bluuebunny/crossref_metadata_2025 huggingface dataset:
Kazakhstan’s nationalistic globalism: Paradox, language, and higher education
Authors: Bayetova Nazgul , Robertson Douglas L
Published: January 2024

Globalism is a neoliberally influenced focus on world markets and the knowledge economy particularly from the perspective of transnational economic entities. Nationalism concentrates on promoting the country as an entity distinct and special among other countries. When combined, as in Kazakhstan’s case, the two perspectives constitute a paradox. This paper explores Kazakhstan’s paradoxical strategy of using success globally to enhance regard nationally. The roles of language and higher education are discussed in pursuing this strategy. The commentary extends a previous qualitative study of the speeches and strategic plans of Nursultan Nazarbayev, Kazakhstan’s primary post-Soviet architect and President, from Kazakhstan’s independence in 1991 to Nazarbayev’s stepping down in 2019. Current events in the region, such as the Russian invasion of Ukraine, are included in the discussion.
Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer
Authors: Huang Zi-Yao , Wen Lei , Ye Liu-Fang , Lu Yu-Ting , Pat Fong William , Zhang Ren-Jing , Wu Si-Xian , Chen Zhi-Gang , Cai Yan-Yu , Xu Rui-Hua , Li Yu-Hong , Du Zi-Ming , Wang De-Shen
Published: January 2024

Background:

Transmembrane E3 ubiquitin ligase ( RNF43) mutations are present in approximately 6–18% of colorectal cancers (CRC) and could enhance Wnt/β-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of RNF43-mutant CRC.

Methods:

A total of 78 patients with RNF43-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, clinical characteristics, treatment regimens used, and survival outcomes were collected and analyzed.

Results:

Our study uncovered that patients with RNF43 mutations in the N-terminal domain (NTD; n = 50) exhibited shorter overall survival (OS; median months, 50.80 versus not reached; p = 0.043) compared to those in the C-terminal domain (CTD; n = 17). Most RNF43 mutations in NTD had positive primary lymph node status, low tumor mutation burden (TMB-L), and correlated with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status. By contrast, RNF43 mutations in CTD were significantly enriched in deficient MMR (dMMR)/microsatellite instability (MSI-H) tumors with high TMB (TMB-H). N-terminal RNF43-mutated tumors harbored a hotspot variant ( RNF43 R117fs), which independently predicted a significantly worse outcome in pMMR/MSS CRC with a median OS of 18.9 months. Patients with RNF43 mutations and the BRAF V600E alterations demonstrated sensitivity to BRAF/EGFR inhibitors. Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy.

Conclusion:

Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.
Development of PARP inhibitors in advanced prostate cancer
Authors: Bourlon Maria Teresa , Valdez Paola , Castro Elena
Published: January 2024

The relatively high prevalence of alterations in the homologous recombination repair (HRR) pathway described in advanced prostate cancer provides a unique opportunity to develop therapeutic strategies that take advantage of the decreased tumor ability to repair DNA damage. Poly ADP-ribose polymerase (PARP) inhibitors have been demonstrated to improve the outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients with HRR defects, particularly in those with BRCA1/2 alterations. To expand the benefit of PARPi to patients without detectable HRR alterations, multiple studies are addressing potential synergies between PARP inhibition (PARPi) and androgen receptor pathway inhibitors (ARSi), radiation, radioligand therapy, chemotherapy, or immunotherapy, and these strategies are also being evaluated in the hormone-sensitive setting. In this review, we summarize the development of PARPi in prostate cancer, the potential synergies, and combinations being investigated as well as the future directions of PARPi for the management of the disease.
Current evidence of PD-1 and PD-L1 immune checkpoint inhibitors for esophageal cancer: an updated meta-analysis and synthesis of ongoing clinical trials
Authors: Zafar Saram , Shehzadi Rabbia , Dawood Hina , Maqbool Moeez , Sarfraz Azza , Sarfraz Zouina
Published: January 2024

Background:

Esophageal cancer (EC) is the sixth leading cause of cancer mortality worldwide, with a poor prognosis and a 5-year survival rate of 5% in advanced cases.

Objectives:

To evaluate the efficacy of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors in EC patients by analyzing phase III clinical trials.

Design:

A meta-analysis following the PRISMA Statement 2020 guidelines.

Methods:

PubMed/MEDLINE, Web of Science, and Embase were searched through 6 December 2022, and the analysis was conducted using Review Manager 5.4.3 (Cochrane).

Results:

Out of 387 studies, 13 phase III clinical trials with 6519 participants were pooled. Overall survival (OS) favored PD-1/PD-L1 inhibitors with a Cohen’s d of 0.28 (95% CI: 0.12–0.43; p = 0.0006), and the likelihood of achieving objective response also favored these inhibitors (OR: 2.04, 95% CI: 1.68–2.48; p < 0.0001).

Conclusion:

This meta-analysis provides strong evidence that PD-1/PD-L1 inhibitors combined with chemotherapy improve OS and objective response rate among patients with advanced EC but do not affect progression-free survival.

Trial registration:

Open Science Framework: osf.io/y27rx.
Virtual Reality Meets Diabetes
Authors: Vaughan Neil
Published: January 2024

Background:

This article provides a detailed summary of virtual reality (VR) and augmented reality (AR) applications in diabetes. The purpose of this comparative review is to identify application areas, direction and provide foundation for future virtual reality tools in diabetes.

Method:

Features and benefits of each VR diabetes application are compared and discussed, following a thorough review of literature on virtual reality for diabetes using multiple databases. The weaknesses of existing VR applications are discussed and their strengths identified so that these can be carried forward. A novel virtual reality diabetes tool prototype is also developed and presented.

Results:

This research identifies three major categories where VR is being used in diabetes: education, prevention and treatment. Within diabetes education, there are three target groups: clinicians, adults with diabetes and children with diabetes. Both VR and AR have shown benefits in areas of Type 1 and Type 2 diabetes.

Conclusions:

Virtual reality and augmented reality in diabetes have demonstrated potential to enhance training of diabetologists and enhance education, prevention and treatment for adults and children with Type 1 or Type 2 diabetes. Future research can continually build on virtual and augmented reality diabetes applications by integrating wide stakeholder inputs and diverse digital platforms. Several areas of VR diabetes are in early stages, with advantages and opportunities. Further VR diabetes innovations are encouraging to enhance training, management and treatment of diabetes.
Sharenting and social media properties: Exploring vicarious data harms and sociotechnical mitigations
Authors: Ugwudike Pamela , Roth Silke , Lavorgna Anita , Middleton Stuart E. , Djohari Natalie , Tartari Morena , Mandal Arpan
Published: January 2024

In this paper, we demonstrate how social media technologies can co-produce data-related harms unless preventative measures are instituted. To this end, we draw on a passive ethnography of a public Facebook group in the UK practicing sharenting which occurs when parents and guardians post sensitive and identifying information about children in their care on social media. Theoretically, we draw on the ‘harm translation’ concept from digital criminology and the ‘seductions of crime’ perspective from cultural criminology. Further we analyse documents on the operations of Facebook's content filtering algorithms published by Meta (Facebook's parent company). With insights from these sources, we demonstrate how platform technologies go beyond facilitation to the inadvertent co-production of harm via embedded mediative properties that shape user perception and action. We show that, in the specific context of sharenting, the properties invite rather than simply facilitate the practice and can also invite subsequent misuses of child-centric data. Through our analysis of these dynamics, we set out an empirical basis for challenging reductive depictions of social media technologies as solely facilitative of human action including harmful conduct. We also outline our vision to integrate insights from the analysis into a new sociotechnical harm prevention framework informed by Natural Language Processing approaches.
A feeling for the algorithm: Diversity, expertise, and artificial intelligence
Authors: Stinson Catherine , Vlaad Sofie
Published: January 2024

Diversity is often announced as a solution to ethical problems in artificial intelligence (AI), but what exactly is meant by diversity and how it can solve those problems is seldom spelled out. This lack of clarity is one hurdle to motivating diversity in AI. Another hurdle is that while the most common perceptions about what diversity is are too weak to do the work set out for them, stronger notions of diversity are often defended on normative grounds that fail to connect to the values that are important to decision-makers in AI. However, there is a long history of research in feminist philosophy of science and a recent body of work in social epistemology that taken together provide the foundation for a notion of diversity that is both strong enough to do the work demanded of it, and can be defended on epistemic grounds that connect with the values that are important to decision-makers in AI. We clarify and defend that notion here by introducing emergent expertise as a network phenomenon wherein groups of workers with expertise of different types can gain knowledge not available to any individual alone, as long as they have ways of communicating across types of expertise. We illustrate the connected epistemic and ethical benefits of designing technology with diverse groups of workers using the examples of an infamous racist soap dispenser, and the millimeter wave scanners used in US airport security.
Evaluation of a Fast Method to Measure High-Frequency Audiometry Based on Bayesian Learning
Authors: Casolani Chiara , Borhan-Azad Ali , Sørensen Rikke Skovhøj , Schlittenlacher Josef , Epp Bastian
Published: January 2024

This study aimed to assess the validity of a high-frequency audiometry tool based on Bayesian learning to provide a reliable, repeatable, automatic, and fast test to clinics. The study involved 85 people (138 ears) who had their high-frequency thresholds measured with three tests: standard audiometry (SA), alternative forced choice (AFC)-based algorithm, and Bayesian active (BA) learning-based algorithm. The results showed median differences within ±5 dB up to 10 kHz when comparing the BA with the other two tests, and median differences within ±10 dB at higher frequencies. The variability increased from lower to higher frequencies. The BA showed lower thresholds compared to the SA at the majority of the frequencies. The results of the different tests were consistent across groups (age, hearing loss, and tinnitus). The data for the BA showed high test–retest reliability (>90%). The time required for the BA was shorter than for the AFC (4 min vs. 13 min). The data suggest that the BA test for high-frequency audiometry could be a good candidate for clinical screening. It would add reliable and significant information without adding too much time to the visit.
Many mountain paths: Perceiving change in the management of community forests in the Hindu Kush Himalaya, Uttarakhand, India
Authors: Stevens Madison , Satterfield Terre
Published: January 2024

India's high mountain, van panchayat forests are a long-standing example of community-led forest governance. These provide vital support for mountain communities’ wellbeing, yet little is known about how environmental and social change is currently perceived or addressed, despite many claims that characterize van panchayats to be in crisis due to policy interventions by state forest actors and erosion of local management institutions. This research investigates how changes in forest dependence, governance, and health drive forest management decisions. Using open-ended interviews with 41 forest stewards and knowledge holders in a high mountain valley in Uttarakhand, our analysis describes managers’ perceptions of environmental and social changes and their implications for management choices. We found that van panchayats are currently navigating stewardship pathways in response to: (a) population shifts and changes to historically forest-dependent livelihoods; (b) a shift in governance regimes across van panchayats, affected by both regulatory changes and local institutional capacity; (c) the effects of global environmental change as it intersects with local influences on mountain ecosystems. Forest stewards’ perceptions of the drivers, trends, significance, and appropriate management responses to these changes varied widely. An overall decline in rightsholders’ dependence on forest resources was commonly reported, as was improved forest health in van panchayats in relation to other forest types. However, van panchayat managers disagreed on whether declining dependence positively or negatively affects forest health, whether the state is absent or actively wresting control from communities, and if successful forest restoration efforts will continue. A lack of shared understanding of these issues complicates forest stewards’ efforts to cooperate towards mutually desired ends, exacerbated by a co-management policy which isolates forest councils’ efforts from neighbouring forests. Accordingly, we encourage policy changes to enhance collaborative decision-making and to address implications of diverse perceptions, priorities and practices of care in mountain forests.
Results From the POINT Pragmatic Randomized Trial: An Emergency Department-Based Peer Support Specialist Intervention to Increase Opioid Use Disorder Treatment Linkage and Reduce Recurrent Overdose
Authors: Watson Dennis P. , Tillson Martha , Taylor Lisa , Xu Huiping , Ouyang Fangqian , Beaudoin Francesca L. , O’Donnell Daniel , McGuire Alan B.
Published: January 2024

Background:

People with opioid use disorder (OUD) frequently present at the emergency department (ED), a potentially critical point for intervention and treatment linkage. Peer recovery support specialist (PRSS) interventions have expanded in US-based EDs, although evidence supporting such interventions has not been firmly established.

Methods:

Researchers conducted a pragmatic trial of POINT (Project Planned Outreach, Intervention, Naloxone, and Treatment), an ED-initiated intervention for harm reduction and recovery coaching/treatment linkage in 2 Indiana EDs. Cluster randomization allocated patients to the POINT intervention (n  = 157) versus a control condition (n  = 86). Participants completed a structured interview, and all outcomes were assessed using administrative data from an extensive state health exchange and state systems. Target patients (n  = 243) presented to the ED for a possible opioid-related reason. The primary outcome was overdose-related ED re-presentation. Key secondary outcomes included OUD medication treatment linkage, duration of medication in days, all-cause ED re-presentation, all-cause inpatient re-presentation, and Medicaid enrollment. All outcomes were assessed at 3-, 6-, and 12-months post-enrollment. Ad hoc analyses were performed to assess treatment motivation and readiness.

Results:

POINT and standard care participants did not differ significantly on any outcomes measured. Participants who presented to the ED for overdose had significantly lower scores (3.5 vs 4.2, P < .01) regarding readiness to begin treatment compared to those presenting for other opioid-related issues.

Conclusions:

This is the first randomized trial investigating overdose outcomes for an ED peer recovery support specialist intervention. Though underpowered, results suggest no benefit of PRSS services over standard care. Given the scope of PRSS, future work in this area should assess more recovery- and harm reduction-oriented outcomes, as well as the potential benefits of integrating PRSS within multimodal ED-based interventions for OUD.
Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment
Authors: Barg Assaf Arie , Livnat Tami , Kenet Gili
Published: January 2024

Factor XI (FXI) deficiency is a rare bleeding disorder that presents complex challenges in patient assessment and bleeding risk management. Despite generally causing mild to moderate bleeding symptoms, clinical manifestations can vary, and bleeding tendency does not always correlate with FXI plasma levels or genotype. Our manuscript delves into the age-related nuances of FXI deficiency across an individual's lifespan. We emphasize issues faced by specific groups, including neonates and females of reproductive age experiencing abnormal uterine bleeding and postpartum hemorrhage. Older patients present unique challenges and concerns related to the management of bleeding as well as thrombotic complications. The current assortment of diagnostic laboratory assays shows limited success in predicting bleeding risk in the perisurgical setting of patients with FXI deficiency. This review explores the intricate interplay between individual bleeding profiles, surgical sites, and FXI activity levels. We also evaluate the accuracy of existing laboratory assays in predicting bleeding and discuss the potential role of investigational global assays in perioperative assessment. Furthermore, we outline our suggested diagnostic approach to refine treatment strategies and decision making. Available treatment options are presented, including antifibrinolytics, replacement products, and recombinant activated FVII. Finally, we discuss promising nonreplacement therapies for the treatment of rare bleeding disorders that can potentially address the challenges faced when managing FXI deficiency–related bleeding complications.
The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
Authors: Radtke Andrea J. , Roschewski Mark
Published: January 2024

Follicular lymphoma (FL) is a generally incurable malignancy that originates from developmentally blocked germinal center B cells residing, primarily, within lymph nodes (LNs). During the long natural history of FL, malignant B cells often disseminate to multiple LNs and can affect virtually any organ. Nonmalignant LNs are highly organized structures distributed throughout the body, in which they perform functions critical for host defense. In FL, the malignant B cells “re-educate” the lymphoid environment by altering the phenotype, distribution, and abundance of other cells such as T cells, macrophages, and subsets of stromal cells. Consequently, dramatic anatomical changes occur and include alterations in the number, shape, and size of neoplastic follicles with an accompanying attenuation of the T-cell zone. Ongoing and dynamic interactions between FL B cells and the tumor microenvironment (TME) result in significant clinical heterogeneity observed both within and across patients. Over time, FL evolves into pathological variants associated with distinct outcomes, ranging from an indolent disease to more aggressive clinical courses with early death. Given the importance of both cell-intrinsic and -extrinsic factors in shaping disease progression and patient survival, comprehensive examination of FL tumors is critical. Here, we describe the cellular composition and architecture of normal and malignant human LNs and provide a broad overview of emerging technologies for deconstructing the FL TME at single-cell and spatial resolution. We additionally discuss the importance of capturing samples at landmark time points as well as longitudinally for clinical decision-making.
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

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

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

This 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

The 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

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

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

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

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

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

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

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.
Community-acquired Staphylococcus aureus skin and soft tissue infection risk assessment using hotspot analysis and risk maps: the case of California emergency departments
Authors: Morgan Bustamante Brittany L. , Fejerman Laura , May Larissa , Martínez-López Beatriz
Published: January 2024

Background

Community-acquired Staphylococcus aureus (CA-Sa) skin and soft tissue infections (SSTIs) are historically associated with densely populated urban areas experiencing high poverty rates, intravenous drug use, and homelessness. However, the epidemiology of CA-Sa SSTIs in the United States has been poorly understood since the plateau of the Community-acquired Methicillin-resistant Staphylococcus aureus epidemic in 2010. This study examines the spatial variation of CA-Sa SSTIs in a large, geographically heterogeneous population and identifies neighborhood characteristics associated with increased infection risk.

Methods

Using a unique neighborhood boundary, California Medical Service Study Areas, a hotspot analysis, and estimates of neighborhood infection risk ratios were conducted for all CA-Sa SSTIs presented in non-Federal California emergency departments between 2016 and 2019. A Bayesian Poisson regression model evaluated the association between neighborhood-level infection risk and population structure, neighborhood poverty rates, and being a healthcare shortage area.

Results

Emergency departments in more rural and mountainous parts of California experienced a higher burden of CA-Sa SSTIs between 2016 and 2019. Neighborhoods with high infection rates were more likely to have a high percentage of adults living below the federal poverty level and be a designated healthcare shortage area. Measures of population structure were not associated with infection risk in California neighborhoods.

Conclusions

Our results highlight a potential change in the epidemiology of CA-Sa SSTIs in California emergency departments. Future studies should investigate the CA-Sa burden in other geographies to identify whether this shift in epidemiology holds across other states and populations. Further, a more thorough evaluation of potential mechanisms for the clustering of infections seen across California neighborhoods is needed.
The impact of racism on subsequent healthcare use and experiences for adult New Zealanders: a prospective cohort study
Authors: Harris Ricci , Cormack Donna , Waa Andrew , Edwards Richard , Stanley James
Published: January 2024

Background

Racism is an important determinant of health and driver of racial/ethnic health inequities. Experience of racism has been linked to negative healthcare use and experiences although most studies have been cross-sectional. This study examines the relationship between reported experience of racism and subsequent use and experience of health services.

Methods

This is a prospective cohort study design. The 2016/2017 adult New Zealand Health Survey (NZHS) provided the sampling frame and baseline data on exposures, health status and confounders. This stand-alone study invited all exposed individuals to participate when sampled based on their reported experience of racism (ever), stratified by broad ethnic groupings (Māori, Pacific, Asian, European/Other). Equal numbers of unexposed participants were selected for invitation using propensity score matching (propensity to experience racism, based on key available predictive factors). Follow-up was one to two years after NZHS interview. Outcome variables (last 12 months) were: unmet healthcare need (overall, for mental health, for a general practitioner); satisfaction with usual medical centre; and experiences with general practitioners (explaining care, involvement in decision-making, treated with respect/dignity, confidence and trust). Logistic regression models examining the association between experience of racism (at baseline) and health service use and experience (at follow-up) used doubly-robust estimation to weight for propensity scores used in the sampling with additional adjustment for confounders.

Results

The study had 2010 participants. Experience of racism (ever) at baseline was associated with higher overall unmet need at follow-up (adjusted OR (aOR) = 1.71, 95% CI 1.31, 2.23), with similar patterns for other unmet need measures. Experience of racism was associated with higher dissatisfaction with a usual medical centre (aOR = 1.41, 95% CI 1.10, 1.81) and with higher reporting of negative patient experiences.

Conclusion

In line with how racism structures oppression, exposure to racism is largely felt by non-European groups in Aotearoa New Zealand. Experiences of racism potentially lead to poorer healthcare and healthcare inequities through higher unmet need, lower satisfaction and more negative experiences of healthcare. The health system has a critical role to play in addressing racism within healthcare and supporting societal efforts to eliminate racism and ethnic inequities.