bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Familial hypocalciuric hypercalcemia type 1 with a novel mutation combined with Gitelman syndrome and a review of the literature
Authors: He Taoyuan , Li Xinyu , Li Guosheng , Wang Wanyang , Fu Hongjun , Gao Zhengnan , Liu Xuhan
Published: February 2025

Introduction

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder caused by an inactivating mutation in the CASR gene, while Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder resulting from a pathogenic mutation in the SLC12A3 gene. Both genetic disorders are relatively rare. This report presents a patient with both FHH and GS, exhibiting unique clinical and genetic complexities.

Case summary

We report a case of a 69-year-old Asian female patient who had previously presented to the hospital on multiple occasions with complaints of joint stiffness, fatigue, dizziness, or other symptoms. The patient was readmitted to the hospital at the age of 66, presenting with the following clinical findings: hypocalciuria, hypercalcemia, normal or mildly elevated parathyroid hormone (PTH) levels, hypokalemia, hypomagnesemia, hypophosphatemia, normal blood pressure, chondrocalcinosis (CC), and diabetes mellitus. Our careful analysis suggested that the patient might have the co-occurrence of GS and FHH. Genetic testing revealed a novel heterozygous CASR p.Tyr161* mutation and a homozygous SLC12A3 p.Thr60Met mutation, which ultimately confirmed the diagnosis of familial hypocalciuric hypercalcemia type 1 (FHH1) combined with GS.

Conclusion

For the first time, we report a case of FHH combined with GS. The novel CASR mutation in this patient expands the variant spectrum of FHH, provides new genetic evidence for its pathogenesis, and underscores the importance of genetic counseling for consanguineous families. This case also suggests a potential association between FHH and CC, the mechanism of which warrants further investigation. In addition, this report highlights possible potential interactions between FHH and GS. Clinically, hypokalemia and hypomagnesemia associated with GS are more detrimental than hypercalcemia linked to FHH and should be prioritized in management. Finally, genetic testing and molecular diagnostics are crucial for pediatric and adolescent populations with FHH and/or GS, and further studies are needed to clarify the genotypic and phenotypic relationships between FHH and GS comorbidities.
Diabetes mediates an inverted L-shaped association between cardiometabolic index and kidney stones: a cross-sectional study from NHANES 2007-2020
Authors: Bi Jinghui , Du Jianwei , Yan Xiaoyi , Chen Rongxin
Published: February 2025

Background

Kidney stones are a chronic metabolic disorder. The cardiometabolic index (CMI) is a new and easily accessible measure used to assess metabolic status. However, the relationship between CMI and the incidence of kidney stones remains unclear.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) was used in our cross-sectional study. A weighted multivariable logistic regression analysis was conducted to assess the relationship between CMI and kidney stone incidence. Subgroup and restricted cubic spline regression analyses were utilized to confirm robustness and assess the non-linearity of the association between CMI and kidney stone incidence.

Results

This study involved 18,043 individuals, of whom 9.89% were diagnosed with kidney stones. After controlling for all covariates, CMI showed a significant positive association with kidney stone incidence (OR: 1.07, 95%CI: 1.02-1.12). Individuals in the highest CMI quartile experienced a 50% higher incidence of kidney stones than those in the lowest quartile (OR: 1.50, 95%CI: 1.18-1.92). Additionally, a significant interaction was observed in the subgroup with a history of diabetes (p < 0.05).

Conclusion

The study identified a notable non-linear relationship between elevated CMI levels and a greater occurrence of kidney stones. This finding suggests that by routinely monitoring CMI levels, physicians can identify individuals at risk for kidney stones early, allowing for timely intervention to mitigate disease progression.
Relationship between systemic inflammatory response index and bone mineral density in children and adolescents aged 8-19 years: a cross-sectional study based on NHANES 2011-2016
Authors: Cun Dejun , Yang Nan , Zhou Lin , Zeng Wenxing , Chen Bin , Pan Zichen , Feng Huang , Jiang Ziwei
Published: February 2025

Objective

This study aims to investigate the relationship between the Systemic Inflammatory Response Index (SIRI) and bone mineral density (BMD) in children and adolescents aged 8-19 years.

Methods

A cross-sectional design was used, utilizing NHANES data from 2011-2016, including 3,205 participants aged 8 to 19 years. Weighted multivariable regression analysis was conducted to assess the association between SIRI and BMD at the lumbar spine, pelvis, trunk, and whole body. Additionally, smooth curve fitting was applied to examine the nonlinear relationship between SIRI and BMD, and subgroup analyses were performed to explore potential interaction effects and modifiers.

Results

SIRI was significantly positively correlated with BMD at the pelvis, trunk, and whole body (p < 0.05). After adjusting for covariates, a one-unit increase in ln(SIRI) was associated with increases in BMD of 0.018 g/cm², 0.006 g/cm², and 0.005 g/cm² for the pelvis, trunk, and whole body, respectively. Nonlinear analysis revealed a saturation effect between ln(SIRI) and BMD, with a more pronounced impact at specific threshold values. Subgroup analysis indicated that gender, age, BMI and total calcium levels modulated the relationship between SIRI and BMD.

Conclusion

SIRI is significantly associated with BMD in children and adolescents, with a positive effect on BMD at specific threshold levels. This finding suggests that SIRI may serve as a potential biomarker for assessing the risk of low bone mineral density, offering theoretical support for the prevention and intervention of bone health issues such as osteoporosis.
CRISPR-mediated genome editing of wheat for enhancing disease resistance
Authors: Waites Joshua , Achary V. Mohan Murali , Syombua Easter D. , Hearne Sarah J. , Bandyopadhyay Anindya
Published: February 2025

Wheat is cultivated across diverse global environments, and its productivity is significantly impacted by various biotic stresses, most importantly but not limited to rust diseases, Fusarium head blight, wheat blast, and powdery mildew. The genetic diversity of modern cultivars has been eroded by domestication and selection, increasing their vulnerability to biotic stress due to uniformity. The rapid spread of new highly virulent and aggressive pathogen strains has exacerbated this situation. Three strategies can be used for enhancing disease resistance through genome editing: introducing resistance (R) gene-mediated resistance, engineering nucleotide-binding leucine-rich repeat receptors (NLRs), and manipulating susceptibility (S) genes to stop pathogens from exploiting these factors to support infection. Utilizing R gene-mediated resistance is the most common strategy for traditional breeding approaches, but the continuous evolution of pathogen effectors can eventually overcome this resistance. Moreover, modifying S genes can confer pleiotropic effects that hinder their use in agriculture. Enhancing disease resistance is paramount for sustainable wheat production and food security, and new tools and strategies are of great importance to the research community. The application of CRISPR-based genome editing provides promise to improve disease resistance, allowing access to a broader range of solutions beyond random mutagenesis or intraspecific variation, unlocking new ways to improve crops, and speeding up resistance breeding. Here, we first summarize the major disease resistance strategies in the context of important wheat diseases and their limitations. Next, we turn our attention to the powerful applications of genome editing technology in creating new wheat varieties against important wheat diseases.
In-depth immunochemical characterization of the serum antibody response using a dual-titration microspot assay
Authors: Kovács Ágnes , Hérincs Zoltán , Papp Krisztián , Kaczmarek Jakub Zbigniew , Larsen Daniel Nyberg , Stage Pernille , Bereczki László , Ujhelyi Eszter , Pfeil Tamás , Prechl József
Published: February 2025

Antigen specific humoral immunity can be characterized by the analysis of serum antibodies. While serological assays for the measurement of specific antibody levels are available, these are not quantitative in the biochemical sense. Yet, understanding humoral immune responses quantitatively on the systemic level would need a universal, complete, quantitative, comparable measurement method of antigen specific serum antibodies of selected immunoglobulin classes. Here we describe a fluorescent, dual-titration immunoassay, which provides the biochemical parameters that are both necessary and sufficient to quantitatively characterize the humoral immune response. For validation of theory, we used recombinant receptor binding domain of SARS-CoV-2 as antigen on microspot arrays and varied the concentration of both the antigen and the serum antibodies from infected persons to obtain a measurement matrix of binding data. Both titration curves were simultaneously fitted using an algorithm based on the generalized logistic function and adapted for analyzing biochemical variables of binding. We obtained equilibrium affinity constants and concentrations for distinct antibody classes. These variables reflect the quality and the effective quantity of serum antibodies, respectively. The proposed fluorescent dual-titration microspot immunoassay can generate truly quantitative serological data that is suitable for immunological, medical and systems biological analysis.
Human pluripotent stem cell-derived hepatic progenitors exhibit a partially hypoimmunogenic phenotype and actively inhibit immune responses
Authors: Gantier Malika , Ménoret Séverine , Fourrier Angélique , Delbos Frédéric , Nguyen Tuan Huy , Anegon Ignacio
Published: February 2025

Introduction

GStemHep cells are human cryopreserved hepatic progenitors derived from pluripotent of stem cells (GStem cells) using a cGMP-compliant protocol. They were highly effective in rescuing mice from acute liver failure.

Methods

The objective of this study was to analyze the immunogenicity and immunoregulatory properties of GStemHep cells.

Results

As compared to GStem cells, GStemHep cells showed complete loss of HLA-I (ABC) and they lacked of expression of HLA-II, HLA-G, HLA-E and PD-L1. GStemHep cells also showed increased expression of CD47, maintained high expression of indoleamine 2,3-dioxygenase (IDO) and heme oxygenase-1 (HO-1) and reduced expression of CD200. In comparison with GStem cells, GStemHep cultured in inflammatory conditions increased the expression of PD-L1, CD200, HO-1, HLA-E, CD47 and HLA-I (ABC) as well as maintained expression of IDO and were negative for HLA-II and HLA-G. GStemHep culture in basal or inflammatory conditions has a low or absent immunogenic activity on T cells, associated to a suppressive effect on proliferation partially mediated by IDO. We observed phagocytosis of GStemHep by macrophages that was partially inhibited by CD47 expression. NK cells were activated by resting GStemHep cells. Upon culture in inflammatory conditions that induced expression of HLA-I molecules in GStemHep cells NK cell activation was reduced. Thus, GStemHep cells are partially hypoimmune cells due to the expression of several immune checkpoint inhibitors and the absence of HLA-I molecules. In inflammatory conditions, the expression of several of these molecules was increased but also of HLA-I that could be immunogenic for T cells but it was inhibitory for NK cells.

Discussion

GStemHep cells show a favorable immunological profile for their use as allogeneic off-the shelf treatment of liver diseases with loss of hepatocyte function.
De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment
Authors: Chou-Wu Elaine , Niemann Matthias , Youngs Danny , Gimferrer Idoia
Published: February 2025

Introduction

The presence of de novo donor-specific antibody (dnDSA) has detrimental effect on allograft outcomes in kidney transplantation. As humoral responses in transplantation are elicited targeting non-self-epitopes on donor HLA proteins, assessing HLA mismatches at the molecular level provides a refined means for immunological risk stratification.

Methods

In the present study, we utilized three HLA molecular mismatch assessment algorithms, Snow, HLAMatchmaker, and PIRCHE-II, to evaluate the independent and synergistic association of B cell and T cell epitope mismatches with dnDSA development in a cohort of 843 kidney transplant recipients.

Results

Our results demonstrated that B cell and T cell epitope mismatches at HLA Class I and DRB1/DQB1 loci are remarkably increased in dnDSA-positive recipients, even after normalization by allele mismatch numbers in individual study subjects. Furthermore, elevated Snow, verified eplet mismatches, and PIRCHE-II scores are significantly associated with dnDSA occurrence individually and in combination.

Conclusion

Our findings highlight the value of utilizing B cell and T cell epitope mismatch evaluation in living donor selection and immunological risk stratification to improve transplant outcomes.
Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch
Authors: Ma Wenjuan , Brenmoehl Julia , Trakooljul Nares , Wimmers Klaus , Murani Eduard
Published: February 2025

In farm animals, little is known about the relationship between energy metabolism of immune cells and their activation state. Moreover, there has recently been evidence that dexamethasone, a powerful glucocorticoid-based drug, can exert its anti-inflammatory effects by interfering with the energy metabolism of immune cells, but the mechanisms are not yet fully understood. To address these knowledge gaps, we explored the connection between the energy metabolism of porcine peripheral blood mononuclear cells (PBMCs) and their response to pro- and anti-inflammatory stimulation with lipopolysaccharide (LPS) and dexamethasone (DEX) in vitro. Interventions in the metabolism of PBMCs with the glycolysis inhibitor 2-deoxy-D-glucose or the HIF-1α inhibitor KC7F2 reduced the LPS-induced TNF-α production, but the mitochondrial ATP synthesis inhibitor oligomycin showed no significant effect. The anti-inflammatory action of DEX was not affected by any of the inhibitors. To investigate the metabolic actions of LPS and DEX in PBMCs, we evaluated glycolysis and mitochondrial respiration following 24 hours stimulation using the Seahorse XFe96 flux analyzer. Our results revealed significantly higher glycolysis in LPS-treated PBMCs, but provided no evidence for a change in mitochondrial respiration. In contrast, DEX reduced LPS-induced glycolysis and, especially when administered alone, significantly lowered mitochondrial respiration. Pretreatment with KC7F2 counteracted the effects of LPS and DEX on glycolysis, and reduced mitochondrial respiration regardless of the inflammatory state of the PBMCs. Gene expression analysis identified the glucose transporter SLC2A3, and the tricarboxylic acid cycle genes IDH1 and SDHB as the main switches for the antagonistic metabolic actions of LPS and DEX, which are closely associated with the inflammatory state of PBMCs.
Longitudinal CNS and systemic T-lymphocyte and monocyte activation before and after antiretroviral therapy beginning in primary HIV infection
Authors: Chan Phillip , Li Xiang , Li Fangyong , Emu Brinda , Price Richard W. , Spudich Serena
Published: February 2025

Background

Trafficking of immune cells to the central nervous system is hypothesized to facilitate HIV entry and immune-induced neuronal injury and is mediated by surface proteins such as chemokine receptors and α4 integrin. We longitudinally assessed immune cell activation and surface marker expression in cerebrospinal fluid (CSF) and blood and their relationship with CSF HIV RNA beginning during primary HIV infection (PHI) before and after antiretroviral therapy (ART).

Methods

Longitudinal paired blood and CSF were obtained in ART-naïve PHI (<12 month since infection) participants; some independently initiated ART during follow up. Multiparameter flow cytometry of fresh samples determined activation (% CD38+HLADR+) and chemokine receptor expression (% CCR5+ and CXCR3+) on CD4+ and CD8+ T cells, and subtype and α4 integrin expression (% and mean fluorescence intensity (mfi) of CD49d+) on monocytes. HIV RNA was quantified by PCR. Analyses employed Spearman correlation, within-subject correlation, and linear mixed models.

Results

51 participants enrolled at a median 3.2 months post HIV transmission with 168 total visits (113 pre-ART, 55 post-ART) and a median of 6.5 months of longitudinal follow up (range 0-40). In pre-ART PHI, frequencies of activated CD4+ and CD8+ T cells were much higher in CSF than in blood, with levels similar to ART-naïve people with chronic HIV infection. Both CSF CD4+ and CD8+ T cell activation increased longitudinally prior to initiation of ART. In multivariate analysis, CSF CD4+ but not CD8+ T cell activation independently predicted CSF HIV RNA. Neither CSF monocyte subtypes or α4 expression correlated with CSF HIV RNA. Blood monocyte α4 MFI correlated with CD4+ and CD8+ T cell activation (p<0.05). Following ART initiation, blood but not CSF T cell activation declined with days on treatment (slope=-0.06, p=0.001). During ART, blood and CSF monocyte α4 MFI correlated with T cell activation (p<0.05).

Conclusions

In untreated early infection after PHI, immune activation increases over time, and CSF CD4+ T cell activation but not monocyte activation correlates with CSF HIV RNA. Intrathecal T cell activation does not decline during early follow up on ART. Immunomodulating therapies may be needed to prevent neuronal injury and HIV neuroinvasion during early HIV.
HIV controllers: hope for a functional cure
Authors: Deng Zhuoya , Yan Hongxia , Lambotte Olivier , Moog Christiane , Su Bin
Published: February 2025

Elite controllers (ECs) and post-treatment controllers (PTCs) represent important models for achieving a functional cure for HIV. This review synthesizes findings from immunological, genetic, and virological studies to compare the mechanisms underlying HIV suppression in ECs and PTCs. Although ECs maintain viral control without antiretroviral therapy (ART), PTCs achieve suppression following ART discontinuation. Both groups rely on adaptive and innate immunity, host genetic factors, and characteristics of the HIV reservoir; however, they exhibit distinct immune responses and genetic profiles. These differences provide insights into strategies for sustained ART-free remission. Understanding the shared and unique mechanisms in ECs and PTCs can inform the development of novel therapeutic approaches, including immune-based therapies and genome editing, to achieve a functional cure for HIV-1.
Geniposidic acid inhibits OVA-induced asthma by suppressing allergic airway inflammation and regulating gut microbiota
Authors: Zheng Yang , Gao Dengyu , Xie Hongyang , Geng Huafeng
Published: February 2025

Asthma is a serious chronic inflammatory disease of the respiratory system. In this study, we aimed to explore the role of geniposidic acid (GPA) in ovalbumin (OVA)-induced asthma in mice and to clarify its underlying mechanism. The mice were divided into control group, OVA group, OVA+GPA (12.5, 25, 50 mg/kg) groups. Inflammatory mediators were measured by ELISA. Gut microbiota was detected by 16S RNA sequencing. The results demonstrated that GPA attenuated OVA-induced lung injury, inflammatory cell infiltration, and mucus hypersecretion. OVA-induced IL-4, IL-5, IL-13, and IgE production was also inhibited by GPA. IFN-γ production was increased by GPA. Furthermore, GPA inhibited OVA-induced NF-κB activation and increased Nrf2 expression. In addition, GPA alleviated the dysbiosis of gut microbiota induced by OVA. After GPA treatment, the diversity and abundance of intestinal microbiota in asthma mice increased. At the phylum level, GPA significantly reduced the relative abundance of Ligilactobacillus, Lachnospiraceae, Helicobacter, and Bacteroidales and significantly increased the relative abundance of Muribaculaceae and Muribaculum. In conclusion, GPA protect mice against OVA-induced asthma through suppressing inflammation and regulating gut microbiota.
Dynamic SARS-CoV-2-specific B-cell and T-cell responses induced in people living with HIV after a full course of inactivated SARS-CoV-2 vaccine
Authors: Wang Xiuwen , Yang Xiaodong , Zhang Xin , Yan Hongxia , Jin Junyan , Ma Zhenglai , Duan Junyi , Zhang Guanghui , Huang Tao , Li Yongzheng , Wu Hao , Zhang Tong , Zhu Aiwei , Jin Cong , Song Xiangrong , Su Bin
Published: February 2025

Objective

Both B-cell- and T-cell-mediated immunity are crucial for the effective clearance of viral infection, but little is known about the dynamic characteristics of SARS-CoV-2-specific B-cell and T-cell responses in people living with HIV (PLWH) after a full course of inactivated SARS-CoV-2 vaccination.

Methods

In this study, fifty people living with HIV (PLWH) and thirty healthy controls (HCs) were enrolled to assess B-cell and T-cell responses at the day before the vaccination (T0), two weeks after the first dose (T1), two months after the first dose (T2), the day of the third dose (T3), one month after the third dose (T4), three months after the third dose (T5) and 12 months (T6) after the third dose.

Results

SARS-CoV-2-specific B-cell and T-cell responses were induced in people living with HIV (PLWH), and these responses lasted at least one year after the third vaccine dose. However, the peak frequencies of Spike-specific B-cell and T-cell responses in PLWH were lower than those in HIV-negative controls. In addition, the expansion of activated B cells, memory B cells and plasma cells after primary vaccination was observed, but the percentages of these cells were decreased at T6 and were comparable to those at T0. Additionally, the percentages of activated T cells, exhausted T cells and SARS-CoV-2-specific T cells with enhanced functional activity were increased following the administration of inactivated SARS-CoV-2 vaccine. In addition, PLWH had lower percentages of plasma cells, RBD-specific B cells, circulating Tfh (cTfh) cells and CD38+ cTfh cells, and the percentages of the latter two types of cells were positively correlated with the titer of neutralizing antibodies, indicating these differences may account for the weaker immune responses induced in PLWH.

Conclusion

These data suggest that specific B-cell and T-cell responses could be sustained for at least one year after receiving the third vaccination. Our findings emphasize that the weak SARS-CoV-2-specific B-cell and T-cell responses induced in PLWH have implications for clinical decision-making and public health policy for PLWH with respect to SARS-CoV-2 infection.
Big data analysis and machine learning of the role of cuproptosis-related long non-coding RNAs (CuLncs) in the prognosis and immune landscape of ovarian cancer
Authors: Kuang Mingqin , Liu Yueyang , Chen Hongxi , Chen Guandi , Gao Tian , You Keli
Published: February 2025

Background

Ovarian cancer (OC) is a severe malignant tumor with a significant threat to women’s health, characterized by a high mortality rate and poor prognosis despite conventional treatments such as cytoreductive surgery and platinum-based chemotherapy. Cuproptosis, a novel form of cell death triggered by copper ion accumulation, has shown potential in cancer therapy, particularly through the involvement of CuLncs. This study aims to identify risk signatures associated with CuLncs in OC, construct a prognostic model, and explore potential therapeutic drugs and the impact of CuLncs on OC cell behavior.

Methods

We analyzed ovarian cancer data (TCGA-OV) from the TCGA database, including transcriptomic and clinical data from 376 patients. Using Pearson correlation and LASSO regression, we identified 8 prognostic CuLncs to construct a risk signature model. Patients were categorized into high- and low-risk groups based on their risk scores. We performed survival analysis, model validation, drug sensitivity analysis, and in vitro experiments to assess the model’s performance and the functional impact of key CuLncs on OC cell proliferation, invasion, and migration.

Results

The prognostic model demonstrated significant predictive power, with an area under the curve (AUC) of 0.702 for 1-year, 0.640 for 3-year, and 0.618 for 5-year survival, outperforming clinical pathological features such as stage and grade. High-risk OC patients exhibited higher Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating stronger immune evasion ability. Drugs such as JQ12, PD-0325901, and sorafenib showed reduced IC50 values in the high-risk group, suggesting potential therapeutic benefits. In vitro experiments revealed that knockdown of LINC01956, a key CuLnc in the risk signature, significantly inhibited the proliferation, invasion, and migration of OC cells (P<0.05).

Conclusion

Our study identified a prognostic risk model based on CuLncs and explored their potential as therapeutic targets in OC. The findings highlight the importance of CuLncs in OC prognosis and immune response, providing new insights for future research and clinical applications.
Co-expression of B7-H3 and LAG3 represents cytotoxicity of CD4+ T cells in humans
Authors: Tamura Yumi , Ohki Shun , Nagai Haruna , Yoshizato Rin , Nishi Shizuki , Jin Yuqi , Kitajima Yasuo , Guo Yun , Ichinohe Tatsuo , Okada Satoshi , Kawano Yohei , Yasuda Tomoharu
Published: February 2025

Recent studies have highlighted the potential contribution of CD4+ T cells with cytotoxic activity (CD4 CTLs) to anti-tumor immunity. However, their precise roles remain elusive, partly due to the absence of specific markers defining CD4 CTLs with target-killing potential in humans. We previously demonstrated that Epstein-Barr virus (EBV)-driven immortalized B cell lines efficiently induce human CD4 CTLs with cytotoxic functions comparable to cytotoxic CD8+ T cells (CD8 CTLs). Here we show that EBV-driven CD4 CTLs exhibit prolonged proliferation and sustained cytotoxicity compared with CD8 CTLs, although their cytotoxic function markedly decreased during long-term culture. Comparative transcriptomic analysis of CD4 CTLs with varying cytotoxic activities identified B7-H3 and LAG3 as surface molecules associated with highly cytotoxic CD4 CTLs. Co-expression of B7-H3 and LAG3 correlated with CD107a expression and was observed on CD4+ T cells with enhanced cytotoxic potential in a target-dependent manner but not on CD8 CTLs. Furthermore, B7-H3+LAG3+ CD4+ T cells were induced during co-culture with bone marrow cells from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). These findings suggest that B7-H3 and LAG3 co-expression represents a characteristic feature of functional CD4 CTLs in humans, providing valuable insights into the role of CD4 CTLs in tumor immunity.
Malaria case management over 15 years (2006–2021) in Jakiri North-West Region Cameroon
Authors: Ndang Ndong Henry , Mengnjo Njodzela Christian , Netongo Palmer Masumbe , Soniran Olajoju Temidayo , Chu Chuo Ennestine , Chiabi Eugene , Amambua-Ngwa Alfred , Cheng Ndong Ignatius
Published: February 2025

Background

Malaria remains a serious health challenge; thus, the need for continual improvements in treatment regimens and the adoption of new treatment guidelines to enhance case management is vital. We report trends in malaria case management over 15 years at the Jakiri Health Centre in Cameroon, an area that has been plagued with civil unrest since 2016.

Methods

Data were collected retrospectively from consultation, laboratory, antenatal care (ANC) and prescription registers, and double entered into Excel. Analysis was conducted using SPSS statistics and Microsoft Excel.

Results

A total of 3,800 febrile patients visited the outpatient department (OPD), and patients received 8,324 prescriptions. Of these, 11.6% (964/8324) were anti-malarials, 3.5% (291/8324) were ferrous sulfate (FS), 40.8% (3,396/8324) were antibiotics (AB), and 44.1% (3,673/8324) were analgesics. The antimalarials prescribed were artemisinin-based combination therapies (ACTs) 83.2% (802/964) and quinine (Q) 16.8% (162/964). No ACTs were prescribed between 2006 and 2011. The 5 to <15 years age group received the most proportion of ACTs 42.3% (189/447), followed by the 1 to <5 years age group 31.8% (127/399). Males were more likely to be prescribed ACTs than females were (OR= 1.336, 95% CI 1.141–1.564; p<0.0001). Between 2006 and 2013, the number of quinine prescriptions increased from 17.2% (21/122) in 2006 to a peak of 26.1% (30/115) in 2009. Antibiotic prescription rates were high across all age groups. The prescription of antimalarials to malaria-negative patients was relatively low over time. ACTs were prescribed to all participants attending the ANC who were confirmed malaria-positive. 97.7% of SP was prescribed as intermittent preventive treatment in pregnancy (IPTp) with highest prescription rates observed among women in their third trimester 96.2% (76/79).

Conclusion

This study demonstrated that recommended malaria treatment guidelines have been adopted by the Jakiri Health Centre, which has transitioned from quinine as a first-line treatment to ACTs. ACTs were not used in the facility until 2012. Though anti-malaria prescription was largely appropriate, antibiotics and analgesics were highly over prescribed. There is great need for continuous monitoring and refresher training for health workers to enforce adherence to the guidelines.
Nomograms of risk prediction and prognosis for the T1-T2 stage gastric cancer with lymph node metastasis: a population-based study
Authors: Nie Guo-Le , Geng Longlong , Zhang Hao , Chu Shicheng , Jiang Hong
Published: February 2025

Background and aims

Lymph node metastasis plays a crucial role in determining the appropriate treatment approach for patients with gastric cancer (GC), particularly those in the T1–T2 stage. Currently available diagnostic strategies for GC with lymph nodes have limited accuracy. The present research aimed to create and validate diagnostic and prognostic nomograms specifically tailored for the T1–T2 stage GC patients with LNM.

Methods

We derived clinicopathological characteristics of patients diagnosed with GC from the Surveillance, Epidemiology, and End Results (SEER) database. We utilized univariate and multivariate logistic analyses to examine the risk factors linked with the occurrence of lymph node metastasis (LNM) in GC patients within the T1–T2 stage. Furthermore, the prognostic factors related to the T1–T2 stage GC patients with LNM were explored by univariate and multivariate cox analyses. Two nomograms were built by the risk factors screened above.

Results

Ultimately, our study included 5,350 patients with T1–T2 stage GC. After identifying age, T stage, tumor size, primary site, grade, and histological type as risk factors for the LNM occurrence, we successfully developed a diagnostic nomogram utilizing these variables. Age, T stage, M stage, tumor size, primary site, grade, radiation, surgery, and chemotherapy were all independent prognostic factors that related to the T1 – T2 GC patients with LNM. The results of the AUC, calibration curve and decision curve analysis (DCA) showed excellent calibration performance and clinical applicability of the two nomograms. The Kaplan–Meier (K-M) curves clearly demonstrated a notable distinction in overall survival between low-risk and high-risk groups, highlighting the prognostic significance of the nomogram.

Conclusion

The establishment and validation of the two nomograms for T1-T2 GC patients with LNM were successful, serving as valuable tools for clinical decision-making and the formulation of personalized treatment approaches.
Effect of acupuncture in patients with postprandial distress syndrome: study protocol for a randomized controlled trial
Authors: Yan Zhaobo , Xu Xuan , Liu Mailan , MuRong Zhimiao , Zhong Huan , Luo Rong , He Haolong , Liu Weiai , Du Geshu , Liu Mi
Published: February 2025

Background

Postprandial distress syndrome (PDS) is the prominent subtype in patients with functional dyspepsia (FD) and currently lacks a satisfactory treatment. Acupuncture has become a promising alternative and complementary therapy for managing FD. However, high-level clinical evidence supporting the use of acupuncture for FD is limited.

Methods

This study is a multicentre, double-dummy, single-blind, randomized, active-controlled trial. Two hundred and one eligible participants will be randomly assigned into three groups: a verum acupuncture plus placebo group, an itopride plus sham acupuncture group, and a sham acupuncture plus placebo group. This study consists of a 1-week screening period, a 4-week treatment period, and a 12-week follow-up period. During the intervention period, participants will receive 12 sessions of verum or sham acupuncture treatment (one session per day, three sessions per week, for 4 weeks) along with 50 mg itopride tablets or 50 mg itopride placebo tablets 3 times a day for 20 days (5 continual days a week for 4 weeks). The response rate (patients who had adequate relief of gastric symptoms will be considered positive responders) and the elimination rate of cardinal symptoms (postprandial fullness and early satiation) are the primary indicators to evaluate the overall acupuncture effect for PDS. Secondary outcome measures will include the Nepean Dyspepsia Symptom Index (NDSI), the short form-Nepean Dyspepsia Life Quality Index (SF-NDLQI), the Hospital Anxiety and Depression Scale (HADS), and related hormone concentrations. Participants’ expectations toward acupuncture treatment will also be assessed, and adverse events will be recorded for safety assessment. All analyses will adhere to an intention-to-treat principle.

Discussion

In conclusion, this trial will determine the efficacy and safety of acupuncture for PDS and provide more high-level evidence to support its application in treating FD.

Trial registration

Identifier [ITMCTR2024000510].
Perceived value and barriers of nursing specialty certifications among clinical nurses in Saudi Arabia: a cross-sectional study
Authors: AlSadah Alawiah T. , Aboshaiqah Ahmad E. , Alanazi Naif H.
Published: February 2025

Introduction

Specialty nursing certifications reflect nurse’s knowledge and competence in certain areas. Obtaining certification allows them to advance their careers and enhance patient care standards as their role and scope of responsibility expands. This study aimed to understand how nurses view specialty certification and related challenges in three university hospitals in Riyadh, Saudi Arabia.

Methods

A cross-sectional, correlational design was used. A survey questionnaire (Perceived Value of Certification-12 Tool) was sent through email, and it had one question for each barrier.

Results

The majority of participants valued certification to verify specialist knowledge (93.9%), enhance achievement (82.8%), and increase competence (79.1%). Certification was associated extrinsically with hiring preference (54.7%), recognition from colleagues (52.3%), and professional autonomy (51.7%). The primary barriers were lack of institutional reward (72.7%) and examination cost (64.8%), with not passing earlier being the least mentioned barrier (2%). The biggest obstacles faced by clinical nurses in obtaining certification include limited institutional rewards because their organization did offer incentives, such as promotions or salary bumps. Age and hospital significantly predicted clinical nurses’ intrinsic value of certification, while age, gender, nationality, and hospital significantly predicted their extrinsic value. Age and gender significantly influenced their overall perceived value of certification.

Discussion

Overall, nurses in Riyadh recognize the value of certification. However, focused interventions must be implemented to overcome identified challenges and amplify the professional benefits of certification. Recommended measures include implementing tailored support initiatives and financial aid programs to address these barriers. A collaborative approach should be developed to provide support and actively promote the pursuit of nursing certification. Future studies should adopt longitudinal and qualitative designs to evaluate the impact of focused strategies.
Viral contamination in cell culture: analyzing the impact of Epstein Barr virus and Ovine Herpesvirus 2
Authors: Bastawecy Iman M. , Abdelmonem Mohamed , Afify Ahmed F. , Saad Norazalina , Shirosaki Yuki , Abdullah Che Azurahanim Che , El Naggar Rania F. , Rohaim Mohammed A. , Munir Muhammad
Published: February 2025

Cell culture techniques are increasingly favored over animal models due to rising costs, time constraints, and ethical concerns regarding animal use. These techniques serve critical roles in disease modeling, drug screening, drug discovery, and toxicity analysis. Notably, cell cultures facilitate primary virus isolation, infectivity assays, biochemical studies, and vaccine production. However, viral contamination in cell cultures poses significant challenges, particularly due to the necessity for complex and sophisticated detection methods. Among the prevalent viruses, Epstein Barr virus (EBV) is ubiquitous across human populations, infecting approximately 98% of individuals. Despite its prevalence, the detection of EBV is often not considered a safety priority, as its detection methods are well-established, including PCR assays that can identify both active and latent forms of the virus. Conversely, ovine herpesvirus 2 (OvHV-2), a relative of EBV, presents a critical concern due to its ability to infect a wide range of organs and species, including over 33 animal species and nearly all domestic sheep. This makes the detection of OvHV-2 crucial for the safety of cell cultures across various species. The literature reveals a gap in the comprehensive understanding of both EBV and OvHv-2 detection in cell culture systems, highlighting an urgent need for developing robust detection methodologies specific to EBV and OvHv-2 to ensure bioprocess safety.
Whole-genome sequencing-based species classification, multilocus sequence typing, and antibiotic resistance mechanisms of the clinical Aeromonas complex
Authors: Lu Junwan , Zhang Lei , Yan Chunxia , Lin Naru , Zhang Yuan , Sha Yuning , Zhao Jingxuan , Lu Jun , Bao Qiyu , Zhang Guozhi
Published: February 2025

Background

Multidrug-resistant strains of the genus Aeromonas can produce various β-lactamases that confer resistance to a broad spectrum of β-lactams, which poses a significant public health threat due to their emergence and spread in clinical settings and natural environments. Therefore, a comprehensive investigation into the antibiotic resistance mechanisms of Aeromonas is scientifically significant.

Methods

Between 2018 and 2021, 78 clinical Aeromonas isolates were collected from human clinical specimens. The MicroScan WalkAway system and average nucleotide identity (ANI) analyses were used to classify the bacterial species. Antibiotic susceptibility was determined through the minimum inhibitory concentration (MIC) test via the agar dilution method. To determine the resistance mechanism and the structure of the resistance gene-related sequences, molecular cloning, whole-genome sequencing and bioinformatic analysis were performed.

Results

Among the 78 Aeromonas isolates studied in this work, obtained from various specimens from different clinical departments, 77 were classified into seven known species by ANI analysis. Most of the isolates were A. caviae (34.6%, 27/78), followed by A. hydrophila (25.6%, 20/78). Multilocus sequence typing (MLST) revealed that they belonged to 72 sequence types (STs), including 52 new STs. A total of 334 resistance genes of 30 antibiotic resistance genotypes were identified from the genomes, more than half (55.99%, 187/334) of which were β-lactamase genes. The isolates showed much higher rates of resistance to penicillins (penicillin G, 98.7%) and first-generation cephalosporins (cefazolin, 96.2%), but lower resistance rates to fourth-generation cephalosporins (cefepime, 6.4%), monobactams (aztreonam, 5.1%), and carbapenems (imipenem, 1.3% and meropenem, 5.1%). Structural analyses of some β-lactamase genes (such as blaNDM-1 and blaPER-3) related sequences revealed that they were generally associated with mobile genetic elements.

Conclusion

The investigation of the correlation between the distribution of β-lactamase genes and Aeromonas resistance phenotypes in this study suggested an urgent need for rigorous monitoring and control to counteract the escalating public health threat posed by the increase in Aeromonas strains harboring extended-spectrum β-lactamase and metallo-β-lactamase genes.
Biological function identification of phage holin Hol-4086 and treatment of Staphylococcus aureus infection
Authors: Zheng Chenyu , Di Yaxin , Wang Yingchun , Zhao Huyang , Wang Ruichong , Li Guiwei , Wang Xiaona , San Zhifu , Jiang Yanping , Cui Wen , Li Jiaxuan , Wang Li , Qiao Xinyuan
Published: February 2025

The treatment of infections caused by drug-resistant Staphylococcus aureus has become increasingly difficult. In this study, the complete genome of phage 4086-1 against S. aureus was sequenced and shown to be 17,960 bp in size, with a GC content of 29.14%. Phylogenetic analysis demonstrated that phage 4086-1 exhibited a close relationship with the Staphylococcus phages SLPW, JPL-50, and LSA2366. BLAST analysis indicated that ORF12 of phage 4086-1 (termed Hol-4086) shares high identity with other reported phage-associated holins. Hol-4086 consists of 140 amino acids and exhibits high sequence identity with some members of the phage_holin_4_1 superfamily (18–125 amino acids). Hol-4086 was then expressed in Escherichia coli and detected using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. The results of a spot test demonstrated that Hol-4086 had substantial bacteriostatic effects on the host bacteria. S. aureus cells were exposed to Hol-4086 and observed using transmission electron microscopy and scanning electron microscopy. Bacterial cells treated with Hol-4086 showed ultrastructural and morphological changes. The detection of biofilm activity showed that Hol-4086 effectively inhibited and removed S. aureus biofilms. In vivo, treatment with Hol-4086 significantly reduced the number of bacteria, relieved inflammatory responses, and alleviated pathological changes in the organs of infected mice 48 h after treatment. These results demonstrate that Hol-4086 exhibits promising antibacterial potential as an alternative therapy for the treatment of infections caused by S. aureus.
An integrated proteo-transcriptomics approach reveals novel drug targets against multidrug resistant Escherichia coli
Authors: Aswal Manisha , Singh Nirpendra , Singhal Neelja , Kumar Manish
Published: February 2025

Infections due to multidrug-resistant (MDR) Escherichia coli are associated with severe morbidity and mortality, worldwide. Microbial drug resistance is a complex phenomenon which is conditioned by an interplay of several genomic, transcriptomic and proteomic factors. Here, we have conducted an integrated transcriptomics and proteomics analysis of MDR E. coli to identify genes which are differentially expressed at both mRNA and protein levels. Using RNA-Seq and SWATH-LC MS/MS it was discerned that 763 genes/proteins exhibited differential expression. Of these, 52 genes showed concordance in differential expression at both mRNA and protein levels with 41 genes exhibiting overexpression and 11 genes exhibiting under expression. Bioinformatic analysis using GO-terms, COG and KEGG functional annotations revealed that the concordantly overexpressed genes of MDR E. coli were involved primarily in biosynthesis of secondary metabolites, aminoacyl-tRNAs and ribosomes. Protein–protein interaction (PPI) network analysis of the concordantly overexpressed genes revealed 81 PPI networks and 10 hub proteins. The hub proteins (rpsI, aspS, valS, lysS, accC, topA, rpmG, rpsR, lysU, and spmB) were found to be involved in aminoacylation of tRNA and lysyl-tRNA and, translation. Further, it was discerned that three hub proteins - smpB, rpsR, and topA were non homologous to human proteins and were involved in several biological pathways directly and/or indirectly related to antibiotic stress. Also, absence of homology ensures a little cross-reactivity of their inhibitors/drugs with human proteins and undesirable side effects. Thus, these proteins might be explored as novel drug targets against both drug-resistant and -sensitive populations of E. coli.
Survey of West Nile virus infection in wildlife species in the Orinoquia region of Colombia
Authors: Matta Nubia E. , Gaitán-Albarracín Felipe Andrés , Fuentes-Rodríguez Gustavo Andrés , Rodríguez-Fandiño Óscar Andrés , Calixto-Botía Iván F. , Correa-Higuera Lady Johana
Published: February 2025

Studies focused on the epidemiological surveillance of arboviruses that cause potentially zoonotic diseases, such as dengue, Zika, or emerging viruses like West Nile virus (WNV), are critical due to their significant impact on public health. Although research on these infectious agents is increasing in Colombia, regions remain where the presence of zoonotic agents is still unknown. To address this knowledge gap, the present study aimed to investigate the current status of WNV circulation in wildlife in two municipalities of the department of Casanare (El Yopal and Paz de Ariporo) from the Colombian region of Orinoquia. Since the arrival of WNV in Colombia, reported in 2004, its detection has typically relied on antibody screening using ELISA. While informative, this technique needs to offer a sufficiently precise time frame to confirm active virus circulation. We employed a molecular approach to overcome this limitation, detecting WNV using qPCR, which provides greater specificity and a narrower time window. A total of 2,553 swab samples were collected from a broad sampling covering 142 birds, 19 mammals, and eight reptile species during 2023 and 2024 across four sampling events conducted during both the dry and wet seasons. The sampling included species with ecological or symbolic value to the region and those with economic importance, such as species used for human consumption (bushmeat). No evidence of WNV was detected in the evaluated species, indicating that these species were not infected with the virus during the sampling periods or that viral loads were below the detection threshold. Our results underscore the importance of further studies, including complementary diagnostic methods, such as antibody detection, to better understand the broader temporal infections and provide a more complete understanding of virus circulation.