bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum
Authors: Trickey Mitchell L. , Chowdury Mrittika , Bramwell Georgina , Counihan Natalie A. , de Koning-Ward Tania F. 
Published: February 2025

Abstract

Background
Malaria parasites establish new permeation pathways (NPPs) at the red blood cell membrane to facilitate the transport of essential nutrients from the blood plasma into the infected host cell. The NPPs are critical to parasite survival and, therefore, in the pursuit of novel therapeutics are an attractive drug target. The NPPs of the human parasite, P. falciparum, have been linked to the RhopH complex, with the monoallelic paralogues clag3.1 and clag3.2 encoding the protein RhopH1/CLAG3 that likely forms the NPP channel-forming component. Yet curiously, the combined knockout of both clag3 genes does not completely eliminate NPP function. The essentiality of the clag3 genes is, however, complicated by three additional clag paralogs (clag2, clag8 and clag9) in P. falciparum that could also be contributing to NPP formation.

Methods
Here, the rodent malaria species, P. berghei, was utilised to investigate clag essentiality since it contains only two clag genes, clagX and clag9. Allelic replacement of the regions encompassing the functional components of P. berghei clagX with either P. berghei clag9 or P. falciparum clag3.1 examined the relationship between the two P. berghei clag genes as well as functional orthology across the two species. An inducible P. berghei clagX knockout was created to examine the essentiality of the clag3 ortholog to both survival and NPP functionality.

Results
It was revealed P. berghei CLAGX and CLAG9, which belong to two distinct phylogenetic clades, have separate non-complementary functions, and that clagX is the functional orthologue of P. falciparum clag3. The inducible clagX knockout in conjunction with a guanidinium chloride induced-haemolysis assay to assess NPP function provided the first evidence of CLAG essentiality to Plasmodium survival and NPP function in an in vivo model of infection.

Conclusions
This work provides valuable insight regarding the essentiality of the RhopH1 clag genes to the NPPs functionality and validates the continued investigation of the RhopH complex as a therapeutic target to treat malaria infections.
Identification and functional analysis of a novel SMARCC2 splicing variant in a family with syndromic neurodevelopmental disorder
Authors: Li Ming , Lin Jingqi , Fei Hongjun , Liu Jinyu , Chen Yiyao , Han Xu , Wang Yanlin , Wang Jian , Hua Renyi , Li Shuyuan , Li Niu 
Published: February 2025

Abstract

Background
To determine the pathogenicity of a novel splicing variant in the SMARCC2 gene identified from a pair of adult male monozygotic twins with neurodevelopmental disorder, and to investigate the genotype-phenotype characteristics associated with SMARCC2 variants.

Methods
Whole-exome sequencing (WES) was conducted on the proband, and candidate variants were validated using Sanger sequencing within the family. The effect of the identified splicing variant on SMARCC2 mRNA processing was analyzed using reverse transcription PCR (RT-PCR) and TA-clone sequencing using samples derived from the proband. The clinical features of the twins were collected and compared with the previously reported patients.

Results
The twin adult males displayed comparable phenotypes, characterized by moderate developmental delay, intellectual and language delays, dense hair, craniofacial anomalies, scoliosis, cryptorchidism, hypotonia, behavioral abnormalities, allergic purpura and eczema, and drug allergies. WES unveiled a previously unreported heterozygous splice variant of the SMARCC2 gene (NM_003075.3: c.1496 + 1G > T). Sanger sequencing confirmed that the variant was de novo in both patients. TA-clone sequencing of the RT-PCR fragments showed that the canonical splicing variant resulted in two distinct aberrant splicing events in SMARCC2 mRNA. Specifically, approximately 80% of the mutant clones resulted from the in-frame insertion of 126 bases in intron 16, while the remaining 20% showed an in-frame deletion of exon 16 (c.1383_1496del). Crystal structure analysis showed that both in-frame alterations hindered the proper formation of the alpha helix structure within the SMARCC2 protein. An analysis of genotype-phenotype correlations indicated that our patients displayed neurological phenotypes of greater severity than those observed in patients with truncating variants, instead aligning more closely with the characteristics of the missense/in-frame variant group.

Conclusion
We identified and reported a pair of twins suffering from syndromic neurodevelopmental disorders caused by a novel splicing variant of SMARCC2. Our findings further reinforce the notion that individuals harboring missense/in-frame variants in SMARCC2 are prone to experiencing more severe neurological phenotypes.
Characteristics of plastic bronchitis in children with infectious pneumonia
Authors: Cai Xulong , Lin Mali , Zhou Li , Sheng Wencai , Jiao Wanyan , Bian Hongliang , Yin Tongjin 
Published: February 2025

Abstract

Background
Multiple studies have reported that infectious pneumonia can induce the production of plastic casts, which threatens children's health. We explored the characteristics of plastic bronchitis (PB) in clinical practice by analysing clinical medical records.

Methods
A retrospective study was conducted. Children with pneumonia and large chest shadows were included in this study. The differences in characteristics between patients with plastic bronchitis and those without plastic bronchitis were analysed. The distribution of pathogens was statistically analysed. Grouping analysis based on PB and pathogen conditions was also conducted.

Results
A total of 185 patients were included in this study. The patients were divided into two groups: the PB group (n = 48) and the non-PB group (n = 137). The duration of illness before hospitalization in the PB group was mostly longer than that in the non-PB group. The frequency distribution of the inspiratory three concave signs in the PB group was significantly greater than that in the non-PB group. Compared with those in the non-PB group, the number of patients with abnormally elevated of D-D dimer, LDH, ALT, and AST in the PB group was significantly greater. Mycoplasma pneumoniae (MP) was the main pathogen observed in both the PB and non-PB groups. In cases of MP infection without plastic bronchitis, treatment with macrolide antibiotics occurred significantly earlier. Most cases of pleural effusion in the PB-MP group were discovered more than 7 days after onset. However, in the PB-nonMP group, most cases of pleural effusion were detected within 7 days of onset. There was a difference observed in the distribution of pulmonary necrosis between the PB group and the non-PB group.

Conclusions
MP is a common pathogen observed in PB cases caused by single-pathogen infections and multiple-pathogen infections. PB may be a potential cause of pulmonary necrosis. Furthermore, PB exhibits diverse clinical manifestations due to host and pathogen factors.
Population characteristics, prescription patterns and glycemic control of users of flash glucose monitoring systems in Brazil: a real-world evidence study
Authors: Santo Karla , Nieri Josué , Risério Karine , Melo Karla F. S. 
Published: February 2025

Abstract

Background
To date, there is a lack of information on the use of flash glucose monitoring system (fCGM) in low-middle income countries, such as Brazil, as well as on digital health platforms most used to calculate the bolus insulin dose. In this study, we aimed to describe the population characteristics, prescription patterns and glycemic control of fCGM users compared to blood glucose monitoring (BGM) system in those who use Glic™, a digital health platform in Brazil, and to assess factors associated with better glycemic control in this population.

Methods
This study is a cross-sectional retrospective study using anonymized aggregated data manually inputted by Glic™ users who self-reported a diagnosis of type 1 diabetes (T1DM), type 2 diabetes (T2DM), gestational diabetes (GDM) and latent autoimmune diabetes in adults (LADA).

Results
Of the 12,727 individuals included in this study, 11,007 (86.5%) reported their glucose monitoring method to be BGM, while 1720 (13.5%) reported using fCGM. Most individuals (70.5%) had T1DM. Compared to BGM, fCGM users were significantly younger, had a higher proportion of males, resided more frequently in the Southeast region of Brazil, had a lower BMI, a longer time since diagnosis, and used Glic™ platform more frequently. fCGM users were prescribed significantly more ultra-long and ultra-rapid acting insulins as their basal and bolus insulin, respectively, and less oral anti-diabetics drugs compared to BGM users. Considering only the T1DM and LADA individuals and their manual glucose inputs, fCGM users had non-significant lower glucose levels than BGM. Use of Glic™ platform and a higher percentage of basal insulin dose were associated with a better glycemic control.

Conclusion
This is the first and largest real-world evidence study that describe and compare fCGM and BGM in users of a digital health patient support platform in Brazil. fCGM users were significantly different from those who perform BGM, in terms of population characteristics and treatment patterns. Glycemic control was better in fCGM users, although not statistically significant due to a restricted sample size. Importantly, a higher frequency of Glic™ use was associated with a higher glucose time in range.
Severe anaemia in people with HIV: demographic, clinical and renal correlates
Authors: Kamvuma Kingsley , Munsaka Sody , Masenga Sepiso K. , Mulemena John Amos , Phiri Christopher Newton , Miyoba Michelo , Hamooya Benson M. 
Published: February 2025

Abstract

Objective
This study aimed to investigate the sociodemographic, clinical and renal correlates associated with severe anaemia among people with HIV.

Methods
We conducted a cross-sectional analysis of people with HIV on antiretroviral therapy (ART) for at least 6 months, stratified by anaemia status. Anaemia was defined based on the World Health Organisation (WHO) classification, as haemoglobin concentration lower than normal i.e. <12 g/dl in females and < 13 g/dl in males and the primary outcome, severe anaemia, as a haemoglobin level below 8 g/dl according to the World Health Organisation.

Results
The study comprised 372 participants receiving ART, of whom 236 (63.4%) were females. The mean age ± SD of the participants was 44.8 ± 12.4 years. The overall prevalence of severe anaemia was 7.8% (95% CI: 0.053–0.111). In multivariable logistic regression analysis, factors significantly associated with severe anaemia were female sex (Adjusted Odds Ratio (AOR: 14.3, 95% CI: 2.14–126.6), albumin (AOR: 0.93 95% CI: 0.88–0.98) and creatinine levels (AOR: 1.01 95% CI: 1.00-1.03).
Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury
Authors: Kim Jungbum , Seo Donghyuk , Yoo So-Yeol , Lee Hye-Jin , Kim Jisun , Yeom Ji Eun , Lee Jae-Young , Park Wooram , Hong Kyung Soo , Lee Wonhwa 
Published: February 2025

Abstract
Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediate intervention. Currently, clinical treatments are limited in symptomatic therapy as mechanical ventilation and corticosteroids, having insufficient efficacy in mitigating the cause of progression to severe illness. Here we report a pulmonary targeting lung-homing nanoliposome (LHN) designed to attenuate excessive Neutrophil Extracellular Trap formation (NETosis) through sivelestat and DNase-1, coupled with an anti-inflammatory effect mediated by 25-hydroxycholesterol (25-HC), offering a promising intervention for the acute phase of ALI. Through intratracheal delivery, we intend prompt and constant action within the lungs to effectively prevent excessive NETosis. Isolated neutrophils from blood samples of severe ARDS patients demonstrated significant anti-NETosis effects, as well as reduced proinflammatory cytokine secretion. Furthermore, in a murine model of LPS-induced ALI, we confirmed improvements in lung histopathology, and early respiratory function. Also, attenuation of systemic inflammatory response syndrome (SIRS), with notable reductions in NETosis and neutrophil trafficking was investigated. This presents a targeted therapeutic approach that can be applied in early stages of high-risk patients to prevent severe pulmonary disease progression.
Survey of medication history of patients with stroke after discharge from an acute hospital ward: a case series study
Authors: Fukuda Yuko , Ito Risa , Kakihana Misaki , Takahashi Tsutomu , Kanemoto Tetsuji , Sahara Toshiyuki , Tsujikawa Masahiko , Onda Mitsuko 
Published: February 2025

Abstract

Background
Stroke is a leading cause of death, reducing disability-free life expectancy. After acute treatment, patients require rehabilitation to prevent recurrence. Continued use of medication is crucial for recurrence prevention and risk management, even after the transition from acute-care institutions to other medical institutions. Although “discharge summaries on medications” are shared between hospitals and community pharmacists, no reports have addressed medication continuity for patients with stroke transferred to other institutions after discharge. This study aimed to clarify medication continuity, particularly for medications adjusted during hospitalization that should be continued even after discharge, by investigating the medication use histories of patients with stroke transferred from acute care hospitals to outpatient hospitals.

Methods
We enrolled patients who were discharged from an acute ward between June 11, 2022, and March 31, 2023, after receiving inpatient care at the Japan Community Healthcare Organization, Hoshigaoka Medical Center for acute stroke, and transferred to other outpatient hospitals. This study was conducted between June 2022 and April 2023. We extracted and assessed prescription continuity and carefully examined clinically relevant discrepancies after comparing the discharge prescription with that at the first outpatient visit.

Results
Of the 42 patients enrolled, seven (16.7%) had one or more discrepancies involving 13 medications. Based on the medicinal efficacy classification, four patients treated with other blood and body fluids-related agents (antiplatelet drugs), three patients treated with agents for hyperlipidemia (statins), two patients with agents for peptic ulcers, two patients with vasodilators, one patient treated with antihypertensives, and one patient with other agents affecting digestive organs (antiemetic agents that acts on the central nervous system) had discrepancies. Furthermore, discrepancies in medication discontinuation or reduction recommended by a stroke specialist, which may increase the risk of stroke recurrence, were identified in five patients (seven drugs: four antiplatelet drugs and three statins). Of 13 discrepancies, community pharmacists inquired about 3 cases with physicians, none were approved.

Conclusion
The medication to prevent stroke recurrence might not be continued after transit to another outpatient after discharge. Reconsidering patient information sharing between hospital and community pharmacists and establishing a more strengthened sharing system is necessary to achieve seamless pharmacotherapy.
Atezolizumab neutralizing assay development: a novel way of evaluating assay cutpoint after sample pretreatment
Authors: Melendez Rachel , Ruppel Jane , Leddy Cecilia , Yang Jenny , Brady Ann , Webb-Vargas Yenny , Brumm Jochen , Kamen Lynn , Song Yuan 
Published: February 2025

Abstract
Atezolizumab, a biotherapeutic monoclonal antibody directed against PD-L1, has been shown to be efficacious in multiple oncology indications. In clinical trials, a subset of patients developed anti-atezolizumab antibodies, necessitating the development of a neutralizing antibody (NAb) assay. A bead-based sample pretreatment method was developed to reduce high levels of therapeutic in patient serum samples. Untreated sample variability is reduced by this sample pretreatment, based on this, a novel approach was taken for determining an appropriate assay decision threshold (cutpoint). The therapeutic was added to the samples to mimic typical patient samples. The resulting assay was successfully validated and applied to sample analysis from multiple clinical trials.
Multi-organ frailty is enhanced by periodontitis-induced inflammaging
Authors: Kase Yoshitaka , Morikawa Satoru , Okano Yuji , Hosoi Tatsuya , Yasui Takazumi , Taki-Miyashita Yoko , Yakabe Mitsutaka , Goto Maraku , Ishihara Kazuyuki , Ogawa Sumito , Nakagawa Taneaki , Okano Hideyuki 
Published: February 2025

Abstract

Background
The incidence of periodontitis is high in older individuals. However, its impact on multi-organ frailty remains unclear. We developed mouse models with varying severity and duration of periodontitis to examine its effects.

Methods
We generated mouse models with mild and severe periodontitis, categorizing the disease duration into 3-month and 5-month periods for analysis. The organs assessed for frailty included the gastrocnemius muscle, soleus muscle, brain, and femur.

Results
Our study found that periodontitis induced systemic inflammation resembling inflammaging and other symptoms characteristic of age-induced frailty. Notably, muscle impairment developed specifically in slow-twitch muscles, and the femur emerged as the most vulnerable bone, exhibiting reduced bone mineral density even with mild and short-duration periodontitis. This condition resulted in the co-occurrence of bone fragility and slow-twitch muscle dysfunction. Cognitive function assessment revealed increased activated microglia and decreased adult neurogenesis in the hippocampus, impairing spatial learning. Thus, periodontitis induced both physical and cognitive frailties. Therapeutic intervention for the periodontitis, which halted the exacerbation of bone resorption markers, did not restore femur bone mineral density.

Conclusion
This study underscores the role of periodontitis in inducing multifaceted organ frailty with vulnerability, varying by organ, and the necessity of early intervention, particularly regarding bone density loss.
Advances in genetic developmental and epileptic encephalopathies with movement disorders
Authors: Yuan Meng , Wang Xiaoqian , Yang Zuozhen , Luo Huan , Gan Jing , Luo Rong 
Published: February 2025

Abstract
Genetic developmental and epileptic encephalopathies (DEE) are often associated with movement disorders. Accurate identification and classification of movement disorders are essential for management of these diseases. In this review, we describe the characteristics of various movement disorders associated with DEE and summarize the distribution of common DEE-related gene mutations reported in previous studies, aiming to provide references for the diagnosis and treatment of these disorders.
Non-coding RNAs and exosomal ncRNAs in colorectal cancer
Authors: Zhoulideh Yalda 
Published: February 2025

Abstract
Colorectal cancer (CRC) is a complex disease with many genetic and epigenetic changes leading to dysregulation of cell signaling pathways. In recent years, increasing attention has been paid to the role of non-coding RNA (ncRNA) and exogenous ncRNA in the development and progression of CRC. ncRNAs play an essential role in the regulation of gene expression and cell function, and dysregulation of ncRNA expression is associated with the onset and progression of CRC. In this review, we discuss the molecular pathways involved in CRC and the emerging roles of ncRNAs and exogenous ncRNAs in the regulation of these pathways. We focus on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and exogenous ncRNAs and their roles in regulating key signaling pathways such as the Wnt/β signaling pathway. β-catenin, PI3K/Akt, and TGF-β. We also discuss the potential of ncRNAs and exogenous ncRNAs as diagnostic and prognostic biomarkers for CRC, as well as their potential as therapeutic targets for CRC. Advances in ncRNA-based therapies present promising opportunities for the development of new therapies for CRC. A better understanding of the roles of ncRNAs and exogenous ncRNAs may lead to the development of new therapeutic strategies for this disease.
Association of functional variants in miRNA genes with the risk of coronary heart disease
Authors: Haq Taqweem Ul , Khan Muhammad Riaz , Ali Sajjad , Aziz Tariq , Albekairi Thamer H. , Shah Aftab Ali 
Published: February 2025

Abstract

Background
Cardiovascular diseases, especially coronary heart disease (CHD), are currently the leading cause of mortality and morbidity. Environmental and genetic factors contribute to the pathophysiology of CHD. In this study, we investigated the associations of miRNA genes MIR222, MIR423, MIR4274, and MIR3117 with the pathogenesis of CHD.

Methods
Genetic inheritance models were applied to explore the association between these miRNA genes and CHD. Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) was used for genotyping, and Sanger sequencing was applied for validation in selected cases.

Results
The codominant [χ2 = 8.058, 2; P value = 0.0178], and recessive (CC vs GC + GG) [OR = 0.4535 (0.2439–0.8669); P value = 0.0187] models demonstrated a statistically significant association between MIR222 (rs2858060) and CHD. Similarly, the co-dominant [χ2 = 6.105, 2, 2; P value = 0.0472], and additive [OR = 1.494 (1.024–2.211); P value = 0.0428] models revealed a significant association (P value < 0.05) between MIR423 (rs6505162) and CHD. In MIR4242, a novel triplet insertion (CAC) was identified exclusively in CHD samples, predicated to disrupt the stem-loop structure ofmiR-4274. However, MIR3117 showed no association with CHD, as confirmed by Sanger sequencing of 40 samples.

Conclusion
Our findings suggest that functional variants rs2858060, rs6505162, and a novel triplet insertion (CAC) in MIR222, MIR423, and MIR4274 respectively are strongly associated with CHD. These results underline the potential of miRNA gene variants as genetic biomarkers for CHD susceptibility.