bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration
Authors: Xie Ran , Jia Bo , Cheng Lu , Zhao Nan , He Xu , Wang Xia , Zhao Xia , Cui Yimin 
Published: February 2024

Abstract

Background
Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate–specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED).

Aim
This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males.

Methods
Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg.

Outcomes
The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography–tandem mass spectrometry.

Results
Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group.

Clinical Implications
Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED.

Strengths and Limitations
This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED.

Conclusion
Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration.

Clinical Trial Registration
CTR20192473 (http://www.chinadrugtrials.org.cn).
Effects of electrolyte supplementation on performance and physiological responses of preconditioning beef calves
Authors: Ferreira Matheus F L , Hernandez Gracia P , Santos Aline C R , Bohnert David , Upah Nathan , Ranches Juliana 
Published: February 2024

Abstract
The objective of this study was to evaluate the effects of electrolyte solution supplementation on the performance and physiological responses of beef calves during a 45-d preconditioning phase. Forty Angus × Hereford steers (230.4 ± 4.8 kg body weight [BW]) were sorted into 20 pens (2 steers/pen) following weaning (day 0). Treatments were randomly assigned to pens: (1) control: access to water only and (2) electrolyte: access to water and electrolyte solution supplementation (10% of total daily water intake) from days 1 to 14. Calf BW and blood samples were collected on days 0, 1, 3, 7, 14, 21, and 44 of the study. Blood samples were analyzed for sodium, potassium, albumin, haptoglobin, ceruloplasmin, and cortisol. All variables were analyzed using the MIXED procedure of SAS. Electrolyte solution consumption was estimated at 0.70 kg/calf daily (SEM ± 0.21). Calves assigned to the Electrolyte treatment had greater water and total liquid intake than control (P &lt; 0.05). No effects of treatment were observed on ADG or BW (P &gt; 0.05). Effects of day (P &lt; 0.004), but not treatment or treatment × day were observed for sodium, potassium, albumin, cortisol, ceruloplasmin, and haptoglobin. Electrolyte solution supplementation during the preconditioning period did not improve performance nor influenced stress-related markers, however improved liquid intake.
Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak
Authors: Wu Zhiyong , Chang Tong , Wang Decheng , Zhang Hongliang , Liu Haizhou , Huang Xinyi , Tian Zhijun , Tian Xiaoxiao , Liu Di , An Tongqing , Yan Yi 
Published: February 2024

Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China’s pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China’s pig industry in the post-epidemic era of ASF.
Endothelium‐mediated regulation of platelet activation: Involvement of multiple protein kinases
Authors: Provenzale Isabella , Solari Fiorella A. , Schönichen Claudia , Brouns Sanne L. N. , Fernández Delia I. , Kuijpers Marijke J. E. , van der Meijden Paola E. J. , Gibbins Jonathan M. , Sickmann Albert , Jones Chris , Heemskerk Johan W. M. 
Published: February 2024

AbstractThe endothelial regulation of platelet activity is incompletely understood. Here we describe novel approaches to find molecular pathways implicated on the platelet–endothelium interaction. Using high‐shear whole‐blood microfluidics, employing coagulant or non‐coagulant conditions at physiological temperature, we observed that the presence of human umbilical vein endothelial cells (HUVEC) strongly suppressed platelet adhesion and activation, via the collagen receptor glycoprotein VI (GPVI) and the PAR receptors for thrombin. Real‐time monitoring of the cytosolic Ca2+ rises in the platelets indicated no major improvement of inhibition by prostacyclin or nitric oxide. Similarly under stasis, exposure of isolated platelets to HUVEC reduced the Ca2+ responses by collagen‐related peptide (CRP‐XL, GPVI agonist) and thrombin (PAR agonist). We then analyzed the label‐free phosphoproteome of platelets (three donors), exposed to HUVEC, CRP‐XL, and/or thrombin. High‐resolution mass spectrometry gave 5463 phosphopeptides, corresponding to 1472 proteins, with good correlation between biological and technical replicates (R > .86). Stringent filtering steps revealed 26 regulatory pathways (Reactome) and 143 regulated kinase substrates (PhosphoSitePlus), giving a set of protein phosphorylation sites that was differentially (44) or similarly (110) regulated by HUVEC or agonist exposure. The differential regulation was confirmed by stable‐isotope analysis of platelets from two additional donors. Substrate analysis indicated major roles of poorly studied protein kinase classes (MAPK, CDK, DYRK, STK, PKC members). Collectively, these results reveal a resetting of the protein phosphorylation profile in platelets exposed to endothelium or to conventional agonists and to endothelium‐promoted activity of a multi‐kinase network, beyond classical prostacyclin and nitric oxide actors, that may contribute to platelet inhibition.
Histone deacetylase 6 deficiency protects the liver against ischemia/reperfusion injury by activating PI3K/AKT/mTOR signaling
Authors: Pan Jie , Yu Qiwen , Song Yaodong , Cui Zongchao , He Qianqian , Cui Mengwei , Mei Chaopeng , Cui Huning , Wang Haifeng , Li Huihui , Chen Sanyang 
Published: February 2024

AbstractLiver transplantation (LT) is the only effective method to treat end‐stage liver disease. Hepatic ischemia‐reperfusion injury (IRI) continues to limit the prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) is a unique HDAC member involved in inflammation and apoptosis. However, its role and mechanism in hepatic IRI have not yet been reported. We examined HDAC6 levels in liver tissue from LT patients, mice challenged with liver IRI, and hepatocytes subjected to hypoxia/reoxygenation (H/R). In addition, HDAC6 global‐knockout (HDAC6‐KO) mice, adeno‐associated virus‐mediated liver‐specific HDAC6 overexpressing (HDAC6‐LTG) mice, and their corresponding controls were used to construct hepatic IRI models. Hepatic histology, inflammatory responses, and apoptosis were detected to assess liver injury. The molecular mechanisms of HDAC6 in hepatic IRI were explored in vivo and in vitro. Moreover, the HDAC6‐selective inhibitor tubastatin A was used to detect the therapeutic effect of HDAC6 on liver IRI. Together, our results showed that HDAC6 expression was significantly upregulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Compared with control mice, HDAC6 deficiency mitigated liver IRI by inhibiting inflammatory responses and apoptosis, whereas HDAC6‐LTG mice displayed the opposite phenotype. Further molecular experiments show that HDAC6 bound to and deacetylated AKT and HDAC6 deficiency improved liver IRI by activating PI3K/AKT/mTOR signaling. In conclusion, HDAC6 is a key mediator of hepatic IRI that functions to promote inflammation and apoptosis via PI3K/AKT/mTOR signaling. Targeting hepatic HDAC6 inhibition may be a promising approach to attenuate liver IRI.
Building a Trauma-Informed Community: Applying Community Building Circles to an Academic Health Research Setting
Authors: Shetty Neha , Pierson Elizabeth , Manders Khamera B. , Sun YiLing , Masciantonio Elizabeth , Sinko Laura 
Published: February 2024

Abstract

Problem
Within health science disciplines, power dynamics exist that can not only perpetuate harm but also foster feelings of powerlessness and disengagement. Although diversity, equity, and inclusion approaches have been prioritized by many institutions to improve student and staff recruitment, few effective structures exist to promote the retention, support, and inclusion of these individuals.

Approach
Restorative justice circles facilitate a collaborative and personal exercise that welcomes the input of all members, thus acting as a catalyst toward broader and more deeply rooted culture changes and conflict resolution. Restorative justice circles can be applied to strengthen academic learning environments by building community and creating intentional dialog spaces to promote accountability and belonging. The Phoenix Gender-based Violence Lab is an interdisciplinary health research lab composed of diverse researchers who meet monthly for a restorative justice–inspired community-building circle and discussion. The lab members participated in community-building circles from August 2021 to August 2022 during which circle facilitators aimed to prioritize safety, trustworthiness, and transparency and provide collaboration opportunities.

Outcomes
All 10 research team members consented to an anonymous evaluation survey to share their perspectives about incorporating this approach into lab time. Research team members expressed many benefits of circle discussions, including mitigated power dynamics (n = 5), increased lab cohesion (n = 9), improved research processes (n = 6), and enhanced honesty and accountability (n = 4).

Next Steps
Circle practice has shown promising results within the Phoenix Gender-based Violence Lab, indicating that other academic and medical settings should consider its potential to enhance group dynamics, foster accountability, and cultivate deeper collaboration and appreciation among group members. Further investigation of circle practice in diverse medical and academic settings is needed to fully comprehend the range of outcomes resulting from this intervention and whether they align with the fundamental principles of restorative justice.
Room for Improvement: The Impact of Guideline-Recommended Extended Thromboprophylaxis in Patients Undergoing Abdominal Surgery for Colorectal and Anal Cancer at a Tertiary Referral Center
Authors: Broccard Sacha P. , Edwards Michael A. , Brennan Emily R. , Spaulding Aaron C. , DeLeon Michelle , Mishra Nitin , Casler John D. , Colibaseanu Dorin T. 
Published: February 2024

BACKGROUND:
Venous thromboembolism occurs in approximately 2% of patients undergoing abdominal and pelvic surgery for cancers of the colon, rectum, and anus, and is considered preventable. The American Society of Colon and Rectal Surgeons recommends extended prophylaxis in high-risk patients, but there is low adherence to the guidelines.

OBJECTIVE:
This study aims to analyze the impact of venous thromboembolism risk-guided prophylaxis in patients undergoing elective abdominal and pelvic surgeries for colorectal and anal cancers from 2016 to 2021.

DESIGN:
This was a retrospective analysis.

SETTING:
The study was conducted at a multisite tertiary referral academic healthcare system.

PATIENTS:
Patients who underwent elective abdominal or pelvic surgery for colon, rectal or anal cancer.

MAIN OUTCOME MEASURES:
Receipt of Caprini-guided venous thromboembolism prophylaxis, 90 days postoperative rate of deep vein thrombosis, pulmonary embolism, venous thromboembolism, and bleeding events.

RESULTS:
A total of 3,504 patients underwent elective operations, of which 2,224 (63%) received appropriate thromboprophylaxis in the inpatient setting. In the post-discharged cohort of 2,769 patients, only 2% received appropriate thromboprophylaxis in which no thromboembolic events were observed. In the group receiving inappropriate thromboprophylaxis, at 90 days post-discharge, the deep vein thrombosis, pulmonary embolism, and venous thromboembolism rates were 0.60%, 0.40%, and 0.88%, respectively. Postoperative bleeding was not different between the two groups.

LIMITATIONS:
Limitations to our study include its retrospective nature, use of aggregated electronic medical records, and single healthcare system experience.

CONCLUSION:
Most patients in our healthcare system undergoing abdominal or pelvic surgery for cancers of the colon, rectum, and anus were discharged without appropriate Caprini-guided VTE prophylaxis. Risk-guided prophylaxis was associated with decreased rates of in-hospital and discharged venous thromboembolism without an increase in bleeding complications. See Video Abstract.
Current Treatment and Immunomodulation Strategies in Acute Myocarditis
Authors: Ferone Emma , Segev Amitai , Tempo Erika , Gentile Piero , Elsanhoury Ahmed , Baggio Chiara , Artico Jessica , Bhatti Prashan , Scott Paul , Bobbio Emanuele , Merlo Marco , Ameri Pietro , Sinagra Gianfranco , Tschöpe Carsten , Bromage Daniel , Cannata Antonio 
Published: February 2024

Abstract:
Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.
Surgical Outcome After Treatment of Radiation-Induced Scleral Necrosis in Patients With Uveal Melanoma
Authors: Jabbarli Leyla , Biewald Eva , Guberina Maja , Le Guin Claudia H.D. , Thomasen Henning , Fiorentzis Miltiadis , Sokolenko Ekaterina , Flühs Dirk , Bornfeld Norbert , Stuschke Martin , Bechrakis Nikolaos E. , Rating Philipp 
Published: February 2024

Purpose:
Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery.

Methods:
All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included. Achievement of the tectonic stability and evaluation of incidence and the risk factors for a repetitive patch surgery (RPS) were the main endpoints.

Results:
The final analysis included 57 patients (mean age: 58.7 years; 63.2% female patients), where 55 individuals underwent a patch grafting, and 2 cases were treated with conjunctival reconstructive surgery. The mean follow-up time after grafting was 38.5 months (0.03–221.1 months). Tectonic stability was achieved in 56 (98.3%) patients. Scleral graft (38/55, 69.1%) was the most frequent patching material, followed by Tutopatch (7/55, 12.7%), corneal graft (7/55, 12.7%), dura graft (2/55, 3.6%), and fascia lata (FL) graft (1/55, 1.8%). Eleven patients (20%) underwent RPS after the mean time of 12.9 months (0.3–50.3 months). In the final multivariate Cox regression analysis, the use of Tutopatch (5/7; 71.4%, adjusted hazard ratio = 4.66, P = 0.044) and RISN progression after patch grafting (9/11; 81.8%, adjusted hazard ratio = 9.67, P = 0.008) were independent risk factors for RPS.

Conclusions:
RISN surgery maintains long-term tectonic stability in most of the cases underwent surgical repair for RISN after brachytherapy for UM. Depending on graft material and, particularly, further RISN progression, an RPS might be necessary in certain cases.
Long-Term Outcomes of 6-Week Treatment of Lotilaner Ophthalmic Solution, 0.25%, for Demodex Blepharitis: A Noninterventional Extension Study
Authors: Sadri Ehsan , Paauw James D. , Ciolino Joseph B. , Nijm Lisa , Simmons Blake , Meyer John , Gaddie Ian Benjamin , Berdy Gregg J. , Holdbrook Mark , Baba Stephanie N. , Jalalat Parisa , Yeu Elizabeth 
Published: February 2024

Purpose:
The aim of this study was to evaluate the long-term outcomes of lotilaner ophthalmic solution, 0.25%, in the treatment of Demodex blepharitis.

Methods:
This observational, extension study included patients with Demodex blepharitis (N = 239) who completed the Saturn-1 study and presented for the day 180 visit. All participants were assessed at days 180 and 365 after the initiation of 6-week treatment with the study drug or its vehicle.

Results:
The proportion of patients with 0 to 2 collarettes (grade 0) was significantly higher in the study group (N = 128 patients) than in the control group (N = 111 patients) (39.8% vs. 2.7% at day 180 and 23.5% vs. 2.9% at day 365; P < 0.0001). Similarly, the proportion of patients with ≤10 collarettes (collarette grade 0–1) in the study group was significantly higher than in the control group (70.3% vs. 18.0% at day 180 and 62.6% vs. 21.9% at day 365; P < 0.0001). In the study group, erythema continued to improve even after completion of the 6-week lotilaner treatment. No serious ocular adverse events were observed in the study group, and there was 1 treatment-related ocular adverse event in the study group, which was considered mild.

Conclusions:
After 6-week treatment with lotilaner ophthalmic solution, 0.25%, for Demodex blepharitis, no long-term concerns were observed during 1 year of follow-up. A high proportion of patients with 0 to 2 collarettes (grade 0) or ≤10 collarettes (collarette grade of 0 or 1) was observed throughout 1 year of follow-up, indicating that the efficacy of lotilaner ophthalmic solution, 0.25%, against Demodex blepharitis may last well after completion of therapy.
Incidence and predictors of acute kidney injury after elective surgery for lumbar degenerative disease: A 13-year analysis of the US Nationwide Inpatient Sample
Authors: Hsieh Yueh-Ying , Wu Lien-Chen , Chen I-Chun , Chiang Chang-Jung 
Published: February 2024

Background:
Acute kidney injury (AKI) is a severe postoperative complication associated with poor clinical outcomes, including the development of chronic kidney disease (CKD) and death. This study aimed to investigate the incidence and determinants of AKI following elective surgeries for degenerative lumbar spine disease.

Methods:
All patient data were extracted from the US Nationwide Inpatient Sample database. After surgery, AKI’s incidence and risk factors were identified for lumbar degenerative disease. ICD-9 and ICD-10 codes defined lumbar spine degenerative disease, fusion, decompression, and AKI. The study cohort was categorized by type of surgery, that is, decompression alone or spinal fusion. Regression analysis was used to identify associations between AKI and risk factors organized by surgery type.

Results:
The incidence of AKI after decompression or fusion was 1.1% and 1.8%, respectively. However, the incidence of AKI in the United States is rising. The strongest predictor of AKI was underlying CKD, which was associated with an 9.0- to 12.9-fold more significant risk of AKI than in subjects without comorbid CKD. In this setting, older age, congestive heart failure, anemia, obesity, coagulopathy and hospital-acquired infections were also strong predictors of AKI. In contrast, long-term aspirin/anticoagulant usage was associated with lowered AKI risk.

Conclusion:
Findings of this study inform risk stratification for AKI and may help to optimize treatment decisions and care planning after elective surgery for lumbar degenerative disease.
Creating Shared Perspectives for Worker Well-being
Authors: Schaefer Camie , Ahonen Emily 
Published: February 2024

Objectives
This study aimed to highlight the utility of a new certificate program in Total Worker Health® (TWH) designed for health professionals in other community health settings (OCHS).

Methods
Stakeholder needs assessment, priority setting, and comparison with existing core competencies in TWH approaches were performed to identify learning objectives and curricular threads in alignment with adult learning principles. Faculty-student pairings were conducted for content and assessment development.

Results
A free six-module training course that prepares OCHS professionals to collaborate with occupational safety and health (OSH) professionals.

Conclusions
TWH can be advanced through collaboration between OSH and OCHS professionals. In service of shared ground, OCHS professionals should articulate the influence of work on health, TWH principles, and OSH vocabulary and concepts. Such training is a necessary step toward facilitating groups for the benefit of all work and workers.