bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic rats
Authors: Abu-Snieneh Asmahan , Gurt Irina , Abedat Suzan , Lotan Chaim , Glikson Michael , Shuvy Mony 
Published: August 2024

IntroductionRenal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process.Methods and resultsThe experimental design consisted of administering a uremia-inducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 ± 3.57 vs. 5.18 ± 0.15 mmol/L, p&lt;0.05) and creatinine (293.93 ± 79.6 vs. 12.82 ± 1.56 µmol/L, p&lt;0.05). R568 treatment markedly reduced parathyroid hormone (PTH) levels in both treated groups (192.63 ± 26.85, 301.23 ± 101.79 vs. 3570 ± 986.63 pg/mL, p&lt;0.05), with no impact on serum calcium and phosphate. von Kossa staining showed increase in AVC in uremic rats compared to control (1409 ± 159.5 vs. 27.33 ± 25.83, p&lt;0.05). AVC was not affected by R568 in both groups (3343 ± 2462, 1593 ± 792 vs. 1409 ± 159.5, NS). Similarly, the inflammatory marker CD68 was elevated in uremic rats (15592 ± 3792 vs. 181.8 ± 15.29, p&lt;0.01), and was not influenced by R568 treatment (8453 ± 818.5, 9318 ± 2232 vs. 15592 ± 3792, NS). Runt-related transcription factor 2 (Runx2), the regulator of osteoblast differentiation, was upregulated in uremic rats (23186 ± 9226 vs. 3184 ± 2495), that accompanied by elevated levels of Osteopontin (158395 ± 45911 vs. 237.7 ± 81.5, p&lt;0.05) and Osteocalcin (22203 ± 8525 vs. 489.7 ± 200.6, p&lt;0.05). R568 had no impact on osteoblastic markers (Runx2: 21743 ± 3193, 23004 ± 10871 vs. 23186 ± 9226, NS; osteopontin: 57680 ± 19522, 137116 ± 60103 vs. 158395 ± 45911, NS; osteocalcin: 10496 ± 5429, 8522 ± 5031 vs. 22203 ± 8525, NS).ConclusionIn an adenine-induced uremic rat model, we showed that short-term R568 therapy had no effect on AVC. Treatment with R568 decreased PTH levels but had no effect on high phosphate levels. Regression of AVC necessitates not only a decrease in PTH levels, but also a decline in phosphate levels. To achieve improved outcomes, it is advisable to consider administering a combination of R568 with other medications, such as calcium supplements or phosphate binders. Additional studies are required for further evaluation of the potential treatment of chronic kidney disease (CKD)-associated AVC.
Association of obesity with osteoporotic fracture risk in individuals with bone metabolism-related conditions: a cross sectional analysis
Authors: Yang Guijun , Jiang Hejun , Xie Dan , Yuan Shuhua , Wu Jinhong , Zhang Jing , Zhang Lei , Yuan Jiajun , Lin Jilei , Chen Jiande , Yin Yong 
Published: August 2024

IntroductionThis study aimed to investigate the individual and composite associations of different indices of obesity on osteoporotic fractures at three different sites among individuals affected by conditions influencing bone metabolism.MethodsParticipants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. BMI and WC were used separately and in combination to evaluate the presence of obesity. Obesity was defined as BMI ≥ 30 kg/m2, WC ≥ 88 cm in females, and WC ≥ 102 cm in males. Associations between obesity and osteoporotic fractures were assessed using multivariable logistic regression and OR curves. Associations modified by age, sex, race, and alcohol consumption were also evaluated.ResultsA total of 5377 participants were included in this study. In multivariable logistic regression analyses, we found that BMI, WC, BMI defining obesity, and WC defining obesity were negatively associated with hip fracture (all p &lt; 0.05). However, harmful associations between WC and BMI defining obesity and spine fracture were found (all p &lt; 0.05). OR curves revealed that BMI and WC had a linear relationship with hip and spine fractures (all P for non-linearity &gt;0.05). Further analyses showed that the highest WC quartile was harmfully associated with a higher risk of spine fractures (p &lt; 0.05). Obese participants diagnosed by both BMI and WC were less likely to have hip fractures but more likely to have spine fractures (all P for trend &lt;0.05). A significant interaction between age (Ref: age &lt; 50 years) and BMI and WC was detected for hip fractures (all P for interaction &lt;0.05).DiscussionIn people with conditions influencing bone metabolism, obesity diagnosed by BMI and WC was associated with a lower risk of hip fracture, while obesity diagnosed by BMI and the highest WC quartile were associated with a higher risk of spine fracture.
Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: a drug-target Mendelian randomization study
Authors: Lin Yilong , Zhang Yue , Wang Songsong , Cao Lin , Zhao Ruidan , Ma Xilai , Yang Qiaolu , Zhang Liyi , Yang Qingmo 
Published: August 2024

BackgroundThe relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration.MethodsA two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study (PheWAS) and MR-PheWAS analysis were used to explore potential treatable diseases and adverse outcomes of SGLT2 inhibitors.ResultsGenetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM [odds ratio (OR) = 0.66 (95% CI 0.53, 0.82), P = 1.57 × 10−4]; prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10−8] and prostate-specific antigen [0.26 (0.08, 0.81), P = 2.07 × 10−2]. The effect of SGLT2 inhibition on prostate cancer was mediated by uridine level, with a mediated proportion of 9.34% of the total effect. In MR-PheWAS, 65 traits were found to be associated with SLGT2 inhibitors (P &lt; 1.78 × 10−5), and among them, 13 were related to diabetes.ConclusionOur study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary to explore how uridine mediates the link between SGLT2 inhibition and prostate cancer.
Auto-luminescence in seedlings: possible indicators for the gravimetric tide?
Authors: Gallep Cristiano de Mello 
Published: August 2024

Germinating seedlings emit light in the visible range spontaneously, and these emissions are related to metabolism and reactive-oxygen species (ROS) processes. Several series of germination tests had such biological auto-luminescence (BAL) recorded in controlled conditions, fostering applications for the non-invasive, real-time evaluation of a seedling’s germinability and vigor when submitted to chemical and/or physical perturbations. However, long-term analysis of the BAL time-series of control samples conducted in different locations around the globe reveals that their BAL signals (and thus their metabolism) appear to follow the local gravimetric tide (g-tide) time profile. This indicates that the small daily and monthly variations in gravity acceleration due to the relative positioning of the Sun and Moon with respect to the Earth’s surface influence these signals. The gravimetric tide is a natural phenomenon that affects all things, fluid or solid, and is an uncontrollable variable in normal laboratory settings on Earth’s crust. All things on Earth have evolved under these pervasive cycles, with periods ranging from ∼12.2 h up to 28 d, which correspond to the Moon cycle. Tide-like cycles occur in living beings of different types, from the simplest bacteria to the most complex human beings, and we speculate that water availability at the molecular level could be a significant physical factor in modulating bio-activity by enabling protein folding and all metabolic pathways that require a synchronized organization to adapt to external environmental conditions. In this study, we summarize published results of a seedling’s BAL with cycle patterns resembling the g-tide in Limeira/BR, Prague/CZ, Leiden/NL, and Hamamatsu/JP and discuss the possible implications of this phenomenon for chronobiological studies.
Repeated seizure-induced brainstem neuroinflammation contributes to post-ictal ventilatory control dysfunction
Authors: Osmani Wasif A. , Gallo Alexander , Tabor Madeline , Eilbes Melissa , Cook-Snyder Denise R. , Hodges Matthew R. 
Published: August 2024

Patients with epilepsy face heightened risk of post-ictal cardiorespiratory suppression and sudden unexpected death in epilepsy (SUDEP). Studies have shown that neuroinflammation, mediated by the activation of microglia and astrocytes, may be a cause or consequence of seizure disorders. Kcnj16 (Kir5.1) knockout rats (SSkcnj16−/−) are susceptible to repeated audiogenic seizures and recapitulate features of human SUDEP, including post-ictal ventilatory suppression, which worsens with repeated seizures and seizure-induced mortality. In this study, we tested the hypothesis that repeated seizures cause neuroinflammation within key brainstem regions that contribute to the control of breathing. Audiogenic seizures were elicited once/day for up to 10 days in groups of adult male SSkcnj16−/− rats, from which frozen brainstem biopsies of the pre-Bötzinger complex/nucleus ambiguus (preBötC/NA), Bötzinger complex (BötC), and raphe magnus (RMg) regions were subjected to a cytokine array. Several cytokines/chemokines, including IL-1α and IL-1ß, were increased selectively in preBötC/NA after 3 or 5 days of seizures with fewer changes in other regions tested. In additional groups of male SSkcnj16−/− rats that underwent repeated seizures, we quantified microglial (IBA-1+) cell counts and morphology, specifically within the preBötC/NA region, and showed increased microglial cell counts, area, and volume consistent with microglial activation. To further test the role of inflammation in physiological responses to seizures and seizure-related mortality, additional groups of SSkcnj16−/− rats were treated with anakinra (IL-1R antagonist), ketoprofen (non-selective COX inhibitor), or saline for 3 days before and up to 10 days of seizures (1/day), and breathing was measured before, during, and after each seizure. Remarkably, IL-1R antagonism mitigated changes in post-ictal ventilatory suppression on days 7–10 but failed to prevent seizure-related mortality, whereas ketoprofen treatment exacerbated post-ictal ventilatory suppression compared to other treatment groups but prevented seizure-related mortality. These data demonstrate neuroinflammation and microglial activation within the key brainstem region of respiratory control following repeated seizures, which may functionally but differentially contribute to the pathophysiological consequences of repeated seizures.
Longitudinal association of adverse childhood experiences with cognitive function trajectories among middle-aged and older adults: group-based trajectory modeling
Authors: He Xingyue , Yang Hui 
Published: August 2024

IntroductionAdverse childhood experiences (ACEs) impact cognitive function, but the relationship remains unclear. We aim to identify cognitive function trajectories and scrutinize the correlation between ACEs and cognitive function.MethodsTo identify cognitive trajectories, we employed a group-based trajectory model, and influential factors were determined using multinomial unordered logistic regression analysis.ResultsThree cognitive decline subgroups emerged: low-start decline, high-start stability, and mid-start decline. There is no dose-response relationship between cumulative adverse childhood experiences and cognitive function. The high-start stability group had specific residence and education traits, while sibling death affected them. The mid-start decline group was vulnerable to parental death, physical abuse, and domestic violence. The low-start decline group should consider age structure and childhood friendships.ConclusionsNo dose-response association between cumulative ACEs and cognitive decline. Still, specific ACE metrics are correlated with cognitive trajectories. We can incorporate patients’ ACEs into cognitive function assessments for early risk factor identification and tailored interventions. Moreover, recognizing the influence of early-life experiences on cognitive function, we can advocate for nurturing positive family and societal environments to optimize cognitive function.
Burnout among Polish paramedics: insights from the Oldenburg Burnout Inventory
Authors: Kosydar-Bochenek Justyna , Religa Dorota , Iwanicka Kamila , Szczupak Mateusz , Krupa-Nurcek Sabina 
Published: August 2024

IntroductionEmergency medical services rely heavily on paramedics who, as frontline responders, face unique stressors that can potentially lead to burnout. This pilot study utilizes the Oldenburg Burnout Inventory (OLBI) to assess burnout levels among Polish paramedics. The aim is to contribute to the understanding of burnout in this specific professional context and identify key factors influencing burnout dimensions. Future research will build on these preliminary findings.Materials and methodsA cross-sectional study was conducted from March 01 to April 30, 2023, utilizing an online survey accessible to Polish paramedics. The OLBI, a validated tool, was employed to measure burnout, focusing on two dimensions: exhaustion and withdrawal of involvement.ResultsAmong the 147 participating paramedics, the majority were male (65.99%). Paramedics exhibited burnout symptoms across both dimensions measured by The Oldenburg Burnout Inventory scale (OLBI), with an average level for lack of commitment recorded at 20.09, an average level for exhaustion at 20.60. The study revealed that 41.5% of paramedics experienced low burnout, 44.9% reported moderate burnout, and 13.6% faced high burnout risks. Analysis showed that women experienced significantly higher levels of exhaustion compared to men (p = 0.01).ConclusionThis pilot study provides valuable initial insights into burnout among Polish paramedics. The OLBI’s two-factor structure, evaluating exhaustion and disengagement, proved reliable and valid in this context. The prevalence of burnout, with over 60% of paramedics experiencing moderate to high levels, highlights the urgency of addressing burnout in this profession. Future research will be essential to explore the underlying causes and develop targeted interventions.Practical implicationsUnderstanding the factors contributing to burnout among paramedics is crucial for developing targeted interventions. Strategies should focus on stress management training, organizational support, and well-being initiatives. Addressing gender-specific differences in burnout experiences is essential for tailoring interventions effectively. Proactive psychological support mechanisms and optimized working conditions can enhance paramedics’ overall well-being, ensuring their continued effectiveness in providing emergency medical services.
ARISGAN: Extreme super-resolution of arctic surface imagery using generative adversarial networks
Authors: Au Christian , Tsamados Michel , Manescu Petru , Takao So 
Published: August 2024

Introduction: This research explores the application of generative artificial intelligence, specifically the novel ARISGAN framework, for generating high-resolution synthetic satellite imagery in the challenging arctic environment. Realistic and high-resolution surface imagery in the Arctic is crucial for applications ranging from satellite retrieval systems to the wellbeing and safety of Inuit populations relying on detailed surface observations.Methods: The ARISGAN framework was designed by combining dense block, multireceptive field, and Pix2Pix architecture. This innovative combination aims to address the need for high-quality imagery and improve upon existing state-of-the-art models. Various tasks and metrics were employed to evaluate the performance of ARISGAN, with particular attention to land-based and sea ice-based imagery.Results: The results demonstrate that the ARISGAN framework surpasses existing state-of-the-art models across diverse tasks and metrics. Specifically, land-based imagery super-resolution exhibits superior metrics compared to sea ice-based imagery when evaluated across multiple models. These findings confirm the ARISGAN framework’s effectiveness in generating perceptually valid high-resolution arctic surface imagery.Discussion: This study contributes to the advancement of Earth Observation in polar regions by introducing a framework that combines advanced image processing techniques with a well-designed architecture. The ARISGAN framework’s ability to outperform existing models underscores its potential. Identified limitations include challenges in temporal synchronicity, multi-spectral image analysis, preprocessing, and quality metrics. The discussion also highlights potential avenues for future research, encouraging further refinement of the ARISGAN framework to enhance the quality and availability of high-resolution satellite imagery in the Arctic.
Improvement effects of tapinarof on the skin barrier function in Japanese patients with atopic dermatitis
Authors: Igarashi Atsuyuki , Tsuji Gaku , Murata Ryusei , Fukasawa Shuichi , Yamane Satoshi 
Published: August 2024

Background: Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. Tapinarof has been shown to be efficacious and have acceptable safety profile in the treatment of atopic dermatitis (AD).Objective: We sought to evaluate the improvement effect of tapinarof on skin barrier function in patients with AD.Methods: This was an open-label, uncontrolled, single-center study. Japanese patients aged ≥20 years with AD (N = 30) were included in this study. Patients applied tapinarof cream 1% once daily to the target areas on the volar forearm for 8 weeks. The primary endpoints were changes from baseline in stratum corneum hydration (SCH) and transepidermal water loss (TEWL) at the target affected area at week 8.Results: The mean SCH value at the target affected area was 13.656 AU at baseline, 16.904 AU at week 4, and 16.423 AU at week 8. The SCH at the target affected area significantly increased from baseline to week 8, with a mean change of 2.826 AU (p = 0.0433). The mean TEWL value at the target affected area was 17.35 g/m2/hr at baseline, 10.01 g/m2/hr at week 4, and 9.52 g/m2/hr at week 8. The TEWL at the target affected area significantly decreased from baseline to week 8, with a mean change of −8.03 g/m2/hr (p &lt; 0.0001). Clinical signs of AD at the target affected area were improved over time. No serious, severe, or treatment-related AEs were reported.Conclusion: Treatment with tapinarof led to an increase in SCH and a decrease in TEWL in patients with AD, indicating the potential improvement effect of tapinarof on skin barrier function.
Antimicrobial Resistance and Genomic Characterization of Campylobacter jejuni and Campylobacter coli Isolated from Retail Chickens in Beijing, China
Authors: Bai Yao , Ma Jiaqi , Li Fengqin , Yang Baowei , Ren Xiu , Wang Yeru , Hu Yujie , Dong Yinping , Wang Wei , Zhang Jing , Yan Shaofei , Cui Shenghui 
Published: August 2024

Objective Campylobacter species are the main causes of foodborne illness worldwide, posing significant threats to public health. This study aimed to investigate the antibiotic resistance and genomic characterization of C. jejuni/C.coli from retail chickens in Beijing. Methods Antimicrobial susceptibility testing was conducted on 126 C. jejuni/C. coli isolated from retail chickens in Beijing, following CLSI protocols. Whole genomes of all isolates were sequenced using the Illumina platform. Results More C. coli (83.82%) showed multi-drug resistance than C. jejuni (8.62%). Genomic analysis demonstrated 42 sequence types (STs) and 12 clonal complexes (CCs), from which CC828 and CC52 were dominant. cdtA, cdtB and cdtC encoding cytotoxic protein were present spontaneously in most C. jejuni but not found in any C. coli isolates. The abundances of antibiotic resistance genes (ARGs) and virulence genes (VGs) in C. jejuni and C. coli were significantly different, with ARGs numbered in C. coli and VGs in C. jejuni. Conclusions High prevalence of multi-drug resistance C. coli and C. jejuni isolated from Beijing chickens were challenging clinical antibiotic usages in the treatment of Campylobacter infection. The surveillance of particular C. jejuni and C. coli STs correlated with higher resistance and virulence needs to be strengthened in the future.
Association of Dialysate Bicarbonate with Arrhythmia in the Monitoring in Dialysis Study
Authors: Ravi Katherine Scovner , Tumlin James A. , Roy-Chaudhury Prabir , Koplan Bruce A. , Costea Alexandru I. , Kher Vijay , Williamson Don , McClure Candace K. , Charytan David M. , Mc Causland Finnian R. ,   on behalf of the MiD Investigators and Committees
Published: August 2024

Key Points

Sudden cardiac death is a major concern for hemodialysis patients. Mortality is higher on dialysis days and is associated with higher dialysate bicarbonate (DBIC).Contrary to our hypothesis, there was no consistent association of higher DBIC with a higher risk of arrhythmia.Further research is needed to assess the optimal DBIC and mechanisms by which it may improve outcomes for maintenance hemodialysis patients.

Background
Sudden death accounts for approximately 25% of deaths among maintenance hemodialysis patients, occurring more frequently on hemodialysis days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis.

Methods
We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed-effects regression models to assess the association of DBIC with clinically significant arrhythmia (ventricular tachycardia ≥115 beats per minute [BPM] for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA—implantable loop recorder-identified or patient-marked event for which a manual review of the stored electrocardiogram tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, hemodialysis vintage, vascular access, and prehemodialysis serum bicarbonate and additionally for serum and dialysate potassium levels.

Results
The mean age was 56±12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio 0.45 [0.27 to 0.75] and adjusted incident rate ratio 0.54 [0.30 to 0.97]), but the association was not significant when adjusting for serum and dialysate potassium levels (adjusted incident rate ratio, 0.60 [0.32 to 1.11]). Otherwise, no associations between DBIC and arrhythmia were identified.

Conclusions
We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.