bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing quasi-linear modified Newtonian dynamics theory with Galactic globular clusters in a weak external field
Authors: Sollima A , Nipoti C , Calura F , Pascale R , Baumgardt H
Published: July 2023

We developed self-consistent dynamical models of stellar systems in the framework of quasi-linear modified Newtonian dynamics (QUMOND). The models are constructed from the anisotropic distribution function of Gunn and Griffin, combined with the modified Poisson equation defining this gravitation theory and take into account the external field effect. We have used these models, and their Newtonian analogues, to fit the projected density and the velocity dispersion profiles of a sample of 18 Galactic globular clusters, using the most updated data sets of radial velocities and Gaia proper motions. We have thus obtained, for each cluster, estimates of the dynamical mass-to-light ratio (M/L) for each theory of gravity. The selected clusters have accurate proper motions and a well-sampled mass function down to the very low-mass regime. This allows us to constrain the degree of anisotropy and to provide, from comparison with stellar evolution isochrones, a dynamics-independent estimate of the minimum mass-to-light ratio (M/L)min. Comparing the best-fitting dynamical M/L with (M/L)min, we find that for none of the analysed clusters the two gravity theories are significantly incompatible with the observational data, although for one of them (NGC 5024) the dynamical M/L predicted by QUMOND lies at 2.8σ below (M/L)min. Though the proposed approach suffers from some limitations (in particular the lack of a treatment of mass segregation), the obtained results suggest that the kinematics of globular clusters in a relatively weak external field can be a powerful tool to prove alternative theories of gravitation.
The problem of dust attenuation in photometric decomposition of edge-on galaxies and possible solutions
Authors: Savchenko Sergey S , Poliakov Denis M , Mosenkov Aleksandr V , Smirnov Anton A , Marchuk Alexander A , Il’in Vladimir B , Gontcharov George A , Seguine Jonah , Baes Maarten
Published: July 2023

The presence of dust in spiral galaxies affects the ability of photometric decompositions to retrieve the parameters of their main structural components. For galaxies in an edge-on orientation, the optical depth integrated over the line of sight is significantly higher than for those with intermediate or face-on inclinations, so it is only natural to expect that for edge-on galaxies, dust attenuation should severely influence measured structural parameters. In this paper, we use radiative transfer simulations to generate a set of synthetic images of edge-on galaxies that are then analysed via decomposition. Our results demonstrate that for edge-on galaxies, the observed systematic errors of the fit parameters are significantly higher than for moderately inclined galaxies. Even for models with a relatively low dust content, all structural parameters suffer offsets that are far from negligible. In our search for ways to reduce the impact of dust on retrieved structural parameters, we test several approaches, including various masking methods and an analytical model that incorporates dust absorption. We show that using such techniques greatly improves the reliability of decompositions for edge-on galaxies.
Cost-Effectiveness of Four Tobacco Control Interventions in Mongolia
Authors: Tuvdendorj Ariuntuya , Feenstra Talitha , Buskens Erik
Published: July 2023

Introduction

The aim of this study is to quantify the cost-effectiveness of four tobacco control interventions: Tobacco taxation, mass media campaigns, school programs, and cessation support, and to illustrate how available evaluation tools can be adapted to the local setting.

Aims and Methods

We used the dynamic population health modeling-health impact assessment tool to project the future smoking prevalence associated with the interventions and to simulate the resulting smoking-related disease burden over time. Applying the most recent available national Mongolian data as input, the costs and effects of four interventions were compared to a business-as-usual scenario, resulting in costs per life year gained and per disability-adjusted life years (DALYs) averted.

Results

Three years after implementation, all interventions reduce the prevalence of current smoking, with the strongest reduction observed with the increase in tobacco tax (5.1% points), followed by mass media campaigns (1.6% points), school programs (1.3% points), and cessation support interventions (0.6% points). School programs were a cost-saving tobacco control intervention compared to current practice in Mongolia, while the other programs resulted in additional costs compared to business as usual. Compared to the World Health Organization (WHO) thresholds, all interventions would be considered “very cost-effective” in terms of cost per DALY averted (below US$ 4295 per DALY averted) in Mongolia.

Conclusions

Large-scale interventions such as taxation and mass media campaigns result in both cost-effectiveness and important health benefits in relation to intervention costs. Reducing the prevalence of smoking among the male population would be particularly worthwhile in Mongolia.

Implications

This study shows that in Mongolia school programs were a cost-saving intervention, while the cost-effectiveness ratios were US$ 25 per disability-adjusted life year (DALY) averted for mass media campaigns, US$ 74 for taxation, and US$ 1961 for cessation support interventions. Compared to the WHO thresholds, all interventions would be considered “very cost-effective” in terms of expenses per DALY averted (<US$ 4295 per DALY averted), making it beneficial to scale up the WHO-Monitor tobacco use and prevention, Protect people from smoke, Offer help to quit smoking, Warn about the danger, Enforce bans, and Raise taxes (MPOWER) interventions to reduce the burden from smoking in Mongolia.
MRI-guided focused ultrasound ablation of painful lumbar facet joints: a retrospective assessment of safety and tolerability in human subjects
Authors: Tiegs-Heiden Christin A , Hesley Gina K , Long Zaiyang , Lu Aiming , Lamer Tim J , Gorny Krzysztof R , Hangiandreou Nicholas J , Lehman Vance T
Published: July 2023

Objective

To evaluate the safety and tolerability of MRI-guided focused ultrasound (MRgFUS) for the treatment of facet joint–mediated pain in human subjects for whom conventional treatment had failed. Secondarily, to evaluate effectiveness of the procedure.

Methods

Consecutive patients who underwent MRgFUS at our institution were retrospectively identified. Chart review was performed to obtain relevant clinical and technical data. All patients had chronic low back pain and positive comparative medial branch blocks.

Results

Twenty-six MRgFUS treatments in 20 patients were included. Mean sonication energy was 1436.6 Joules. The procedure was technically successful in all patients. Of the treated patients, 29.6% experienced short-term worsening of low back pain immediately after the procedure, all by 1–4 points on a 0–10 scale. One patient (3.8%) reported temporary worsening of preexisting radicular symptoms after the procedure. Of 21 treatments with clinical follow-up of at least 3 months available, 12 (57.1%) had >3 months’ pain relief, 2 (10%) had <3 months’ benefit, 6 (30%) reported no benefit, and 1 (5%) patient was lost to follow-up. In patients who reported at least some benefit with prior conventional radiofrequency ablation, 8/10 (80%) benefited from the MRgFUS procedure.

Conclusion

The present study demonstrates that MRgFUS ablation of the lumbar facet joints is a safe and tolerable procedure in human subjects and could provide another option for patients for whom radiofrequency ablation had failed. More than half of all patients received significant durable pain relief, which jumped to 80% for patients who had experienced at least some benefit from prior radiofrequency ablations.
Factors Associated with Interviewers’ Evaluations of Respondents’ Performance in Telephone Interviews: Behavior, Response Quality Indicators, and Characteristics of Respondents and Interviewers
Authors: Garbarski Dana , Dykema Jennifer , Schaeffer Nora Cate , Jones Cameron P , Neman Tiffany S , Edwards Dorothy Farrar
Published: July 2023

Interviewers’ postinterview evaluations of respondents’ performance (IEPs) are paradata, used to describe the quality of the data obtained from respondents. IEPs are driven by a combination of factors, including respondents’ and interviewers’ sociodemographic characteristics and what actually transpires during the interview. However, relatively few studies examine how IEPs are associated with features of the response process, including facets of the interviewer-respondent interaction and patterns of responding that index data quality. We examine whether features of the response process—various respondents’ behaviors and response quality indicators—are associated with IEPs in a survey with a diverse set of respondents focused on barriers and facilitators to participating in medical research. We also examine whether there are differences in IEPs across respondents’ and interviewers’ sociodemographic characteristics. Our results show that both respondents’ behaviors and response quality indicators predict IEPs, indicating that IEPs reflect what transpires in the interview. In addition, interviewers appear to approach the task of evaluating respondents with differing frameworks, as evidenced by the variation in IEPs attributable to interviewers and associations between IEPs and interviewers’ gender. Further, IEPs were associated with respondents’ education and ethnoracial identity, net of respondents’ behaviors, response quality indicators, and sociodemographic characteristics of respondents and interviewers. Future research should continue to build on studies that examine the correlates of IEPs to better inform whether, when, and how to use IEPs as paradata about the quality of the data obtained.
Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study
Authors: Nygaard Louis , Polcwiartek Christoffer , Nelveg-Kristensen Karl Emil , Carlson Nicholas , Kristensen Salome , Torp-Pedersen Christian ,   DANVAS Investigators, Gregersen Jon Waarst
Published: July 2023

Objective

To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV.

Methods

Using a nested case–control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date.

Results

A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48–3.75)] and 1.3% [HR 1.98 (95% CI 1.39–2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05–16.32)] and MACE [HR 5.78 (95% CI 2.67–12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA).

Conclusions

AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease.
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

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.
Feasibility of diffusion kurtosis imaging in evaluating cervical spinal cord injury in multiple sclerosis
Authors: Bian BingYang , Zhou BoXu , Shao ZhiQing , Zhu XiaoNa , Jie YiGe , Li Dan
Published: July 2023

This research aimed to assess gray matter (GM), white matter (WM), lesions of multiple sclerosis (MS) and the therapeutic effect using diffusion kurtosis imaging (DKI). From January 2018 to October 2019, 78 subjects (48 of MS and 30 of health) perform routine MR scan and DKI of cervical spinal cord. The MS patients were divided into 2 groups according to the presence or absence of T2 hyperintensity. DKI-metrics were measured in the lesions, normal-appearing GM and WM. Significant differences were detected in DKI metrics between MS and healthy (P < .05) and between patients with cervical spinal cord T2-hyperintense and without T2-hyperintense (P < .001). Compared to healthy, GM-mean kurtosis (MK), GM-radial kurtosis, and WM-fractional anisotropy, WM-axial diffusion were statistically reduced in patients without T2-hyperintense (P < .05). Significant differences were observed in DKI metrics between patients with T2-hyperintense after therapy (P < .05), as well as GM-MK and WM-fractional anisotropy, WM-axial diffusion in patients without T2-hyperintense (P < .05); Expanded Disability Status Scale was correlated with MK values, as well as Expanded Disability Status Scale scores and MK values after therapy. Our results indicate that DKI-metrics can detect and quantitatively evaluate the changes in cervical spinal cord micropathological structure.
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.
Practical Guidance for the Development of Rosie, a Health Education Question-and-Answer Chatbot for New Mothers
Authors: Mane Heran Y. , Channell Doig Amara , Marin Gutierrez Francia Ximena , Jasczynski Michelle , Yue Xiaohe , Srikanth Neha Pundlik , Mane Sourabh , Sun Abby , Moats Rachel Ann , Patel Pragat , He Xin , Boyd-Graber Jordan Lee , Aparicio Elizabeth M. , Nguyen Quynh C.
Published: July 2023

Communities of color experience higher maternal and infant mortality, as well as a host of other adverse outcomes, during pregnancy and postpartum. To address this, our team is developing a free, user-friendly, question-answering chatbot called Rosie. Chatbots have gained significant popularity due to their scalability and success in individualizing resources. In recent years, scientific communities and researchers have started recognizing this technology's potential to inform communities, promote health outcomes, and address health disparities. The development of Rosie is an interdisciplinary project, with teams focused on the technical build of the application (app), the development of machine learning models, and community outreach, making Rosie a chatbot built with the input from the communities it aims to serve. From June to October 2022, more than 20 demonstration sessions were conducted in Washington, District of Columbia, Maryland, and Virginia, where a total of 109 pregnant women and new mothers of color could interact with Rosie. Results from the live demonstrations showed that 75% of mothers searched for maternity and baby-related information at least once a week and more than 90% of participants expressed the likelihood to use the app. Most of the participants inquired about their baby's development, nutrition for babies, and identifying and addressing the causes of certain symptoms and conditions, accounting for about 80% of the total questions asked. Mother-related questions in the community demonstrations were mainly about pregnancy. The high level of interest in the chatbot is a clear indication of the need for more resources. Rosie aims to help close the racial gap in maternal and infant health disparities by providing new mothers with easy access to reliable health information.
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

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

Introduction 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.
Shewanella metallivivens sp. nov., a deep-sea hydrothermal vent tube worm endobiont capable of dissimilatory anaerobic metalloid oxyanion reduction
Authors: Maltman Chris , Kuzyk Steven B. , Kyndt John A. , Lengyel George , Yurkov Vladimir
Published: July 2023

A polyphasic taxonomic study was carried out on a Gram-stain-negative and rod-shaped strain, ER-Te-42B-LightT, isolated from the tissue of a tube worm, Riftia pachyptila, collected near a deep-sea hydrothermal vent of the Juan de Fuca Ridge in the Pacific Ocean. This bacterium was capable of performing anaerobic respiration using tellurite, tellurate, selenite and orthovanadate as terminal electron acceptors. While facultatively anaerobic, it could aerobically resist tellurite, selenite and orthovanadate up to 2000, 7000 and 10000 µg ml−1, respectively, reducing each oxide to elemental forms. Nearly complete 16S rRNA gene sequence similarity related the strain to

Shewanella

, with 98.8 and 98.7 % similarity to

Shewanella basaltis

and

Shewanella algicola

, respectively. The dominant fatty acids were C16 : 0 and C16 : 1. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol and MK-7 was the predominant quinone. DNA G+C content was 42.5 mol%. Computation of average nucleotide identity and digital DNA–DNA hybridization values with the closest phylogenetic neighbours of ER-Te-42B-LightT revealed genetic divergence at the species level, which was further substantiated by differences in several physiological characteristics. Based on the obtained results, this bacterium was assigned to the genus

Shewanella

as a new species with the name Shewanella metallivivens sp. nov., type strain ER-Te-42B-LightT (=VKM B-3580T=DSM 113370T).
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

Obesity, 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 POINTS

Hydroxyhexanoic 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

Folate 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

MicroRNAs 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.
Spliceosomal complex components are critical for adjusting the C:N balance during high-light acclimation
Authors: Araguirang Gali Estopare , Venn Benedikt , Kelber Nadja-Magdalena , Feil Regina , Lunn John , Kleine Tatjana , Leister Dario , Mühlhaus Timo , Richter Andreas S.
Published: July 2023

Plant acclimation to an ever-changing environment is decisive for growth, reproduction and survival. Light availability limits biomass production on both ends of the intensity spectrum. Therefore, the adjustment of plant metabolism is central to high-light (HL) acclimation, and accumulation of photoprotective anthocyanins is commonly observed. However, mechanisms and factors regulating the HL acclimation response are less clear. Two Arabidopsis mutants of spliceosome components exhibiting a pronounced anthocyanin overaccumulation in HL were isolated from a forward genetic screen for new factors crucial for plant acclimation. Time-resolved physiological, transcriptome and metabolome analysis revealed a vital function of the spliceosome components for rapidly adjusting gene expression and metabolism. Deficiency of INCREASED LEVEL OF POLYPLOIDY1 (ILP1), NTC-RELATED PROTEIN1 (NTR1), and PLEIOTROPIC REGULATORY LOCUS1 (PRL1) resulted in a marked overaccumulation of carbohydrates and strongly diminished amino acid biosynthesis in HL. While not generally limited in N-assimilation,ilp1,ntr1,andprl1mutants showed higher glutamate levels and reduced amino acid biosynthesis in HL. The comprehensive analysis reveals a function of the spliceosome in the conditional regulation of the carbon:nitrogen-balance and the accumulation of anthocyanins during HL acclimation. The importance of gene expression, metabolic regulation, and re-direction of carbon towards anthocyanin biosynthesis for HL acclimation are discussed.
Flow in fetoplacental microvessels in vitro enhances perfusion, barrier function, and matrix stability
Authors: Cherubini Marta , Erickson Scott , Padmanaban Prasanna , Haberkant Per , Stein Frank , Beltran-Sastre Violeta , Haase Kristina
Published: July 2023

Proper placental vascularization is vital for pregnancy outcomes, but assessing it with animal models and human explants has limitations. Here, we present a 3Din vitromodel of human placenta terminal villi that includes fetal mesenchyme and vascular endothelium. By co-culturing HUVEC, placental fibroblasts, and pericytes in a macro-fluidic chip with a flow reservoir, we generate fully perfusable fetal microvessels. Pressure-driven flow is crucial for the growth and remodeling of these microvessels, resulting in early formation of interconnected placental vascular networks and maintained viability. Computational fluid dynamics simulations predict shear forces, which increase microtissue stiffness, decrease diffusivity and enhance barrier function as shear stress rises. Mass-spec analysis reveals the deposition of numerous extracellular proteins, with flow notably enhancing the expression of matrix stability regulators, proteins associated with actin dynamics, and cytoskeleton organization. Our model provides a powerful tool for deducing complexin vivoparameters, such as shear stress on developing vascularized placental tissue, and holds promise for unraveling gestational disorders related to the vasculature.
Age-related development in prefrontal-subcortical resting-state functional connectivity in nonhuman primates
Authors: Deshpande Harshawardhan U. , Kohut Stephen J.
Published: July 2023

Introduction

Understanding age-related changes in functional connectivity (FC) with regards to the maturation trajectories of cortical-subcortical circuits is critical for identifying biomarkers for disease vulnerability. The present study investigated resting-state FC in adolescent and adult nonhuman primates to characterize developmentally-sensitive functional brain circuits.

Methods

Resting-state fMRI data were acquired in adolescent (33.3±1.59 months; n=22) and adult (117.29±2.86 months; n=15) squirrel monkeys and FC was compared in seven prefrontal and ten subcortical regions-of-interest (ROIs). The effect of subject age on FC between each pair of ROIs was evaluated to identify nodes with the most age-sensitive connections (hubs) which were then used in seed-to-whole-brain FC analyses. A subset of adolescents (n=7) was also assessed over 3 longitudinal scans to track changes in hub connectivity throughout adolescence.

Results

A significant effect of age on ROI-ROI FC was found for adolescent (p<0.001), but not adult, subjects (p=0.8). Evaluation of parameter estimates (β) for each ROI-ROI pair found three within-prefrontal (dorsolateral (dlPFC), dorsomedial (dmPFC), and medial orbitofrontal cortices), two within-subcortical (R amygdala and L hippocampus), and three between prefrontal-subcortical (dlPFC, dmPFC, L caudate) hubs with the highest number of age-related connections. Large-scale organizational differences were also observed between the adolescent and adult groups. Longitudinal scans found within-subject changes in FC consistent with group effect.

Conclusions

The relationship between changes in FC and age during adolescence indicates dynamic maturation of several prefrontal–subcortical circuits in nonhuman primates. These findings provide specificity in our understanding of the development of functional brain circuits during and into late adolescence.

Significance

Adolescence marks a period of rapid development in the brain, but also increased vulnerability to mental health disorders. Age-related prefrontal-subcortical resting-state functional connectivity was evaluated in awake adolescent and adult squirrel monkeys. Identification of functional connectivity differences highlight a network of hubs with a high number of connections evolving from early to late adolescence, indicating selectivity in maturation during different stages of aging. Compared to adults, adolescents also show several large-scale organizational differences in circuits originating from important seed regions-of-interest. Longitudinal analysis reveals functional connectivity trajectories emerging from early adolescence and maturing into adult-like patterns during late adolescence. These findings identify functional connections that change dramatically during adolescence suggesting specific circuits that could be at heightened sensitivity to disease vulnerability.