bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal alteration of serum bilirubin levels and its renoprotective effects in diabetic kidney disease: exploring the hormonal mechanisms
Authors: Cao Can , Wei Shuwu , He Leijuan , Li Chunyao , Lu Yizhen , Sun Weiwei , Wang Yaoxian 
Published: May 2024

ObjectiveThis current study represents a novel endeavor to scrutinize the correlation between the temporal alteration in serum total bilirubin (TBIL) concentrations and the rate of estimated glomerular filtration rate (eGFR). Additionally, this study aims to probe the plausible molecular mechanism underpinning the renoprotective effects of bilirubin concerning its hormonal characteristics.Materials and methodsIn this study, a cohort of 103 patients diagnosed with DKD and receiving medical care at Dongzhimen Hospital were recruited and monitored over a period of 2-7 years. The progression of DKD was ascertained using a threshold of eGFR decline &gt; -5.48%/year. To assess the relationship between the annual change in serum TBIL levels (%/year) and the slope of eGFR, multivariate binary logistic regression analysis was employed. Furthermore, the ROC curve analysis was employed to determine the cut-off value for TBIL levels (%/year).ResultsThe use of multivariate binary logistic regression models revealed that serum TBIL levels (%/year) exhibited a significant correlation with the slope of eGFR. Moreover, the ROC curve analysis indicated a cut-off value of -6.729%/year for TBIL levels (%/year) with a sensitivity of 0.75 and specificity of 0.603, in diagnosing eGFR decline &gt;-5.48%/year.ConclusionsThe findings of this study suggest that the sustained elevation of serum bilirubin concentration within the physiological range can effectively retard the progression of Diabetic Kidney Disease (DKD). Furthermore, the hormonal attributes of bilirubin may underlie its renoprotective effects.
Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease
Authors: Wu Miaoling , Hou Weiming , Qin Ruonan , Wang Gang , Sun Da , Geng Ye , Du Yinke 
Published: May 2024

BackgroundPrevious studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk.MethodsWe investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment.ResultsSerum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively.ConclusionsCumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.
Patterns of distant metastasis and survival outcomes in de novo metastatic breast cancer according to age groups
Authors: Liu Ke , Huang An-Le , Chen Xue-Qin , Wu San-Gang 
Published: May 2024

BackgroundIs de novo metastatic breast cancer (dnMBC) the same disease in the elderly as in younger breast cancer remains unclear. This study aimed to determine the metastatic patterns and survival outcomes in dnMBC according to age groups.MethodsWe included patients from the Surveillance Epidemiology and End Results program. Chi-square test, multivariate logistic regression analyses, and multivariate Cox regression models were used for statistical analyses.ResultsA total of 17719 patients were included. There were 3.6% (n=638), 18.6% (n=3290), 38.0% (n=6725), and 39.9% (n=7066) of patients aged &lt;35, 35-49, 50-64, and ≥65 years, respectively. Older patients had a significantly higher risk of lung metastasis and a significantly lower risk of liver metastasis. There were 19.1%, 25.6%, 30.9%, and 35.7% of patients with lung metastasis in those aged &lt;35, 35-49, 50-64, and ≥65 years, respectively. Moreover, the proportion of liver metastasis was 37.6%, 29.5%, 26.3%, and 19.2%, respectively. Age was the independent prognostic factor associated with breast cancer-specific survival (BCSS) and overall survival (OS). Those aged 50-64 years had significantly inferior BCSS (P&lt;0.001) and OS (P&lt;0.001) than those aged &lt;35 years. Patients aged ≥65 years also had significantly lower BCSS (P&lt;0.001) and OS (P&lt;0.001) than those aged &lt;35 years. However, similar outcomes were found between those aged 35-49 and &lt;35 years.ConclusionOur study suggests that different age groups may affect the metastatic patterns among patients with dnMBC and the survival of younger patients is more favorable than those of older patients.
Vision impairment and food insecurity in the national health and aging trends study
Authors: Lee Moon J. , Almidani Louay , Samuel Laura , Swenor Bonnielin K. , Ehrlich Joshua R. , Varadaraj Varshini 
Published: May 2024

IntroductionVision impairment (VI) may further exacerbate older adults’ vulnerability to experiencing food insecurity and may be a unique and important target for policies addressing access to nutritional food. The purpose of this study is to determine the association of VI in older adults with food insecurity.MethodsThis is a cross-sectional analysis of round 11 (2021) of the National Health and Aging Trends Study (NHATS), a nationally representative survey of U.S. Medicare beneficiaries ages 65 and older. Participants include 2,815 older adults with complete data on at least one objective measure of vision (distance, near or contrast sensitivity) and food insecurity. Food insecurity was assessed using a previously developed indicator of food insecurity in NHATS. VI was defined as binocular visual acuity (VA) worse than 0.3 logMAR (Snellen equivalent 20/40) at distance or its near equivalent, or contrast sensitivity (CS) worse than 1.55 logUnits. Continuous VI measures included distance and near VA (per 0.1 logMAR), and CS (per 0.1 logCS).ResultsParticipants were majority White (82%) and female (55%), and 3% had food insecurity. Older adults with any VI had a greater prevalence of food insecurity than adults without VI (5.0% vs. 2.0%, p &lt; 0.05). In fully adjusted regression analyses, individuals with any VI experienced double the odds of food insecurity than individuals without VI (OR: 2.1, 95% CI: 1.2–3.6). Distance VI (measured continuously) was associated with 1.2 times the odds of food insecurity (OR = 1.2; 95% CI: 1.0–1.3, per 0.1 logMAR). All other vision measures trended towards higher odds of food insecurity, though not statistically significant.DiscussionOlder adults with VI experience higher rates of food insecurity than their peers. Interventions to improve food security should be targeted towards addressing the specific barriers faced by visually impaired older adults.
Morphological responses of root hairs to changes in soil and climate depend on plant life form
Authors: Zhou Yingtong , Wang Cunguo , Tang Qinrong , Wang Junni , Li Mai-He 
Published: May 2024

IntroductionRoot hairs increase the surface area of a plant’s root system that is in contact with the soil, thus facilitating plant water and nutrient uptake. However, little is known about the characteristics of the root hairs of herbaceous and woody plants and their specific response patterns to biotic and abiotic variables from the perspective of resource acquisition strategies in the context of global change.MethodsHere, we analyzed 74 published case studies with 1074 observations of root hair traits to identify patterns of root hair length, density and diameter in relation to soil (e.g., soil pH, nutrient levels), growing environments (e.g., greenhouse, field) and climatic factors (e.g., air temperature), as well as genome size and plant age.ResultsRoot hairs were longer, denser and thicker in woody plants compared with herbaceous plants, and the length and diameter of root hairs in herbaceous plants increased with genome size. With increasing plant age, woody plants had significantly longer and thicker root hairs, while root hair density and diameter declined significantly for herbaceous plants. Soil-cultured plants had longer root hairs than solution-cultured plants. The length and density of root hairs were greater in greenhouse-cultured plants than in field-grown plants, and the latter had thicker root hairs than the former. As soil pH increased, root hair length increased but diameter decreased in woody plants, while root hair density increased in herbaceous plants. Increased soil total nitrogen (N) and potassium (K) significantly increased root hair length, density and diameter in herbaceous plants, while soil total N significantly decreased root hair density in woody plants. Root hair length increased significantly, while root hair density decreased significantly, with higher mean annual temperature and greater precipitation seasonality, while the opposite pattern was true for a wider annual temperature range.DiscussionOur findings emphasize the life-form-specific responses of root hairs to soil and climatic variables. These findings will help deepen our understanding of resource acquisition strategies and their mechanisms in different plant forms under global climate change.
Influence of metallic particles and TNF on the transcriptional regulation of NLRP3 inflammasome-associated genes in human osteoblasts
Authors: Sellin Marie-Luise , Hansmann Doris , Bader Rainer , Jonitz-Heincke Anika 
Published: May 2024

IntroductionThe release of mature interleukin (IL-) 1β from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome. These danger signals include wear products resulting from aseptic loosening of joint arthroplasty. However, inflammasome activation requires two different signals: a nuclear factor-kappa B (NF-κB)-activating priming signal and an actual inflammasome-activating signal. Since human osteoblasts react to wear particles via Toll-like receptors (TLR), particles may represent an inflammasome activator that can induce both signals.MethodsTemporal gene expression profiles of TLRs and associated intracellular signaling pathways were determined to investigate the period when human osteoblasts take up metallic wear particles after initial contact and initiate a molecular response. For this purpose, human osteoblasts were treated with metallic particles derived from cobalt-chromium alloy (CoCr), lipopolysaccharides (LPS), and tumor necrosis factor-alpha (TNF) alone or in combination for incubation times ranging from one hour to three days. Shortly after adding the particles, their uptake was observed by the change in cell morphology and spectral data.ResultsExposure of osteoblasts to particles alone increased NLRP3 inflammasome-associated genes. The response was not significantly enhanced when cells were treated with CoCr + LPS or CoCr + TNF, whereas inflammation markers were induced. Despite an increase in genes related to the NLRP3 inflammasome, the release of IL-1β was unaffected after contact with CoCr particles.DiscussionAlthough CoCr particles affect the expression of NLRP3 inflammasome-associated genes, a single stimulus was not sufficient to prime and activate the inflammasome. TNF was able to prime the NLRP3 inflammasome of human osteoblasts.
Krameria lappacea root extract’s anticoccidial properties and coordinated control of CD4 T cells for IL-10 production and antioxidant monitoring
Authors: Abdel-Gaber Rewaida , Alamari Ghada , Dkhil Mohamed A. , Meryk Andreas , Al-Shaebi Esam M. , Al-Quraishy Saleh 
Published: May 2024

IntroductionRecently, the use of botanicals as an alternative to coccidiostats has been an appealing approach for controlling coccidiosis. Therefore, this study was conducted to evaluate the potential role of aqueous methanolic extract (200 mg/kg) of Krameria lappacea (roots) (KLRE) against infection induced by Eimeria papillata.MethodsA total of 25 male C57BL/6 mice were divided into five groups (I, II, III, IV, and V). On 1st day of the experiment, all groups except groups I (control) and II (non-infected-treated group with KLRE), were inoculated orally with 103 sporulated E. papillata oocysts. On the day of infection, group IV was treated with KLRE. Group V served as an infected-treated group and was treated with amprolium (coccidiostat).ResultsTreatment with extract and coccidiostat was continued for five consecutive days. While not reaching the efficacy level of the reference drug (amprolium), KLRE exhibited notable anticoccidial activity as assessed by key criteria, including oocyst suppression rate, total parasitic stages, and maintenance of nutrient homeostasis. The presence of phenolic and flavonoid compounds in KLRE is thought to be responsible for its positive effects. The Eimeria infection increased the oxidative damage in the jejunum. KLRE treatment significantly increased the activity of catalase and superoxide dismutase. On the contrary, KLRE decreased the level of malondialdehyde and nitric oxide. Moreover, KLRE treatment decreased macrophage infiltration in the mice jejunal tissue, as well as the extent of CD4 T cells and NFkB. E. papillata caused a state of systemic inflammatory response as revealed by the upregulation of inducible nitric oxide synthase (iNOs)-mRNA. Upon treatment with KLRE, the activity of iNOs was reduced from 3.63 to 1.46 fold. Moreover, KLRE was able to downregulate the expression of pro-inflammatory cytokines interferon-γ, nuclear factor kappa B, and interleukin-10 -mRNA by 1.63, 1.64, and 1.38 fold, respectively. Moreover, KLRE showed a significant reduction in the expression of IL-10 protein level from 104.27 ± 8.41 pg/ml to 62.18 ± 3.63 pg/ml.ConclusionCollectively, K. lappacea is a promising herbal medicine that could ameliorate the oxidative stress and inflammation of jejunum, induced by E. papillata infection in mice.
Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review
Authors: BinAmir Hussain A. , AlAhmari Ali , AlQahtani AlWaleed , Mohamed Gamal , Alotaibi Fawaz , AlShamrani Mohamed , AlSaeed Ali , AlGhanmi Suwaidi , Heji Alaa , Alreshaid Abdulrahman , AlKawi Ammar , AlHazzani Adel , AlZawahmah Mohamed , Shuaib Ashfaq , Al-Ajlan Fahad , AlMohareb Fahad 
Published: May 2024

IntroductionPosterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression.MethodsThis is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances.ResultsDuring ten years follow-up (2011–2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs.ConclusionPRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.
A scale-free model of acute and ventilator-induced lung injury: a network theory approach inspired by seismology
Authors: Gottman Drew C. , Smith Bradford J. 
Published: May 2024

IntroductionAcute respiratory distress syndrome (ARDS) presents a significant clinical challenge, with ventilator-induced lung injury (VILI) being a critical complication arising from life-saving mechanical ventilation. Understanding the spatial and temporal dynamics of VILI can inform therapeutic strategies to mitigate lung damage and improve outcomes.MethodsHistological sections from initially healthy mice and pulmonary lavage-injured mice subjected to a second hit of VILI were segmented with Ilastik to define regions of lung injury. A scale-free network approach was applied to assess the correlation between injury regions, with regions of injury represented as ‘nodes’ in the network and ‘edges’ quantifying the degree of correlation between nodes. A simulated time series analysis was conducted to emulate the temporal sequence of injury events.ResultsAutomated segmentation identified different lung regions in good agreement with manual scoring, achieving a sensitivity of 78% and a specificity of 85% across ‘injury’ pixels. Overall accuracy across ‘injury’, ‘air’, and ‘other’ pixels was 81%. The size of injured regions followed a power-law distribution, suggesting a ‘rich-get-richer’ phenomenon in the distribution of lung injury. Network analysis revealed a scale-free distribution of injury correlations, highlighting hubs of injury that could serve as focal points for therapeutic intervention. Simulated time series analysis further supported the concept of secondary injury events following an initial insult, with patterns resembling those observed in seismological studies of aftershocks.ConclusionThe size distribution of injured regions underscores the spatially heterogeneous nature of acute and ventilator-induced lung injury. The application of network theory demonstrates the emergence of injury ‘hubs’ that are consistent with a ‘rich-get-richer’ dynamic. Simulated time series analysis demonstrates that the progression of injury events in the lung could follow spatiotemporal patterns similar to the progression of aftershocks in seismology, providing new insights into the mechanisms of injury distribution and propagation. Both phenomena suggest a potential for interventions targeting these injury ‘hubs’ to reduce the impact of VILI in ARDS management.
Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis
Authors: Janani Majid , Poorkhani Amirhoushang , Amiriani Taghi , Donyadideh Ghazaleh , Ahmadi Farahnazsadat , Jorjanisorkhankalateh Yalda , Beheshti-Nia Fereshteh , Kalaei Zahra , Roudbaraki Morad , Soltani Mahsa , Khori Vahid , Alizadeh Ali Mohammad 
Published: May 2024

IntroductionFibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and metastasis. A systematic review and a meta-analysis were performed to associate future metastasis with FAP-α expression in cancer.MethodsIn our meta-analysis, relevant studies published before 20 February 2024 were systematically searched through online databases that included PubMed, Scopus, and Web of Science. The association between FAP-α expression and metastasis, including distant metastasis, lymph node metastasis, blood vessel invasion, vascular invasion, and neural invasion, was evaluated. A pooled odds ratio (OR) with 95% confidence intervals (CI) was reported as the measure of association.ResultsA total of 28meta-analysis. The random-effects model for five parameters showed that a high FAP-α expression was associated with blood vessel invasion (OR: 3.04, 95% CI: 1.54–5.99, I2 = 63%, P = 0.001), lymphovascular invasion (OR: 3.56, 95% CI: 2.14–5.93, I2 = 0.00%, P &lt; 0.001), lymph node metastasis (OR: 2.73, 95% CI: 1.96–3.81, I2 = 65%, P &lt; 0.001), and distant metastasis (OR: 2.59; 95% CI: 1.16–5.79, I2 = 81%, P &lt; 0.001). However, our analysis showed no statistically significant association between high FAP-α expression and neural invasion (OR: 1.57, 95% CI: 0.84–2.93, I2 = 38%, P = 0.161).ConclusionsThis meta-analysis indicated that cancer cells with a high FAP-α expression have a higher risk of metastasis than those with a low FAP-α expression. These findings support the potential importance of FAP-α as a biomarker for cancer metastasis prediction.