bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-disciplinary, protocolised care for hip fracture surgeries shortens hospital stay, time to admission and surgery
Authors: Wong Khai Cheong , Cheok Gideon Jia Wei , Tay Kenny Xian Khing , Koh Joyce Suang Bee , Howe Tet Sen , Ng Yeong Huei
Published: February 2025

Background

Our institution implemented a multi-disciplinary protocolised care for surgically managed hip fractures in 2017, initiating measures pre-operatively to provide early access to surgery, and post-operatively to ensure early mobilisation and smooth transition to step down care.

Objectives

Key performance indicators (time to admission and time to surgery) and acute outcomes (length of stay, discharge disposition and inpatient mortality) were evaluated to determine the impact of multi-disciplinary protocolised care on surgically managed hip fracture patients.

Methods

935 patients in the POST-PROTOCOL group (between February 2017 to January 2020) were compared with 701 patients in the PRE-PROTOCOL group (between January 2015 to January 2017) in terms of key performance indicators and acute outcomes.

Results

In the POST-PROTOCOL group, a higher proportion were of ASA class III and IV ( p = .026). More patients in the POST-PROTOCOL group were admitted to the ward within 4 hours (97.2% vs 86.0%; p < .001) and operated on within 48 hours (56.4% vs 36.8%; p < .001). Mean length of stay was shorter in the POST-PROTOCOL group (11.2 ± 9.0 vs 14.8 ± 13.0 days; 95% CI, 2.5 to 4.7; p < .001), with more patients discharged within 9 days (55.6% vs 43.2%; p < .001). Inpatient mortality rate was similar ( p = .213).

Conclusion

Despite having a higher proportion of patients with poorer physiological status, time to admission, time to surgery and length of stay improved in the POST-PROTOCOL group.
Sound effects have only minor contribution to perceptions of anthropomorphism and animacy of simple animated shapes
Authors: Collins K , Murad Maya , Manji Adel
Published: February 2025

While studies of anthropomorphism have spanned many decades, there is little evidence of the role that sound effects may play. We present two studies into sound's influence on perceptions of anthropomorphism and animacy using simple geometric animated shapes. For the first study, conducted on 149 participants, we simplified the animation to just two “bumping” squares. Study Two recreated the Heider-Simmel study of 1944, and was conducted on 250 participants under five conditions: without sound, and with one of two different sound types (interface sounds and “anthropomorphic” robot sounds) with two stereo modes (fixed in stereo position, or binaurally panned with the movement). We had participants answer both the Individual Differences in Anthropomorphism Questionnaire and the Godspeed Questionnaire, with three additional questions added. Results showed that the sound had a minor impact on anthropomorphism and potency in Study One, but did not impact animacy. Study Two showed no significant effect on anthropomorphism or animacy, but did show an impact on perceived intelligence and perceptions of activity.
Dupilumab-induced psoriasis in a patient with atopic dermatitis successfully treated with Upadacitinib: A case report
Authors: Cirone Katrina D , Lovegrove Fiona E
Published: February 2025

Dupilumab, a monoclonal antibody that targets interleukin-4 and interleukin-13, is one of the approved biologic treatments for moderate-to-severe atopic dermatitis. While it is extremely well tolerated with low rates of adverse events, there have been reports of patients with atopic dermatitis managed on Dupilumab developing new-onset psoriasis. The development of psoriasis in patients with atopic dermatitis on Dupilumab therapy is believed to occur due to a decrease in T helper 2 activity and resultant dysregulation of the T helper 1 and T helper 17 pathways involved in psoriasis pathogenesis. Upadacitinib, an oral, selective Janus kinase 1 inhibitor, approved for use in moderate-to-severe atopic dermatitis as well as psoriatic arthritis may have a potential role in psoriasis treatment. We describe a case of a patient who initially presented with longstanding atopic dermatitis that underwent a psoriasiform switch while managed on Dupilumab and is currently stable on Upadacitinib.
Deepening the data divide: Marginalised perspectives and non-profit priorities in Australian data sharing reforms
Authors: Yao Xiaofang , McCosker Anthony , Kang Yong-Bin
Published: February 2025

This paper investigates open public data and data sharing reforms in Australia (2018–2022) and their potential role in deepening the ‘data divide’. In the contemporary datafied welfare state, open public data and data sharing are increasingly vexed issues in times of data-driven artificial intelligence (AI). We scrutinise public consultation surrounding the establishment of the Australian Data Availability and Transparency Act 2022 (DAT Act). Through topic modelling and critical discourse analysis, the study examines the representation and concerns of marginalised groups in the reform process. We highlight the overlooked role of non-profits and civil society in the public data ecosystem. The analysis emphasises the significant yet unacknowledged contributions of these organisations in advocating for data equity and justice. We argue that responsible and equitable public data practices do not just depend on administrative and technical procedures for data sharing but are fundamentally entwined with the social and institutional hierarchies in which public data is produced and used. The study calls for greater inclusion and support for civil society organisations to bridge the data divide, contributing to broader debates on the merits and challenges of open data and data sharing practices within a data justice framework.
Special Education Teachers’ Perspectives on Preparing Students With Intellectual and Developmental Disabilities for College
Authors: Rooney-Kron Magen , Bumble Jennifer L. , Gilson Carly B.
Published: February 2025

As more opportunities for students with intellectual and developmental disabilities (IDD) to attend college emerge, it is important for secondary special education teachers to be knowledgeable about how to prepare students with IDD for college. We conducted a survey of 1,048 secondary special education teachers from Illinois, Missouri, and Texas to understand their prior experiences with receiving education and training addressing college options for students with IDD, the instruction and activities their students with IDD participate in to prepare for college, and teachers’ perceptions of their own mastery of college preparation domains. We also investigated the extent to which teachers’ demographics, education and training, caseload, and school demographics were associated with their perceptions of their own mastery of college preparation domains. Our results suggest teachers’ perceived levels of mastery and the types of activities in which students with IDD participate in vary significantly by college preparation domain. We discuss implications our results have for teacher preparation programs, middle and high schools, special education teachers, and researchers.
Development and Validation of the Patient Experience Assessment Scale (PXAS) in Tertiary Care Hospital - Oman
Authors: Al-Bulushi Naima Khamis , Al-Mukhaini Zainab Ali , Al Fannah Jehan , Al Zadjali Afaf Ali , Al Zidi Huda , Al-Balushi Zubaida Mahmood , Al-Hadidi Aida Khalfan , Al-Adawi Samir
Published: February 2025

Background: Evaluating the patient's perspective is crucial for high-quality healthcare. Traditional satisfaction surveys have limitations due to subjectivity. Valid ecological measures are lacking in non-western populations. Objective: Validate Patient Experience Assessment Scale (PXAS) for tertiary care hospital. Methods: The development of PXAS involved domain identification, scale creation, language review, and validity assessment. Experts crafted a 12-question scale with a net promoter score (NPS). Language experts reviewed for clarity and equivalence. The content and face validity were evaluated using the content validity index (CVI) and the face validity index. SPSS analyzed data for reliability and test-retest over 3 to 4 weeks. Results: 464 participants were included, mainly aged 31 to 40, participated. PXAS showed good reliability (Cronbach's alpha = 0.88) and test-retest (r = 0.72). The content validity (I-CVI: 0.83-1.0; S-CVI = 0.93) and the validity of the face (98.3% agreement) were excellent. Most were satisfied (45% excellent and 41.2% very good), and 37% would highly recommend the hospital. Conclusions: PXAS is reliable and valid scale to assess the patient experience in tertiary hospitals. Further studies of its properties are warranted.
IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy
Authors: Garcia-Lacarte Marcos , Grijalba Sara C , Melchor Sánchez Javier , Pascual Marién , Goñi Enrique , Clemente-Larramendi Iñigo , Morales-Sánchez Sandra , Burrell Maria A , Blanco Oscar , Arnaiz-Leché Adrián , Berrozpe Blanca S , Amann Maria , Klein Christian , Umaña Pablo , Canales Miguel Angel , Martínez-Climent José Ángel , Lasarte Juan Jose , Sarobe Pablo , Novo Francisco J , Roa Sergio
Published: February 2025

The contribution of IL-10 secreted by tumoral B cells to the progression and shaping of the microenvironment in diffuse large B-cell lymphoma (DLBCL) with activated B-cell (ABC) phenotype is not yet completely understood. To shed light on this issue, we generated an immunocompetent mouse model of ABC-DLBCL with conditional knock-out of IL-10 specifically in malignant B cells. Paradoxically, these mice had significantly worse overall survival when left untreated, but experienced increased sensitivity to conventional anti-CD20 immunotherapy or regulatory T cell (Treg) depletion. We identified various immunomodulatory mechanisms involved in this behavior. In particular, we show that IL-10-deficient lymphomas acquire a highly immunosuppressed and T-cell exhausted microenvironment with increased angiogenesis that results in a more aggressive phenotype, refractory to PD-1 immune checkpoint blockade (ICB). However, the response of IL-10-deficient mice to anti-CD20 immunotherapy was greatly enhanced by upregulation of calcium channels in B cells. In general, IL-10 autocrine signaling promotes survival of malignant B cells, while the paracrine action of B cell-derived IL-10 maintains an immunoreactive microenvironment that influences the efficacy of emerging immunotherapy strategies aimed at the lymphoma microenvironment (LME). Furthermore, IL-10-associated transcriptional signatures derived from our studies may correctly predict clinical outcomes of DLBCL patients treated with R-CHOP. Thus, our work provides important functional and mechanistic insights into the role of B cell-derived IL-10 in the biology of ABC-DLBCL.
How I approach pharmacological thromboprophylaxis in children
Authors: Sochet Anthony A. , Kiskaddon Amy , Goldenberg Neil A
Published: February 2025

The incidence of venous thromboembolism in children continues to rise, with the most recent analysis from the Pediatric Hospital Information Systems database in the United States reporting a 200-fold increase in pediatric hospitalization-related venous thromboembolism diagnoses over the past two decades. In the past decade, several pediatric venous thromboembolism risk prediction models have been published, in some cases derived from multi-institutional data and multicenter randomized clinical trials of thromboembolism prevention in specific pediatric subpopulations have been conducted. Yet, apart from children hospitalized for COVID-19, guidelines for thromboprophylaxis (TP) in children that address several distinct at-risk subpopulations and settings for venous thromboembolism are presently lacking. It is becoming increasingly apparent that approaches to pharmacological TP for hospitalized children should be risk-stratified regarding a priori risks of both venous thromboembolism and clinically-relevant bleeding. In this manuscript, we present model cases of common inpatient clinical scenarios and review the evidence related to venous thromboembolism risk models and pharmacological TP clinical trials in children, describing a pragmatic approach to pharmacological TP for each scenario. We then conclude by describing our evidence-informed, subpopulation- and setting-specific approach to pharmacological TP for the clinical scenarios and reviewing critical knowledge gaps well-suited for future pediatric trials to inform thromboprophylaxis in children.
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

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

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

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

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

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

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

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

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

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

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

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

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.
Neural processes linking joint hypermobility and anxiety: key roles for the amygdala and insular cortex
Authors: Kampoureli Christina N. , Rae Charlotte L. , Gould Van Praag Cassandra , Harrison Neil A. , Garfinkel Sarah N. , Critchley Hugo D. , Eccles Jessica A.
Published: February 2025

Background

Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.

Aim

To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.

Method

We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (N = 30) and a non-anxious comparison group (N = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).

Results

Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.

Conclusions

The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.
Application of strongly intensive quantity in the investigation of forward-backward correlation in UrQMD simulated pp collisions at √s=13 TeV
Authors: Bhattacharyya Swarnapratim
Published: February 2025

This work utilizes the novel approach of the strongly intensive quantity Σ_FBto investigate the forward-backward multiplicity correlation in UrQMD simulated pp collisions at √s=13 TeV. Evidence of forward-backward correlation has been noted in UrQMD simulated pp collisions at different separation between the forward and backward pseudo-rapidity zones. The strongly intensive quantity Σ_FBhas been found to increase slowly with increasing the separation (η_gap) between the forward and backward pseudo-rapidity zones. Comparison of this analysis with PYTHIA tuned with Monash 2013 simulated values, EPOS3 simulated values and ALICE collaboration values (for minimum bias events) have also been presented.
Update on Antiseizure Medications 2025
Authors: Abou-Khalil Bassel W.
Published: February 2025

OBJECTIVE

This article is an update from the article on antiseizure medication therapy published in the three previous Continuum issues on epilepsy and is intended to cover the vast majority of agents currently available to neurologists in the management of patients with epilepsy. This article addresses antiseizure medications individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.

LATEST DEVELOPMENTS

Since the most recent version of this article was published, one new antiseizure medication, ganaxolone, has been approved by the US Food and Drug Administration (FDA), and the indications of some approved medications were expanded. Older antiseizure medications are effective but have tolerability and pharmacokinetic disadvantages. Several newer antiseizure medications have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older antiseizure medications as first-line therapy for focal epilepsy. These agents include lamotrigine, oxcarbazepine, levetiracetam, topiramate, zonisamide, and lacosamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy for focal epilepsy. Other newer antiseizure medications with a variety of mechanisms of action are suitable for adjunctive therapy.

ESSENTIAL POINTS

Knowledge of antiseizure medication pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate antiseizure medication therapy for patients with epilepsy. Rational antiseizure medication combinations should avoid antiseizure medications with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.
The Demographic and Socioeconomic Consequences of Restricting Access to Marriage for Young Immigrant Women in Denmark
Authors: Cuzulan Bojana , Schultz-Nielsen Marie Louise , Fallesen Peter
Published: February 2025

In July 2002, Danish reforms limited the marriage opportunities for all Danish and non–European Union (EU) citizens younger than 24 living in Denmark who wished (or whose parents wished for them) to marry someone from outside the EU. Before the reform, more than 80% of first- and second-generation immigrants from outside the EU married spouses from their parents’ origin countries; the reform drastically changed their marriage market. We examine the policy's effects on subsequent marriage behavior, the transition to motherhood, human capital accumulation, and labor market activities using full-population administrative data on 578,380 Danish-born first- and second-generation non-EU immigrants born in 1972–1990 and a difference-in-differences design. We find that the policy delayed marriages among individuals with an immigrant background, extended premarital cohabitation, changed the composition of spouses, and delayed and decreased in-wedlock fertility. Finally, the duration of obtained formal education increased. Our results emphasize that reforms constraining access to external marriage markets can have lasting impacts on marriage demographics among immigrants.
TAZ interactome analysis using nanotrap-based affinity purification–mass spectrometry
Authors: Kelebeev Jonathan , MacKeracher Anastasia , Miyake Tetsuaki , McDermott John C.
Published: February 2025

Characterization of protein–protein interactions (PPIs) is a fundamental goal in the post-genomic era. Here, we document a generally applicable approach to identify cellular protein interactomes using a combination of nanobody-based affinity purification (AP) coupled with liquid chromatography and tandem mass spectrometry (LC–MS/MS). The Hippo signaling regulator TAZ (also known as WWTR1) functions as a transcriptional co-repressor or activator depending on its PPI network; we therefore undertook an unbiased proteomic screen to identify TAZ PPIs in striated muscle cells. A GFP nanotrap-based AP approach coupled with protein identification through LC–MS/MS was used to document a comprehensive list of known and novel TAZ interactome components. Informatic analysis of the interactome documented known components of the Hippo signaling pathway and multiple epigenetic regulators such as the NuRD, FACT and SWI/SNF complexes and the pro-myogenic CARM1 methyltransferase. Hippo pathway reporter gene (HOP/HIP) analysis indicated that CARM1 represses TAZ transcriptional co-activator function, promoting TAZ Ser89 phosphorylation and TAZ cytoplasmic sequestration. MS analysis revealed that CARM1 dimethylates TAZ at Arg77 in a PGPR*LAGG consensus peptide, resulting in enhanced TAZ Ser89 phosphorylation. These studies underline the utility of a nanobody-based AP approach for interactome analysis.
Drosophila AHR limits tumor growth and stem cell proliferation in the intestine
Authors: Tsai Minghua , Sun Jiawei , Alexandre Cyrille , Shapiro Michael , Franchet Adrien , Li Ying , Gould Alex P. , Vincent Jean-Paul , Stockinger Brigitta , Diny Nicola Laura
Published: February 2025

Background The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, the Drosophila homolog of AHR, has only been studied in the context of development but not in the adult intestine. Methods The role of Spineless in the Drosophila midgut was studied by overexpression or knockdown of Spineless in infection and tumour models and RNA sequencing of sorted midgut progenitor cells. Results We show that spineless is upregulated in the adult intestinal epithelium after infection with Pseudomonas entomophila (P.e.). Spineless knockdown increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using either Notch RNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism. Conclusions These findings demonstrate a new role for Spineless in the adult Drosophila midgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium.
The genome sequence of the Lesser Sea-spurrey, Spergularia marina (L.) Besser
Authors: Ruhsam Markus ,   Royal Botanic Garden Edinburgh Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Plant Genome Sizing collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2025

We present a genome assembly from a specimen of Spergularia marina (Lesser Sea-spurrey; Streptophyta; Magnoliopsida; Caryophyllales; Caryophyllaceae). The genome sequence has a total length of 499.30 megabases. Most of the assembly is scaffolded into 18 chromosomal pseudomolecules, suggesting the individual is an allotetraploid (2n = 4x = 36). The mitochondrial and plastid genome assemblies have lengths of 327.07 kilobases and 152.28 kilobases, respectively. Gene annotation of this assembly on Ensembl identified 37,641 protein-coding genes.
Terrorism as a factor geopolitical restructuring in the Sahel region
Authors: Kante Mady Ibrahim
Published: February 2025

Since the beginning of the new millennium, extremism has emerged as a major challenge facing the African continent. This phenomenon significantly impedes economic and political development, prompting individual states to fight terrorism through various initiatives. Despite these efforts, tangible results have been elusive due to the transfer of extremist ideologies across state borders, leading to external interventions under the guise of the “fight against terrorism in the Sahel.” Although jihadist terrorist groups have long been present in Africa, the Sahel countries and African organizations have not adopted effective strategies to combat violent extremism. Since 2011, terrorist organizations have seized control of areas in the Sahel, with Boko Haram conducting numerous operations that threaten regional security and stability.
In response, African organizations such as the African Union and regional bodies have implemented policies and initiatives aimed at curbing the spread of violent extremism through military interventions and economic and social development projects in the Sahel. These efforts include alliances like the Lake Chad Basin Commission and G5 Sahel, comprising five Sahel countries. Given the regional and international ramifications of extremism on Western interests and economically powerful states, African nations and organizations have engaged in serious cooperation with the international community and major powers. This collaboration includes efforts with the United Nations, France, and other entities in peacekeeping missions and initiatives to combat terrorism and extremism.   
Keywords: Africa, Sahel, geopolitics, terrorism, war, counterterrorism, military intervention, security.
New and Old Ideas: African Military Marxism
Authors: Besenyo Janos
Published: February 2025

Book Review