bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating end-of-life decision-making in nursing: a systematic review of ethical challenges and palliative care practices
Authors: Alanazi Majed Awad , Shaban Marwa Mamdouh , Ramadan Osama Mohamed Elsayed , Zaky Mohammed Elsayed , Mohammed Huda Hamdy , Amer Fatma Gomaa Mohamed , Shaban Mostafa 
Published: July 2024

Abstract
Objectives
This systematic review aimed to synthesize evidence on the ethical dilemma’s nurses encounter in end-of-life care and effective palliative care practices. The objectives were to understand key ethical issues, evaluate communication and decision-making strategies, and identify approaches to support nurses and patients.

Methods
A comprehensive search of major databases was conducted according to the PRISMA guidelines. Studies directly relating to nursing ethics, challenges in end-of-life decision-making, and palliative care practices were included. The risk of bias was assessed using ROBVIS-II. Data on ethical issues, palliative interventions, and outcomes was extracted and analyzed thematically.

Results
22 studies met the inclusion criteria. Key themes that emerged were: (1) Effective communication and involving patients in decision-making are essential but complex. (2) Nurses face dilemmas around balancing autonomy, beneficence and relational issues. (3) Integrating palliative care principles enhances symptom management and aligns care with patient values. (4) Education and organizational support are needed to equip nurses with skills and coping strategies.

Conclusion
Navigating end-of-life care requires addressing interconnected ethical, communication and support needs. While studies provided insights, further research is required on cultural competence training, standardized education programs and longitudinal evaluations.
Adolescent girls and young women’s (AGYW) access to and use of contraception services in Cape Town: perspectives from AGYW and health care providers
Authors: Tolla Tsidiso , Bergh Kate , Duby Zoe , Gana Nandipha , Mathews Catherine , Jonas Kim 
Published: July 2024

Abstract
Background
Access and use of contraception services by adolescent girls and young women (AGYW) remains suboptimal, exposing AGYW to early and often unexpected pregnancy. Unexpected pregnancies are a public health concern, associated with poor neonatal and maternal health outcomes, as well as school dropout, which may result in economic hardships. This study aimed to explore (a) AGYW perceptions and experiences of receiving contraception services from health care providers and (b) health care providers’ perceptions and experiences of providing contraception services to AGYW.

Methods
Data were collected through semi-structured individual interviews with AGYW aged 15–24 years old and health care providers working in eight health care facilities around the Cape Town metropolitan area, in South Africa’s Western Cape Province. Thematic analysis was used to analyse the data.

Results
AGYW and health care providers voiced varying, and often contrasting, perceptions of some of the barriers that hinder AGYW’s access to contraception services. AGYW indicated that provider-imposed rules about when to access contraceptive services hindered access, while health care providers felt that these rules were necessary for coordinating their work. In addition, AGYW highlighted health care providers’ hostile attitudes towards them as an important factor discouraging access. On the contrary, health care providers did not think that their attitudes hampered AGYW’s access to and use of contraception services, instead they emphasised that challenges at the health system level were a major issue, which they feel they have little control over. Such challenges made health care providers’ work unpleasant and frustrating, impacting on their work approach and how they receive and offer services to AGYW.

Conclusion
The expectation of negative attitudes from health care providers continues to be at the centre of AGYW discouragement towards accessing contraception services. System challenges are among some of the key drivers of health care provider’s hostile attitudes, posing challenges to the efficient provision of services. In order to improve AGYW’s access to and use of contraception services, and subsequently achieve the country’s SDGs, conscious efforts need to be directed towards improving the workload and working conditions of health care providers.
Toxicological insight of metiram: immuno-oxidative, neuro-behavioral, and hemato-biochemical changes during acute exposure of Nile tilapia (Oreochromis niloticus)
Authors: Shaalan Mohamed , Elbealy Mohamed A. , Darwish Mahmoud I. M. , Younis Elsayed M. , Abdelwarith Abdelwahab A. , Abdelaty Asmaa I. , Davies Simon J. , Ibrahim Rowida E. , Rahman Afaf N. Abdel 
Published: July 2024

Abstract
Background
The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture.

Objective
This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system.

Methods
Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish’s behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET’s impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored.

Results
The lethal concentration (LC50) of MET estimated using Finney’s probit technique was 3.77 mg/L. The fish’s behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure.

Conclusion
According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.
Mendelian randomization analysis reveals higher whole body water mass may increase risk of bacterial infections
Authors: Yan Peng , Yao Jiahuizi , Ke Ben , Fang Xiangdong 
Published: July 2024

Abstract
Background and purpose
The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections.

Methods
BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted.

Results
Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10− 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10− 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10− 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10− 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits.

Conclusions
In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.
Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial
Authors: Fitchett David , Zinman Bernard , Inzucchi Silvio E. , Wanner Christoph , Anker Stefan D. , Pocock Stuart , Mattheus Michaela , Vedin Ola , Lund Søren S. 
Published: July 2024

Abstract
Background
The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.

Methods
This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply–demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type.

Results
There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620–0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61–1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41–1.10)].

Conclusions
In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2.
Trail Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01131676.
Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer
Authors: Fu Yifan , Tao Jinxin , Liu Tao , Liu Yueze , Qiu Jiangdong , Su Dan , Wang Ruobing , Luo Wenhao , Cao Zhe , Weng Guihu , Zhang Taiping , Zhao Yupei 
Published: July 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has collectively revealed the heterogeneity of the TME from a multiomics perspective, outlined the development trajectories of cell lineages, and revealed important functions of previously underrated myeloid cells and tumor stroma cells. Concurrently, these findings necessitated more refined annotations of biological functions at the cell cluster or single-cell level. Precise identification of all cell clusters is urgently needed to determine whether they have been investigated adequately and to identify target cell clusters with antitumor potential, design compatible treatment strategies, and determine treatment resistance. Here, we summarize recent research on the PDAC TME at the single-cell multiomics level, with an unbiased focus on the functions and potential classification bases of every cellular component within the TME, and look forward to the prospects of integrating single-cell multiomics data and retrospectively reusing bulk sequencing data, hoping to provide new insights into the PDAC TME.
Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies
Authors: Shen Chang , Yang Qianjie , Chen Kuangqi , Ma Huiling , Wang Xiawei , Tong Jianping , Shen Ye , Cui Hongguang 
Published: July 2024

Abstract
Purpose
Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease.

Methods
Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype.

Results
Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice.

Conclusion
This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.
The association between osteoporosis and frailty: a cross-sectional observational study and mendelian randomization analysis
Authors: Que Zhiqiang , Lin Yilong , Chen Dingqiang , Xiao Keyi , Xu Wenbin , Sun Naikun , Yang Qingmo , Rui Gang 
Published: July 2024

Abstract
Background
Osteoporosis and frailty are two common features in the elderly population. Despite many review articles mentioning the association between osteoporosis and frailty, there is a lack of original research directly investigating their relationship. Therefore, this study was conducted to examine the correlation between osteoporosis and frailty.

Methods
We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES), using logistic regression analysis to assess the association of osteoporosis with the frailty index. In addition, we further explored the causal relationship between them using Mendelian randomization (MR) study.

Results
In the cross-sectional study, 19,091 non-frailty participants and 5878 frailty participants were included in this study. We observed a significant positive association between osteoporosis and frailty after adjusting for demographic characteristics, body mass index (BMI), smoking, and alcohol use (OR = 1.454, 95% CI [1.142,1.851], P = 0.003). Moreover, the MR study showed a bidirectional causal relationship between osteoporosis and frailty. When osteoporosis was used as an exposure factor, the frailty pooled OR value calculated utilizing the inverse variance weighted (IVW) method was 2.81 (95% CI [1.69, 4.68], P = 6.82 × 10− 5). When frailty was used as an exposure factor, the OR value calculated using the IVW method was 1.01 (95% CI [1.00,1.01], P = 3.65 × 10− 7).

Conclusions
Osteoporosis was positively correlated with frailty, and the results remained robust after adjusting for covariates. Further, MR studies have shown a bidirectional causal relationship between osteoporosis and frailty.
Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series
Authors: Hoarau Cyrille , Maleki Alireza , Bouillet Laurence , Boccon-Gibod Isabelle 
Published: July 2024

Abstract
Background
Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting.

Results
Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan.

Conclusions
Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.
Short and long-term acceptability and efficacy of extended-release cornstarch in the hepatic glycogen storage diseases: results from the Glyde study
Authors: Weinstein DA , Jackson RJ , Brennan EA , Williams M , Davison JE , Boer F de , Derks TGJ , Ellerton C , Faragher B , Gribben J , Labrune P , McKittrick KM , Murphy E , Ross KM , Steuerwald U , Voillot C , Woodward AJM , Mundy HR 
Published: July 2024

Abstract
Background
Hypoglycaemia is the primary manifestation of all the hepatic types of glycogen storage disease (GSD). In 2008, Glycosade®, an extended-release waxy maize cornstarch, was reported as an alternative to uncooked cornstarch (UCCS) which could prolong the duration of fasting in the GSD population. To date, there has been minimal published experience in (a) young children, (b) the ketotic forms of GSD, and (c) with daytime dosing. The Glyde study was created as a prospective, global initiative to test the efficacy and tolerance of Glycosade use across a broader and more diverse population.

Methods
A randomised double-blind cross-over fasting study assessing the tolerance and efficacy of Glycosade compared with cornstarch was performed across disease types and ages. Participants and clinicians chose the product deemed superior, whilst still blinded. Participants were followed for 2 years to assess long-term metabolic control, growth, and quality of life.

Results
Sixty-one participants (age 2–62 years; 59% female) were enrolled, and 58 participants completed the fasting studies (28 GSD I; 30 GSD III, VI, IX). Glycosade improved duration of fasting in GSD I and duration of fasting without ketosis in the ketotic forms. Chronic Glycosade use was chosen by 69% of participants. Those treated with Glycosade for the 2-year chronic phase used fewer doses of therapy while markers of metabolic control remained stable.

Conclusion
The Glyde study is the first multi-centre international trial demonstrating the efficacy and tolerance of Glycosade in a large cohort of hepatic GSD patients across a diverse international population. The ability to use fewer doses of therapy per day and avoidance of overnight therapy may improve compliance, safety, and quality of life without sacrificing metabolic control.