bluuebunny/crossref_metadata_2025_split huggingface dataset:
The homeostatic function of Regnase‐2 restricts neuroinflammation
Authors: Sowinska Weronika , Wawro Mateusz , Biswas Debolina D. , Kochan Jakub , Pustelny Katarzyna , Solecka Aleksandra , Gupta Angela S. , Mockenhaupt Karli , Polak Jarosław , Kwinta Borys , Kordula Tomasz , Kasza Aneta 
Published: February 2023

AbstractThe precise physiological functions and mechanisms regulating RNase Regnase‐2 (Reg‐2/ZC3H12B/MCPIP2) activity remain enigmatic. We found that Reg‐2 actively modulates neuroinflammation in nontransformed cells, including primary astrocytes. Downregulation of Reg‐2 in these cells results in increased mRNA levels of proinflammatory cytokines IL‐1β and IL‐6. In primary astrocytes, Reg‐2 also regulates the mRNA level of Regnase‐1 (Reg‐1/ZC3H12A/MCPIP1).Reg‐2is expressed at high levels in the healthy brain, but its expression is reduced during neuroinflammation as well as glioblastoma progression. This process is associated with the upregulation ofReg‐1. Conversely, overexpression of Reg‐2 is accompanied by the downregulation ofReg‐1in glioma cells in a nucleolytic NYN/PIN domain‐dependent manner. Interestingly, low levels ofReg‐2and high levels ofReg‐1correlate with poor‐glioblastoma patients' prognoses. WhileReg‐2restricts the basal levels of proinflammatory cytokines in resting astrocytes, its expression is reduced in IL‐1β‐activated astrocytes. Following IL‐1β exposure, Reg‐2 is phosphorylated, ubiquitinated, and degraded by proteasomes. Simultaneously, theReg‐2transcript is destabilized by tristetraprolin (TTP) andReg‐1through the AREs elements and conservative stem‐loop structure present in its 3′UTR. Thus, the peer‐control loop, of Reg‐1 and Reg‐2 opposing each other, exists. The involvement of TTP inReg‐2mRNA turnover is confirmed by the observation that high TTP levels correlate with the downregulation of theReg‐2expression in high‐grade human gliomas. Additionally, obtained results reveal the importance of Reg‐2 in inhibiting human and mouse glioma cell proliferation. Our current studies identify Reg‐2 as a critical regulator of homeostasis in the brain.
An outpatient pain plan and ED pain pathway for adults with sickle cell disease
Authors: Mercado Stephanie Harris 
Published: February 2023

ABSTRACT
Sickle cell disease (SCD), one of the most common inherited diseases, is associated with lifetime morbidity and reduced life expectancy. In the United States, SCD primarily affects Black patients and, to a lesser degree, those of Hispanic descent. These populations are known to have healthcare disparities related to lower socioeconomic status, limited access to healthcare, and racial bias. The quality-adjusted life expectancy of patients with SCD is less than 35 years, because of progressive complications of the disease. The most common complication is severe episodic pain related to vaso-occlusive ischemic events. Despite guidelines, pain management often is delayed as patients struggle with resistance from clinicians based on concerns over opioid use or abuse, overdose, or drug-seeking behavior. Effective pain management can be accomplished with collaboration between clinicians and patients, a documented outpatient pain management plan, and when necessary, an ED clinical pain pathway for acute SCD pain management.
The complexity in DNA methylation analysis of allergic diseases
Authors: Legaki Evangelia , Taka Styliani , Papadopoulos Nikolaos G. 
Published: February 2023

Purpose of review
This review aims to report all the recent studies that are implicated in DNA methylation analysis in the field of allergy and to underline the complexity of the study methodologies and results.

Recent findings
Although the growing number of DNA methylation studies have yet to point to a specific mechanism, herein we provide an overview of the majority of pathways considered to be implicated and highlight particular genes, like KNH2, ATPAF2 and ZNF385A, for their potential as biomarkers.

Summary
The epigenetic profile of respiratory allergic diseases, and particularly DNA methylation, has been investigated in various populations, so as to gain a better understanding of its role in pathogenesis. Through our analysis, multiple links are presented between differential DNA methylation loci and IgE sensitization, lung functionality and severity of the disease. Additionally, associations of this epigenetic change with maternal asthma, age, sex and environmental factors are described, thus uncovering specific gene families that, after further examination could be used as methylation biomarkers in cases of allergic disease.
Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type– and Sex-specific Effects during Development in Mice
Authors: Song Shao-yong , Peng Ke , Meng Xiao-wen , Shan Xi-sheng , Chen Qing-cai , Zhao Wei-ming , Shen Biyu , Qiu Hong , Liu Hong , Liu Hua-yue , Ji Fu-hai 
Published: February 2023

Background
Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell type–specific information after sevoflurane exposure limits the mechanistic understanding of these effects. In this study, the authors tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type–specific effects in mice of both sexes.

Methods
Neonatal mice were exposed to 3% sevoflurane for 2 h at postnatal days 6, 8, and 10 and analyzed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. The Morris Water Maze test was performed to test neurocognitive function.

Results
The authors found sex-specific distribution of hippocampal cell types in control mice alongside cell type– and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice after sevoflurane exposure regarding the proportions of cornu ammonis 1 neurons (control vs. sevoflurane, males: 79.9% vs. 32.3%; females: 27.3% vs. 24.3%), dentate gyrus (males: 4.2% vs. 23.4%; females: 36.2% vs. 35.8%), and oligodendrocytes (males: 0.6% vs. 6.9%; females: 5.9% vs. 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand–receptor pairs in the cornu ammonis 1, cornu ammonis 3, and dente gyrus trisynaptic circuit (control vs. sevoflurane, cornu ammonis 1–cornu ammonis 3: 18 vs. 42 in males and 15 vs. 21 in females; cornu ammonis 1–dentate gyrus: 21 vs. 35 in males and 12 vs. 20 in females; cornu ammonis 3–dentate gyrus: 25 vs. 45 in males and 17 vs. 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased cornu ammonis 1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes.

Conclusions
This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and nonneuronal cell type– and sex-specific effects of sevoflurane during development.

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Management of Segmental Tibial Bone Defects With the Magnetic Motorized Intramedullary Transport Nail: A Case Series
Authors: Geiger Erik J. , Geffner Adam D. , Rozbruch S. Robert , Fragomen Austin T. 
Published: February 2023

Summary:
Critical-sized bone defects in the tibia can arise as sequelae of trauma, infection, tumor, or the treatment of congenital limb deficiencies. Treatment of these defects often requires bone transport, which has traditionally been accomplished using circular external fixators. The development of a bone transport nail facilitated tibia reconstruction through distraction osteogenesis using an all-internal device, thus avoiding the complications associated with chronic external fixation. Given the rarity of these cases, few studies have been published on the reconstruction outcomes using this implant. We sought to investigate the bone healing indices (including regenerate consolidation and time to docking site union) associated with the use of a magnetically controlled all-internal bone transport nail for the reconstruction of 4 patients treated for posttraumatic tibial bone loss. Perioperative and device-related complications are also reported.
Cephalomedullary Nailing of Unstable Geriatric Intertrochanteric Fractures on a Traction Table Combined With Percutaneous Reduction Techniques Is Safe and Results in a Low Rate of Cutout
Authors: Somasundaram Vivek , Owen Aaron R. , Hidden Krystin A. , Barlow Jonathan D. , Cross William W. , Sems Stephen A. , Yuan Brandon J. 
Published: February 2023

Objectives:
To describe a reproducible technique for reduction assessment and percutaneous reduction of unstable intertrochanteric fractures treated with a cephalomedullary nail on a traction table.

Design:
Retrospective cohort study.

Setting:
Level-1 trauma center.

Patients:
Two-hundred 20 consecutive patients with intertrochanteric fractures.

Intervention:
Initial closed reduction performed on a traction table. Accessory incisions were used to facilitate a reduction in 77 patients (35%). All fractures were stabilized with a cephalomedullary nail.

Main Outcome Measurements:
Radiographic outcome including union, cutout, and fracture collapse (FC). Surgical outcomes including infection and hematoma were also reported.

Results:
Mechanical complications (nonunion, cutout, and varus collapse) occurred in 8.8% of patients at 1 year. Eleven of 13 patients who developed these complications had either suboptimal implant placement (tip-to-apex distance >25 mm) or a varus reduction. There was no difference in the incidence of reoperation, nonunion, lag screw cutout, or posttraumatic arthritis based on the use of an accessory incision for fracture reduction. There was a significant increase in FC in patients who received an accessory incision (6.8 mm vs. 5.4 mm, P = 0.04). One patient (1%) developed a hematoma in the accessory incision cohort, and 1 patient (0.7%) who did not have an accessory incision developed a postoperative infection.

Conclusions:
The current study suggests utilization of accessory incisions assist in reduction is safe and is associated with a low rate of complications. The surgeon should prioritize fracture reduction and optimal implant placement and not hesitate to use an accessory incision to assist with fracture reduction.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Effect of inferior vena cava respiratory variability-guided fluid therapy after laparoscopic hepatectomy: a randomized controlled clinical trial
Authors: Ji Jingjing , Ma Qian , Tian Yali , Shi Xueduo , Chen Luning , Zhu Xinhua , Yu Decai , Qiu Yudong , Li Bingbing 
Published: February 2023

Abstract

Background:
After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU).

Methods:
This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy.

Results:
Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9–36.7] mg/L vs. 44.8 [95%CI: 26.9–63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D-lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups.

Conclusion:
Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR.

Trial Registration:
ChiCTR-INR-17013093.
Artificial Intelligence and Machine Learning Approaches to Facilitate Therapeutic Drug Management and Model-Informed Precision Dosing
Authors: Poweleit Ethan A. , Vinks Alexander A. , Mizuno Tomoyuki 
Published: February 2023

Background:
Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) approaches for supporting clinical research and support is increasing. However, AI and ML applications for precision dosing have been evaluated only recently. Given the capability of ML to handle multidimensional data, such as from electronic health records, opportunities for AI and ML applications to facilitate TDM and MIPD may be advantageous.

Methods:
This review summarizes relevant AI and ML approaches to support TDM and MIPD, with a specific focus on recent applications. The opportunities and challenges associated with this integration are also discussed.

Results:
Various AI and ML applications have been evaluated for precision dosing, including those related to concentration or exposure prediction, dose optimization, population pharmacokinetics and pharmacodynamics, quantitative systems pharmacology, and MIPD system development and support. These applications provide an opportunity for ML and pharmacometrics to operate in an integrated manner to provide clinical decision support for precision dosing.

Conclusions:
Although the integration of AI with precision dosing is still in its early stages and is evolving, AI and ML have the potential to work harmoniously and synergistically with pharmacometric approaches to support TDM and MIPD. Because data are increasingly shared between institutions and clinical networks and aggregated into large databases, these applications will continue to grow. The successful implementation of these approaches will depend on cross-field collaborations among clinicians and experts in informatics, ML, pharmacometrics, clinical pharmacology, and TDM.
Lifetime history of interpersonal partner violence is associated with insomnia among midlife women veterans
Authors: Goldstein Lizabeth A. , Jakubowski Karen P. , Huang Alison J. , Seal Karen H. , Maguen Shira , Inslicht Sabra S. , Byers Amy L. , Gibson Carolyn J. 
Published: February 2023

Abstract

Objective
Over a third of women in the United States report a lifetime history of intimate partner violence. Although a recent review found that intimate partner violence is related to poor subjective sleep, the majority of studies involved reproductive-aged women and used suboptimal measures of interpersonal violence and/or insomnia. We examined the relationship between lifetime intimate partner violence and current clinical insomnia in a cross-sectional sample of midlife women veterans.

Methods
Cross-sectional data were drawn from the Midlife Women Veterans Health Survey. Women Veterans (N = 232) aged 45 to 64 years enrolled in Department of Veterans Affairs health care in Northern California completed an adapted version of the Extended-Hurt, Insult, Threaten, Scream to assess lifetime history of intimate partner violence (screening threshold score and any physical, sexual, and psychological intimate partner violence) and the Insomnia Severity Index to assess current insomnia.

Results
In multivariable analyses, lifetime history of intimate partner violence was associated with twofold to fourfold odds of current clinical insomnia, including overall intimate partner violence (odds ratio, 3.24; 95% confidence interval, 1.57‐6.69), physical intimate partner violence (odds ratio, 2.01; 95% confidence interval, 1.09‐3.70), psychological intimate partner violence (odds ratio, 3.98; 95% confidence interval, 2.06‐7.71), and sexual intimate partner violence (odds ratio, 2.09; 95% confidence interval, 1.08‐4.07).

Conclusions
Lifetime history of intimate partner violence is common and may be associated with clinical insomnia during midlife. Findings highlight the importance of screening midlife women for intimate partner violence and recognizing the potential role of this traumatic exposure on women's health.
Neurodevelopment in the Congenital Heart Disease Population as Framed by the Life Course Health Development Framework
Authors: Smith Lindsay M. , Harrison Tondi M. 
Published: February 2023

Background
Adverse neurodevelopment is a common comorbidity associated with congenital heart disease (CHD). The consequences of adverse neurodevelopment are seen across the life course. The cause of adverse neurodevelopment is multifactorial, and use of a life course perspective can assist with understanding and enhancing neurodevelopment in individuals with CHD.

Purpose
The purposes of this article are to (1) apply the Life Course Health Development framework to neurodevelopment in the population with CHD and (2) discuss how exposure to the pediatric cardiac intensive care unit (PCICU) environment during infancy is a point of intervention for improving neurodevelopmental outcomes.

Conclusion
Individuals with CHD are at an increased risk for adverse neurodevelopment across the life course. The PCICU environment is a point of intervention for improving neurodevelopmental outcomes. Stress can lead to changes in brain structure and function that are associated with negative outcomes in terms of outward behavioral and functional capacity, and the PCICU environment is a source of stressful stimuli. Infancy is a period of rapid brain growth, and the brain is more susceptible to stress during this period of the life course, putting infants receiving care in the PCICU at an increased risk of adverse neurodevelopment.

Clinical Implications
Interventions to support optimal neurodevelopment should focus on the PCICU environment during infancy. Developmentally supportive care models should be explored as a means of modifying the PCICU environment. In addition, more research is needed on the relationship between the PCICU and neurodevelopment. The conceptual model introduced can serve as a starting point for this research.
Noncognitive Factors of Grit and Mindset Do Not Predict Performance on the National Physical Therapy Exam
Authors: Huebner Bethany , Mattocks Alma , Pitt Jason 
Published: February 2023

Introduction.
National Physical Therapy Exam (NPTE) performance is predicted to some degree by cognitive measures, such as grade point average (GPA) and the Graduate Record Exam scores. Researchers have begun to explore noncognitive measures, for example, grit and mindset, which could account for other potential determinants of student success in physical therapist (PT) education programs and the NPTE.

Review of Literature.
There is a paucity of evidence that has explored non‐cognitive factors related to academic performance compared to cognitive factors. Constructs such as grit and mindset have been identified as reliable measures; however, mixed results occur in the literature as how these scales predict NPTE performance. Cognitive factors continue to demonstrate stronger correlations to NPTE performance.

Subjects.
Four PT student cohorts (n = 43, 45, 50, and 49) were enrolled in a prospective cohort study.

Methods.
Grit and mindset were measured by self-reported questionnaires. Cognitive measures were obtained, including undergraduate cumulative GPA (cGPA), undergraduate science GPA (sGPA), graduate GPA (gGPA), Academic Practice Exam and Assessment Tool (Academic PEAT) scores, and NPTE scores. Pairwise Pearson’s correlation coefficients were calculated for each cohort. National Physical Therapy Exam scores from 2 graduating cohorts were analyzed using multiple linear regression to identify variables that predicted successful outcomes.

Results.
Neither grit nor mindset correlated with any cognitive measures. Furthermore, neither grit nor mindset were significantly associated with NPTE scores or outcomes in multivariate regression models. National Physical Therapy Exam scores were significantly associated with gGPA (β = 148.4, 95% confidence interval [CI] = 93.4–203.5) and Academic PEAT scores (β = 0.28, 95% CI = 0.08–0.49).

Discussion and Conclusion.
Among PT students at a small liberal arts institution in the midwest, grit and mindset were not associated with any indicators of academic success (e.g., cGPA, sGPA, gGPA, Academic PEAT, or NPTE scores). NPTE outcomes were best predicted by gGPA and Academic PEAT scores. These findings conflict with previous reports that grit and mindset are potential markers for academic success and support monitoring gGPA and Academic PEAT scores to identify students who may require additional preparation before sitting for the NPTE.
Health Maintenance and Preventative Care in Inflammatory Bowel Disease
Authors: Weissman Simcha , Systrom Hannah K. , Bangolo Ayrton , Elias Daniel , Awasi Marcel , Zahdeh Tamer , Ogbu Chukwuemeka E. , Kim Mishka Hoo , Kalra Meenal , Khota Kavya , Kasarapu Ritu B. , Mutabi Erasmus , Makrani Moinulhaq , Nemalikanti Sanskrita , Thomas Jim , Jijo Joseph P. , Thwe Hla M. , Salib Yousstina , Narayan Kiran L. , Ahmed Kareem , Aziz Muhammad , Elias Sameh , Feuerstein Joseph D. 
Published: February 2023

Background & Aims:
Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD.

Methods:
A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021. All guidelines were reviewed for the transparency of conflicts of interest and funding, recommendation quality and strength, external guideline review, patient voice inclusion, and plan for update—as per Institute of Medicine standards. In addition, recommendations and their quality were compared between societies.

Results:
Fifteen distinct societies and a total of 89 recommendations were included. Not all guidelines provided recommendations on the key aspects of preventative care in IBD—such as vaccinations, cancer prevention, stress reduction, and diet/exercise. Sixty-seven percent of guidelines reported on conflicts of interest, 20% underwent external review, and 27% included patient representation. In all, 6.7%, 21.3%, and 71.9% of recommendations were based on high, moderate, and low-quality evidence, respectively. Twenty-seven percent, 23.6%, and 49.4% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence (P=0.28) and strong recommendations (P=0.41) did not significantly differ across societies.

Conclusions:
Many guidelines do not provide recommendations on key aspects of preventative care in IBD. As over 70% of recommendations are based on low-quality evidence, further studies on preventative care in IBD are warranted to improve the overall quality of evidence.