bluuebunny/crossref_metadata_2025_split huggingface dataset:
#612 Serum citrulline level is associated with oxidative stress and chronic kidney disease progression
Authors: Korol Lesya , Stepanova Natalia , Vasylchenko Victoria 
Published: May 2024

Abstract

Background and Aims
Citrulline, an α-amino acid crucial for the urea cycle and nitric oxide production, plays a protective role against free radicals and is indirectly related to protein metabolism. It is synthesized in the intestine and efficiently absorbed by the proximal renal tubules, where it is converted to urea via arginine. Although citrulline has multiple physiological effects, its involvement in the progression of chronic kidney disease (CKD) has not been explored. This cross-sectional study aimed to investigate the relationship between serum citrulline levels, CKD progression, and markers of oxidative stress.

Method
A total of 135 subjects were enrolled in this cross-sectional study. This cohort included 30 relatively healthy individuals who constituted the control group and 105 CKD patients who were categorized according to their estimated glomerular filtration rate (eGFR). We measured serum citrulline concentrations along with markers of oxidative stress, including paraoxonase 1 (PON-1), myeloperoxidase (MPO), and malondialdehyde (MDA), using the spectrophotometric method.
Data were expressed as mean (M) and standard deviation (SD) or median and interquartile range [Me (Q25-Q75)] according to the data distribution and compared with the Kruskal-Wallis test. Spearmen correlation test was performed to evaluate the correlation between the studied data.

Results
Our findings revealed a significant increase in citrulline and MDA concentrations and MPO activity and a significant decrease in PON-1 in the CKD group compared with the control group. Moreover, a significant association emerged between serum citrulline levels and the severity of CKD, as determined by eGFR. Specifically, patients in advanced CKD stages exhibited elevated serum citrulline concentrations in contrast to those in earlier stages (Table 1).
Furthermore, a significant correlation was established between serum citrulline and oxidative stress markers, with higher citrulline levels positively associated with increased concentrations of MDA (r = 0.46, p = 0.002) and heightened MPO activity (r = 0.85, p &lt; 0.001), and demonstrating an inverse relationship with PON-1 in CKD stages 1-2 and 5 (r = -0.64, p &lt; 0.001 and r = -0.47, p = 0.004, respectively).

Conclusion
This cross-sectional study suggests that serum citrulline level is associated with both CKD progression and oxidative stress intensity in patients with CKD. These findings highlight the potential role of citrulline as a biomarker for CKD progression and its implications in the management of oxidative stress in CKD. Further research is warranted to elucidate the underlying mechanisms and explore the therapeutic potential of citrulline supplementation in CKD patients.
#1664 Assessing vascular access thrombectomy service adherence to GIRFT recommendations: single centre experience
Authors: Donne Rosemary , Eltahan Alshymaa , Pondor Zulfikar , Lewis David , Raman Maharajan , Gleave Paula , Poulikakos Dimitrios 
Published: May 2024

Abstract

Background and Aims
Studies showed that early thrombectomy of dialysis vascular access (VA) is associated with better outcomes [1], especially for native VA [2]. Timely treatment of VA thrombosis within 24-48 hours is recommended by GIRFT to minimize access loss and requirement for dialysis line insertion [3]. Our centre has approximately 430 HD patients but has no on-site vascular surgery or vascular access interventional radiology (IR) service. Wait time for elective VA surgery or fistuloplasty is &gt;8 weeks and VA surveillance is based on routine clinical monitoring. VA prevalence is 62% AV fistula (AVF), 2% AV graft (AVG), 36% central venous catheter (CVC). Fistula thrombectomy is provided at another centre, with increasing waiting times over recent years due to shortage of interventional radiologists. This study evaluates adherence to GIRFT recommendations for patients at our centre requiring thrombectomy and will identify potential local strategies to reduce fistula thrombosis and CVC use.

Method
In a 24-months’ retrospective cohort analysis of maintenance HD patients with permanent VA, we obtained data on:

Results
44 patients with permanent VA developed VA thrombosis. The median waiting time for thrombectomy was 8 days (Fig. 1). Post-intervention primary patency rate was 71% at 3-months and 60% at 6-months (Fig. 2). 61% of patients required hospital admission with a 12-day median length of stay, with total inpatient admission days of 403 days over 2 years (2022-2023), and total cost of £246,065 (Figs. 3 and 4). The median CFD-extended was 356 days, i.e. 9 days/patient/year with VA-related complications (Fig. 5).

Conclusion
This study shows that our centre's VA thrombectomy service falls far outside the GIRFT recommendation of intervention within 24-48 hours. The high associated rates of CVC use, inpatient bed days and avoidable costs place a heavy burden on patient outcomes and NHS resources. The ideal solution of an on-site thrombectomy service is difficult to achieve due to lack of vascular IR support. In response to this study, we now aim to reduce thrombosis rates by training additional interventional nephrologists in elective fistuloplasty, implementing a robust VA surveillance to improve early detection of malfunctioning VA suitable for elective intervention and improving staff education on fistula care.
#2075 Impact of chronic obstructive pulmonary disease on the outcomes of hemodialysis patients
Authors: Hagai Keren Cohen , Benchetrit Sydney , Wand Ori , Amer Abu Husseine 
Published: May 2024

Abstract

Background and Aims
Chronic obstructive pulmonary disease, COPD, is a common cause of morbidity and mortality. Comorbidities are frequent among COPD patients, some of which are explained by shared risk factors of smoking and increased age. Chronic kidney disease, leading to end-stage renal disease requiring hemodialysis (HD) is not uncommon in patients with COPD, and vice-versa. The prevalence and the impact of coexistence of COPD among HD patients was not extensively described.
We aimed to measure the prevalence of COPD among a cohort of HD patients, and study how it relates to significant outcomes of mortality, morbidity, including unplanned hospital admissions, and kidney transplantation (KT).

Method
A retrospective study of subjects who initiated HD during 2015-2018. Participants were categorized into one of two groups, with or without COPD. Clinical, laboratory and pulmonary function tests data were extracted from medical records, as were outcomes of mortality, morbidity, and KT (until December 31st, 2021, or until death).

Results
Forty-three of 234 were diagnosed with COPD (18.4%). Their average FEV1%pred was 60%. Thirty-eight subjects in the COPD group (88.4%) were hospitalized for severe COPD exacerbations during a mean follow-up of 36.1 months, averaging 3.6 severe exacerbations per patient. Despite this, maintenance inhaler therapy was underutilized.
All-cause mortality rates were higher for HD patients with COPD (72.1% vs. 47.1%, p=0.003), as were rates of acute coronary syndrome (39.5% vs. 23.6%, p=0.026).

Conclusion
COPD is common among HD patients and is associated with significant morbidity and increased mortality.
#829 Renoprotective effects of laxative linaclotide: inhibition of acute kidney injury and fibrosis in a rat model of renal ischemia-reperfusion
Authors: Hitaka Yukihiro , Yamaguchi Misuhiro , Nakamura Kimihiko , Toshiya Hiroyoshi , Isoyama Naohito , Nagao Kazuhiro , Tsuji Shunya , Asagiri Asagirimasataka , Shiraishi Koji 
Published: May 2024

Abstract

Background and Aims
Acute kidney injury caused by renal ischemia/reperfusion (I/R) is a major clinical problem in many aspects of urology fields such as kidney transplantation and partial nephrectomy, but there is no effective treatment. Linaclotide, a guanylate cyclase C agonist clinically approved as a laxative, has recently been shown to be renoprotective in a chronic kidney disease (CKD) model. Therefore, the present study investigated the possibility that the renoprotective effects of linaclotide in renal I/R may extend beyond its gastrointestinal effects.

Method
The left renal pelvis of adult male Wistar rats was clamped for 45 minutes to induce renal I/R injury. Kidney tissue, colon, and blood were collected 24 hours and 14 days later. Linaclotide was administered for 14 days preoperatively and until postoperative tissue collection. Tissue sections were stained with standard histologic techniques such as HE, Sirius Red, F4/80, etc. As genes associated with I/R, TGF-β and related fibrosis markers α-SMA, MMP2, TIMP1 and inflammatory cytokines TNF, IL-1β and IL-6 were analyzed by quantitative PCR analysis.

Results
Serum creatinine levels decreased significantly after linaclotide administration, indicating improved renal function. Histologic examination showed less tubular damage and less collagen deposition on Sirius Red staining. Further analysis showed decreased expression of TGF-β and related fibrosis markers α-SMA, MMP2 and TIMP1, suggesting downregulation of the fibrotic TGF-β pathway by linaclotide. Furthermore, 1 day after I/R injury, linaclotide significantly reduced macrophage infiltration and suppressed key proinflammatory cytokines such as TNF, IL-1β, and IL-6.

Conclusion
These results suggest that linaclotide, with its established safety profile, could extend its benefits beyond gastrointestinal issues and potentially serve as a therapeutic intervention in many aspects of kidney surgeries. In addition, it could provide immediate and practical insights into the selection of laxatives for the management of patients with AKI or CKD, regardless of cause, and for those receiving dialysis or transplant therapy.
#804 The nonlinear association between body mass index and chronic kidney disease: a prospective cohort study and Mendelian randomization analysis
Authors: Zeng Xiaoxi , Yu Zhenzhen , Chen Jing 
Published: May 2024

Abstract

Background and Aims
Previous studies mainly focused on linear association between body mass index (BMI) and the risk of chronic kidney disease (CKD). In the current research, we conducted a prospective cohort observational study and Mendelian Randomization analysis to explore whether non-linear relationship exists between BMI and CKD.

Method
In the prospective cohort study, 495,465 participants from the UK biobank were included. The Cox proportional hazards model with fractional polynomial transformation was used to estimate the hazard ratio of BMI for incident CKD. In addition, nonlinear Mendelian Randomization analysis was performed using the fractional polynomial method to verify the causality of the association.

Results
In the observational analysis, a J-shaped association was observed between BMI and the risk of CKD. The risk of CKD was lowest when the BMI was around 18-20 kg/m2, and the hazard of developing CKD increased in participants with lower or higher BMI (Fig. 1). When assessing the causal relationship, in Mendelian Randomization analysis, despite that a nonlinear relationship still held true (P-value for non-linearity = 0.008), the odds ratio for CKD monotonically rised with increasing BMI (Fig. 2).

Conclusion
The J-shape association between BMI and CKD revealed by the observational cohort study was not supported by the Mendelian Randomization, which indicated a monotonically causal relationship that the risk of CKD rised with increasing BMI.
#305 Global health inequalities of CKD: a systematic review and meta-analysis examining prevalence and disparities in age, sex and socio-economic status
Authors: Duff Rachael , Awofala Omodolapo , Arshad Muhammad Tahir , Lambourg Emilie , Gallacher Peter , Dhaun Neeraj , Bell Samira 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is a significant contributor to global morbidity and mortality. Age, sex and socio-economic status are considered to be influential in the development, progression and outcomes from CKD. This study investigated disparities in age, sex and socio-economic status in CKD and updated global prevalence estimates through systematic review and meta-analysis.

Method
Five databases (MEDLINE/PubMed, Embase, Cochrane CENTRAL Library, CINAHL, Web of Science) were searched from 2014 to 2022, with 14,871 articles screened, 119 papers included and data analysed on 29,159,948 participants. Studies were included if they described CKD prevalence in participants over the age of 18 and were carried out in the general population. CKD was defined on the basis of albuminuria/proteinuria and/or an estimated glomerular filtration rate of &lt;60 ml/min/m2. Random effects meta-analyses using generalised linear mixed models were conducted to determine overall prevalence, prevalence of stages 3–5 and prevalence in males and females. Influences of age, sex and socio-economic status were assessed in subgroup analyses, and risk of bias assessment and meta-regressions were conducted to explore heterogeneity.

Results
Overall prevalence of CKD was 13.0% (11.3–14.8%) and 6.6% (5.6–7.8%) for stages 3–5. Prevalence was higher in studies where all participants were over the age of 60 (19.3% for stages 1–5. 15.0% for stages 3–5) and meta-regression demonstrated association of age, body mass index, diabetes and hypertension with prevalence of CKD stages 3–5. The prevalence of CKD stages 1–5 was similar in males and females (13.1% versus 13.2%) but prevalence of stages 3–5 was higher in females (6.4% versus 7.5%). Overall prevalence was 11.4%, 15.0% and 10.8% in low, middle and high-income countries respectively; for stages 3–5 prevalence was 4.0%, 6.7% and 6.8%, respectively. Risk of bias of included studies was generally moderate or high, with 8% at low risk of bias, 44% at moderate risk of bias and 48% at high risk of bias.

Conclusion
With nearly 30 million participants, this study is the largest systematic review on CKD prevalence to date, with prevalence demonstrated to be persistently high globally. It has highlighted that important disparities related to age, sex and socio-economic status may exist, and addressing these concerns should be a priority for policymakers. Future research should focus on targeted screening and treatment approaches, improving access to care and more effective data monitoring, particularly in low and middle income countries.
#2717 Fermentable and viscous dietary fiber types improve cortical bone in a rat model of chronic kidney disease-mineral and bone disorder
Authors: Biruete Annabel , Metzger Corinne , Blacklock Karis , Srinivasan Shruthi , O'neill Kalisha , Siles Samantha , Gallant Kathleen Hill , Allen Matthew , Chen Neal X , Moe Sharon 
Published: May 2024

Abstract

Background and Aims
Renal osteodystrophy is highly prevalent among people with chronic kidney disease (CKD). We recently showed that inulin, a prebiotic fermentable dietary fiber, improved cortical bone parameters in rats with moderate-to-severe CKD. Our objective was to evaluate if this effect was unique to the prebiotic fibers or if other fiber properties, such as viscosity, could be beneficial to bone in a rat model of CKD-mineral and bone disorder (CKD-MBD).

Method
22-week-old Cy/+ male rats (50% kidney function compared to normal; CKD hereafter) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (−fermentability, −viscosity), 2) Inulin (+fermentability, −viscosity), 3) Psyllium husk (−fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). These diets were formulated with a semi-purified, casein-based background diet with 0.7% calcium and 0.7% phosphorus. Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure; ∼15% of normal). Micro-computed tomography (μCT) at 12-μm resolution was performed on the proximal tibia. Serum creatinine, plasma phosphorus, and plasma calcium were analyzed using colorimetric assays. One-way ANOVA was used to test the effect of dietary fiber types on outcome measures.

Results
At 32 weeks of age, serum creatinine was lower in the inulin, psyllium, and pectin-treated CKD rats (&lt;0.04). Plasma calcium concentrations were similar between treatments, but phosphorus was lower in the psyllium and pectin-treated CKD rats (p &lt; 0.02). Bone cortical area was higher in the inulin and psyllium-treated CKD rats compared to cellulose-treated rats (p &lt; 0.007). Cortical thickness was higher in the inulin, psyllium, and pectin-treated CKD rats compared to cellulose-treated rats (p &lt; 0.02). There was less cortical porosity in the inulin, psyllium, and pectin-treated rats (p &lt; 0.02). Fermentable or viscous fibers did not impact trabecular bone volume, thickness, spacing, and number (p &lt; 0.05). Plasma phosphorus was negatively associated with cortical area (r = −0.56; p &lt; 0.0001) and cortical thickness (r = −0.75; p &lt; 0.0001), and positively associated with cortical porosity (r = 0.74; p &lt; 0.0001).

Conclusion
Fermentable and viscous fibers improved cortical bone but had no effect on trabecular bone. This effect may be, at least in part, due to the fiber's ability to lower plasma phosphorus and likely parathyroid hormone.
#1506 Uremic toxicity: gaining novel insights through AI-driven literature review
Authors: Zhang Hanjie , Kotanko Peter 
Published: May 2024

Abstract

Background and Aims
The rapidly growing scientific literature poses a significant challenge for researchers seeking to distill key insights. We utilized Retrieval-Augmented Generation (RAG), a novel AI-driven approach, to efficiently process and extract meaningful information from published literature on uremic toxins. RAG is a general AI framework for improving the quality of responses generated by Large Language Models (LLMs) by supplementing the LLM's internal representation of information with curated expert knowledge.

Method
First, we collected on PubMed all abstracts related to the topic of “uremic toxins” through Metapub, a Python library designed to facilitate fetching metadata from PubMed. Second, we set up a RAG system that comprises 2 steps. In a retrieval step, the questions on topic (“uremic toxins”) and the documents (=all collected abstracts and manuscripts) are encoded into vectors (i.e., high-dimensional numerical representations). Similarity measures are used to find the best matches between documents and the questions on topic. Second, in the augmented generation step, the LLM (e.g., ChatGPT) uses these best matches of documents to generate a coherent and informed response.

Results
We collected 3497 abstracts from the PubMed and 191 expert-curated publications in PDF format related to the topic “uremic toxin”. These 191 publications were broken down to 5756 documents, each with a manageable size of text. The final vector database comprised 9253 vectors. Using RAG, we requested responses from the LLM on multiple questions related to “uremic toxins”. Some examples are shown in Table 1. The first and second responses given by the LLM are reasonable. However, the third answer shows the phenomenon of ‘hallucination’—where models generate plausible and convincingly sounding yet factually incorrect information.

Conclusion
The use of RAG improves the capability of LLMs to answer questions by leveraging the information contained within curated abstracts and publications. Despite the improvements with RAG, the phenomenon of ‘hallucination’ persists. A concerning feature of hallucinations is their eloquent and convincing language. For the time being, LLM output—even when improved with RAG—requires scrutiny and human verification.
High-value breast cancer care within resource limitations
Authors: Verhoeven Didier , Siesling Sabine , Allemani Claudia , Roy Pankaj Gupta , Travado Luzia , Bhoo-Pathy Nirmala , Rhayns Clifford , Junkermann Hans , Nakamura Seigo , Lasebikan Nwamaka , Tucker Forrest Lee 
Published: May 2024

Abstract
Breast cancer care is a costly global health issue where effective management depends on early detection and treatment. A breast cancer diagnosis can result in financial catastrophe especially in low- and middle-income countries (LMIC). Large inequities in breast cancer care are observed and represent a global challenge to caregivers and patients. Strategies to improve early diagnosis include awareness and clinical breast examination in LMIC, and screening in high-income countries (HIC). The use of clinical guidelines for the management of breast cancer is needed. Adapted guidelines from HIC can address disparities in populations with limited resources. Locally developed strategies still provide effective guidance in improving survival. Integrated practice units (IPU) with timely multidisciplinary breast care conferences and patient navigators are required to achieve high-value, personalized breast cancer management in HIC as well as LMIC. Breast cancer patient care should include a quality of life evaluation using ideally patient-reported outcomes (PROM) and experience measurements (PREM). Evaluation of breast cancer outcomes must include the financial cost of delivered care. The resulting value perspective should guide resource allocation and program priorities. The value of care must be improved by translating the findings of social and economic research into practice and resolving systemic inequity in clinical breast cancer research. Cancer survivorship programs must be put in place everywhere. The treatment of patients with metastatic breast cancer must require more attention in the future, especially in LMIC.
Cybersecurity, Ethics, and Collective Responsibility
Authors: Miller Seumas , Bossomaier Terry 
Published: May 2024

Abstract
The advent of the internet, the exponential growth in computing power and the rapid developments in artificial intelligence have given rise to numerous ethical questions in relation to cybersecurity across various domains, not least by virtue of the dual-use character of cybertechnology—it can be used to provide great benefits to humankind, but also to do great harm. The domains in question intersect and include business (e.g., data security, data ownership and privacy), public communication (e.g., disinformation and computational propaganda), health (e.g., privacy, ransomware attacks), law enforcement (e.g., data security, predictive policing), and interstate conflict (e.g., cyberwar, autonomous weapons). This work undertakes analyses of the key ethical concepts in play, such as privacy, freedom of communication, security, and the right to self-defence. This work also develops sets of ethical guidelines to give direction to the regulation of cyberspace in these various domains. It does so from a liberal democratic perspective that seeks to protect individual rights while ensuring the collective good of cybersecurity. A central informing idea is that of institutionally embedded collective moral responsibilities that function as “webs of prevention” against cyberattacks. Cybersecurity is, in the end, a collective moral responsibility of both individual citizens and organizations, but a collective responsibility the discharging of which requires new regulation and the redesign of institutional roles, as well as technical countermeasures to cyberattacks, such as passwords, encryption, firewalls, patching, and the like. It also involves at times, we suggest, offensive as well as defensive measures.