bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors
Authors: Cárdenas-Robledo Simón , Arenas-Vargas Laura Estefanía , Arenas Rubén Darío , Gaspar-Toro Jorge Mario , Muñoz-Rosero Ángela María , Tafur-Borrero Aranza Helena , Marín-Medina Daniel Stiven , Acosta-Fajardo Hernan Andrés , Guío-Sánchez Claudia , López-Reyes Lorena
Published: April 2024

Background

Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown.

Objectives

To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS.

Methods

We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan–Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality.

Results

Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01–1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs.

Conclusions

A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.
Migraine treatment: quo vadis? Real-world data study (2015–2022) in Spain
Authors: Pozo-Rosich Patricia , Carmo Mafalda , Muñiz Alejandro , Armada Beatriz , Moya-Alarcón Carlota , Pascual Julio
Published: April 2024

Background

Migraine is a leading cause of disability, estimated to affect one-in-ten people in Spain. This study aimed to describe the management of migraine in Spain and identify improvement areas.

Methods

Non-interventional, retrospective, cross-sectional cohort study conducted using an electronic medical records database covering visits to public healthcare providers for 3% of the Spanish population. Patients with a migraine diagnosis (ICD-9 346) between 01/2015 and 04/2022 were included, as well as their demographic and clinical characteristics, prescribed migraine treatments and the specialty of the prescribing physicians.

Results

The database included 61,204 patients diagnosed with migraine. A migraine treatment had been prescribed to 50.6% of patients over the last 24 months (only acute to 69.5%, both acute and preventive to 24.2%, and only preventive to 6.3%). The most frequently prescribed treatments were NSAIDs (56.3%), triptans (44.1%) and analgesics (28.9%). Antidepressants were the most common preventive treatment (prescribed to 17.9% of all treated patients and 58.7% of those treated with a preventive medication), and anti-CGRP monoclonal antibodies the least prescribed (1.7%; 5.7%). In 13.4% of cases, preventive medications were the first treatment: alone in 5.8% of cases and together with an acute medication in 7.6%. A fifth of patients who were initially prescribed with only acute treatment were later prescribed a preventive medication (20.7%). On average, it took 29.4 months for this change to occur. Two-thirds of patients started their preventive treatment in primary care (64.2%). The percentage of patients treated by a neurologist increased with the number of received preventive medications. However, 28.8% of patients who had already been prescribed five or more distinct preventive treatments were not treated by a neurologist. Migraine patients had between 1.2- and 2.2-times higher prevalence of comorbidities than the general population, age-gender adjusted.

Conclusions

Our study emphasizes the need for improved management of migraine in Spain to reduce the risk of chronification and improve patient outcomes. More training and coordination across healthcare professionals is necessary to recognize and address risk factors for migraine progression, including multiple associated comorbidities and several lines of treatment, and to provide personalized treatment plans that address the complex nature of the condition.
Recreating the village: the patient experience with a hybrid model of Group Perinatal Care (GPPC) in an academic family health team
Authors: Biringer Anne , Morson Natalie , Walji Sakina , Tregaskiss Natalie , Merritt Susannah , Makuwaza Tutsirai , Forte Milena
Published: April 2024

Background

Group prenatal care (GPC) has been shown to have a positive impact on social support, patient knowledge and preparedness for birth. We developed an interprofessional hybrid model of care whereby the group perinatal care (GPPC) component was co-facilitated by midwives (MW) and family medicine residents (FMR) and alternating individual visits were provided by family physicians (FP’s) within our academic family health team (FHT) In this qualitative study, we sought to explore the impact of this program and how it supports patients through pregnancy and the early newborn period.

Methods

Qualitative study that was conducted using semi-structured telephone interviews with 18 participants who had completed GPPC in the Mount Sinai Academic Family Health Team in Toronto, Canada and delivered between November 2016 and October 2018. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted by team members using grounded theory.

Results

Four over-arching themes emerged from the data: (i) Participants highly valued information they received from multiple trusted sources, (ii) Participants felt well cared for by the collaborative and coordinated interprofessional team, (iii) The design of GPPC enabled a shared experience, allowing for increased support of the pregnant person, and (iv) GPPC facilitated a supportive transition into the community which positively impacted participants’ emotional well- being.

Conclusions

The four constructs of social support (emotional, informational, instrumental and appraisal) were central to the value that participants found in GPPC. This support from the team of healthcare providers, peers and partners had a positive impact on participants’ mental health and helped them face the challenges of their transition to parenthood.
Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area
Authors: Wu Zhiyuan , Zhang Qingyun , Jin Yiting , Zhang Xinju , Chen Yanli , Yang Can , Tang Xuemei , Jiang Haowen , Wang Xiaoyi , Zhou Xinli , Yu Feng , Wang Bing , Guan Ming
Published: April 2024

Background

Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group.

Methods

We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers.

Results

Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months).

Conclusion

The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.
Knockdown of NCAPD3 inhibits the tumorigenesis of non-small cell lung cancer by regulation of the PI3K/Akt pathway
Authors: Yang Fan , Zheng Yunfeng , Luo Qiong , Zhang Suyun , Yang Sheng , Chen Xiangqi
Published: April 2024

Background

Accumulating evidence indicates that aberrant non-SMC condensin II complex subunit D3 (NCAPD3) is associated with carcinogenesis of various cancers. Nevertheless, the biological role of NCAPD3 in the pathogenesis of non-small cell lung cancer (NSCLC) remains unclear.

Methods

Immunohistochemistry and Western blot were performed to assess NCAPD3 expression in NSCLC tissues and cell lines. The ability of cell proliferation, invasion, and migration was evaluated by CCK-8 assays, EdU assays, Transwell assays, and scratch wound healing assays. Flow cytometry was performed to verify the cell cycle and apoptosis. RNA-sequence and rescue experiment were performed to reveal the underlying mechanisms.

Results

The results showed that the expression of NCAPD3 was significantly elevated in NSCLC tissues. High NCAPD3 expression in NSCLC patients was substantially associated with a worse prognosis. Functionally, knockdown of NCAPD3 resulted in cell apoptosis and cell cycle arrest in NSCLC cells as well as a significant inhibition of proliferation, invasion, and migration. Furthermore, RNA-sequencing analysis suggested that NCAPD3 contributes to NSCLC carcinogenesis by regulating PI3K/Akt/FOXO4 pathway. Insulin-like growth factors-1 (IGF-1), an activator of PI3K/Akt signaling pathway, could reverse NCAPD3 silence-mediated proliferation inhibition and apoptosis in NSCLC cells.

Conclusion

NCAPD3 suppresses apoptosis and promotes cell proliferation via the PI3K/Akt/FOXO4 signaling pathway, suggesting a potential use for NCAPD3 inhibitors as NSCLC therapeutics.
Non-canonical transcriptional regulation of the poor prognostic factor UGT2B17 in chronic lymphocytic leukemic and normal B cells
Authors: Rouleau Michèle , Villeneuve Lyne , Allain Eric P. , McCabe-Leroux Jules , Tremblay Sophie , Nguyen Van Long Flora , Uchil Ashwini , Joly-Beauparlant Charles , Droit Arnaud , Guillemette Chantal
Published: April 2024

Background

High expression of the glycosyltransferase UGT2B17 represents an independent adverse prognostic marker in chronic lymphocytic leukemia (CLL). It also constitutes a predictive marker for therapeutic response and a drug resistance mechanism. The key determinants driving expression of the UGT2B17 gene in normal and leukemic B-cells remain undefined. The UGT2B17 transcriptome is complex and is comprised of at least 10 alternative transcripts, identified by previous RNA-sequencing of liver and intestine. We hypothesized that the transcriptional program regulating UGT2B17 in B-lymphocytes is distinct from the canonical expression previously characterized in the liver.

Results

RNA-sequencing and genomics data revealed a specific genomic landscape at the UGT2B17 locus in normal and leukemic B-cells. RNA-sequencing and quantitative PCR data indicated that the UGT2B17 enzyme is solely encoded by alternative transcripts expressed in CLL patient cells and not by the canonical transcript widely expressed in the liver and intestine. Chromatin accessible regions (ATAC-Seq) in CLL cells mapped with alternative promoters and non-coding exons, which may be derived from endogenous retrotransposon elements. By luciferase reporter assays, we identified key cis-regulatory STAT3, RELA and interferon regulatory factor (IRF) binding sequences driving the expression of UGT2B17 in lymphoblastoid and leukemic B-cells. Electrophoretic mobility shift assays and pharmacological inhibition demonstrated key roles for the CLL prosurvival transcription factors STAT3 and NF-κB in the leukemic expression of UGT2B17.

Conclusions

UGT2B17 expression in B-CLL is driven by key regulators of CLL progression. Our data suggest that a NF-κB/STAT3/IRF/UGT2B17 axis may represent a novel B-cell pathway promoting disease progression and drug resistance.
Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions
Authors: Sulavikova Zuzana , Sustykevicova Zuzana , Kacerik Marek , Kozak Igor
Published: April 2024

Purpose

This study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion.

Methods

A retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography.

Results

The mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 μm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression.

Conclusion

We observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.
Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report
Authors: Na Jia , Cui Lang , Zhen Zhen , Chen Xi , Li Qirui , Gao Lu , Yuan Yue
Published: April 2024

Background

Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case.

Case presentation

A 7-year-old girl was admitted to the Cardiology Department of Beijing Children’s Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation.

Conclusions

The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.
Association of childhood trauma, social support, cognition, and suicidality in females with bipolar disorder
Authors: Yang Min , Li Jiaxin , Fu Yaqian , Wang Guotao , Liu Minghui , Chen Jindong , Liu Jieyu
Published: April 2024

Background

Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD.

Methods

This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales.

Results

Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016).

Conclusions

This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.
Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia
Authors: He Jingqi , Li Jinguang , Wei Yisen , He Zhangyin , Liu Junyu , Yuan Ning , Zhou Risheng , He Xingtao , Ren Honghong , Gu Lin , Liao Yanhui , Chen Xiaogang , Tang Jinsong
Published: April 2024

Background

Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels.

Methods

Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).

Result

The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.

Conclusion

Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.
Social support predicted subsequent subjective well-being during the COVID-19 pandemic: a prospective study
Authors: Mao Yanhui , Chen Junpeng , Liu Xinqi , Dang Junhua , Schiöth Helgi B.
Published: April 2024

Background

Subjective well-being (SWB) is associated with social support in cross-sectional studies. However, it remains unclear whether and how social support predicts SWB longitudinally, especially during the COVID-19 contingency.

Methods

By adopting a prospective design, the current work addressed this research question in a sample of 594 participants from the U.K. The data were collected via the online platform, Prolific, at two time points (June, 2020 and August, 2021) with a 14-month interval. Descriptive analysis and a moderated mediation model were conducted to test the proposed hypotheses.

Results

Baseline social support was a significant predictor of subjective well-being (SWB) 14 months later, even after controlling for baseline SWB and other covariates such as personality traits. Additionally, affect balance (i.e., the affective component of SWB) fully mediated the link between baseline social support and subsequent life satisfaction (i.e., the cognitive component of SWB). Moreover, household income moderated this relationship, indicating a stronger mediation for individuals with lower monthly household income.

Conclusion

The present work sheds light on the underlying mechanism and boundary condition of the association between social support and different components of SWB during the COVID-19 pandemic.
The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks
Authors: Wang Hsin-Yi , Tsai Shih-Chuan , Lin Yi-Ching , Hou Jing-Uei , Chao Chih-Hao
Published: April 2024

Background

The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure.

Methods

Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated.

Results

The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant.

Discussion

This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.
Neq2X7: a multi-purpose and open-source fusion DNA polymerase for advanced DNA engineering and diagnostics PCR
Authors: Hernández-Rollán Cristina , Ehrmann Anja K. , Vlassis Arsenios , Kandasamy Vijayalakshmi , Nørholm Morten H. H.
Published: April 2024

Thermostable DNA polymerases, such as Taq isolated from the thermophilic bacterium Thermus aquaticus, enable one-pot exponential DNA amplification known as polymerase chain reaction (PCR). However, properties other than thermostability - such as fidelity, processivity, and compatibility with modified nucleotides - are important in contemporary molecular biology applications. Here, we describe the engineering and characterization of a fusion between a DNA polymerase identified in the marine archaea Nanoarchaeum equitans and a DNA binding domain from the thermophile Sulfolobus solfataricus. The fusion creates a highly active enzyme, Neq2X7, capable of amplifying long and GC-rich DNA, unaffected by replacing dTTP with dUTP in PCR, and tolerant to various known PCR inhibitors. This makes it an attractive DNA polymerase for use, e.g., with uracil excision (USER) DNA assembly and for contamination-free diagnostics. Using a magnification via nucleotide imbalance fidelity assay, Neq2X7 was estimated to have an error rate lower than 2 ∙ 10−5 bp−1 and an approximately 100x lower fidelity than the parental variant Neq2X, indicating a trade-off between fidelity and processivity – an observation that may be of importance for similarly engineered DNA polymerases. Neq2X7 is easy to produce for routine application in any molecular biology laboratory, and the expression plasmid is made freely available.
Effect of evidence-based nursing practices training programme on the competency of nurses caring for mechanically ventilated patients: a randomised controlled trial
Authors: Elhabashy Sameh , Moriyama Michiko , Mahmoud Eman Ibrahim El-Desoki , Eysa Basem
Published: April 2024

Background

Evidence-Based Practice (EBP) has been recognised worldwide as a standardised approach for enhancing the quality of healthcare and patient outcomes. Nurses play a significant role in integrating EBP, especially in Intensive Care Unit (ICU). Consequently, this study aims to examine the effect of an adapted evidence-based nursing practices training programme on the competency level of nurses caring for mechanically ventilated patients.

Methods

A prospective open-label parallel 1:1 randomised controlled trial was conducted on 80 nurses caring for ICU patients at the National Hepatology and Tropical Medicine Research Institute, Egypt. The trial was carried out between November 2022 and February 2023 under the registration number NCT05721664. The enrolled nurses were randomly divided into intervention and control groups. The intervention group received the evidence-based nursing practice training programme (EBNPTP) in accordance with the Johns Hopkins EBP conceptional model, whereas the control group received traditional in-service education. Four assessments (one pre- and three post-assessments) were conducted to evaluate nurses’ competency level over time using the adapted evidence-based nursing competency assessment checklist. The primary endpoint was an increase the competency levels among nurses caring for mechanically ventilated patients.

Results

The current study results revealed statistically significant differences between intervention and control groups in relation to their level of competency across the three post-assessments, with (p <.001). The study also demonstrated that the nurses’ competency level continued to decline significantly over time, with (p <.001). Additionally, a significant correlation was found between the nurses’ pre-assessment and educational level, acting as independent variables (predictors), and the third endpoint assessment (p <.01), indicated by multiple linear regression.

Conclusion

The EBP training programme demonstrated a significant increase in the nurses’ level of competency compared with traditional in-service education. This suggests that by training the nurses in various settings with the essential skills and knowledge for EBP, their competency level can be enhanced, leading to the delivery of effective care and improving patient outcomes. However, the long-term sustainability of the EBP adoptions was insufficient; further studies are needed to investigate the factors that affect the durability of EBP adoption.

Trial registration

The study was registered with Clinical Trials.gov (Registration # NCT05721664) on 10/02/2023.
“To do or not to do”, male nurses’ experiences of providing intimate care to female patients in China, a constructivist grounded theory study
Authors: Lyu Xiao-Chen , Sun Xiang-Yun , Lee Li-Hung , Yang Cheng-I
Published: April 2024

Background

Some studies suggest that female patients have more concerns about receiving intimate care from male than female nurses. Thus, providing intimate care to female patients is a challenging experience for male nurses. The purpose of this study was to explore Chinese male nurses’ experiences and process of providing intimate clinical care to female patients.

Methods

A constructivist grounded theory approach was used to develop a theoretical understanding of male nurses’ experiences. This study included participants from 3 hospitals in different locations in China. Twenty-five male nurses were recruited using purposive and theoretical sampling. Semi-structured interviews were conducted. Data analysis was completed using initial coding, focused coding, theoretical coding and memo writing to produce core concepts and categories, and theory development.

Results

Chinese male nurses’ experiences of providing intimate care to female patients can be constructed as a three-stage process: (1) anticipation of the level of embarrassment, (2) deciding on the process: do it or not do it and (3) protecting both parties and dealing with embarrassment. Additionally, seven themes and associated categories were identified to represent the important factors in the process of male nurses providing intimate care to female patients in China.

Conclusions

Chinese traditional culture may affect the embarrassment in Chinese male nurses providing intimate care to female patients. The embarrassing situation can be divided into three different stages, and male nurses have different main concerns in each stage. Hospital nursing administrators should consider the experiences and needs of male nurses in providing intimate care and provide them with psychological support, education and training.
Building resilience: analysis of health care leaders’ perspectives on the Covid-19 response in Region Stockholm
Authors: Savage Carl , Tragl Leonard , Castillo Moa Malmqvist , Azizi Louisa , Hasson Henna , Sundberg Carl Johan , Mazzocato Pamela
Published: April 2024

Background

The Covid-19 pandemic has tested health care organizations worldwide. Responses have demonstrated great variation and Sweden has been an outlier in terms of both strategy and how it was enacted, making it an interesting case for further study. The aim of this study was to explore how health care leaders experienced the challenges and responses that emerged during the initial wave of the Covid-19 pandemic, and to analyze these experiences through an organizational resilience lens.

Methods

A qualitative interview study with 12 senior staff members who worked directly with or supervised pandemic efforts. Transcripts were analyzed using traditional content analysis and the codes directed to the Integrated Resilience Attributes Framework to understand what contributed to or hindered organizational resilience, i.e. how organizations achieve their goals by utilizing existing resources during crises.

Results/Findings

Organizational resilience was found at the micro (situated) and meso (structural) system levels as individuals and organizations dealt with acute shortages and were forced to rapidly adapt through individual sacrifices, resource management, process management, and communications and relational capacity. Poor systemic resilience related to misaligned responses and a lack of learning from previous experiences, negatively impacted the anticipatory phase and placed greater pressure on individuals and organizations to respond. Conventional crisis leadership could hamper innovation, further cement chronic challenges, and generate a moral tension between centralized directives and clinical microsystem experiences.

Conclusions

The pandemic tested the resilience of the health care system, placing undue pressure on micro and meso systems responses. With improved learning capabilities, some of this pressure may be mitigated as it could raise the anticipatory resilience potential, i.e. with better health systems learning, we may need fewer heroes. How crisis leadership could better align decision-making with frontline needs and temper short-term acute needs with a longer-term infinite mindset is worth further study.
A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus
Authors: White Billy , Ng S. M. , Agwu J. C. , Barrett T. G. , Birchmore N. , Kershaw M. , Drew J. , Kavvoura F. , Law J. , Moudiotis C. , Procter E. , Paul P. , Regan F. , Reilly P. , Sachdev P. , Sakremath R. , Semple C. , Sharples K. , Skae M. , Timmis A. , Williams E. , Wright N. , Soni A.
Published: April 2024

Background

Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes.

Methods

Multidisciplinary professionals from The Association of Children’s Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.

Results and discussion

Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events.

Conclusions

This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.
Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study
Authors: Wang Feihang , Zhao Danyang , Xu Wang-yang , Liu Yiying , Sun Huiyi , Lu Shanshan , Ji Yuan , Jiang Jingjing , Chen Yi , He Qiye , Gong Chengxiang , Liu Rui , Su Zhixi , Dong Yi , Yan Zhiping , Liu Lingxiao
Published: April 2024

Background

Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy.

Methods

This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes.

Results

The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies.

Conclusions

This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.
Goat flock abortion: a retrospective study at Abergelle Agricultural Research Center, Tigray, Ethiopia
Authors: Assefa Guash Abay , Teklue Teshale , Hagazi Mebrahtom , Mezgebe Gebretnsae , Aregawi Weldegebrial G. , Tesfaye Adehanom Baraki
Published: April 2024

Background

Small ruminants are the principal component of livestock production in Tigray region, Ethiopia. But their productivity is affected by various factors. According to farmers and expert observation, goat abortion is among the leading causes of production losses in Tanqua-Abergelle district. However, study findings that examine the extent of distribution and economic impact of abortion cases in goats in the district are scarce. This retrospective study investigated the occurrence of abortion and its associated risk factors in three goat breed types at Abergelle Agricultural Research Center goat breeding site over a seven year period. The study included a total of does above one year old, and data were collected from a casebook that was specifically prepared for abortion cases. A thorough follow up was conducted to identify abortion cases. Additionally, a community survey was conducted in selected villages where the research center is located.

Results

The overall abortion proportion was 29.8% in the goat farm. Begait goat breeds had the highest abortion proportion (50.9%, CI 0.36–0.64) in 2015/16. Multivariate logistic regression analysis identified year, season, age and breed as major risk factors of abortion occurrence at flock level. Accordingly, the likelihood of goats experiencing abortion during the dry season (proportion = 34) was 1.87 times higher compared to those in the wet season (proportion = 22.8). Begait breeds had a higher incidence of abortion (proportion 37.5%, OR 4.87, CI 2.49–10.35) compared to other breeds. Age was negatively associated with abortion, suggesting that older goats (OR = 0.67) had a higher relative risk than younger goats (OR = 0.57). Moreover, the study noted a high incidence of abortion during the years 2014/15 to 2016/17 (proportion = 35.7–39.7). Within-breed analysis revealed that age and season were significant risk factors for Abergelle and Begait breeds, respectively by using a multivariate logistic regression analysis. A community survey indicated that 89.7% households responded their goats experienced abortion.

Conclusions

This study highlighted the high prevalence of goat abortion at Abergelle and identifies important risk factors associated with its occurrence. The findings can inform targeted interventions to reduce abortion rates and improve goat productivity in the district.
A WNT mimetic with broad spectrum FZD-specificity decreases fibrosis and improves function in a pulmonary damage model
Authors: Patel Mehaben , Post Yorick , Hill Natalie , Sura Asmiti , Ye Jay , Fisher Trevor , Suen Nicholas , Zhang Mengrui , Cheng Leona , Pribluda Ariel , Chen Hui , Yeh Wen-Chen , Li Yang , Baribault Hélène , Fletcher Russell B.
Published: April 2024

Background

Wnt/β-catenin signaling is critical for lung development and AT2 stem cell maintenance in adults, but excessive pathway activation has been associated with pulmonary fibrosis, both in animal models and human diseases such as idiopathic pulmonary fibrosis (IPF). IPF is a detrimental interstitial lung disease, and although two approved drugs limit functional decline, transplantation is the only treatment that extends survival, highlighting the need for regenerative therapies.

Methods

Using our antibody-based platform of Wnt/β-catenin modulators, we investigated the ability of a pathway antagonist and pathway activators to reduce pulmonary fibrosis in the acute bleomycin model, and we tested the ability of a WNT mimetic to affect alveolar organoid cultures.

Results

A WNT mimetic agonist with broad FZD-binding specificity (FZD1,2,5,7,8) potently expanded alveolar organoids. Upon therapeutic dosing, a broad FZD-binding specific Wnt mimetic decreased pulmonary inflammation and fibrosis and increased lung function in the bleomycin model, and it impacted multiple lung cell types in vivo.

Conclusions

Our results highlight the unexpected capacity of a WNT mimetic to effect tissue repair after lung damage and support the continued development of Wnt/β-catenin pathway modulation for the treatment of pulmonary fibrosis.
Harnessing alkaline-pH regulatable promoters for efficient methanol-free expression of enzymes of industrial interest in Komagataella Phaffii
Authors: Albacar Marcel , Casamayor Antonio , Ariño Joaquín
Published: April 2024

Background

The yeast Komagataella phaffii has become a very popular host for heterologous protein expression, very often based on the use of the AOX1 promoter, which becomes activated when cells are grown with methanol as a carbon source. However, the use of methanol in industrial settings is not devoid of problems, and therefore, the search for alternative expression methods has become a priority in the last few years.

Results

We recently reported that moderate alkalinization of the medium triggers a fast and wide transcriptional response in K. phaffii. Here, we present the utilization of three alkaline pH-responsive promoters (pTSA1, pHSP12 and pPHO89) to drive the expression of a secreted phytase enzyme by simply shifting the pH of the medium to 8.0. These promoters offer a wide range of strengths, and the production of phytase could be modulated by adjusting the pH to specific values. The TSA1 and PHO89 promoters offered exquisite regulation, with virtually no enzyme production at acidic pH, while limitation of Pi in the medium further potentiated alkaline pH-driven phytase expression from the PHO89 promoter. An evolved strain based on this promoter was able to produce twice as much phytase as the reference pAOX1-based strain. Functional mapping of the TSA1 and HSP12 promoters suggests that both contain at least two alkaline pH-sensitive regulatory regions.

Conclusions

Our work shows that the use of alkaline pH-regulatable promoters could be a useful alternative to methanol-based expression systems, offering advantages in terms of simplicity, safety and economy.
Triglyceride to high-density lipoprotein cholesterol ratio associated with long-term adverse clinical outcomes in patients deferred revascularization following fractional flow reserve
Authors: Li Fanqi , Li Xiaofang , Zhou Jiabao , Lin Qiuzhen , Zhou Yong , Zhu Jiayi , Wu Keke , Zhao Donghui , Li Qiuyu , Wang Haixiong , Liu Qiming
Published: April 2024

Background

Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR.

Methods

This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs.

Results

47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05–6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65–4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C.

Conclusion

The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.
The interaction of inflammasomes and gut microbiota: novel therapeutic insights
Authors: Manshouri Shirin , Seif Farhad , Kamali Monireh , Bahar Mohammad Ali , Mashayekh Arshideh , Molatefi Rasol
Published: April 2024

Inflammasomes are complex platforms for the cleavage and release of inactivated IL-1β and IL-18 cytokines that trigger inflammatory responses against damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). Gut microbiota plays a pivotal role in maintaining gut homeostasis. Inflammasome activation needs to be tightly regulated to limit aberrant activation and bystander damage to the host cells. Several types of inflammasomes, including Node-like receptor protein family (e.g., NLRP1, NLRP3, NLRP6, NLRP12, NLRC4), PYHIN family, and pyrin inflammasomes, interact with gut microbiota to maintain gut homeostasis. This review discusses the current understanding of how inflammasomes and microbiota interact, and how this interaction impacts human health. Additionally, we introduce novel biologics and antagonists, such as inhibitors of IL-1β and inflammasomes, as therapeutic strategies for treating gastrointestinal disorders when inflammasomes are dysregulated or the composition of gut microbiota changes.