bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncoding mutations drive persistence of a founder preleukemic clone which initiates late relapse in T-ALL
Authors: O’Connor David , Valle-Inclán Jose Espejo , Conde Lucia , Bloye Gianna , Rahman Sunniyat , Costa Joana R. , Bartram Jack , Adams Stuart , Wright Gary , Elrick Hillary , Wall Kerry , Dyer Sara , Howell Christopher , Jigoulina Galina , Herrero Javier , Cortes-Ciriano Isidro , Moorman Anthony V. , Mansour Marc R. 
Published: January 2024

Abstract
T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
Clinical and functional spectrum of RAC2-related immunodeficiency
Authors: Donkó Ágnes , Sharapova Svetlana O. , Kabat Juraj , Ganesan Sundar , Hauck Fabian H. , Bergerson Jenna R. E. , Marois Louis , Abbott Jordan , Moshous Despina , Williams Kelli W. , Campbell Nicholas , Martin Paul L. , Lagresle-Peyrou Chantal , Trojan Timothy , Kuzmenko Natalia B. , Deordieva Ekaterina A. , Raykina Elena V. , Abers Michael S. , Abolhassani Hassan , Barlogis Vincent , Milla Carlos , Hall Geoffrey , Mousallem Talal , Church Joseph , Kapoor Neena , Cros Guilhem , Chapdelaine Hugo , Franco-Jarava Clara , Lopez-Lerma Ingrid , Miano Maurizio , Leiding Jennifer W. , Klein Christoph , Stasia Marie José , Fischer Alain , Hsiao Kuang-Chih , Martelius Timi , Sepännen Mikko R. J. , Barmettler Sara , Walter Jolan , Masmas Tania N. , Mukhina Anna A. , Falcone Emilia Liana , Kracker Sven , Shcherbina Anna , Holland Steven M. , Leto Thomas L. , Hsu Amy P. 
Published: January 2024

Abstract
Mutations in the small Rho-family guanosine triphosphate hydrolase RAC2, critical for actin cytoskeleton remodeling and intracellular signal transduction, are associated with neonatal severe combined immunodeficiency (SCID), infantile neutrophilic disorder resembling leukocyte adhesion deficiency (LAD), and later-onset combined immune deficiency (CID). We investigated 54 patients (23 previously reported) from 37 families yielding 15 novel RAC2 missense mutations, including one present only in homozygosity. Data were collected from referring physicians and literature reports with updated clinical information. Patients were grouped by presentation: neonatal SCID (n = 5), infantile LAD-like disease (n = 5), or CID (n = 44). Disease correlated to RAC2 activity: constitutively active RAS-like mutations caused neonatal SCID, dominant-negative mutations caused LAD-like disease, whereas dominant-activating mutations caused CID. Significant T- and B-lymphopenia with low immunoglobulins were seen in most patients; myeloid abnormalities included neutropenia, altered oxidative burst, impaired neutrophil migration, and visible neutrophil macropinosomes. Among 42 patients with CID with clinical data, upper and lower respiratory infections and viral infections were common. Twenty-three distinct RAC2 mutations, including 15 novel variants, were identified. Using heterologous expression systems, we assessed downstream effector functions including superoxide production, p21-activated kinase 1 binding, AKT activation, and protein stability. Confocal microscopy showed altered actin assembly evidenced by membrane ruffling and macropinosomes. Altered protein localization and aggregation were observed. All tested RAC2 mutant proteins exhibited aberrant function; no single assay was sufficient to determine functional consequence. Most mutants produced elevated superoxide; mutations unable to support superoxide formation were associated with bacterial infections. RAC2 mutations cause a spectrum of immune dysfunction, ranging from early onset SCID to later-onset combined immunodeficiencies depending on RAC2 activity. This trial was registered at www.clinicaltrials.gov as #NCT00001355 and #NCT00001467.
Nanoparticles assisted intra and transdermic delivery of antifungal ointment: an updated review
Authors: Tarannum Nazia , Pooja Km. , Jakhar Shivani , Mavi Anshika 
Published: January 2024

AbstractThis review paper highlights the trans-dermic delivery of nanoparticles (NPs) based antifungal ointments with the help of nanotechnology. It also describes the novel trans-dermal approach utilizing various nanoparticles which enables an efficient delivery to the target site. This current review gives an overview about past research and developments as well as the current nanoparticle-based ointments. This review also presents data regarding types, causes of infection, and different pathogens within their infection site. It also gives information about antifungal ointments with their activity and side effects of antifungal medicines. Additionally, this review also focuses on the future aspects of the topical administration of nanoparticle-based antifungal ointments. These nanoparticles can encapsulate multiple antifungal drugs as a combination therapy targeting different aspects of fungal infection. Nanoparticles can be designed in such a way that they can specifically target fungal cells and do not affect healthy cells. Nanoparticle based antifungal ointments exhibit outstanding potential to treat fungal diseases. As further research and advancements evolve in nanotechnology, we expect more development of nanoparticle-based antifungal formulations shortly. This paper discusses all the past and future applications, recent trends, and developments in the various field and also shows its bright prospective in the upcoming years.
Graphical abstract
Fractal feature selection model for enhancing high-dimensional biological problems
Authors: Alsaeedi Ali Hakem , Al-Mahmood Haider Hameed R. , Alnaseri Zainab Fahad , Aziz Mohammad R. , Al-Shammary Dhiah , Ibaida Ayman , Ahmed Khandakar 
Published: January 2024

AbstractThe integration of biology, computer science, and statistics has given rise to the interdisciplinary field of bioinformatics, which aims to decode biological intricacies. It produces extensive and diverse features, presenting an enormous challenge in classifying bioinformatic problems. Therefore, an intelligent bioinformatics classification system must select the most relevant features to enhance machine learning performance. This paper proposes a feature selection model based on the fractal concept to improve the performance of intelligent systems in classifying high-dimensional biological problems. The proposed fractal feature selection (FFS) model divides features into blocks, measures the similarity between blocks using root mean square error (RMSE), and determines the importance of features based on low RMSE. The proposed FFS is tested and evaluated over ten high-dimensional bioinformatics datasets. The experiment results showed that the model significantly improved machine learning accuracy. The average accuracy rate was 79% with full features in machine learning algorithms, while FFS delivered promising results with an accuracy rate of 94%.
The combination of physical activity with fruit and vegetable intake associated with life satisfaction among middle-aged and older adults: a 16-year population-based cohort study
Authors: Wang Richard Szewei , Huang Yu-Ni , Wahlqvist Mark L. , Wan Thomas T. H. , Tung Tao-Hsin , Wang Bing-Long 
Published: January 2024

Abstract
Background
Life satisfaction (LS) is part of a positive psychological feeling that protects individuals from a physical decline in old age. A healthy lifestyle, including physical activity (PA) and a healthy diet, such as the intake of fruits and vegetables (F&V), can lead to a better experience of LS in older adults. However, the association between PA and F&V intake habits when occurring together in older adults is still unclear for LS. The study aimed to investigate the combined association of PA and F&V intake on LS among a cohort of older Taiwanese adults.

Methods
Five waves of population-based data gathered by the Taiwan Longitudinal Survey on Aging between 1999 and 2015 were analyzed. The year 1999 was set as the baseline, and the number of respondents was 4,440. The independent variables included the frequency, duration, and intensity of PA and the frequency of F&V intake. LS was assessed by using the Life Satisfaction Index. We performed generalized estimating equations (GEE) analysis with adjustment for covariates of health behaviors and health indicators.

Results
After adjusting for confounders, model 1 showed that moderate and high-PA levels significantly correlated with LS (odds ratio [OR] = 1.41, 95% CI = 1.12–1.79) and OR = 1.74, 95% CI = 1.50–2.02). Moreover, high-F&V intake significantly correlated with LS (OR = 2.07, 95% CI = 1.69–2.53). Regarding the combined association shown in model 2, compared with both the low PA and F&V intake group, there were significantly higher LS in the both-high-group (OR = 4.69, 95% CI = 3.49–6.31), only-high-F&V intake (OR = 2.87, 95% CI = 2.14–3.85), only-high-PA (OR = 2.48, 95% CI = 1.74–3.52).

Conclusions
Our findings show the significant combined association of PA and F&V intake on LS among older adults. In addition, older adults who engaged in higher frequency, duration, and intensity of daily PA combined more than seven times a week of F&V intake had significantly higher LS than those who only engaged in low PA or only intake less F&V. Adopting multiple healthy behaviors in daily life is a safe and effective approach to promote LS among older adults.
Serum MicroRNA profiles in chronic hepatitis C Egyptian patients before and after combined sofosbuvir and daclatasvir treatment
Authors: Ezzat Wafaa M. , Amr Khalda S. , Tawfeek Salwa , Elbatae Hassan , Bayomi Eman A. , Heiba Ahmed , Elhosary Yasser 
Published: January 2024

Abstract
Background
MicroRNAs (miR) are small sequence of nucleotides that can affect multiple genes involved in the hepatitis C virus (HCV) life cycle and disease development. The purpose of the present study was to investigate the clinical significance of serum microRNA profiles in a cohort of Egyptian patients with chronic HCV infection before and after combined sofosbuvir and daclatasvir treatment, as well as to gain a better understanding of the exact interaction mechanism in HCV transcriptional activity via differentially expressed miRNAs. For 12 weeks, 50 patients were eligible for and received sofosbuvir (400 mg daily) and daclatasvir (60 mg daily) treatment. Each patient’s blood was obtained twice: once before therapy began and again three months afterwards.

Results
The current study found that serum levels of circulating miR-122, miR-221, miR-23a, miR-125, miR-217, miR-224, and miR-181a were high in HCV pre-treatment patients, but after 12 weeks of direct-acting antiviral (DAAs) treatment, there was a statistically significant reduction in expression levels of miR-122, miR-221, miR-23a, miR-125, miR-217, and miR-224 (p < 0.001). There is no statistical significance for miR-181a.

Conclusion
The key differentially expressed microRNAs before and after the direct-acting antiviral (DAA) regimen were connected to the dynamics of chronic HCV infection, suggesting their potential as predictive biomarkers for HCV clearance after sofosbuvir and daclatasvir therapy.
Prevalence of Cryptosporidium and Giardia infections in under-five children with diarrhoea in Blantyre, Malawi
Authors: Bitilinyu-Bangoh Joseph E. V. , Riesebosch Samra , Rebel Marije , Chiwaya Paul , Verschoor Sjoerd P. , Voskuijl Wieger P. , Schallig Henk D. F. H. 
Published: January 2024

Abstract
Background
Diarrhoeal diseases are common among children in low- and middle-income countries and are major causes of morbidity and mortality. Cryptosporidium and Giardia are considered to be the main parasitic causes of diarrhoea in children. The aim of the present study was to determine the prevalence and associated factors of Cryptosporidium and Giardia infection in children under five years of age presenting at two health centres (Ndirande and Limbe) in Blantyre, Malawi.

Methods
This cross-sectional study was performed from February to July 2019 and included 972 children under 5 years of age with diarrhoea. Stool samples were immediately tested after collection at enrolment with a rapid diagnostic test for Cryptosporidium and Giardia infection. Descriptive statistics were used to assess the prevalence of these protozoan parasitic infections, and differences in the basic demographic and anthroponotic variables (between children with diarrhoea and parasite infection, being either Cryptosporidium and Giardia or both versus children with diarrhoea but no RDT confirmed parasite infection) were assessed. Their association with Cryptosporidium and Giardia infection was analysed using simple logistic regressions.

Results
Of the children recruited, 88 (9.1%) tested positive for Cryptosporidium and 184 (18.9%) for Giardia. Children with only a Giardia infection or a coinfection (of both parasites) were significantly older (mean age 24–26 months) compared to children with only a Cryptosporidium infection (mean age 13 months) or no parasitic infection (mean age 14 months). No significant differences were found with respect to gender, body temperature, stunting or wasting between the different groups of children with moderate to severe diarrhoea. Children attending the Ndirande health centre had almost two times higher odds of testing positive for both infections than those attending Limbe health centre.

Conclusion
Cryptosporidium and Giardia infections are highly prevalent in children < 5 years with moderate to severe diarrhoea attending the Limbe and Ndirande health centres in Blantyre, Malawi.
Diagnostic accuracy of the Clock Drawing Test in screening for early post-stroke neurocognitive disorder: the Nor-COAST study
Authors: Navickaite Egle , Saltvedt Ingvild , Lydersen Stian , Munthe-Kaas Ragnhild , Ihle-Hansen Hege , Grambaite Ramune , Aam Stina 
Published: January 2024

Abstract
Background
Post-stroke neurocognitive disorder, though common, is often overlooked by clinicians. Moreover, although the Montreal Cognitive Assessment (MoCA) has proven to be a valid screening test for neurocognitive disorder, even more time saving tests would be preferred. In our study, we aimed to determine the diagnostic accuracy of the Clock Drawing Test (CDT) for post-stroke neurocognitive disorder and the association between the CDT and MoCA.

Methods
This study is part of the Norwegian Cognitive Impairment After Stroke study, a multicentre prospective cohort study following patients admitted with acute stroke. At the three-month follow-up, patients were classified with normal cognition, mild neurocognitive disorder, or major neurocognitive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Any neurocognitive disorder compromised both mild- and major neurocognitive disorder. The CDT at the three-month assessment was given scores ranging from 0 to 5. Patients able to complete the CDT and whose cognitive status could be classified were included in analyses. The CDT diagnostic accuracy for post-stroke neurocognitive disorder was identified using receiver operating characteristic curves, sensitivity, specificity, positive predictive value, and negative predictive value. The association between the MoCA and CDT was analysed with Spearman’s rho.

Results
Of 554 participants, 238 (43.0%) were women. Mean (SD) age was 71.5 (11.8) years, while mean (SD) National Institutes of Health Stroke Scale score was 2.6 (3.7). The area under the receiver operating characteristic curve of the CDT for major neurocognitive disorder and any neurocognitive disorder was 0.73 (95% CI, 0.68–0.79) and 0.68 (95% CI, 0.63–0.72), respectively. A CDT cutoff of < 5 yielded 68% sensitivity and 60% specificity for any neurocognitive disorder and 78% sensitivity and 53% specificity for major neurocognitive disorder. Spearman’s correlation coefficient between scores on the MoCA and CDT was 0.50 (95% CI, 0.44–0.57, p < .001).

Conclusions
The CDT is not accurate enough to diagnose post-stroke neurocognitive disorder but shows acceptable accuracy in identifying major neurocognitive disorder. Performance on the CDT was associated with performance on MoCA; however, the CDT is inferior to MoCA in identifying post-stroke neurocognitive disorder.

Trial registration
ClinicalTrials.gov (NCT02650531). Retrospectively registered January 8, 2016.
Assessing COVID-related concerns and their impact on antenatal and delivery care among pregnant women living with HIV in Kenya: a brief report
Authors: Wexler Catherine , Maloba May , Mokua Sharon , Babu Shadrack , Maosa Nicodemus , Staggs Vincent , Goggin Kathy , Acharya Harshdeep , Hurley Emily A. , Finocchario-Kessler Sarah 
Published: January 2024

Abstract
Background
Some studies indicate that pregnant Kenyan women were concerned about Coronavirus disease 2019 (COVID-19) exposure during maternity care. We assessed concern regarding COVID-19 exposure and any impact on antenatal care (ANC) enrollment and/or hospital delivery among pregnant women living with human immunodeficiency virus (HIV) in Kenya.

Methods
Data were collected from 1,478 pregnant women living with HIV enrolled in prevention of mother to child transmission of HIV (PMTCT) care at 12 Kenyan hospitals from October 2020 to July 2022. Surveys were conducted when women first presented for PMTCT services at the study hospital and asked demographic questions as well as items related to concerns about COVID-19. A 5-point Likert scale (strongly disagree to strongly agree) assessed concerns about COVID-19 exposure and travel challenges. Gestational age at PMTCT enrollment, number of ANC appointments attended, and delivery location were compared among women who expressed COVID-19 concerns and those who did not.

Results
Few women reported delaying antenatal care (4.7%), attending fewer antenatal care appointments (5.0%), or having concerns about a hospital-based delivery (7.7%) because of COVID-19. More (25.8%) reported travel challenges because of COVID-19. There were no significant differences in gestational age at enrollment, number of ANC appointments, or rates of hospital-based delivery between women with concerns about COVID-19 and those without,

Conclusion
Few pregnant women living with HIV expressed concerns about COVID-19 exposure in the context of routine ANC or delivery care. Women with and without concerns had similar care seeking behaviors. The recognized importance of routine ANC care and facility-based deliveries may have contributed to these positive pregnancy indicators, even among women who worried about COVID-19 exposure.

Trial registration
www.clinicaltrials.gov identifier NCT04571684.
Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer
Authors: Gao Hongyu , Ouyang Dengjie , Guan Xinyu , Xu Jiachi , Chen Qitong , Zeng Liyun , Pang Jian , Zou Qiongyan , Qian Ke , Yi Wenjun 
Published: January 2024

Abstract
Background
In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape.

Methods
The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients.

Results
Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy.

Conclusions
These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.
A systems framework for implementing healthy food retail in grocery settings
Authors: Zorbas Christina , Blake Miranda R. , Brown Andrew D. , Peeters Anna , Allender Steve , Brimblecombe Julie , Cameron Adrian J. , Whelan Jill , Ferguson Megan , Alston Laura , Boelsen-Robinson Tara 
Published: January 2024

Abstract
Background
Food retailers can be reluctant to initiate healthy food retail activities in the face of a complex set of interrelated drivers that impact the retail environment. The Systems Thinking Approach for Retail Transformation (START) is a determinants framework created using qualitative systems modelling to guide healthy food retail interventions in community-based, health-promoting settings. We aimed to test the applicability of the START map to a suite of distinct healthy food marketing and promotion activities that formed an intervention in a grocery setting in regional Victoria, Australia.

Methods
A secondary analysis was undertaken of 16 previously completed semi-structured interviews with independent grocery retailers and stakeholders. Interviews were deductively coded against the existing START framework, whilst allowing for new grocery-setting specific factors to be identified. New factors and relationships were used to build causal loop diagrams and extend the original START systems map using Vensim.

Results
A version of the START map including aspects relevant to the grocery setting was developed (“START-G”). In both health-promoting and grocery settings, it was important for retailers to ‘Get Started’ with healthy food retail interventions that were supported by a proof-of-concept and ‘Focus on the customer’ response (with grocery-settings focused on monitoring sales data). New factors and relationships described perceived difficulties associated with disrupting a grocery-setting ‘Supply-side status quo’ that promotes less healthy food and beverage options. Yet, most grocery retailers discussed relationships that highlighted the potential for ‘Healthy food as innovation’ and ‘Supporting cultural change through corporate social responsibility and leadership’.

Conclusions
Several differences were found when implementing healthy food retail in grocery compared to health promotion settings. The START-G map offers preliminary guidance for identifying and addressing commercial interests in grocery settings that currently promote less healthy foods and beverages, including by starting to address business outcomes and supplier relationships.