bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the mechanisms underlying per- and polyfluoroalkyl substance-induced hippocampal neurotoxicity as determined by network pharmacology and molecular docking analyses
Authors: Li Shirui , Gao Zhihui , Zhong Meihan , Bi Haoran , Li Jianan 
Published: November 2023

Abstract

Background
Per- and polyfluoroalkyl substances (PFASs) are a class of environmental contaminants that pose significant health risks to both animals and humans. Although the hippocampal neurotoxic effects of numerous PFASs have been reported, the underlying mechanisms of combined exposure to PFASs-induced hippocampal neurotoxicity remain unclear.

Methods
In this study, network pharmacology analysis was performed to identify the intersectional targets of PFASs for possible associations with hippocampal neurotoxicity. The evaluation of the influence of PFASs on intersectional targets was assessed using a weighted method. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the screened targets were performed, the intersected hub targets calculated by various algorithms were screened in the network and molecular docking was also used to analyze binding activities.

Results
Our results indicated that eight PFASs, which acted on key targets (MYC, ESR1, STAT3, RELA, MAPK3) impacted the NF-κB signaling pathway, STAT3 signaling pathway, and MAPK signaling pathways to exert neurotoxicity in the hippocampus. The molecular docking results revealed that PFASs have strong binding potential to the hub targets.

Conclusions
Our findings provided a basis for future studies to investigate the detailed mechanisms of PFASs-induced hippocampal neurotoxicity and to develop preventative and control strategies.
Toxicological mechanisms and potencies of organophosphate esters in KGN human ovarian granulosa cells as revealed by high-throughput transcriptomics
Authors: Wang Xiaotong , Rowan-Carroll Andrea , Meier Matthew J , Williams Andrew , Yauk Carole L , Hales Barbara F , Robaire Bernard 
Published: November 2023

Abstract
Despite the growing number of studies reporting potential risks associated with exposure to organophosphate esters (OPEs), their molecular mechanisms of action remain poorly defined. We used the high-throughput TempO-Seq platform to investigate the effects of frequently detected OPEs on the expression of ∼3000 environmentally responsive genes in KGN human ovarian granulosa cells. Cells were exposed for 48 h to 1 of 5 OPEs (0.1–50 μM): tris(methylphenyl) phosphate (TMPP), isopropylated triphenyl phosphate (IPPP), tert-butylphenyl diphenyl phosphate (BPDP), triphenyl phosphate (TPHP), or tris(2-butoxyethyl) phosphate (TBOEP). The sequencing data indicate that 4 OPEs induced transcriptional changes, whereas TBOEP had no effect within the concentration range tested. Multiple pathway databases were used to predict alterations in biological processes based on differentially expressed genes. At lower concentrations, inhibition of the cholesterol biosynthetic pathway was the predominant effect of OPEs; this was likely a consequence of intracellular cholesterol accumulation. At higher concentrations, BPDP and TPHP had distinct effects, primarily affecting pathways involved in cell cycle progression and other stress responses. Benchmark concentration modeling revealed that BPDP had the lowest transcriptomic point of departure. However, in vitro to in vivo extrapolation modeling indicated that TMPP was bioactive at lower concentrations than the other OPEs. We conclude that these new approach methodologies provide information on the mechanism(s) underlying the effects of data-poor compounds and assist in the derivation of protective points of departure for use in chemical read-across and decision-making.
A Convolutional Neural Network for Automated Detection of Cervical Ossification of the Posterior Longitudinal Ligament using Magnetic Resonance Imaging
Authors: Qu Zhe , Deng Bin , Sun Wei , Yang Ranran , Feng Hu 
Published: November 2023

Study Design:
Retrospective cohort study.

Objective:
We aimed to develop and validate a convolutional neural network (CNN) model to distinguish between cervical ossification of posterior longitudinal ligament (OPLL) and multilevel degenerative spinal stenosis using Magnetic Resonance Imaging (MRI) and to compare the diagnostic ability with spine surgeons.

Summary of Background Data:
Some artificial intelligence models have been applied in spinal image analysis and many of promising results were obtained; however, there was still no study attempted to develop a deep learning model in detecting cervical OPLL using MRI images.

Materials and Methods:
In this retrospective study, 272 cervical OPLL and 412 degenerative patients underwent surgical treatment were enrolled and divided into the training (513 cases) and test dataset (171 cases). CNN models applying ResNet architecture with 34, 50, and 101 layers of residual blocks were constructed and trained with the sagittal MRI images from the training dataset. To evaluate the performance of CNN, the receiver operating characteristic curves of 3 ResNet models were plotted and the area under the curve were calculated on the test dataset. The accuracy, sensitivity, and specificity of the diagnosis by the CNN were calculated and compared with 3 senior spine surgeons.

Results:
The diagnostic accuracies of our ResNet34, ResNet50, and ResNet101 models were 92.98%, 95.32%, and 97.66%, respectively; the area under the curve of receiver operating characteristic curves of these models were 0.914, 0.942, and 0.971, respectively. The accuracies and specificities of ResNet50 and ResNet101 models were significantly higher than all spine surgeons; for the sensitivity, ResNet101 model achieved better values than that of the 2 surgeons.

Conclusion:
The performance of our ResNet model in differentiating cervical OPLL from degenerative spinal stenosis using MRI is promising, better results were achieved with more layers of residual blocks applied.
Chemoprophylactic Anticoagulation After Spine Surgery Does Not Increase Epidural Hematoma Risk
Authors: Cloney Michael B. , Dhillon Ekamjeet , Hopkins Benjamin , El Tecle Najib , Koski Tyler R. , Dahdaleh Nader S. 
Published: November 2023

Study design:
A retrospective cohort study.

Objective:
To calculate the magnitude of any increased risk of epidural hematoma (EDH) associated with chemoprophylactic anticoagulation (chemoprophylaxis), if any.

Summary of Background Data:
Chemoprophylaxis for the prevention of venous thromboembolic events may be associated with an increased risk of EDH after spine surgery.

Materials and Methods:
A total of 6869 consecutive spine surgeries performed at our institution were identified, and clinical and demographic data were collected. We identified cases in which symptomatic EDHs were evacuated within 30 days postoperatively. Patients receiving chemoprophylaxis and controls were matched using K-nearest neighbor propensity score matching to calculate the effect of anticoagulation on the rate of postoperative EDH.

Results:
After propensity score matching, 1071 patients who received chemoprophylaxis were matched to 1585 controls. Propensity scores were well balanced between populations (Rubin B=20.6, Rubin R=1.05), and an 89.6% reduction in bias was achieved, with a remaining mean bias of 3.2%. The effect of chemoprophylaxis on EDH was insignificant (P=0.294). Symptomatic EDH was independently associated with having a transfusion [odds ratio (OR)=7.30 (1.15, 46.20), P=0.035], having thoracic-level surgery [OR=41.19 (3.75, 452.4), P=0.002], and increasing body mass index [OR=1.44 (1.04, 1.98), P=0.028] but was not associated with chemoprophylaxis. Five out of 13 patients who developed EDH (38.5%) were receiving some form of anticoagulation, including 1 patient on therapeutic anticoagulation, 1 concurrently on aspirin and chemoprophylaxis, and 2 who were also found to have developed thrombocytopenia postoperatively. The median time on anticoagulation before EDH was 8.1 days. A higher proportion of patients who developed EDH also developed venous thromboembolic events than the general population [38.5% vs. 2.4%, OR=25.34 (9.226, 79.68), P<0.0001], and 1 EDH patient died from pulmonary embolism while off chemoprophylaxis.

Conclusions:
Chemoprophylactic anticoagulation did not cause an increase in the rate of spinal EDH in our patient population.
Alcohol-induced epigenetic changes prevent fibrosis resolution after alcohol cessation in miceresolution
Authors: Schonfeld Michael , O’Neil Maura , Weinman Steven A. , Tikhanovich Irina 
Published: November 2023

Background and Aims:
Alcohol-associated liver disease is a major cause of alcohol-associated mortality. Recently, we identified hepatic demethylases lysine demethylase (KDM)5B and KDM5C as important epigenetic regulators of alcohol response in the liver. In this study, we aimed to investigate the role of KDM5 demethylases in alcohol-associated liver disease resolution.

Approach and Results:
We showed that alcohol-induced liver steatosis rapidly resolved after alcohol cessation. In contrast, fibrosis persisted in the liver for up to 8 weeks after the end of alcohol exposure. Defects in fibrosis resolution were in part due to alcohol-induced KDM5B and KDM5C-dependent epigenetic changes in hepatocytes. Using cell-type–specific knockout mice, we found that adeno-associated virus-mediated knockout of KDM5B and KDM5C demethylases in hepatocytes at the time of alcohol withdrawal promoted fibrosis resolution. Single-cell ATAC sequencing analysis showed that during alcohol-associated liver disease resolution epigenetic cell states largely reverted to control conditions. In addition, we found unique epigenetic cell states distinct from both control and alcohol states and identified associated transcriptional regulators, including liver X receptor (LXR) alpha (α). In vitro and in vivo analysis confirmed that knockout of KDM5B and KDM5C demethylases promoted LXRα activity, likely through regulation of oxysterol biosynthesis, and this activity was critical for the fibrosis resolution process. Reduced LXR activity by small molecule inhibitors prevented fibrosis resolution in KDM5-deficient mice.

Conclusions:
In summary, KDM5B and KDM5C demethylases prevent liver fibrosis resolution after alcohol cessation in part through suppression of LXR activity.
Risk Factors for Recurrence in the Treatment of Recurrent Pterygium
Authors: Kusano Yuki , Den Seika , Yamaguchi Takefumi , Nishisako Sota , Fukui Masaki , Shimazaki Jun 
Published: November 2023

Purpose:
The aim of this study was to identify the postoperative recurrence rate of recurrent pterygium and to evaluate risk factors for the recurrence.

Methods:
This study was a retrospective interventional nonrandomized consecutive case series. In this single-center study, 119 eyes of patients with recurrent pterygium who underwent surgery with a follow-up period of >12 months after the surgery were analyzed. The clinical characteristics of pterygium were classified according to the length of corneal involvement and Tan grade. The main outcome was the recurrence rate. The secondary outcome was the risk factors for recurrence.

Results:
The mean follow-up period was 42 ± 28.6 months. Recurrence was observed in 15 patients (12.6%). The average postoperative recurrence period was 7.7 ± 6.7 months. Twelve patients experienced a recurrence within 12 months. Eyes with recurrence had a significantly greater length of corneal involvement (2.47 ± 0.72 mm) and number of previous surgery (1.9 ± 1.3) than those without (1.97 ± 0.74 mm, and 1.3 ± 0.7, both P = 0.04). Multivariate analysis showed that recurrence was significantly associated with the length of corneal involvement (odds ratio [OR] 2.38, 95% confidence interval [CI], 1.02–5.57, P = 0.05) and the number of previous surgeries (OR: 1.91, 95% CI, 1.03–3.58, P = 0.04) but not with sex (OR: 3.71, 95% CI, 0.90–15.2, P = 0.07), age (OR: 0.99, 95% CI, 0.94–1.04, P = 0.59), and use of mitomycin C (OR: 0.31, 95% CI, 0.07–1.21, P = 0.09).

Conclusions:
The postoperative recurrence rate of recurrent pterygium was 12.6%. The preoperative length of corneal involvement and number of previous pterygium surgeries were significantly correlated with recurrence. Male sex and nonuse of mitomycin C tended to correlate with recurrence.
Behavior Intervention Response Team: Piloting an Effective Means to Manage Patient- and Family-Disruptive Behaviors
Authors: Katzenstein Jennifer M. , Boatman Sondra L. , Newman Kevin , Maier Kristin 
Published: November 2023

Goal:
This article describes the development and implementation of a behavior intervention response team (BIRT). Pilot data indicate the successful implementation of BIRT interventions with patients and families and the positive staff response to these interventions.

Methods:
Patient- and family-disruptive behaviors are increasing in hospitals. Those behaviors arise from stress, financial burdens, and the mental weight of the patient's medical condition on the family. These distressed patients and their families tax an already overwhelmed staff, exacerbating the caregivers' exhaustion, depersonalization, and frustration. We recognized the need to proactively address these disruptions at our children's hospital with an interdisciplinary response. Disciplines engaged in the BIRT development included risk management, behavioral health, child life, service excellence, patient and family services, social work, and chaplaincy. Following multiple brainstorming sessions, we created a comprehensive, clear intervention strategy to engage with a disruptive patient or family. The BIRT was developed to work with both the family and their medical team to intervene at the first signs of potential disruption.

Principal Findings:
With the BIRT, we were able to reduce disruptive behaviors and limit the subsequent removal of problematic individuals from the facility. Of the families who worked with the BIRT, 75.8% required no postintervention follow-up.

Practical Applications:
The development of a BIRT can help head off disruptive behaviors and improve family–medical team relationships to support the highest quality and safest healthcare.
Do oral antiviral drugs used in the treatment of chronic hepatitis B cause erectile dysfunction?
Authors: Üzel Ali , Ebik Berat , Bucaktepe Gamze Erten , Yolaçan Ramazan , Karabulut Ümit , Uçmak Feyzullah 
Published: November 2023

Objective
The effect of antiviral drugs on the erectile dysfunction (ED) problem expressed by some patients using antiviral drugs due to chronic hepatitis B infection (HBV) was investigated.

Methods
A total of 102 male patients receiving antiviral therapy for HBVinfection without any known non-cirrhotic and comorbid disease that may cause ED and whodon’t use any drugs with an ED formation potential were analyzed through the InternationalIndex of Erectile Function test.

Results
Among the patients admitted to the study, anxiety disorder was detected as 24.5% (n = 25) and depression as 46.1% (n = 47). 70.6% (n = 72) of the patients suffered ED. Severe ED was only detected in 3 (n = 2.9%) patients. ED was detected in 70.6% of the entecavir, 64.2% of tenofovir, and 80% of Tenofovir alafenamide users (P = 0.287). On the other hand, the logistics regression analysis revealed that the most important factors that increase the risk of ED are age (>55 age; RR: 2.66; P < 0.001), and anxiety disorder (RR: 2.30; P < 0.0001). The cumulative effect of antiviral drugs on ED was 5.7% (RR: 0.8; P = 0.156).

Conclusion
We could not find any mounting evidence relating to the effect ofcommonly used antiviral drugs for hepatitis B causing ED. The incidence rate of ED on ourpatients was at a similar rate with population studies in the literature based on society. It is notappropriate to terminate antiviral therapy in hepatitis B for this reason.
Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis
Authors: Tan Shufa , Ou Yan , Yang Yunyi , Huang Shuilan , Chen Shikai , Gao Qiangqiang 
Published: November 2023

Background
The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs.

Methods
We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs.

Results
Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs.

Conclusion
DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.
A Cost Analysis of Rethink the Strip
Authors: Spees Lisa P. , Young Laura A. , Rees Jennifer , Mottus Kathleen , Leeman Jennifer , Boynton Marcella H. , Richman Erica , Vu Maihan B. , Donahue Katrina E. 
Published: November 2023

Background:
Routine self-monitoring of blood glucose is a low-value practice that provides limited benefit for patients with non–insulin-treated type 2 diabetes mellitus.

Objectives:
We estimated the costs of Rethink the Strip (RTS), a multistrategy approach to the de-implementation of self-monitoring of blood glucose in primary care.

Research Design:
RTS was conducted among 20 primary care clinics in North Carolina. We estimated the non–site-based and site-based costs of the 5 RTS strategies (practice facilitation, audit and feedback, provider champions, educational meetings, and educational materials) from the analytic perspective of an integrated health care system for 12 and 27-month time horizons. Material costs were tracked through project records, and personnel costs were assessed using activity-based costing. We used nationally based wage estimates.

Results:
Total RTS costs equaled $68,941 for 12 months. Specifically, non–site-based costs comprised $16,560. Most non–site-based costs ($11,822) were from the foundational programming and coding updates to the electronic health record data to develop the audit and feedback reports. The non–site-based costs of educational meetings, practice facilitation, and educational materials were substantially lower, ranging between ~$400 and $1000. Total 12-month site-based costs equaled $2569 for a single clinic (or $52,381 for 20 clinics). Educational meetings were the most expensive strategy, averaging $1401 per clinic. The site-based costs for the 4 other implementation strategies were markedly lower, ranging between $51 for educational materials and $555 for practice facilitation per clinic.

Conclusions:
This study provides detailed cost information for implementation strategies used to support evidence-based programs in primary care clinics.
Exploratory analysis of cortical thickness in low- and high-fit young adults
Authors: Wang Yi Ran , Boré Arnaud , Tremblay Jonathan , Descoteaux Maxime , Champoux François , Théoret Hugo 
Published: November 2023

Objective
Studies have shown changes in the human brain associated with physical activity and cardiorespiratory fitness (CRF). The effects of CRF on cortical thickness have been well-described in older adults, where a positive association between CRF and cortical thickness has been reported, but the impact of sustained aerobic activity in young adults remains poorly described. Here, exploratory analysis was performed on cortical thickness data that was collected in groups of fit and sedentary young adults.

Methods
Twenty healthy sedentary individuals (<2 h/week physical activity) were compared to 20 active individuals (>6 h/week physical activity) and cortical thickness was measured in 34 cortical areas. Cortical thickness values were compared between groups, and correlations between cortical thickness and VO2 max were tested.

Results
Cardiorespiratory fitness was significantly higher in active individuals compared to sedentary individuals. Cortical thickness was lower in regions of the left (lateral and medial orbitofrontal cortex, pars orbitalis, pars triangularis, rostral anterior cingulate cortex, superior temporal cortex and frontal pole) and right (lateral and medial orbitofrontal cortex and pars opercularis) hemispheres. Only the left frontal pole and right lateral orbitofrontal cortical thickness remained significant after false discovery rate correction. Negative correlations were observed between VO2 max and cortical thickness in the left (frontal pole) and right (caudal anterior cingulate and medial orbitofrontal cortex) hemispheres.

Conclusion
The present exploratory analysis supports previous findings suggesting that neuroplastic effects of cardiorespiratory fitness may be attenuated in young compared with older individuals, underscoring a moderating effect of age on the relationship between fitness and cortical thickness.
Improving the quality of self-management in discharged patients with multiple sclerosis: a best practice implementation project
Authors: Xu Yafang , Lizarondo Lucylynn , Zhao Yan , Quan Chao , Cao Yanpei 
Published: November 2023

ABSTRACTObjectives:This project determined current compliance with best practice recommendations for self-management in patients with multiple sclerosis (MS) and used a web-based intervention to implement strategies to improve the quality of self-management in discharged patients with MS.Methods:Guided by the JBI Evidence-based Model of Health care, this project applied the 7 phases of the JBI Evidence Implementation Framework to improve the quality of self-management in MS patients.Results:After implementation, compliance significantly improved across all criteria compared with the baseline audit. All patients were assessed to determine their ability to self-manage (Criterion 1). All health care providers were trained to facilitate self-management and behavioral change (Criterion 2). All patients had self-management goals and action plans that were set together by both health care providers and patients (Criteria 3, 5, 6, 7). All patients received education through online patient education courses and were given an education handbook (Criterion 4). The agreed action plan was documented (Criterion 8). All members of the multidisciplinary team coordinated the services required by the patients (Criterion 9) and provided appropriate support to help patients achieve their goals and solve problems through a WeChat group and the communication module on the self-management online platform (Criterion 10).Conclusion:This implementation project effectively promoted practice change by enhancing patients’ knowledge of self-management and staff awareness of delivering self-management support to MS patients.