increase over the whole year for over 50 years) and a control (contemporary conditions) Baltic Sea bay during four different seasons across a year. RNA transcript counts were then used to investigate eukaryotic community changes under long-term warming. The composition of active species in the heated and control bay sediment eukaryotic communities differed, which was mainly attributed to salinity and temperature. The family level RNA transcript alpha diversity in the heated bay was higher during May but lower in November, compared with the control bay, suggesting altered seasonal activity patterns and dynamics. In addition, structures of the active eukaryotic communities varied between the two bays during the same season. Hence, this study revealed that long-term warming can change seasonality in eukaryotic diversity patterns. Relative abundances and transcript expression comparisons between bays suggested that some taxa that now have lower mRNA transcripts numbers could be favored by future warming. Furthermore, long-term warming can lead to a more active metabolism in these communities throughout the year, such as higher transcript numbers associated with diatom energy production and protein synthesis in the heated bay during winter. In all, these data can help predict how future global warming will affect the ecology and metabolism of eukaryotic community in coastal sediments.
The assessment of executive function abilities in healthy and neurodegenerative aging—A selective literature review
Authors: Idowu Mojitola I. , Szameitat Andre J. , Parton Andrew
Published: March 2024

Numerous studies have examined executive function (EF) abilities in cognitively healthy older adults and those living with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, there are no standard accepted protocols for testing specific EFs; thus, researchers have used their preferred tool, which leads to variability in assessments of decline in a particular ability across studies. Therefore, there is a need for guidance as to the most sensitive tests for assessing EF decline. A search of the most current literature published between 2000 and 2022 on EF studies assessing cognitively healthy older adults and individuals living with MCI and AD was conducted using PubMed/Medline, PsycINFO, Embase, Web of Science, and Google Scholar. Emphasis was placed on the EF's dual-tasking, inhibition, shifting or switching, and working memory updating. Many tasks and their outcomes were reviewed. Of particular importance was the difference in outcomes for tasks applied to the same group of participants. These various EF assessment tools demonstrate differences in effectively identifying decline in EF ability due to the aging process and neurodegenerative conditions, such as MCI and AD. This review identifies various factors to consider in using particular EF tasks in particular populations, including task demand and stimuli factors, and also when comparing differing results across studies.
The evolution of ventral intermediate nucleus targeting in MRI-guided focused ultrasound thalamotomy for essential tremor: an international multi-center evaluation
Authors: Jameel Ayesha , Akgun Sena , Yousif Nada , Smith Joely , Jones Brynmor , Nandi Dipankar , Bain Peter , Gedroyc Wladyslaw
Published: March 2024

Background

The ventral intermediate nucleus (VIM) is the premiere target in magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for tremor; however, there is no consensus on the optimal coordinates for ablation. This study aims to ascertain the various international VIM targeting approaches (VIM-TA) and any evolution in practice.

Methods

International MRgFUS centers were invited to share VIM-TAs in 2019 and 2021. Analyses of any modification in practice and of anatomical markers and/or tractography in use were carried out. Each VIM-TA was mapped in relation to the mid-commissural point onto a 3D thalamic nucleus model created from the Schaltenbrand–Wahren atlas.

Results

Of the 39 centers invited, 30 participated across the study period, providing VIM-TAs from 26 centers in 2019 and 23 in 2021. The results are reported as percentages of the number of participating centers in that year. In 2019 and 2021, respectively, 96.2% (n = 25) and 95.7% (n = 22) of centers based their targeting on anatomical landmarks rather than tractography. Increased adoption of tractography in clinical practice and/or for research was noted, changing from 34.6% to 78.3%. There was a statistically significant change in VIM-TAs in the superior-inferior plane across the study period; the percentage of VIM-TAs positioned 2 mm above the intercommissural line (ICL) increased from 16.0% in 2019 to 40.9% in 2021 (WRST, p < 0.05). This position is mapped at the center of VIM on the 3D thalamic model created based on the Schaltenbrand–Wahren atlas. In contrast, the VIM-TA medial-lateral and anterior-posterior positions remained stable. In 2022, 63.3% of participating centers provided the rationale for their VIM-TAs and key demographics. The centers were more likely to target 2 mm above the ICL if they had increased experience (more than 100 treatments) and/or if they were North American.

Conclusion

Across the study period, FUS centers have evolved their VIM targeting superiorly to target the center of the VIM (2 mm above the ICL) and increased the adoption of tractography to aid VIM localization. This phenomenon is observed across autonomous international centers, suggesting that it is a more optimal site for FUS thalamotomy in tremors.
Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization
Authors: Rinaldo Sara , Cilia Roberto , Leta Valentina , Gammone Mariarosaria , Andreasi Nico Golfrè , Colucci Fabiana , Braccia Arianna , Telese Roberta , Poli Marco Fusar , Levi Vincenzo , Romito Luigi Michele Antonio , Ghilemetti Francesco , De Martin Elena , Fumagalli Maria Luisa , Epifani Francesca , Prioni Sara , Amami Paolo , Piacentini Sylvie , Elia Antonio Emanuele , Devigili Grazia , Nazzi Vittoria , Ciceri Elisa Francesca Maria , Stanziano Mario , Grisoli Marina , Caldiera Valentina , Catotti Marisa , DiMeco Francesco , Moreschi Giacomina Clara , Eleopra Roberto
Published: March 2024

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson’s disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.
Effect of quinoa (Chenopodium quinoa W.) flour supplementation in breads on the lipid profile and glycemic index: an in vivo study
Authors: Marak Natasha R. , Das Pranati , Das Purkayastha Manashi , Baruah Luna Dutta
Published: March 2024

Quinoa is a gluten-free pseudocereal, with an excellent nutrient profile containing considerable amounts of fiber and minerals and rich in antioxidants such as polyphenols. The purpose of this research was to investigate the effects of quinoa bread on physical, chemical, bioactive components, glycaemic index (GI), and biochemical parameters. Human subjects aged between 20 and 50 years with the absence of morbid factors were fed daily with quinoa bread for 3 months in order to study its pre-and post-treatment effects on blood glucose, glycosylated haemoglobin, and lipid profile. The effort was made to incorporate the maximum amount of quinoa into the bread without compromising the acceptability of the bread. Of the 14 formulations, TQ13, containing 20% quinoa flour with 3% wheat bran, was selected for further analysis. The GI study revealed that quinoa bread peaked at 45 min with a gradual increase after ingestion of the bread and a steady decline thereafter. The observed value for blood glucose levels, before and after supplementation with quinoa-incorporated bread, was 86.96 ± 15.32 mg/dL and 84.25 ± 18.26 mg/dL, respectively. There was a statistically significant (p ≤ 0.05) decrease in levels of triglycerides, total cholesterol, low-density lipoprotein (LDL), and very-LDL (VLDL) level before and after supplementation. However, non-significant changes were observed for high-density lipoprotein levels from the pre- and post-treatment with the quinoa-incorporated bread. Quinoa-incorporated bread possessed low GI (42.00 ± 0.83) compared to control (69.20 ± 1.84) and long-term consumption proved to contain functional efficacies in terms of hypolipidemic effect.
Prognostic and clinical pathological significance of the systemic immune-inflammation index in urothelial carcinoma: a systematic review and meta-analysis
Authors: Wang Yao , Hao Xiaoming , Li Gang
Published: March 2024

Background

A new non-invasive biomarker, the Systemic Immune-Inflammation Index (SII), has been proven to have prognostic value in multiple cancers. This systematic review and meta-analysis aimed to investigate the prognostic and clinical pathological significance of SII in urothelial carcinoma.

Methods

A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Embase, Cochrane Library, and CNKI. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated to evaluate the prognostic value of SII before treatment on survival outcomes, and odds ratios (OR) with 95%CI were used to assess the correlation between SII before treatment and clinical pathological features.

Results

This meta-analysis included a total of 10 studies (11 datasets) with 6,333 patients. The pooled analysis showed that high SII before surgery was significantly associated with poor survival outcomes in patients with urothelial carcinoma, including overall survival (OS) (HR=1.55, 95%CI 1.24-1.95, p<0.001), cancer-specific survival (CSS) (HR=2.74, 95%CI 1.67-4.49, p<0.001), recurrence-free survival (RFS) (HR=2.74, 95%CI 1.67-4.49, p<0.001), and progression-free survival (PFS) (HR=1.66, 95%CI 1.36-2.02, p<0.001). In addition, patients with elevated preoperative SII values were more likely to have adverse pathological features, including larger tumor size and advanced pathological T stage (p<0.001).

Conclusion

These findings suggest a significant association between high SII levels before treatment and poor survival outcomes, as well as certain clinical pathological features, in patients with urothelial carcinoma.
Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment
Authors: Cheng Cong , Deng Dao-Xing , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Sun Yu-Qian , Huang Xiao-Jun , Mo Xiao-Dong
Published: March 2024

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%–26.1%), 22.8% (95% CI 14.2%–31.4%) and 32.8% (95% CI 24.1%–41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%–84.9%), 72.7% (95% CI 63.7%–81.7%), and 62.3% (95% CI 53.5%–71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.
EhVps35, a retromer component, is involved in the recycling of the EhADH and Gal/GalNac virulent proteins of Entamoeba histolytica
Authors: Díaz-Valdez Joselin , Javier-Reyna Rosario , Montaño Sarita , Talamás-Lara Daniel , Orozco Esther
Published: March 2024

The retromer is a highly conserved eukaryotic complex formed by the cargo selective complex (CSC) and the sorting nexin (SNX) dimer subcomplexes. Its function is protein recycling and recovery from the endosomes to conduct the target molecules to the trans-Golgi network or the plasma membrane. The protozoan responsible for human amoebiasis, Entamoeba histolytica, exhibits an active membrane movement and voracious phagocytosis, events in which the retromer may be fully involved. In this work, we studied the structure of EhVps35 the central member of the CSC retromeric subcomplex as it binds EhVps26 and EhVps29, the other two CSC members, allowing the position of the retromer in the membranes. We also studied the EhVps35 role in the recycling of virulence proteins, particularly those involved in phagocytosis. Confocal microscopy assays revealed that EhVps35 is located in the plasmatic and endosomal membranes and in the phagocytic cups and channels. In addition, it follows the target cell from the moment it is in contact with the trophozoites. Molecular docking analyses, immunoprecipitation assays, and microscopy studies revealed that EhVps35 interacts with the EhADH, Gal/GalNac lectin, and actin proteins. In addition, experimental evidence indicated that it recycles surface proteins, particularly EhADH and Gal/GalNac proteins, two molecules highly involved in virulence. Knockdown of the Ehvps35 gene induced a decrease in protein recycling, as well as impairments in the efficiency of adhesion and the rate of phagocytosis. The actin cytoskeleton was deeply affected by the Ehvps35 gene knockdown. In summary, our results revealed the participation of EhVps35 in protein recycling and phagocytosis. Furthermore, altogether, our results demonstrated the concert of finely regulated molecules, including EhVps35, EhADH, Gal/GalNac lectin, and actin, in the phagocytosis of E. histolytica.
Arthroscopic fixation techniques for tibial eminence fractures in pediatric patients: a review
Authors: Li Canfeng , Huang Xiancheng , Yang Qingjun , Luo Yong , Li Jiatong , Ye Sufen , Lu Wenqian , Zhang Xintao , You Tian
Published: March 2024

The introduction of new internal fixation devices and arthroscopic techniques has led to significant changes in the surgical treatment of tibial eminence fractures (TEFs) in children. In recent years, arthroscopic surgery has arisen as the gold standard for the treatment of TEFs. This popularity of arthroscopic techniques has reduced surgical complications and improved patient prognosis. In this paper, we investigate the current situation of the use of arthroscopic fixation techniques for pediatric TEFs. We searched the PubMed database using the terms “arthroscopic treatment and tibial eminence,” “arthroscopic treatment and tibial spine,” “tibial eminence avulsion”, “tibial spine fracture”, with no limit on the year of publication. From these articles, we reviewed the use of various arthroscopic TEFs fixation techniques reported in the current literature. Overall, we found that the choice of fixation method seems to have no effect on clinical outcomes or imaging results. However, if an easy, strong fixation that is less prone to epiphyseal damage is desired, as a junior practitioner, the anchor technique should be mastered first, whereas for senior practitioners, a variety of fixation techniques for TEFs should be mastered, including anchors, sutures, and screws, so that personalized fixation can be achieved with the least amount of trauma, operative time, and complications. Higher quality studies are needed in the future to provide Useful evidence to determine the optimal fixation technique in terms of clinical outcomes, function, and complications.
Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential
Authors: Sun Min , Sun Jilei , Sun Wei , Li Xiaonan , Wang Zhe , Sun Liwei , Wang Yuehui
Published: March 2024

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.
Hybridization, polyploidization, and morphological convergence make dozens of taxa into one chaotic genetic pool: a phylogenomic case of the Ficus erecta species complex (Moraceae)
Authors: Wang Xiaomei , Liao Shuai , Zhang Zhen , Zhang Jianhang , Mei Li , Li Hongqing
Published: March 2024

The Ficus erecta complex, characterized by its morphological diversity and frequent interspecific overlap, shares pollinating fig wasps among several species. This attribute, coupled with its intricate phylogenetic relationships, establishes it as an exemplary model for studying speciation and evolutionary patterns. Extensive researches involving RADseq (Restriction-site associated DNA sequencing), complete chloroplast genome data, and flow cytometry methods were conducted, focusing on phylogenomic analysis, genetic structure, and ploidy detection within the complex. Significantly, the findings exposed a pronounced nuclear-cytoplasmic conflict. This evidence, together with genetic structure analysis, confirmed that hybridization within the complex is a frequent occurrence. The ploidy detection revealed widespread polyploidy, with certain species exhibiting multiple ploidy levels, including 2×, 3×, and 4×. Of particular note, only five species (F. abelii, F. erecta, F. formosana, F. tannoensis and F. vaccinioides) in the complex were proved to be monophyletic. Species such as F. gasparriniana, F. pandurata, and F. stenophylla were found to encompass multiple phylogenetically distinct lineages. This discovery, along with morphological comparisons, suggests a significant underestimation of species diversity within the complex. This study also identified F. tannoensis as an allopolyploid species originating from F. vaccinioide and F. erecta. Considering the integration of morphological, molecular systematics, and cytological evidences, it is proposed that the scope of the F. erecta complex should be expanded to the entire subsect. Frutescentiae. This would redefine the complex as a continuously evolving group comprising at least 33 taxa, characterized by blurred species boundaries, frequent hybridization and polyploidization, and ambiguous genetic differentiation.
Generation of transgene-free canker-resistant Citrus sinensis cv. Hamlin in the T0 generation through Cas12a/CBE co-editing
Authors: Jia Hongge , Omar Ahmad A. , Xu Jin , Dalmendray Javier , Wang Yuanchun , Feng Yu , Wang Wenting , Hu Zhuyuan , Grosser Jude W. , Wang Nian
Published: March 2024

Citrus canker disease affects citrus production. This disease is caused by Xanthomonas citri subsp. citri (Xcc). Previous studies confirmed that during Xcc infection, PthA4, a transcriptional activator like effector (TALE), is translocated from the pathogen to host plant cells. PthA4 binds to the effector binding elements (EBEs) in the promoter region of canker susceptibility gene LOB1 (EBEPthA4-LOBP) to activate its expression and subsequently cause canker symptoms. Previously, the Cas12a/CBE co-editing method was employed to disrupt EBEPthA4-LOBP of pummelo, which is highly homozygous. However, most commercial citrus cultivars are heterozygous hybrids and more difficult to generate homozygous/biallelic mutants. Here, we employed Cas12a/CBE co-editing method to edit EBEPthA4-LOBP of Hamlin (Citrus sinensis), a commercial heterozygous hybrid citrus cultivar grown worldwide. Binary vector GFP-p1380N-ttLbCas12a:LOBP1-mPBE:ALS2:ALS1 was constructed and shown to be functional via Xcc-facilitated agroinfiltration in Hamlin leaves. This construct allows the selection of transgene-free regenerants via GFP, edits ALS to generate chlorsulfuron-resistant regenerants as a selection marker for genome editing resulting from transient expression of the T-DNA via nCas9-mPBE:ALS2:ALS1, and edits gene(s) of interest (i.e., EBEPthA4-LOBP in this study) through ttLbCas12a, thus creating transgene-free citrus. Totally, 77 plantlets were produced. Among them, 8 plantlets were transgenic plants (#HamGFP1 - #HamGFP8), 4 plantlets were transgene-free (#HamNoGFP1 - #HamNoGFP4), and the rest were wild type. Among 4 transgene-free plantlets, three lines (#HamNoGFP1, #HamNoGFP2 and #HamNoGFP3) contained biallelic mutations in EBEpthA4, and one line (#HamNoGFP4) had homozygous mutations in EBEpthA4. We achieved 5.2% transgene-free homozygous/biallelic mutation efficiency for EBEPthA4–LOBP in C. sinensis cv. Hamlin, compared to 1.9% mutation efficiency for pummelo in a previous study. Importantly, the four transgene-free plantlets and 3 transgenic plantlets that survived were resistant against citrus canker. Taken together, Cas12a/CBE co-editing method has been successfully used to generate transgene-free canker‐resistant C. sinensis cv. Hamlin in the T0 generation via biallelic/homozygous editing of EBEpthA4 of the canker susceptibility gene LOB1.