bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health
Authors: Davis Allan Peter , Wiegers Thomas C , Wiegers Jolene , Wyatt Brent , Johnson Robin J , Sciaky Daniela , Barkalow Fern , Strong Melissa , Planchart Antonio , Mattingly Carolyn J 
Published: July 2023

Abstract
The molecular mechanisms connecting environmental exposures to adverse endpoints are often unknown, reflecting knowledge gaps. At the Comparative Toxicogenomics Database (CTD), we developed a bioinformatics approach that integrates manually curated, literature-based interactions from CTD to generate a “CGPD-tetramer”: a 4-unit block of information organized as a step-wise molecular mechanism linking an initiating Chemical, an interacting Gene, a Phenotype, and a Disease outcome. Here, we describe a novel, user-friendly tool called CTD Tetramers that generates these evidence-based CGPD-tetramers for any curated chemical, gene, phenotype, or disease of interest. Tetramers offer potential solutions for the unknown underlying mechanisms and intermediary phenotypes connecting a chemical exposure to a disease. Additionally, multiple tetramers can be assembled to construct detailed modes-of-action for chemical-induced disease pathways. As well, tetramers can help inform environmental influences on adverse outcome pathways (AOPs). We demonstrate the tool’s utility with relevant use cases for a variety of environmental chemicals (eg, perfluoroalkyl substances, bisphenol A), phenotypes (eg, apoptosis, spermatogenesis, inflammatory response), and diseases (eg, asthma, obesity, male infertility). Finally, we map AOP adverse outcome terms to corresponding CTD terms, allowing users to query for tetramers that can help augment AOP pathways with additional stressors, genes, and phenotypes, as well as formulate potential AOP disease networks (eg, liver cirrhosis and prostate cancer). This novel tool, as part of the complete suite of tools offered at CTD, provides users with computational datasets and their supporting evidence to potentially fill exposure knowledge gaps and develop testable hypotheses about environmental health.
Analyzing author collaborations by developing a follower-leader clustering algorithm and identifying top co-authoring countries: Cluster analysis
Authors: Lin Che-Kuang , Ho Sam Yu-Chieh , Chien Tsair-Wei , Chou Willy , Chow Julie Chi 
Published: July 2023

Background:
This study aimed to explore suitable clustering algorithms for author collaborations (ACs) in bibliometrics and investigate which countries frequently coauthored with others in recent years. To achieve this, the study developed a method called the Follower-Leading Clustering Algorithm (FLCA) and used it to analyze ACs and cowords in the Journal of Medicine (Baltimore) from 2020 to 2022.

Methods:
This study extracted article metadata from the Web of Science and used the statistical software R to implement FLCA, enabling efficient and reproducible analysis of ACs and cowords in bibliometrics. To determine the countries that easily coauthored with other countries, the study observed the top 20 countries each year and visualized the results using network charts, heatmaps with dendrograms, and Venn diagrams. The study also used chord diagrams to demonstrate the use of FLCA on ACs and cowords in Medicine (Baltimore).

Results:
The study observed 12,793 articles, including 5081, 4418, and 3294 in 2020, 2021, and 2022, respectively. The results showed that the FLCA algorithm can accurately identify clusters in bibliometrics, and the USA, China, South Korea, Japan, and Spain were the top 5 countries that commonly coauthored with others during 2020 and 2022. Furthermore, the study identified China, Sichuan University, and diagnosis as the leading entities in countries, institutes, and keywords based on ACs and cowords, respectively. The study highlights the advantages of using cluster analysis and visual displays to analyze ACs in Medicine (Baltimore) and their potential application to coword analysis.

Conclusion:
The proposed FLCA algorithm provides researchers with a comprehensive means to explore and understand the intricate connections between authors or keywords. Therefore, the study recommends the use of FLCA and visualizations with R for future research on ACs with cluster analysis.
Fall-related Injuries and Opioid Administration Among Veterans With Dementia in US Department of Veterans Affairs Community Living Centers
Authors: Wang Huiying , Cai Shubing , Caprio Thomas , Goulet Joseph , Intrator Orna 
Published: July 2023

Objectives:
Opioid use is associated with fall-related injuries (FRI) among older adults, especially those with dementia. We examined FRI following changes in national opioid safety initiatives over 3 regulatory periods [preinitiatives baseline (period 1): October 2012 to June 2013; post-Veteran Affairs (VA) opioid safety initiative (period 2): January 2014 to November 2015; post-VA and CDC opioid prescribing guidelines (period 3): March 2017 to September 2018] among Department of VA Community Living Center (CLC) long-stay residents with dementia.

Data:
VA provided and purchased care records, Medicare claims, CLC Minimum Data Set (MDS) assessments. VA bar-code medication administration data, VA outpatient prescription refill data, and Medicare Part D data were used to capture medication from inpatient, outpatient, and Medicare sources.

Settings and Participants:
A total of 12,229 long-stay CLC residents with dementia between October 2012 and September 2018.

Methods:
We applied Veteran-regulatory period level (1) generalized linear model to examine the unadjusted and adjusted trends of FRI, and (2) difference-in-difference model with propensity score weighting to examine the relationship between opioid safety initiatives and FRI in 3 regulatory periods. We applied propensity score weighting to enable the cohorts in periods 2 and 3 had similar indications for opioid administration as in period 1.

Results:
FRI prevalence per month among CLC residents with Alzheimer disease and related dementias decreased from 3.1% in period 1 to 1.6% and 1.2% in periods 2 and 3, and the adjusted probability of FRI was 17% and 40% lower in periods 2 and 3 compared with period 1. The any, incident, and continued opioid administration were significantly associated with higher FRI, whereas the differences in FRI probabilities between opioid and nonopioid users had no significant changes over the 3 regulatory periods.

Conclusions:
FRI was reduced among CLC residents with Alzheimer disease and related dementias receiving care in VA CLCs over the 3 regulatory periods, but the FRI reduction was not significantly associated with opioid safety initiatives. Other interventions that potentially targeted falls are likely to have helped reduce these fall events. Future studies could examine whether opioid use reduction ultimately benefitted nursing home residents by focusing on other possible outcomes or whether such reduction only resulted in more untreated pain.
Image Quality and Lesion Detectability of Pancreatic Phase Thin-Slice Computed Tomography Images With a Deep Learning–Based Reconstruction Algorithm
Authors: Nakamoto Atsushi , Onishi Hiromitsu , Tsuboyama Takahiro , Fukui Hideyuki , Ota Takashi , Ogawa Kazuya , Yano Keigo , Kiso Kengo , Honda Toru , Tatsumi Mitsuaki , Tomiyama Noriyuki 
Published: July 2023

Objective
To evaluate the image quality and lesion detectability of pancreatic phase thin-slice computed tomography (CT) images reconstructed with a deep learning–based reconstruction (DLR) algorithm compared with filtered-back projection (FBP) and hybrid iterative reconstruction (IR) algorithms.

Methods
Fifty-three patients who underwent dynamic contrast-enhanced CT including pancreatic phase were enrolled in this retrospective study. Pancreatic phase thin-slice (0.625 mm) images were reconstructed with each FBP, hybrid IR, and DLR. Objective image quality and signal-to-noise ratio of the pancreatic parenchyma, and contrast-to-noise ratio of pancreatic lesions were compared between the 3 reconstruction algorithms. Two radiologists independently assessed the image quality of all images. The diagnostic performance for the detection of pancreatic lesions was compared among the reconstruction algorithms using jackknife alternative free-response receiver operating characteristic analysis.

Results
Deep learning–based reconstruction resulted in significantly lower image noise and higher signal-to-noise ratio and contrast-to-noise ratio than hybrid IR and FBP (P < 0.001). Deep learning–based reconstruction also yielded significantly higher visual scores than hybrid IR and FBP (P < 0.01). The diagnostic performance of DLR for detecting pancreatic lesions was highest for both readers, although a significant difference was found only between DLR and FBP in one reader (P = 0.02).

Conclusions
Deep learning–based reconstruction showed improved objective and subjective image quality of pancreatic phase thin-slice CT relative to other reconstruction algorithms and has potential for improving lesion detectability.
Complications of Cancer Therapy in Children: A Comprehensive Review of Body Imaging Findings
Authors: Snyder Elizabeth J. , Sarma Asha , Krishnasarma Rekha , Pruthi Sumit 
Published: July 2023

Abstract
Complications of cancer therapy in children can result in a spectrum of toxicities that can affect any organ system and result in a range of morbidity. Complications may occur at the initiation of therapy or years following treatment. Although childhood cancer remains rare, increasing survival rates means more children are living longer following their treatment. Radiologists often play an important role in the diagnosis and evaluation of these complications, and thus, awareness of their imaging findings is essential to guide management and avoid misdiagnosis. This second part of a 2-part review aims to illustrate the typical body imaging findings of cancer therapy-related toxicities, including both early and late treatment effects. The article also discusses the differential diagnosis of imaging findings, highlighting pearls and pitfalls in making the appropriate diagnosis.
Quantitative DECT of Iodine in Chronic Subdural Hematoma as Surrogate of Membrane Exudation: A Pilot Feasibility Study
Authors: Bodanapally Uttam K. , Aarabi Bizhan , Liang Yuanyuan , Khalid Mazhar , Fleiter Thorsten R. , Gandhi Dheeraj 
Published: July 2023

Objective
We explore the feasibility to estimate the exudation from chronic subdural hematoma (CSDH) membranes, by using dual-energy computed tomography (DECT) quantification of iodine leak and test if the derived quantitative variables and membrane morphology correlates with hematoma volume, internal architecture (homogeneous, laminar, separated, and trabecular types), and fractional hyperdense hematoma at presentation.

Methods
In this retrospective study, consecutive CSDH patients with postcontrast DECT head images from January 2020 and June 2021 were analyzed. Predictor variables derived from DECT were correlated with outcome variables followed by mixed-effects regression analysis.

Results
The study included 36 patients with 50 observations (mean age, 72.6 years; standard deviation, 11.6 years); 31 were men. Dual-energy CT variables that correlated with hematoma volume were external membrane volume (ρ, 0.37; P = 0.008) and iodine concentration (ρ, −0.29; P = 0.04). Variables that correlated with separated type of hematoma were total iodine leak (median [Q1, Q3], 68.3 mg [48.5, 88.9] vs 38.8 mg [15.5, 62.9]; P = 0.001) and iodine leak per unit membrane volume (median [Q1, Q3], 16.47 mg/mL [10.19, 20.65] vs 8.68 mg/mL [5.72, 11.41]; P = 0.002). Membrane grade was the only variable that correlated with fractional hyperdense hematoma (ρ, 0.28; P = 0.05). Regression analysis showed total iodine leak as the strongest predictor of separated type hematoma (odds ratio [95% confidence interval], 1.06 per mg [1.01, 1.1]).

Conclusions
Dual-energy CT demonstrates iodine leak from CSDH membranes. The variables derived from DECT correlated with hematoma volume, internal architecture, and fractional hyperdense hematoma.
Ileal Pouch-anal Anastomosis in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease (PSC-IBD)
Authors: Maspero Marianna , Holubar Stefan D. , Raj Roma , Yilmaz Sumeyye , Prien Christopher , Lavryk Olga , Pita Alejandro , Hashimoto Koji , Steele Scott R. , Hull Tracy L. 
Published: July 2023

Objective:
To compare the effect of liver transplantation (LT) on ileal pouch-anal anastomosis outcomes in patients with primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD)

Summary Background Data:
Patients with PSC-IBD may require both IPAA for colitis and LT for PSC.

Methods:
Patients with PSC-IBD from out institutional pouch registry (1985 – 2022) were divided according to LT status and timing of LT (before and after IPAA) and their outcomes analyzed.

Results:
A total of 160 patients were included: 112 (70%) non-transplanted at last follow-up; 48 (30%) transplanted, of which 23 (14%) before IPAA and 25 (16%) after. Non-transplanted patients at IPAA had more laparoscopic procedures (37 [46%] vs 8 [18%], P=0.002) and less blood loss (median 250 cc vs 400 cc, P=0.006). Morbidity and mortality at 90-days were similar. Chronic pouchitis was higher in transplanted compared to non-transplanted patients (32 [67%] vs 51 [45.5%], P=0.03), but non-transplanted patients had a higher rate of chronic antibiotic refractory pouchitis. Overall survival was similar, but non-transplanted patients had more PSC-related deaths (12.5% vs 2%, P=0.002). Pouch survival at 10 years was 90% for non-transplanted patients and 100% for transplanted patients, log rank P=0.052. Timing of LT had no impact on chronic pouchitis, pouch failure, or overall survival. PSC recurrence was 6% at 10 years. For transplanted patients, graft survival was similar regardless of IPAA timing.

Conclusions:
In patients with PSC-IBD and IPAA, liver transplantation is linked to an increased pouchitis rate, but does not affect overall and pouch survival. Timing of LT does not influence short- and long-term pouch outcomes.
Ethical and Psychosocial Factors in the Decision-Making and Informed Consent Process for Upper Extremity Vascularized Composite Allotransplantation: A Mixed-Methods Study
Authors: Gordon Elisa J. , Gacki-Smith Jessica , Kuramitsu Brianna R. , Downey Max , Vanterpool Karen B. , Nordstrom Michelle J. , Riggleman Tiffany , Cooney Carisa M. , Jensen Sally , Dumanian Gregory , Tintle Scott , Levan Macey , Brandacher Gerald 
Published: July 2023

Background.
Although upper extremity (UE) vascularized composite allotransplantation (VCA) aims to improve quality of life, relatively few have been performed worldwide to support evidence-based treatment and informed decision-making.

Methods.
We qualitatively examined factors contributing to anticipated and actual decision-making about UE VCA and perceptions of the elements of informed consent among people with UE amputations, and UE VCA candidates, participants, and recipients through in-depth interviews. Thematic analysis was used to analyze qualitative data.

Results.
Fifty individuals participated; most were male (78%) and had a mean age of 45 y and a unilateral amputation (84%). One-third (35%) were “a lot” or “completely” willing to pursue UE VCA. UE VCA decision-making themes included the utility of UE VCA, psychosocial impact of UE VCA and amputation on individuals’ lives, altruism, and anticipated burden of UE VCA on lifestyle. Most respondents who underwent UE VCA evaluation (n = 8/10) perceived having no reasonable treatment alternatives. Generally, respondents (n = 50) recognized the potential for familial, societal, cultural, medical, and self-driven pressures to pursue UE VCA among individuals with amputations. Some (n = 9/50, 18%) reported personally feeling “a little,” “somewhat,” “a lot,” or “completely” pressured to pursue UE VCA. Respondents recommended that individuals be informed about the option of UE VCA near the amputation date.

Conclusions.
Our study identified psychosocial and other factors affecting decision-making about UE VCA, which should be addressed to enhance informed consent. Study participants’ perceptions and preferences about UE VCA suggest re-examination of assumptions guiding the UE VCA clinical evaluation process.
Prevention of risky sexual behavior in primary health care: a best practice implementation project
Authors: Cunha-Oliveira Aliete , Menino Eva , Santos Diana , Cardoso Daniela , Neves Marília , Martins Maria J. , Gonçalves Ana M. , Dias Clara , Gonçalves Maria L. , Santos Rita , Sambango Arão , Rodrigues Rogério 
Published: July 2023

ABSTRACTIntroduction and objectives:Sexually transmitted infections are a public health problem affecting 45% of adolescents and young adults worldwide. The evidence suggests that primary care settings are uniquely positioned to implement preventive interventions. The aim of this project was to improve nurses’ interventions for preventing risky sexual behaviors in adolescents attending nursing consultations in a primary health care unit.Methods:This project was guided by the JBI Evidence Implementation Framework. A baseline audit was conducted to evaluate current practice against recommended best practices. Barriers to compliance with the best practices were identified, and strategies were adopted to overcome them. A follow-up audit was conducted to measure changes in compliance with best practices, using the same approach as the baseline audit.Results:Compliance rates improved for four criteria from baseline to follow-up audit.Conclusion:Through auditing and feedback, evidence-based interventions were implemented to prevent sexual risky behavior in adolescents in primary care settings. Further best practice implementation projects should be conducted to improve adolescent health outcomes.
A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance
Authors: Sebag Sara C. , Qian Qingwen , Upara Chawin , Ding Qiong , Cao Huojun , Hong Liu , Yang Ling 
Published: July 2023

ABSTRACTObesity, a worldwide health problem, increases the risk for developing metabolic diseases such as insulin resistance and diabetes. It is well recognized that obesity-associated chronic inflammation plays a key role in the pathogenesis of systemic metabolic dysfunction. Previously, we revealed an anti-inflammatory role for spent culture supernatants isolated from the oral commensal bacterial speciesStreptococcus gordonii (Sg-SCS).Here, we identified that 6-hydroxyhexanoic acid (6-HHA), a medium chain fatty acid (MCFA), is the one of the key components ofSg-SCS. We found that treatment of 6-HHA in mice fed a high-fat diet (HFD) significantly reduced HFD-mediated weight gain which was largely attributed to a decrease in fat mass. Systemically, 6-HHA improves obesity-associated glucose intolerance and insulin resistance. Furthermore, administration of 6-HHA suppressed obesity-associated systemic inflammation and dyslipidemia. At the cellular level, treatment of 6-HHA ameliorated aberrant inflammatory and metabolic transcriptomic signatures in white adipose tissue of mice with diet-induced obesity (HFD). Mechanistically, we found that 6-HHA suppressed adipocyte-proinflammatory cytokine production and lipolysis, the latter through Gαi-mediated signaling. This work provides direct evidence for the anti-obesity effects of a novel MCFA, which could be a new therapeutic treatment for combating obesity.KEY POINTSHydroxyhexanoic medium chain fatty acids (MCFAs) are dietary and bacterial-derived energy sources, however, the outcomes of using MCFAs in treating metabolic disorders are diverse and complex.The MCFA 6-hydroxyhexanoic acid (6-HHA) is a metabolite secreted by the oral bacterial commensal speciesStreptococcus gordonii;here we investigated its role in modulating high-fat diet (HFD)-induced metabolic dysfunction.In a murine model of obesity, we found 6-HHA-mediated improvement of diet-mediated adiposity, insulin resistance and inflammation were in part due to actions on white adipose tissue (WAT).6-HHA suppressed proinflammatory cytokine production and lipolysis through Gi-mediated signaling in differentiated white adipocytes.
Non-canonical function of folate/folate receptor 1 during neural tube formation
Authors: Balashova Olga A. , Panoutsopoulos Alexios A. , Visina Olesya , Selhub Jacob , Knoepfler Paul S. , Borodinsky Laura N. 
Published: July 2023

AbstractFolate supplementation reduces the occurrence of neural tube defects, one of the most common and serious birth defects, consisting in the failure of the neural tube to form and close early in pregnancy. The mechanisms underlying neural tube defects and folate action during neural tube formation remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. Knockdown of FOLR1 in human neural organoids as well as in theXenopus laevis in vivomodel leads to neural tube defects that are rescued by pteroate, a folate precursor that binds to FOLR1 but is unable to participate in metabolic pathways. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein (CD2AP), a molecule that we find is essential for apical endocytosis and the spatiotemporal turnover of the cell adherens junction component C-cadherin in neural plate cells. The counteracting action of FOLR1 on these processes is mediated by regulating CD2AP protein level via a degradation-dependent mechanism. In addition, folate and pteroate increase Ca2+transient frequency in the neural plate in a FOLR1-dependent manner, suggesting that folate/FOLR1 signal intracellularly to regulate neural plate folding. This study identifies a mechanism of action of folate distinct from its vitamin function during neural tube formation.
MiR-324-5p regulates the structure of dendritic spines and is essential for hippocampal long-term potentiation
Authors: Parkins Emma V , Brager Darrin H , Rymer Jeffrey K , Burwinkel John M , Rojas Diego , Tiwari Durgesh , Hu Yueh-Chiang , Gross Christina 
Published: July 2023

AbstractMicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes them interesting candidates in the study of synaptic plasticity. Here, we demonstrate that the proconvulsive microRNA miR-324-5p regulates excitatory synapse structure and function in the hippocampus of mice. BothMir324knockout (KO) and miR-324-5p antagomir treatment significantly reduce dendritic spine density in the hippocampal CA1 subregion, andMir324KO, but not miR-324-5p antagomir treatment, shift dendritic spine morphology, reducing the proportion of thin, “unstable” spines. Western blot and quantitative Real-Time PCR revealed changes in protein and mRNA levels for potassium channels, cytoskeletal components, and synaptic markers, including MAP2 and Kv4.2, which are essential for long-term potentiation (LTP). In line with these findings, slice electrophysiology revealed that LTP is severely impaired inMir324KO mice, while baseline excitatory activity remains unchanged. Overall, this study demonstrates that miR-324-5p regulates dendritic spine density, morphology, and plasticity in the hippocampus, potentially via multiple cytoskeletal and synaptic modulators.