bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling mechanisms that drive acute oral toxicity in mammals and its prediction via machine learning
Authors: Wijeyesakere Sanjeeva J , Auernhammer Tyler , Parks Amanda , Wilson Dan 
Published: March 2023

Abstract
We present a mechanistic machine-learning quantitative structure-activity relationship (QSAR) model to predict mammalian acute oral toxicity. We trained our model using a rat acute toxicity database compiled by the US National Toxicology Program. We profiled the database using new and published profilers and identified the most plausible mechanisms that drive high acute toxicity (LD50 ≤ 50 mg/kg; GHS categories 1 or 2). Our QSAR model assigns primary mechanisms to compounds, followed by predicting their acute oral LD50 using a random-forest machine-learning model. These predictions were further refined based on structural and mechanistic read-across to substances within the training set. Our model is optimized for sensitivity and aims to minimize the likelihood of underpredicting the toxicity of assessed compounds. It displays high sensitivity (76.1% or 76.6% for compounds in GHS 1–2 or GHS 1–3 categories, respectively), coupled with ≥73.7% balanced accuracy. We further demonstrate the utility of undertaking a mechanistic approach when predicting the toxicity of compounds acting via a rare mode of action (MOA) (aconitase inhibition). The mechanistic profilers and framework of our QSAR model are route- and toxicity endpoint-agnostic, allowing for future applications to other endpoints and routes of administration. Furthermore, we present a preliminary exploration of the potential role of metabolic clearance in acute toxicity. To the best of our knowledge, this effort represents the first accurate mechanistic QSAR model for acute oral toxicity that combines machine learning with MOA assignment, while also seeking to minimize underprediction of more highly potent substances.
Genome Resource Announcement for Two Isolates of Phytophthora sansomeana with Varying Levels of Pathogenicity on Soybean
Authors: Hebb Linda M. , Poelstra Jelmer W. , Dorrance Anne E. 
Published: March 2023

Phytophthora sansomeana was recognized as a distinct species in 2009. It has since been detected in Phytophthora surveys across the North Central region of the United States in recent years. Two isolates of P. sansomeana with moderate and high levels of pathogenicity (Psan_MP and Psan_HP, respectively), based on lesion development on soybean tap roots, were chosen for Oxford Nanopore Technologies long-read genome sequencing to allow within-species genomic comparisons between isolates with different levels of pathogenicity on soybean. The genome assembly size, number of predicted protein-encoding genes, and number of candidate effectors were greater in the highly pathogenic isolate (Psan_HP) than in the moderately pathogenic isolate (Psan_MP). Future work should more closely examine the context of P. sansomeana pathogenicity mechanisms relative to other Phytophthora species. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts
Authors: Gui Yuan , Palanza Zachary , Fu Haiyan , Zhou Dong 
Published: March 2023

AbstractAcute kidney injury (AKI) and diabetes mellitus (DM) are public health problems that cause a high socioeconomic burden worldwide. In recent years, the landscape of AKI etiology has shifted: Emerging evidence has demonstrated that DM is an independent risk factor for the onset of AKI, while an alternative perspective considers AKI as a bona fide complication of DM. Therefore, it is necessary to systematically characterize the features of AKI in DM. In this review, we summarized the epidemiology of AKI in DM. While focusing on circulation‐ and tissue‐specific microenvironment changes after DM, we described the active cellular and molecular mechanisms of increased kidney susceptibility to AKI under DM stress. We also reviewed the current diagnostic and therapeutic strategies for AKI in DM recommended in the clinic. Updated recognition of the epidemiology, pathophysiology, diagnosis, and medications of AKI in DM is believed to reveal a path to mitigate the frequency of AKI and DM comorbidity that will ultimately improve the quality of life in DM patients.
Myofascial Pain as an Unseen Comorbidity in Osteoarthritis
Authors: Duarte Felipe C.K. , Chien Richard , Ghazinour Golnaz , Murnaghan Kent , West Daniel W.D. , Kumbhare Dinesh A. 
Published: March 2023

Objective:This review aimed to identify, summarize, and appraise the evidence supporting the coexistence of myofascial pain (MPS) and trigger points (MTrP) in osteoarthritis (OA), and the effectiveness of MTrPs treatments in OA-related pain and physical function outcomes.Methods:Three databases were searched from inception to June 2022. We included observational and experimental studies to fulfill our 2 study aims. Two independent reviewers conducted 2-phase screening procedures and risk of bias using checklist tools for cross-sectional, quasi-experimental, and randomized control trials. Patient characteristics, findings of active and latent MTrPs in relevant muscles, treatments, and pain and physical function outcomes were extracted from low-risk bias studies.Results:The literature search yielded 2898 articles, of which 6 observational and 7 experimental studies had a low bias risk and the data extracted. Active MTrPs in knee OA patients was more evident in the quadriceps and hamstring muscles than in healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. In knee OA, dry needling on latent or active MTrPs improved pain and functional outcomes compared with sham needling but did not result in better pain and physical outcomes when combined with a physical exercise program.Discussion:The presence of active versus latent MTrPs seems to be a more sensitive discriminating feature of OA given that latent is often present in OA and healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. However, the small sample size and the few number of studies limit any firm recommendation on the treatment.Registry:The study protocol was prospectively registered in Open Science Framework (https://doi.org/10.17605/OSF.IO/8DVU3).
The effect of HIV on COVID-19 vaccine responses
Authors: Levy Itzchak , Rahav Galia 
Published: March 2023

Purpose of review
Persons living with HIV (PLWH) may have a moderately increased risk of morbidity and mortality from COVID-19 infection, especially if viral load is not controlled and if they are immunosuppressed. Vaccination against SARS-CoV-2 is the most effective measure to prevent morbidity and mortality. However, individuals with HIV/AIDS may have less protection after vaccination. The purpose of this review is to summarize some of the recent studies focused on examining the safety, immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines.

Recent findings
The safety of all anti-SARS-CoV-2 vaccines among PLWH is not different from the safety of these vaccines among HIV-negative individuals and is acceptable. PLWH with viral suppression and immune reconstitution (CD4+ cell count > 350 cells/μl) may reach almost same immunogenicity such as people without HIV albeit antibody levels and neutralization may decline more rapidly than in people without HIV. PLWH with viremia or immunosuppressed, especially AIDS, have less immunogenicity.

Summary
Full vaccination against SARS-CoV-2 is a well tolerated and efficient way to prevent mortality and morbidity from COVID-19 among PLWH and AIDS patients. It is very important to follow recommended booster vaccination for a continuous and prompt immunogenicity.
Investigating the Anatomic Location of Soft Tissue Fillers in Noninflammatory Nodule Formation: An Ultrasound-Imaging–Based Analysis
Authors: Schelke Leonie W. , Decates Tom S. , Cartier Hugues , Cotofana Sebastian , Velthuis Peter J. 
Published: March 2023

INTRODUCTIONNoninflammatory nodules may be persistent to dissolve. To evaluate the possible reasons, a case series of ultrasound images and medical data of patients who were prospectively referred with noninflammatory nodules were evaluated.MATERIALS AND METHODSA total of 27 patients with nodules but without signs of inflammation were included. All cases were assessed with an 18-MHz linear ultrasound device. Exact location of the filler material was noted. Relations with clinical data were analyzed using chi-square tests.RESULTSEarly onset of complaints (<2 weeks) was found in 16 patients and late onset (>2 weeks) in 11. All patients had multiple nodules. In all cases, the filler nodule was found to be located inside the fascia. Extension to the subcutaneous tissue was seen in 8 cases and to the deeper planes in 5. In 14 cases, the filler material was completely located inside layers of the fascia, and migration was observed in 5 cases.DISCUSSIONAccumulation of filler material in the superficial musculoaponeurotic system or fascia may be an important cause for the occurrence of persistent noninflammatory nodules, either by initial faulty injection technique or by later accumulation through the pathway generated with a needle or cannula. Ultrasound-guided injections are helpful to dissolve the nodule.
Sepsis-induced endothelial dysfunction drives acute-on-chronic liver failure through Angiopoietin-2-HGF-C/EBPβ pathway
Authors: Elias Grant , Schonfeld Michael , Saleh Sara , Parrish Mark , Barmanova Marina , Weinman Steven A. , Tikhanovich Irina 
Published: March 2023

Background and Aims:
Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patients with previously stable cirrhosis. A common cause of ACLF is sepsis secondary to bacterial infection. Sepsis-associated ACLF involves a loss of differentiated liver function in the absence of direct liver injury, and its mechanism is unknown. We aimed to study the mechanism of sepsis-associated ACLF using a novel mouse model.

Approach and Results:
Sepsis-associated ACLF was induced by cecal ligation and puncture procedure (CLP) in mice treated with thioacetamide (TAA). The combination of TAA and CLP resulted in a significant decrease in liver synthetic function and high mortality. These changes were associated with reduced metabolic gene expression and increased CCAAT enhancer binding protein beta (C/EBPβ) transcriptional activity. We found that C/EBPβ binding to its target gene promoters was increased. In humans, C/EBPβ chromatin binding was similarly increased in the ACLF group compared with control cirrhosis. Hepatocyte-specific Cebpb knockout mice had reduced mortality and increased gene expression of hepatocyte differentiation markers in TAA/CLP mice, suggesting that C/EBPβ promotes liver failure in these mice. C/EBPβ activation was associated with endothelial dysfunction, characterized by reduced Angiopoietin-1/Angiopoietin-2 ratio and increased endothelial production of HGF. Angiopoietin-1 supplementation or Hgf knockdown reduced hepatocyte C/EBPβ accumulation, restored liver function, and reduced mortality, suggesting that endothelial dysfunction induced by sepsis drives ACLF through HGF-C/EBPβ pathway.

Conclusions:
The transcription factor C/EBPβ is activated in both mouse and human ACLF and is a potential therapeutic target to prevent liver failure in patients with sepsis and cirrhosis.
Sutureless Amniotic Membrane Transplantation Using Pediatric Nasogastric Tube for Patients With Acute Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis
Authors: Ceylan Ali , Mergen Burak , Aydin Fahri Onur , Avci Emre , Yildirim Yusuf 
Published: March 2023

Purpose:
Evaluation of the results of sutureless amniotic membrane transplantation (AMT) using a pediatric nasogastric tube (NGT) for patients with acute Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) was aimed.

Methods:
Twenty-six eyes of 13 patients with SJS/TEN with ocular involvement at a single tertiary care hospital between May 2020 and January 2022 were included in the study. An amniotic membrane was implanted to the ocular surface and conjunctival fornix using a modified symblepharon ring (MR) created by inserting NGT end-to-end. Patients were followed for at least 6 months. The mean duration of the surgery was recorded. The presence of corneal epithelial defect and vascularization, meibomian gland dysfunction (MGD) grade, conjunctival scarring, eyelid margin keratinization, symblepharon, and trichiasis were recorded.

Results:
The mean age of the patients was 38.4±17.6 years. Amniotic membrane transplantation was performed only once for eight patients and twice for five patients. The mean duration of the surgery was 3.2±0.4 min. The modified symblepharon ring was removed 28 days after its application. At the first examination, 20 eyes (76.9%) had a corneal epithelial defect and 6 (23.1%) had early symblepharon. At the postoperative 6 months, although seven eyes (26.9%) had conjunctival scarring and 5 (19.2%) had eyelid margin keratinization, all patients were without any corneal defect, corneal vascularization, or symblepharon. Only 11 eyes (42.3%) showed MGD, and 1 eye (3.8%) showed trichiasis.

Conclusions:
This study showed that sutureless AMT using pediatric NGT could be a potentially fast and inexpensive treatment option for the treatment of SJS/TEN with ocular involvement at the bedside without the need for general anesthesia.
Pain and insomnia as risk factors for first lifetime onsets of anxiety, depression, and suicidality in adolescence
Authors: Soltani Sabine , Noel Melanie , Bernier Emily , Kopala-Sibley Daniel C. 
Published: March 2023

Abstract
Chronic pain and mental health problems have both been identified as public health emergencies and co-occur at high rates. This prospective, longitudinal investigation examined whether chronic pain status, pain-related symptoms (intensity, interference), pain catastrophizing, and insomnia severity predicted first lifetime onset of depressive and/or anxiety disorders as well as suicidality in a cohort of youth with a parental history of mood and/or anxiety disorders. Participants included 145 youth (M
age = 13.74 years; 64% female) who completed structured diagnostic interviews at baseline and at 9- and 18-month follow-up to assess depressive and anxiety disorders as well as suicidality. Participants completed baseline questionnaires assessing depressive and anxiety symptoms, pain symptoms and characteristics, pain interference, pain catastrophizing, and insomnia severity. Approximately 25% of youth reported having chronic pain at baseline. Nearly half (47.3%) developed a depressive disorder (21.3%), anxiety disorder (15.7%), or both (10.3%), and 34% endorsed experiencing suicidality at follow-up. Increased pain interference, intensity, catastrophizing, and insomnia severity predicted increased likelihood of first lifetime onset of a depressive disorder at follow-up, over and above sex and baseline symptoms. Chronic pain at baseline was associated with the increased likelihood of onset of suicidality at follow-up. Increased pain intensity and interference at baseline predicted increased severity of suicidality at follow-up. Insomnia severity predicted increased likelihood of anxiety disorder onset. The presence of chronic pain and elevated pain-related symptoms and insomnia are premorbid risk factors for the development of significant mental health disorders and issues in youth.
Effect modifiers of virtual reality in pain management: a systematic review and meta-regression analysis
Authors: Lier Elisabeth J. , de Vries Marjan , Steggink Eline M. , ten Broek Richard P.G. , van Goor Harry 
Published: March 2023

Abstract
There is a rapidly growing body of evidence for the application of virtual reality (VR) in pain management, however, with varying effectiveness. Little is known about patient-related and VR-related factors affecting efficacy of VR. A systematic review and meta-analysis was performed including 122 randomised controlled trials (9138 patients), reporting on subjectively reported pain scores comparing an immersive VR intervention to a non-VR control group. Virtual reality significantly reduced pain in the pooled analysis (standardized mean difference = −0.65, 95% CI −0.76 to −0.54, P < 0.001). Subgroup analyses showed no significant differences between type of pain, ie, VR effects were similar in acute, chronic, and procedural pain conditions. Univariate and multivariate meta-regression analyses were performed to investigate the effect of intervention, patient, and pain characteristics on VR. Virtual reality effectively reduced pain, especially in patients reporting moderate to severe pain and in younger subjects. Studies comparing VR with a control group receiving no distraction methods were associated with higher effect sizes. The effect of VR was not related to a specific frequency or duration of use. Type of software and interaction level were related to VR effects in the univariable, but not in the multivariable, meta-regression analysis. Heterogeneity was considerable for all meta-analyses, and risk of bias was moderate to high in most included studies. Studies on mechanisms behind VR analgesia in younger patients and patients reporting moderate to severe pain are recommended to confirm our hypotheses while taking into account risk of bias and the comparator. Optimal application of VR using treatment modules for long-term pain conditions are an important issue for future research.
Dietary approaches for normalizing dysbiosis induced by high-fat, obesogenic diets
Authors: Djuric Zora 
Published: March 2023

Purpose of review
Given the world-wide problem of obesity, this review considers what types of dietary changes can be utilized to minimize the adverse effects of an obesogenic diet on the intestinal microbiota.

Recent findings
In rodents fed high-fat diets containing lard or Western blend fats to induce obesity, switching to high-fat diets formulated to contain higher amounts of fiber or fiber-containing foods, plant extracts, omega-3 fatty acids or whole grains has beneficial effects on body weight, metabolic alterations, and the intestinal microbiota. Several studies show that the intestinal microbiota has a role in mediating the beneficial health effects of these dietary factors. Many aspects of the microbiota observed in animals when healthful dietary components were added to the feed have also been observed in humans who follow healthful dietary patterns.

Summary
The data shows that specific foods and macronutrients can normalize the obesity-associated microbiota and improve metabolic health. These findings support the design of dietary interventions that would allow individuals to focus on diet quality independently of weight loss to mitigate the adverse sequelae of obesity.
Considerations when administering medications enterally in the critically ill
Authors: MacLaren Robert 
Published: March 2023

Purpose of review
Enteral administration of medications to critically ill patients may be advantageous to other routes of administration. This review summarizes key considerations for the bedside clinician when medications are administered through enteral access devices (EADs).

Recent findings
Critical illness is associated with gastrointestinal dysfunction that inconsistently affects drug dispersion and absorption and may enhance or reduce bioavailability. Other factors such as the first-pass metabolism, microbiome alterations and the concomitant use of other medications (vasopressors, acid suppressants) may influence drug absorption. Concurrent administration of medications with enteral nutrition is fraught with potential errors. Drug-nutrient and drug-drug interactions may lead to tube occlusion. Although liquid formulations of medications are preferred over solid dosage forms for EAD administration, they may be hyperosmotic or contain sorbitol to cause gastrointestinal disturbances. The size and placement of the EAD tube may influence drug dispersion and absorption to affect the pharmacokinetic profile and efficacy of a particular drug.

Summary
The therapeutic effect may be diminished, or toxicity enhanced when medications are administered through EADs in the critically ill. The bedside clinician must be aware of factors impacting the bioavailability of enterally administered medications and be cognizant that the effect will differ by medication.
Brain FDG PET for visualizing the relation between impaired lung function and cognitive decline in lung cancer: a preliminary study
Authors: Son Seung Hyun , Ahn June Hong , Shin Kyeong Cheol , Kim Hae Won , Kong Eunjung 
Published: March 2023

Objective
Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer.

Methods
A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables.

Results
After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions.

Conclusion
Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion.