bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical and clinical evaluation of PSO, modified PSO and VCR treating OVCF kyphosis: a finite element analysis
Authors: Li Junyu , Xu Lizhi , Wang Haotian , Liu Yinhao , Sun Zhuoran , Wang Yongqiang , Yu Miao , Li Weishi , Zeng Yan
Published: December 2024

Objective

To confirm the effect of surgery on spinal column biomechanics and to provide theoretical support for the advantages and disadvantages of different surgical methods and their clinical efficacy.

Methods

33 continuous patients with no significant difference in risk factors related to the mechanical complications were enrolled in this retrospective study. Sagittal parameters were measured in the pre-, post-operative and following-up lateral radiograph of spine. An finite element (FE) model was created using CT scanning from a female volunteer with osteoporotic vertebral compression fracture (OVCF) with solely kyphosis. Pedicle subtraction osteotomy (PSO), vertebral column resection (VCR) and modified PSO(mPSO) for OVCF were simulated on FE model. Stress distribution and deformation of the FE model were measured.

Results

Clinical - All differences in preoperative spinal sagittal parameters were not statistically significant. mPSO showed it is superior to PSO and VCR in multiple postoperative and following-up spinal sagittal parameters. The operation duration and intraoperative blood loss of mPSO are less than the other two. For postoperative mechanical complications, no statistically significant differences were observed. Biomechanical - Six operating conditions (flexion, extension, left/right bending, left/right twisting) for each post-operative FE model have been examined. In most conditions, the displacement of mPSO is similar to that of PSO, with both larger than that of VCR. All the maximum equivalent stress on the vertebral body is within the safe range. The stress is mainly distributed on the T10 vertebral body and the fixed vertebral body L2, while the stress of VCR is greater than that of mPSO and PSO. The intervertebral disc pressure is highest in VCR, followed by PSO, and lowest in mPSO under all conditions. The maximum pressure on the intervertebral discs is located between T10 and T11.

Conclusion

The finite element analysis showed that mPSO has a similar spine stability to PSO, and possibly creates a better environment for bone-to-bone fusion and prevents adjacent segments degeneration. Combined with its less surgical risks, we believe that the modified pedicle subtraction osteotomy may be an appropriate strategy for indicated cases of OVCF.
T-cadherin modulates adipogenic differentiation in mesenchymal stem cells: insights into ligand interactions
Authors: Sysoeva Veronika , Semina Ekaterina , Klimovich Polina , Kulebyakin Konstantin , Dzreyan Valentina , Sotskaya Ekaterina , Shchipova Anna , Popov Vladimir , Shilova Alena , Brodsky Ilya , Khabibullin Nikita , Voloshin Nikita , Tkachuk Vsevolod , Rubina Kseniya
Published: December 2024

Introduction

T-cadherin, a non-canonical member of the cadherin superfamily, was initially identified for its involvement in homophilic recognition within the nervous and vascular systems. Apart from its adhesive function, T-cadherin acts as a receptor for two ligands: LDL, contributing to atherogenic processes, and HMW adiponectin, a hormone with well-known cardiovascular protective properties. However, the precise role of T-cadherin in adipose tissue remains elusive. Previously, we generated Cdh13∆Exon3 mice lacking exon 3 in the Cdh13 gene, which encodes the T-cadherin protein, and characterized their phenotype.

Methods

Using wild-type (WT) and T-cadherin-deficient mice (Cdh13ΔExon3), we isolated and cultured mesenchymal stem cells to explore the role of T-cadherin in adipogenic differentiation. The experimental approaches employed include culturing cells under standard or adipogenic conditions, performing Oil Red O and Nile Red staining followed by quantitative analysis, conducting rescue experiments to reintroduce T-cadherin using lentiviral constructs in T-cadherin-deficient cells combined with automated adipocyte differentiation quantification via a neural network. Additionally, Western blotting, ELISA assays, and statistical analysis were utilized to verify the results.

Results

In this study, we demonstrate for the first time that T-cadherin influences the adipogenic differentiation of MSCs. The presence of T-cadherin dictates distinct morphological characteristics in MSCs. Lack of T-cadherin leads to spontaneous differentiation into adipocytes with the formation of large lipid droplets. T-cadherin-deficient cells (T−/− MSCs) exhibit an enhanced adipogenic potential upon induction with differentiating factors. Western Blot, ELISA assays, and rescue experiments collectively corroborate the conclusion that T−/− MSCs are predisposed toward adipogenic differentiation. We carried out an original comparative analysis to explore the effects of T-cadherin ligands on lipid droplet accumulation. LDL stimulate adipogenic differentiation, while T-cadherin expression mitigates the impact of LDL on lipid droplet accumulation. We also examined the effects of both low molecular weight (LMW) and high molecular weight (HMW) adiponectin on lipid droplet accumulation relative to T-cadherin. LMW adiponectin suppressed lipid droplet accumulation independently of T-cadherin, while the absence of T-cadherin enhanced susceptibility to the suppressive effects of HMW adiponectin on adipogenesis.

Discussion

These findings shed light on the role of T-cadherin in adipogenic differentiation and suggest an interplay with other receptors, such as LDLR and AdipoRs, wherein downstream signaling may be modulated through lateral interactions with T-cadherin.
Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies
Authors: Yu Fei , Zhu Yue , Li Shenghao , Hao Liyuan , Li Na , Ye Fanghang , Jiang Zhi , Hu Xiaoyu
Published: December 2024

In the context of chronic hepatitis B virus (HBV) infection, the continuous replication of HBV within host hepatocytes is a characteristic feature. Rather than directly causing hepatocyte destruction, this replication leads to immune dysfunction and establishes a state of T-B immune tolerance. Successful clearance of the HBV virus is dependent on the close collaboration between humoral and cellular immunity. Humoral immunity, mediated by B-cell subpopulations, and cellular immunity, dominated by T-cell subpopulations show varying degrees of dysfunction during chronic hepatitis B (CHB). Notably, not all T- and B-cells produce positive immune responses. This review examine the most recent developments in the mutual regulation of T-B cells during chronic HBV infection. Our focus is on the prevailing immunotherapeutic strategies, such as T cell engineering, HBV-related vaccines, PD-1 inhibitors, and Toll-like receptor agonists. While nucleos(t)ide analogues (NUCs) and interferons have notable limitations, including inadequate viral suppression, drug resistance, and adverse reactions, several HBV entry inhibitors have shown promising clinical efficacy. To overcome the challenges posed by NUCs or monotherapy, the combination of immunotherapy and novel antiviral agents presents a promising avenue for future CHB treatment and potential cure.
Patients’ suggestions for improvements to text-based e-consultations. An online survey of users of the national health portal in Norway
Authors: Kristiansen Eli , Atherton Helen , Bergmo Trine Strand , Zanaboni Paolo
Published: December 2024

Background

In recent years, text-based e-consultations have been widely implemented in general practice and are appreciated by patients for their convenience and efficiency. Policymakers aim to enhance patient access to clinical services with the general practitioner (GP) through text-based e-consultations. However, concerns are raised about their efficiency and security. We aimed to investigate users’ perceptions of potential improvements in the text-based e-consultation service provided by the national health portal in Norway.

Method

We conducted an online survey among users of text-based e-consultations with the GP on the national health portal Helsenorge. The survey was available from January-February 2023 and consisted of 20 questions. This study focused on the free-text answers to the question “Do you have any suggestions to improve the service?” The framework method was used for a thematic analysis of the answers.

Results

The analysis of 2,954 free-text answers from users of the national e-consultation service resulted in six areas where suggestions for improvement were expressed. According to users, the service would benefit from: (1) a better set-up to facilitate the formulation of the patient's problem, (2) better value for money (in regards to both price and quality), (3) faster response time, (4) improved information and predictability about the status of the e-consultation (e.g., if it is received and when to expect an answer), (5) improvement in technical issues, and (6) improvement of access to dialogue-based services to replace or complement e-consultations.

Conclusion

The analysis of users’ suggestions for improvements to the e-consultation service emphasised the need to customise the service to address individual patient needs. Users found a one-size-fits-all approach with mandatory questions, fixed pricing, and inflexible response times less appreciated. Some also felt forced to rely on e-consultations due to the perceived poor availability of other GP services. This highlights the importance of perceiving e-consultations not as a replacement for dialogue-enabled services, but rather as a potentially efficient addition, ensuring a well-tailored setup for appropriate patient use.
Methane emission reduction through hydrogen blending in a large bore 2-stroke lean-burn natural gas compressor engine
Authors: Vieira Greg , Lorenzen Rachel , Patterson Mark , Olsen Daniel
Published: December 2024

Impending and increasingly stringent emissions regulations regarding natural gas compressor engines drive the research behind blending hydrogen with natural gas to make these internal combustion engines and their combustion process more efficient. This investigation seeks to answer two fundamental questions: will blending hydrogen with natural gas reduce overall engine fuel consumption, and can greenhouse gas emissions be reduced by blending hydrogen with natural gas? A 4-cylinder Cooper–Bessemer GMV engine, housed at Colorado State University’s Powerhouse facility, was investigated for hydrogen–natural gas blending using multiple engine configurations. A lean-burn engine uses an active pre-combustion chamber as its ignition source, along with electronically activated high pressure fuel injection in the main combustion chamber. One configuration tested utilized high-pressure fuel injection and blending in hydrogen, up to 40% by volume, in both the main chamber and pre-combustion chamber fuel supplies. A second configuration, where the main combustion chamber fuel was solely natural gas and only the pre-combustion chamber received hydrogen-blended natural gas, was also tested. The final configuration to be tested used low pressure fuel injection with mechanically actuated valves in the main chamber with a traditional spark plug ignition source. All engine configurations saw reductions in methane emissions of up to 30% using blended natural gas and hydrogen. Carbon dioxide emissions were also shown to be reduced for the two configurations. A reduction in brake-specific fuel consumption of up to 2% was also seen for two configurations. These results support the hypothesis that blending hydrogen into natural gas can reduce engine total fuel consumption and reduce greenhouse gas emissions.
Exploration of the pathogenesis of nephrotic syndrome and traditional Chinese medicine intervention based on gut microbiota
Authors: Li Jing , Xu Yupei , Sun Tianhao , Zhang Xiaotian , Liang Huimin , Lin Wei , Yu Hangxing , Yang Bo , Yang Hongtao
Published: December 2024

Nephrotic syndrome (NS) represents a prevalent syndrome among various chronic kidney disease pathologies and is known for its higher severity and worse prognosis compared with chronic glomerulonephritis. Understanding its pathogenesis and identifying more effective treatment modalities have long been a concern of kidney specialists. With the introduction of the gut–kidney axis concept and the progress in omics technologies, alterations in the gut microbiota have been observed in primary and secondary NS. This link has been extensively researched in conditions such as diabetic nephropathy and immunoglobulin A (IgA) nephropathy. Thus, dysbiosis of the gut microbiota is seen as a crucial contributing factor in NS; however, there is a lack of comprehensive reviews that elucidate the changes in the gut microbiota across different NS conditions and that describe its mechanistic role in the disease. Moreover, serving as an innate regulator of the gut microbiota, traditional Chinese medicine (TCM) has the potential to exert a profound impact on the expression of inflammation-promoting agents, decreasing the levels of endotoxins and uremic toxins. In addition, it strengthens the stability of the intestinal barrier while controlling the metabolic function of the body through its efficient modulation of the gut microbiota. This intricate process yields far-reaching consequences for NS.
Long non-coding RNAs are involved in the crosstalk between cancer-associated fibroblasts and tumor cells
Authors: Yang Chenbo , Shu Jiao , Li Yiwei , Zhao Na , Liu Xiaonan , Tian Xiangyu , Sun Zexin , Tabish Muhammad Saud , Hong Yichen , Chen Kuisheng , Sun Miaomiao
Published: December 2024

The proliferation of tumors is not merely self-regulated by the cancer cells but is also intrinsically connected to the tumor microenvironment (TME). Within this complex TME, cancer-associated fibroblasts (CAFs) are pivotal in the modulation of tumor onset and progression. Rich signaling interactions exist between CAFs and tumor cells, which are crucial for tumor regulation. Long non-coding RNAs (LncRNAs) emerge from cellular transcription as a class of functionally diverse RNA molecules. Recent studies have revealed that LncRNAs are integral to the crosstalk between CAFs and tumor cells, with the capacity to modify cellular transcriptional activity and secretion profiles, thus facilitating CAFs activation, tumor proliferation, metastasis, drug resistance, and other related functionalities. This comprehensive review revisits the latest research on LncRNA-mediated interactions between CAFs and tumor cells, encapsulates the biological roles of LncRNAs, and delves into the molecular pathways from a broader perspective, aspiring to offer novel perspectives for a deeper comprehension of the etiology of tumors and the enhancement of therapeutic approaches.
MS4A superfamily molecules in tumors, Alzheimer’s and autoimmune diseases
Authors: Luo Xuejiao , Luo Bin , Fei Lei , Zhang Qinggao , Liang Xinyu , Chen Yongwen , Zhou Xueqin
Published: December 2024

MS4A (membrane-spanning 4-domain, subfamily A) molecules are categorized into tetraspanins, which possess four-transmembrane structures. To date, eighteen MS4A members have been identified in humans, whereas twenty-three different molecules have been identified in mice. MS4A proteins are selectively expressed on the surfaces of various immune cells, such as B cells (MS4A1), mast cells (MS4A2), macrophages (MS4A4A), Foxp3+CD4+ regulatory T cells (MS4A4B), and type 3 innate lymphoid cells (TMEM176A and TMEM176B). Early research confirmed that most MS4A molecules function as ion channels that regulate the transport of calcium ions. Recent studies have revealed that some MS4A proteins also function as chaperones that interact with various immune molecules, such as pattern recognition receptors and/or immunoglobulin receptors, to form immune complexes and transmit downstream signals, leading to cell activation, growth, and development. Evidence from preclinical animal models and human genetic studies suggests that the MS4A superfamily plays critical roles in the pathogenesis of various diseases, including cancer, infection, allergies, neurodegenerative diseases and autoimmune diseases. We review recent progress in this field and focus on elucidating the molecular mechanisms by which different MS4A molecules regulate the progression of tumors, Alzheimer’s disease, and autoimmune diseases. Therefore, in-depth research into MS4A superfamily members may clarify their ability to act as candidate biomarkers and therapeutic targets for these diseases. Eighteen distinct members of the MS4A (membrane-spanning four-domain subfamily A) superfamily of four-transmembrane proteins have been identified in humans, whereas the MS4A genes are translated into twenty-three different molecules in mice. These proteins are selectively expressed on the surface of various immune cells, such as B cells (MS4A1), macrophages (MS4A4A), mast cells (MS4A2), Foxp3+CD4+ regulatory T cells (MS4A4B), type 3 innate lymphoid cells (TMEM176A and TMEM176B) and colonic epithelial cells (MS4A12). Functionally, most MS4A molecules function as ion channels that regulate the flow of calcium ions [Ca2+] across cell membranes. Recent studies have revealed that some MS4A proteins also act as molecular chaperones and interact with various types of immune receptors, including pattern recognition receptors (PRRs) and immunoglobulin receptors (IgRs), to form signaling complexes, thereby modulating intracellular signaling and cellular activity. Evidence from preclinical animal models and human genetic studies suggests that MS4A proteins play critical roles in various diseases (2). Therefore, we reviewed the recent progress in understanding the role of the MS4A superfamily in diseases, particularly in elucidating its function as a candidate biomarker and therapeutic target for cancer.
Intraspecific phenotypic differentiation by habitat depth in deep demersal fish species
Authors: Steeds Natasha , Zulqurnain Zulqurnain , Regnier Thomas , Gibb Fiona , Stirling David , Hoelzel A. Rus
Published: December 2024

Introduction

Ocean habitat characteristics change with depth. This is due to physical properties such as light, temperature and hydrostatic pressure, but also species community. In some cases, this generates a boundary (e.g. when light is lost in the bathypelagic), and in others it varies continuously (e.g. for hydrostatic pressure). Various studies have noted general morphometric adaptations to living at different depths seen among species, even though vertical migration can cause their ranges to overlap. However, few have looked at intraspecific changes.

Methods

Here we investigate intraspecific variation for four species of demersal fish that inhabit a broad range of depths (200 m to over 2000 m). We test the hypothesis that intraspecific morphological variation will be similar to that seen among species.

Results

We find that there are significant phenotypic differences between fish taken at different habitat depths, especially associated with mouth gape size, eye size, body shape and organ mass, despite the potential for vertical migration. However, we find that these patterns vary among species.

Discussion

We consider the possible drivers and implications for maintaining intraspecific phenotypic differences.
A model of co-creation: strengthening primary health care (PHC) in Ghana through an innovative “Nyansapo” partnership
Authors: Acheampong Princess Ruhama , Kulasegaram Kulamakan , Mensah Kofi Akohene , Ndiaye Marie-Therese , Owusu-Ansah Wilberforce , Owusu-Dabo Ellis , Owusu Joseph , Rodas Jamie , Rouleau Katherine , Wilson Jennifer , Wilson Olivia
Published: December 2024

The Africa Health Collaborative (AHC) initiative embarked on a transformative ten-year collaboration with Kwame Nkrumah University of Science and Technology (KNUST) and the University of Toronto (U of T) to co-create continuing education programs geared toward augmenting the proficiency of primary care practitioners in Ghana. While upholding core principles within the AHC framework, emphasizing respect, inclusivity, equity, reciprocity, ethics, dynamism, and stewardship, seven teams of U of T and KNUST faculty engaged in collaborative efforts to design, administer, and evaluate five in-person “short courses” in Ghana on Palliative Care, Quality Improvement for Health Professionals, Prehospital Emergency Care, Community Emergency Care, and Emergency Preparedness and Response to Epidemic-Prone Diseases to approximately 100 Ghanaian primary care professionals. This paper describes a model of co-creation, highlights lessons learned from a robust evaluation process, and proposes that this co-creation model can strengthen primary health care in Ghana and ultimately transform health systems in Africa.
Conjunctival ultraviolet autofluorescence as a biomarker of outdoor time in myopic children
Authors: de la Puente Miriam , Bilbao-Malavé Valentina , González-Zamora Jorge , Claici Aura Ortega , Bezunartea Jaione , Gomez-Arteta Leire , Alonso Elena , Hernández María , Fernández-Robredo Patricia , de Viteri Manuel Sáenz , Calvo Nerea Martín , García-Layana Alfredo , Barrio-Barrio Jesús , Recalde Sergio
Published: December 2024

Introduction

The prevalence of myopia has increased significantly in recent years including an earlier onset of myopia development on the pediatric population. The main objective of the study is to compare CUVAF (Conjunctival Ultraviolet Autofluorescence) in children with and without myopia to validate its usefulness as an outdoor protective biomarker.

Methods

A case–control observational study was conducted in a child cohort from subjects that attended to the Ophthalmology Department of Clínica Universidad de Navarra for an ophthalmological examination. The general exclusion criteria were (among others): amblyopia, congenital myopia, general ophthalmic disease, and any conjunctival alteration that might difficult the measurement of the CUVAF area. All participants underwent an automatic objective refraction under cycloplegic effect, biometry to measure axial length (AL) and central corneal radius (CCR), and completed a questionnaire about their lifestyle habits. A total of 4 images of the bulbar conjunctiva were taken with blue light in order to quantify the CUVAF area.

Results

A total of 263 subjects (6 to 17 years old) were analyzed with no significant differences in demographic data between case group and control group. There were 50 non-myopic subjects (19%) and 213 myopic subjects (81%). In relation to the outdoor activities (OA), myopic subjects spent significantly fewer hours per week outdoors than the control-group (p = 0.03). About the CUVAF area, the differences between groups were statistically significant, showing that the myopic group has a significantly smaller CUVAF area than the control-group (0.33 ± 0.72 mm2 vs. 0.78 ± 1.22 mm2; p = 0.0023), likewise, the frequency of CUVAF area absence between both groups showed an odds ratio (OR) of 2.52 (CI95% 1.33–4.74). A Pearson correlation test was done, obtaining a strong significant inverse correlation between myopia degree-CUVAF area (r = 0.1877; IC95% 0.068–0.302), and also ratio (AL/CCR)-CUVAF area (p = 0.002 and p = 0.04) respectively.

Conclusion

CUVAF is a useful biomarker for OA and it has an inverse relationship with myopia degree also in pediatric age, especially after the age of 12, so it could be useful to differentiate the risk of developing myopia. Having a CUVAF area greater than that corresponding to age, protect to myopia 2.5 times, being almost 5 times the protection in case of high myopia.
High activity and specificity of bacteriophage cocktails against carbapenem-resistant Klebsiella pneumoniae belonging to the high-risk clones CG258 and ST307
Authors: Tellez-Carrasquilla Sara , Salazar-Ospina Lorena , Jiménez J. Natalia
Published: December 2024

Introduction

The widespread clinical and environmental dissemination of successful clones of carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a serious global public health threat. In this context, lytic bacteriophages have emerged as a promising alternative for controlling these pathogens. This study describes the biological, structural, and genomic characteristics of lytic bacteriophages against the high-risk CRKP clones CG258 and ST307 and describes their performance in combination.

Methods

An experimental study was carried out. Bacteriophages were isolated from hospital wastewater and from wastewater treatment plants (WWTP). Bacteriophages were isolated using the double layer agar technique and their characterization included host range (individual and cocktail), plating efficiency (EOP), infection or bacterial killing curve, one-step curve, bacteriophage stability at pH and temperature conditions, transmission electron microscopy (TEM) and whole genome sequencing.

Results

After purification, five active bacteriophages against CRKP were obtained, three bacteriophages (FKP3, FKP4 and FKP14) had targeted activities against CG258 CRKP and two (FKP10 and FKP12) against ST307 isolates. Seven cocktails were prepared, of which Cocktail 2, made up of the bacteriophages FKP3, FKP10, and FKP14, showed the best activity against 85.7% (n = 36/42) of CRKP isolates belonging to both clones, CG258 (80.8%; n = 21/26) and ST307 (93.8%, n = 15/16). The efficiency of the plating (EOP), infection curve, and one-step growth curve showed that the cocktail phages efficiently infected other CRKP isolates (EOP ≥ 0.5), controlled bacterial growth up to 73.5%, and had short latency periods, respectively, (5–10 min). In addition, they were stable at temperatures between 4°C and 50°C and pH between 4 and 10. All bacteriophages belonged to the Caudoviricetes class, and no genes associated with virulence factors or antibiotic resistance were detected.

Conclusion

These findings showed bacteriophages and phage cocktails with high specificity against CRKP belonging to the successful clones CG258 and ST307 with promising characteristics, making them an alternative for controlling these clones in different environmental or health settings, biocontrol agents, or disinfectants in industry and in the field of diagnosis.
Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation
Authors: Wang Yaxin , Wang Qingyun , Ren Hanyun , Dong Yujun , Wang Qingya , Liang Zeyin , Yin Yue , Liu Wei , Xu Weilin , Han Na , Li Yuan
Published: December 2024

Introduction

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.

Methods

To evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).

Results

The median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).

Conclusions

This retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.
Comprehensive analysis of IRF8-related genes and immune characteristics in lupus nephritis
Authors: Yu Zhibin , Zheng Chenghui , Wang Yilun
Published: December 2024

Background

There are currently no reliable diagnostic biomarkers or treatments for lupus nephritis (LN), a complication of systemic lupus erythematosus. Objective: We aimed to explore gene networks and potential biomarkers for LN by analyzing the GSE32591 and GSE113342 datasets from the Gene Expression Omnibus database, focusing on IRF8 and IRF8-related genes.

Methods

We used differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and the CIBERSORT algorithm for immune infiltration assessment. To validate the expression levels of the IRF8 gene in the kidneys of lupus mice models, we used quantitative real-time PCR (qRT-PCR) and Western blotting (WB). A diagnostic classifier was built using the RandomForest method to evaluate the diagnostic potential of selected key genes. To bridge our findings with potential therapeutic implications, we used the drug-gene interaction database to predict drugs targeting the identified genes.

Results

Twenty co-differentially expressed genes (DEGs) were identified, with IRF8 exhibiting significant expression differences and potential as a biomarker. Functional enrichment analysis revealed pathways associated with immune response. Validation through qRT-PCR and WB confirmed that the IRF8 gene and its protein exhibited elevated expression levels in the kidneys of lupus mice compared to control groups. The diagnostic classifier revealed impressive accuracy in differentiating LN from control samples, achieving a notable area under the curve values across various datasets. Additionally, immune infiltration analysis indicated significant differences in the immune cell profiles between the LN and control groups.

Conclusion

IRF8 and its related genes show promise as biomarkers and therapeutic targets for LN. These findings contribute to a deeper understanding of the molecular mechanisms involved in LN and may support the development of precision medicine strategies for improved patient outcomes.
Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis
Authors: Jiang Zhangyu , Yan Mingjuan , Qin Yanmi , Liu Zhenglin , Duan Yilin , Wang Yingju , Zhang Ruisen , Lin Wenjia , Li Yanwu , Xie Tian , Ke Junyu
Published: December 2024

Introduction

Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.

Methods

A comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.

Results

Network analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.

Discussion

The ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.
A prospective, self-controlled study of sub-plateau heart rate variability in healthy adults
Authors: Ye Xianglin , Liu Hao , Yang Haixia , Zhang Hongyang , Gong Meiting , Duan Zhen , Fu Yan , Xiong Shiqiang , Dan Xiaoping , Pei Haifeng
Published: December 2024

Background

The low-pressure, hypoxic environment characteristic of high-altitude regions significantly affects the cardiovascular and autonomic nervous system functions of individuals, consequently impairing their sleep quality. Heart rate variability, a non-invasive indicator of autonomic nervous system activity and balance within the cardiovascular system, has not been thoroughly investigated in terms of its patterns during acclimatization and de-acclimatization phases for individuals traveling to and residing in high-altitude areas and its relationship with sleep stability.

Methods

Data was collected from 22 medical staff members who traveled from Chengdu to Yecheng, with measurements taken before leaving Chengdu, 1 week in Yecheng, 3 months in Yecheng, and 1 week after returning to Chengdu. The study analyzed changes in heart rate variability during acclimatization and de-acclimatization at 1,400 m above sea level. It also examined arrhythmia and sleep disorders based on circadian groups.

Results

1. Following 1 week of acclimatization to the sub-plateau environment of Yecheng, significant decreases were observed in SDANN, SDNN and SD2 indices compared to departure from Chengdu (P < 0.05). After 3 months of sub-plateau acclimatization, these indices significantly increased (P < 0.05). Upon returning to Chengdu and undergoing de-acclimatization for 1 week, these indices further significantly increased (P < 0.05). 2. During the period of sub-plateau acclimatization and de-acclimatization, significant changes were noted in average heart rate and minimum heart rate (P < 0.05), with the average heart rate showing a continuous decrease and the minimum heart rate exhibiting an initial increase followed by a decrease. No significant changes were observed in maximum heart rate or the incidence of arrhythmias (P > 0.05). 3. When stratified by day and night, the trends for SDANN, RMSSD, and TP were consistent with the overall trend at night (P < 0.05), but opposite during the day (P < 0.05). 4. During the sub-plateau acclimatization period, stable sleep duration was significantly reduced, and increased markedly after de-acclimatization, although it did not return to pre-acclimatization levels (P < 0.05).

Conclusion

Acclimatization to the sub-plateau environment of Yecheng affects the autonomic nervous system, heart rate, and sleep in healthy adults. De-acclimatization can ameliorate these effects. Furthermore, the impact of sub-plateau acclimatization on the autonomic nervous system exhibits a distinct circadian rhythmicity.
BRA-YOLOv7: improvements on large leaf disease object detection using FasterNet and dual-level routing attention in YOLOv7
Authors: Ye Rong , Gao Quan , Li Tong
Published: December 2024

Tea leaf diseases are significant causes of reduced quality and yield in tea production. In the Yunnan region, where the climate is suitable for tea cultivation, tea leaf diseases are small, scattered, and vary in scale, making their detection challenging due to complex backgrounds and issues such as occlusion, overlap, and lighting variations. Existing object detection models often struggle to achieve high accuracy in detecting tea leaf diseases. To address these challenges, this paper proposes a tea leaf disease detection model, BRA-YOLOv7, which combines a dual-level routing dynamic sparse attention mechanism for fast identification of tea leaf diseases in complex scenarios. BRA-YOLOv7 incorporates PConv and FasterNet as replacements for the original network structure of YOLOv7, reducing the number of floating-point operations and improving efficiency. In the Neck layer, a dual-level routing dynamic sparse attention mechanism is introduced to enable flexible computation allocation and content awareness, enhancing the model’s ability to capture global information about tea leaf diseases. Finally, the loss function is replaced with MPDIoU to enhance target localization accuracy and reduce false detection cases. Experiments and analysis were conducted on a collected dataset using the Faster R-CNN, YOLOv6, and YOLOv7 models, with Mean Average Precision (mAP), Floating-point Operations (FLOPs), and Frames Per Second (FPS) as evaluation metrics for accuracy and efficiency. The experimental results show that the improved algorithm achieved a 4.8% improvement in recognition accuracy, a 5.3% improvement in recall rate, a 5% improvement in balance score, and a 2.6% improvement in mAP compared to the traditional YOLOv7 algorithm. Furthermore, in external validation, the floating-point operation count decreased by 1.4G, FPS improved by 5.52%, and mAP increased by 2.4%. In conclusion, the improved YOLOv7 model demonstrates remarkable results in terms of parameter quantity, floating-point operation count, model size, and convergence time. It provides efficient lossless identification while balancing recognition accuracy, real-time performance, and model robustness. This has significant implications for adopting targeted preventive measures against tea leaf diseases in the future.
Signaling pathways mediating the induction of preharvest fruit drop in litchi
Authors: Wang Jun , Ma Wuqiang , Wang Fei , He Zidi , Ye Xiangyang , Deng Jiahui , Zhao Minglei , Li Jianguo
Published: December 2024

Certain litchi varieties, such as “Nuomici”, are highly susceptible to preharvest fruit drop, which leads to significant losses in fruit yield and economic value. However, the precise molecular mechanisms underlying this issue are not yet fully understood. In this study, we aimed to elucidate the signaling pathways that facilitate preharvest fruit drop in litchi, using “Nuomici” and “Huaizhi” cultivars as examples, which demonstrate high and low preharvest fruit drop rates, respectively. Our findings revealed that “Nuomici” experienced a substantial preharvest fruit drop, with a cumulative rate of 41.68%, significantly higher than the 1.44% observed in “Huaizhi”. Cellulase activity assays showed a significant increase in cellulase activity in the abscission zone of “Nuomici”, which coincided with the occurrence of preharvest fruit drop, in contrast to the relatively low levels in “Huaizhi”. Phytohormone assays indicated lower indole-3-acetic acid content in the pericarp, aril, and seeds of “Nuomici” during the preharvest stage compared to “Huaizhi”, coupled with higher abscisic acid levels in the seeds of “Nuomici”. Furthermore, transcriptomic analysis identified 180, 282, 655, and 241 differentially expressed genes (DEGs) in the pericarp, aril, seed, and abscission zone, respectively, between the two cultivars during preharvest fruit drop. These DEGs are intricately involved in the generation and transmission of abscission signals from fruit tissues, encompassing PIN, PIN-LIKES, LAX, and SAUR genes related to polar auxin transport, ethylene diffusion, as well as perceiving these signals and activating the abscission process within the abscission zone. This includes ACO and ILR genes involved in hormone biosynthesis and signal transduction, regulation by WRKY, NAC, and bHLH transcription factors, AAO genes involved in response to reactive oxygen species, and EXP, EG, and PG genes involved in cell wall degradation in the abscission zone. Based on these comprehensive findings, we propose a model for preharvest fruit drop triggered by a series of molecular events in litchi, providing valuable insights into the complex mechanisms governing this phenomenon.
Alinéa suicide postvention program: a codesigned early proactive intervention for survivors
Authors: Coquelin Mélanie , Kopp-Bigault Céline , Barinoil Canelle , Berrouiguet Sofian , Guarnaccia Cinzia
Published: December 2024

Background

Bereavement following suicide is a risk factor for major depression, post-traumatic stress disorder, suicidal behavior, the emergence of bipolar disorders and prolonged mourning. The scientific literature agrees on the need to deploy support services tailored to the specificities of post-suicide bereavement. Alinéa responds to these specificities with an early and proactive individual postvention program.

Method

This article presents the process of co-designing Alinéa by involving participants who have been exposed to suicide either through the loss of a loved one or in the course of their work. This co-design led to the creation of a collaborative system for early, proactive professional intervention. The Alinéa program, design intervention objectives and protocol, are presented in this article.

Discussion

The Alinéa system is committed to research and is developing different types of research: evaluative research, fundamental research and action research.
A boundedly rational model for category learning
Authors: Houser Troy M.
Published: December 2024

The computational modeling of category learning is typically evaluated in terms of the model's accuracy. For a model to accurately infer category membership of stimuli, it has to have sufficient representational precision. Thus, many category learning models infer category representations that guide decision-making and the model's fitness is evaluated by its ability to accurately choose. Substantial decision-making research, however, indicates that noise plays an important role. Specifically, noisy representations are assumed to introduce an element of stochasticity to decision-making. Noise can be minimized at the cost of cognitive resource expenditure. Thus, a more biologically plausible model of category learning should balance representational precision with costs. Here, we tested an autoencoder model that learns categories (the six category structures introduced by Roger Shepard and colleagues) by balancing the minimization of error with minimization of resource usage. By incorporating the goal of reducing category complexity, the currently proposed model biases category decisions toward previously learned central tendencies. We show that this model is still able to account for category learning performance in a traditional category learning benchmark. The currently proposed model additionally makes some novel predictions about category learning that future studies can test empirically. The goal of this paper is to make progress toward development of an ecologically and neurobiologically plausible model of category learning that can guide future studies and theoretical frameworks.
The use of combined cognitive training and non-invasive brain stimulation to modulate impulsivity in adult populations: a systematic review and meta-analysis of existing studies
Authors: Khalifa Najat R. , Alabdulhadi Yousef , Vazquez Pilar , Wun Charlotte , Zhang Peng
Published: December 2024

Introduction

Impulsivity, a tendency to act rashly and without forethought, is a core feature of many mental disorders that has been implicated in suicidality and offending behaviours. While research supports the use of non-invasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS), to modulate brain functions, no studies specifically reviewed the use of combined cognitive training and NIBS to modulate impulsivity.

Methods

We aimed to conduct a systematic review and meta-analysis to synthesise the literature on the use of combined cognitive training and NIBS to modulate impulsivity and its subdomains (motor, delay discounting, reflection). We searched Scopus, PsychInfo, Medline, and Cinahl electronic databases, dissertations database, and Google scholar up to September 2024.

Results

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four randomised controlled studies involving the use of combined cognitive training and tDCS in 127 subjects were included in the study. These studies included subjects with substance use disorders, obesity, and Parkinson’s disease. Meta-analysis showed that combined cognitive training and tDCS had no statistically significant effects on motor impulsivity as measured using reaction times on the Stop Signal Task and Go/No Go tasks. One study that measured impulsiveness scores on a delay discounting task also showed no significant results. No studies measured reflection or cognitive impulsivity.

Discussion

There is a dearth of literature on the use of combined cognitive training and NIBS for impulsivity. This in conjunction of clinical heterogeneity across studies makes it difficult to draw definitive conclusions about the neuromodulation of impulsivity and its subdomains using combined cognitive training and NIBS. The findings of this study highlight the need to conduct more studies in the field.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD 42024511576.