bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative Analysis of the Lived Experience of Reproductive and Pediatric Health Care in the Military Health Care System
Authors: Musilli Megan G , Fuller Shara M , Wyatt Brelahn , Ryals Teri R , Haischer-Rollo Gayle , Drumm Caitlin M , Vereen Rasheda J , Plowden Torie C , Blevins Erin M , Spalding Carmen N , Konopasky Abigail , Lutgendorf Monica A 
Published: May 2024

ABSTRACT

Introduction
Persistent inequities exist in obstetric and neonatal outcomes in military families despite universal health care coverage. Though the exact underlying cause has not been identified, social determinants of health may uniquely impact military families. The purpose of this study was to qualitatively investigate the potential impact of social determinants of health and the lived experiences of military individuals seeking maternity care in the Military Health System.

Materials and Methods
This was an Institutional Review Board-approved protocol. Nine providers conducted 31 semi-structured interviews with individuals who delivered within the last 5 years in the direct or purchased care market. Participants were recruited through social media blasts and clinic flyers with both maximum variation and homogenous sampling to ensure participation of diverse individuals. Data were coded and themes were identified using inductive qualitative research methods.

Results
Three main themes were identified: Requirements of Military Life (with subthemes of pregnancy notification and privacy during care, role of pregnancy instructions and policies, and role of command support), Sociocultural Aspects of the Military Experience (with subthemes of pregnancy as a burden on colleagues and a career detractor, postpartum adjustment, balancing personal and professional requirements, pregnancy timing and parenting challenges, and importance of friendship and camaraderie in pregnancy), and Navigating the Healthcare Experience (including subthemes of transfer between military and civilian care and TRICARE challenges, perception of military care as inferior to civilian, and remote duty stations and international care).

Conclusions
The unique stressors of military life act synergistically with the existing health care challenges, presenting opportunities for improvements in care. Such opportunities may include increased consistency of policies across services and commands. Increased access to group prenatal care and support groups, and increased assistance with navigating the health care system to improve care transitions were frequently requested changes by participants.
The Evolution of Transglutaminases Underlies the Origin and Loss of Cornified Skin Appendages in Vertebrates
Authors: Sachslehner Attila Placido , Surbek Marta , Holthaus Karin Brigit , Steinbinder Julia , Golabi Bahar , Hess Claudia , Eckhart Leopold 
Published: May 2024

Abstract
Transglutaminases (TGMs) cross-link proteins by introducing covalent bonds between glutamine and lysine residues. These cross-links are essential for epithelial cornification which enables tetrapods to live on land. Here, we investigated which evolutionary adaptations of vertebrates were associated with specific changes in the family of TGM genes. We determined the catalog of TGMs in the main clades of vertebrates, performed a comprehensive phylogenetic analysis of TGMs, and localized the distribution of selected TGMs in tissues. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM, with orthologs being expressed in the cornified teeth of the lamprey, a basal vertebrate. Gene duplications led to the origin of TGM10 in stem vertebrates, the origin of TGM2 in jawed vertebrates, and an increasing number of epithelium-associated TGM genes in the lineage leading to terrestrial vertebrates. TGM9 is expressed in the epithelial egg tooth, and its evolutionary origin in stem amniotes coincided with the evolution of embryonic development in eggs that are surrounded by a protective shell. Conversely, viviparous mammals have lost both the epithelial egg tooth and TGM9. TGM3 and TGM6 evolved as regulators of cornification in hair follicles and underwent pseudogenization upon the evolutionary loss of hair in cetaceans. Taken together, this study reveals the gain and loss of vertebrate TGM genes in association with the evolution of cornified skin appendages and suggests an important role of TGM9 in the evolution of amniotes.
#955 Real-world validation of the mortality box score to predict death following kidney transplantation: an international study
Authors: Lombardi Yannis , Rudrapatna Vivek , Truchot Agathe , Divard Gillian , Debiais Charlotte , Raynaud Marc , Butte Atul , Loupy Alexandre 
Published: May 2024

Abstract

Background and Aims
The mortality box score (mBox) is a validated risk prediction score developed by the Paris Transplant Group (NCT03474003), aimed at predicting mortality after kidney transplantation (KT) using data available at the time of surgery. However, its applicability using data routinely collected in institutions' electronic health records (EHRs), enabling automatic computation, needs to be investigated.

Method
We assessed the mBox's prediction performance in two EHR-based multicenter cohorts of adult kidney transplant recipients (KTRs) transplanted between 2017 and 2021 from: 1) the Greater Paris University Hospitals (AP-HP); and 2) the University of California San Francisco's Hospitals (UCSF). These cohorts were built using solely structured data, routinely collected in the institutions' EHRs. The mBox's discriminative ability to predict death at 3 years following KT was assessed by computing the AUC. Adequation between predicted and observed risk of death was assessed with calibration.

Results
Out of 10 367, 191 and 5 885 623 patients, we identified 2 560 and 2 028 consecutive KTRs meeting the inclusion criteria in the AP-HP and UCSF cohorts, respectively. In the AP-HP cohort, 344 (13.4%) patients died, during a median follow-up of 3.1 years (interquartile range [IQR]: 1.8 to 4.1). In the UCSF cohort, 150 (7.4%) patients died, during a median follow-up of 2.7 years (IQR: 1.2 to 4.1). The mBox's AUC to predict death within 3 years following KT was 0.780 (95% confidence interval [CI]: 0.752 to 0.801) in the AP-HP cohort and 0.720 (95% CI: 0.672 to 0.768) in the UCSF cohort. Visual examination of the calibration curves showed that the mBox accurately estimated the actual risk of death in the UCSF cohort, and tended to underestimate the actual risk of death in the AP-HP cohort.

Conclusion
In this real-world international study, performed on 4 588 kidney transplant recipients, relying solely on data routinely collected in institutions' electronic health records, we demonstrate a fair accuracy of the mBox risk prediction score in predicting patient death following transplantation.
#1640 Alternative complement pathway disorders in the transplant setting—experience from a large volume center
Authors: Simunov Bojana , Jurekovic Zeljka , Zibar Lada , Laganovic Mario 
Published: May 2024

Abstract

Background and Aims
Complement alternative pathway disorders, atypical hemolytic-uremic syndrome (aHUS) and C3 glomerulopathy (C3G), are rare diseases with a high rate of recurrence after kidney transplantation. Due to limited availability of testing, patients may go undiagnosed, indicating testing during pretransplant evaluation. Posttransplant thrombotic microangiopathy (TMA) is a rare complication of transplantation. A large number of post transplant TMAs is regarded as secondary, either to immunosuppressive drugs or transplant itself. In select cases, complement alternative pathway disorders analysis is warranted.

Method
We retrospectively reviewed all patients in whom complement system diagnostic work-up was performed in the transplant setting in our center, from 2017 to 2022. Complement system analysis in isolated histological TMA of the allograft, without extrarenal manifestations and with known cause of native kidneys ESRD, was not performed routinely.
Patients in whom alternative pathway disorders were confirmed were compared with those with no abnormalities detected by complement system analysis.

Results
12 patients were identified, 75% male, median age 39.5 years (IQR 28-60.25). 8 patients were evaluated before transplantation. 4 of the 8 patients were referred for transplantation with diagnosed aHUS. Genetic testing was used for recurrence risk stratification. In living donor transplantations 2 donors were tested as well. One patient was referred from a neighboring resource poor country and was not on eculizumab therapy. He was homozygous for a high risk causative mutation. He was declined for living related donor kidney transplant, due to risk to the donor and unavailability of eculizumab. Compassionate use request was initiated. One patient was referred as possible C3G and repeat complement analysis revealed elevated C3Nef. Out of 3 patients, previously diagnosed as CKD of unknown origin or immune complex-mediated membranoproliferative glomerulonephritis, 2 were diagnosed during pretransplant evaluation: one as C3G and the other as aHUS. 4 patients were evaluated posttransplant. One analysis was performed due to recurrent C3G of the allograft, with confirmed competent dysregulation. 2 analyses were in liver transplant recipients, both with systemic TMA. Severe overactivation with consumption of complement was proven in one and treated with eculizumab. The characteristics of patients with diagnosed disorders of the complement system and those without are shown in Table 1.

Conclusion
Transplant physicians should keep a high volume of suspicion for complement dysregulation disorders, both during the pretransplant work-up and when evaluating TMA and recurrent GN posttransplant. Special caution should be advised when a patient is referred as chronic GN, MPGN or unknown cause ESKD at a young age.
#1206 Combination therapy with Lisinopril and Dapagliflozin rescues GFR decline and glomerular damage in the KKAy mouse model of diabetic kidney disease
Authors: van Koppen Arianne , Hinke Simon , Nguyen Tri , Dendooven Amélie , Tseng Tzu-Ling , Hsu Wei-Chan , Bajema Ingeborg , Menke Aswin , van Goor Harry , Stoop Reinout 
Published: May 2024

Abstract

Background and Aims
Male KKAy mice develop diabetic kidney disease (DKD) with progressive decline of GFR upon high fat diet feeding which is accelerated by the vasoconstrictor LNNA. In this study, efficacy of combination therapy with clinical relevant therapeutics in the form of an ACE-inhibitor (Lisinopril) and SGLT2-inhibitor (Dapagliflozin) on renal function and histopathology was investigated.

Method
Male KKAy mice underwent uninephrectomy (UNX). After recovery mice received high fat diet (45% LARD) and 50 mg/L LNNA in drinking water (wk0). At week 4, Lisinopril (2.5 mg/kg/day in drinking water) and at week 8 Dapagliflozin (5 and 20 mg/kg/day in diet) were started. Body weight, blood glucose, food and water intake and albuminuria were determined regularly. GFR was measured transdermally by FITC-sinistrin clearance. Mice were terminated at week 16 and renal histology was scored by a team of renal histopathologists. Non-induced and induced non-treated mice were used as controls.

Results
Treatment of KKAy mice on HFD+LNNA with Dapagliflozin reduced blood glucose immediately. Combination therapy with Lisinopril and Dapagliflozin (5 mg/kg/day) rescued the progressive GFR decline to levels seen in non-induced chow-controls (p &lt; 0.05 vs UNX+HFD+LNNA). Pathology showed that the percentage of healthy glomeruli increased from 14% to 26% after combination therapy (Dapa 5). Interstitial fibrosis and tubular atrophy were significantly reduced by combination therapy (p &lt; 0.05 vs UNX+HFD+LNNA).

Conclusion
Male KKAy mice on a HFD and LNNA developed DKD resulting in CKD. Combination therapy with Lisinopril and Dapagliflozin rescued GFR decline and reduced glomerular damage and interstitial fibrosis and tubular atrophy This indicates the clinical relevance of the model which can be used to study compound efficacy in both early and more advanced stages of DKD.
#2023 The role of neutrophil extracellular traps in cisplatin-induced acute kidney injury
Authors: Cao Jingyuan , Liu Haifei , Hu Xinhui , Ni Weijie , Wang Ze , Liu Hong 
Published: May 2024

Abstract

Background and Aims
Acute kidney injury (AKI) is a public health problem that seriously endangers human health. The exact pathogenesis of AKI has not been fully elucidated. Previous studies have shown that the immune system plays a key role in the inflammatory response of AKI in the acute phase, especially innate immunity. Recent discoveries have highlighted that neutrophils, in particular the neutrophil extracellular traps (NETs), have central roles in the occurrence and development of AKI. However, the specific role and mechanism of NETs in AKI of different etiologies are remain unclear. This study aimed to investigate the role of NETs in the development of cisplatin-induced AKI and provide potential therapeutic targets for AKI treatment.

Method
Wild-type (WT) and NETs-deficient (PAD4-/-) mouse models of AKI were constructed by intraperitoneal injection of cisplatin. Mice were weighed at 24, 48, and 72 hours after modeling, and sacrificed at 72 hours. Serum and kidney specimens were collected for renal function analysis, pathological, immunohistochemical staining, and molecular biology experiments. Mouse bone marrow neutrophils were isolated from healthy mouse. NETs were induced in vitro by adding phorbol 12 myristate 13-acetate (PMA). Primary renal tubular epithelial cells (TECs) of mouse kidney were extracted, and the cells were collected after 24 h of cisplatin and cisplatin combined with NETs intervention, respectively. The inflammatory indicators such as TNF-α, IL-1β, MCP-1, and renal injury indicators such as KIM-1 and Ngal were detected by RT-PCR.

Results
Compared with the WT-cisplatin group, the PAD4-/- -cisplatin group showed a reduced degree of weight loss after modeling, lower serum creatinine and urea nitrogen levels, and significantly improved renal function. The PAD4-/- -cisplatin group showed a significant decrease in the inflammatory indicators TNF-α, IL-1β, IL-6, and renal injury indicators KIM-1 and Ngal. Cisplatin intervention for 6 hours could induce the generation of NETs. Compared with the cisplatin intervention group, the expression of inflammatory indicators TNF-α, IL-1β, and MCP-1 were significantly higher in the cisplatin combined with NETs intervention TECs group.

Conclusion
Cisplatin directly induces neutrophils to generate NETs, which can exacerbate cisplatin-induced injury to TECs in vitro. The inhibition of NETs by PAD4-/- improves cisplatin-induced AKI. The inhibition of NETs may be a novel target for the treatment of cisplatin AKI.
#1663 Utilizing the MELD-Na score to predict renal replacement therapy and mortality among adult patients with leptospirosis-associated acute kidney injury
Authors: Soco Marc Lawrence , Ong Aaron Lemuel , Dinsay Mark Gavin , Lao Janice Jill 
Published: May 2024

Abstract

Background and Aims
Leptospirosis is a zoonotic disease with manifestations ranging from mild to severe. Acute kidney injury (AKI) in leptospirosis is usually a marker of poor prognosis and there remains a paucity of scoring systems utilized to predict renal replacement therapy (RRT) and mortality. The Model for End-Stage Liver Disease-Sodium (MELD-Na) was originally developed to predict survival in patients with liver cirrhosis. The components of the MELD-Na score evaluate renal and hepatic dysfunction, which are frequent complications in leptospirosis. This study aims to evaluate the prognostic significance of the admission MELD-Na score in predicting renal replacement therapy and mortality among patients with leptospirosis-associated AKI.

Method
A retrospective, single-center, cross-sectional study was conducted at a tertiary hospital in Manila, Philippines. The study enrolled patients from January 2018 to September 2023 and collected demographic and clinical data, along with laboratory values taken on admission. The MELD-Na score was developed using these values and its distribution was visualized by histogram. Receiver operating characteristic curve analysis was used to determine the score's predictive ability and the optimum cut-off was determined by the cut-point with the highest Youden index.

Results
The study included a total of 298 patients. The median age of the participants was 39, with 88.59% being males, and 77.52% having no known comorbidities. Of the study population, 74.16% underwent RRT, while the in-hospital mortality rate was 12.08%. Univariate analysis revealed that oliguria, serum creatinine, arterial pH, serum bicarbonate, and administration of methylprednisolone pulse therapy were among the predictive factors for RRT, in line with clinical practice guidelines. Other parameters found to be predictive of RRT were serum sodium and bilirubin. An admitting MELD-Na score of &gt;26 predicted RRT with 91.0% sensitivity [86.4, 94.4] and 87.7% specificity [76.3, 94.9], yielding an area under the curve (AUC) of 0.953 (95% CI). Conversely, an admitting MELD-Na score &gt;31 was found to be 77.8% sensitive [60.8, 89.9] and 64.9% specific [58.8, 70.7] for predicting mortality, with an AUC of 0.748 (95% CI).

Conclusion
The MELD-Na is a good predictor of renal replacement therapy and in-hospital mortality among patients with leptospirosis-associated AKI. This scoring system holds the potential to serve as a tool for risk stratification and prognostication in moderate to severe cases of the disease. A validation cohort study is recommended for formulating a prediction scoring system based on the individual components of the MELD-Na score, such as bilirubin and sodium.
#475 Association between hospital-acquired acute kidney injury and the risk of kidney cancer
Authors: Liu Jiao , Gao Qi , Lin Yuxin , Nie Sheng , Xu Xin 
Published: May 2024

Abstract

Background and Aims
The effects of hospital-acquired acute kidney injury (HA-AKI) on kidney cancer remain unclear. The study aimed to investigate the association between HA-AKI and kidney cancer by a large multicenter cohort study.

Method
The real-world cohort study included Chinese adults with at least two serum creatinine (SCr) tests within 7 days during hospitalization from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥26.5 μmol/l increase in serum creatinine concentration within 48 hours or a ≥50% increase over the baseline within 7 days. The primary outcome was a new diagnosis of kidney cancer, while the secondary outcomes included death attributed to kidney cancer and new diagnoses of other cancers of the urinary system. The Cox proportional hazard model was employed for analyses.

Results
Of the 342861 patients (median age, 57.06 [43.68, 68.54] yr; men, 179096 [52.2%]), 9337 patients experienced HA-AKI. During a mean follow-up of 2.03 years, 195 (0.57‰) patients with a new diagnosis of kidney cancer were detected. After multivariable adjustment, HA-AKI was significantly associated with a higher risk of kidney cancer (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.37-4.17, P = 0.003) and kidney cancer-specific death (adjusted HR, 3.19; 95% CI, 1.90-5.37, P &lt; 0.001). We also found that relationships between HA-AKI and cancers of the urinary system, excluding kidney cancer, such as bladder cancer, prostate cancer, were not statistically significant.

Conclusion
HA-AKI was significantly associated with increased risk of kidney cancer and death attributed to kidney cancer. Our findings highlight the importance of monitoring HA-AKI patients for early detection of kidney cancer.
#2719 Hypoalbuminemia as a mortality risk factor in acute kidney injury
Authors: Pešić Snežana , Stopić Bojan , Djuric Petar , Dimkovic Nada , Naumovic Radomir 
Published: May 2024

Abstract

Background and Aims
Preexisting hypoalbuminemia in many studies was an independent factor of mortality in patients with acute kidney injury (AKI). Albumin replacement in patients with AKI did not affect their survival. Each 1.0 g/l decrease in serum albumin was associated with an increased probability of developing AKI (OR 1.685). Also, it was shown that serum albumin level below 32 g/l is a significant risk factor for the occurrence of AKI. The mortality of patients with AKI is extremely high, approximately 50%, in patients with AKI who require dialysis treatment it is 50-70%, while in patients on supportive ventilation or with multisystem organ failure it is even 80-90%.

Method
The retrospective study included 280 patients diagnosed with AKI in the period from 2014 to 2018. Demographic, laboratory parameters and therapeutic procedures were analyzed in order to determine their influence on the treatment outcome. Binary logistic regression was used to test statistical significance to identify potential mortality factors.

Results
The incidence of AKI was 6.5%. The mean age was 67.8±13.8 years (19, 91) without statistically significant difference by gender (50.4% men) (p = 0.22). The most prevalent is prerenal AKI 57.1%, followed by renal 24.3% and postrenal 18.6%. Renal replacement therapy is required in 15.7% of patients. Intermittent HD was applied statistically significantly more often, 90.9%, and continuous renal replacement therapy (CRRT) procedures were applied in 9.1% of patients (p &lt; 0.001). Mortality was 18.6%. With each increase in the patient's age by one year, the probability of a fatal outcome increases by 1.045 times (p = 0.000; OR: 1.045). Hypoproteinemia and hypoalbuminemia increase the probability of death. For each unit decrease in albumin by 1 g/l, the risk of death increases by 13% (p = 0.000; OR: 0.872), and each decrease in protein by 1 g/l increases the risk of death by 7% (p = 0.000 ; OR: 0.939). Among other factors that showed statistical significance are hyperphosphatemia (p = 0.001; OR: 1.990), acidosis (p = 0.007; OR: 0.002), inflammation (p = 0.029; OR: 1.003).

Conclusion
Acute kidney injury is accompanied by a high mortality rate. Low serum albumin levels at the time of diagnosis are a significant independent factor of acute kidney function impairment and death. Other risk factors that contribute to a poor outcome in patients with AOB are age, hyperphosphatemia, acidosis, and inflammation.