bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to rest a hypothesis? Accumulating evidence that periodic leg movements during sleep are not increased in children with attention-deficit hyperactivity disorder (ADHD): results of a case–control study and a meta-analysis
Authors: Fulda Stephany , Miano Silvia 
Published: March 2023

Abstract

Study Objectives
To address the hypothesis that periodic leg movements during sleep (PLMS) are more frequent in children with attention-deficit hyperactivity disorder (ADHD) when compared with typically developing (TD) children. To that end, we analyzed PLMS in a recent case–control study and conducted a systematic review and meta-analysis of PLMS frequency in children with ADHD and TD children.

Methods
In our case–control study, we compared the PLMS frequency of 24 children with ADHD (mean age 11 years, 17 males) to that of 22 age-matched typically developing (TD) children (mean age 10 years, 12 males). A subsequent meta-analysis included 33 studies that described PLMS frequency in groups of children with ADHD and/or groups of TD children.

Results
The case–control study did not show any differences in the frequency of PLMS between children with ADHD and TD children, a result that was consistent across a range of different definitions of PLMS, which in turn had a significant and systematic effect on PLMS frequency. The meta-analysis compared the average PLMS indices and the proportion of children with elevated PLMS indices between children with ADHD and TD children and across a number of analyses did not find any meta-analytic results that supported the hypothesis that PLMS are more frequent in children with ADHD.

Conclusions
Our results suggest that PLMS are not more frequent in children with ADHD compared with TD children. A finding of frequent PLMS in a child with ADHD should therefore be considered a separate disorder and prompt specific diagnostic and therapeutic strategies.
Characterization of Intestinal Mesenchymal Stromal Cells From Patients With Inflammatory Bowel Disease for Autologous Cell Therapy
Authors: Anbazhagan Murugadas , Geem Duke , Venkateswaran Suresh , Pelia Ranjit , Kolachala Vasantha L , Dodd Anne , Maddipatla Sushma C , Cutler David J , Matthews Jason D , Chinnadurai Raghavan , Kugathasan Subra 
Published: March 2023

AbstractTherapy with mesenchymal stromal cells (MSCs) has shown promise in inflammatory bowel disease—leveraging their immunosuppressive and regenerative properties. However, the potential immunogenic complications of allogenic MSCs sourced from different tissues raise concern. Thus, we assessed the fitness and functionality of autologous intestinal MSCs as a potential platform for cellular therapy. Mucosal biopsy-derived MSCs from Crohn’s disease (n = 11), ulcerative colitis (n = 12), and controls (n = 14) were analyzed by microscopy and flow cytometry for doubling-time, morphology, differentiation potential, and immunophenotype. Gene expression, cell-subtype composition, along with surface marker and secretome changes after IFN-γ priming were measured by bulk and single-cell RNA sequencing coupled with a 30-plex Luminex panel. MSCs expanded ex vivo demonstrate canonical MSC markers, similar growth kinetics, and tripotency regardless of the patient phenotype. Global transcription patterns were similar at baseline though inflammatory bowel disease (IBD) rectal MSCs showed changes in select immunomodulatory genes. IFN-γ priming resulted in upregulation of shared immunoregulatory genes (particularly in PD-1 signaling) and overrode the transcriptional differences observed at baseline. Furthermore, MSCs secrete key immunomodulatory molecules at baseline and in response to IFN-γ including CXCL10, CXCL9, and MCP-1. Overall, MSCs from IBD patients have normal transcriptional and immunomodulatory properties with therapeutic potential and can be sufficiently expanded.
Metabolic Rewiring and Stemness: A Critical Attribute of Pancreatic Cancer Progression
Authors: Ogunleye Ayoola O , Nimmakayala Rama Krishna , Batra Surinder K , Ponnusamy Moorthy P 
Published: March 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases with a poor 5-year survival rate. PDAC cells rely on various metabolic pathways to fuel their unlimited proliferation and metastasis. Reprogramming glucose, fatty acid, amino acid, and nucleic acid metabolisms contributes to PDAC cell growth. Cancer stem cells are the primary cell types that play a critical role in the progression and aggressiveness of PDAC. Emerging studies indicate that the cancer stem cells in PDAC tumors are heterogeneous and show specific metabolic dependencies. In addition, understanding specific metabolic signatures and factors that regulate these metabolic alterations in the cancer stem cells of PDAC paves the way for developing novel therapeutic strategies targeting CSCs. In this review, we discuss the current understanding of PDAC metabolism by specifically exploring the metabolic dependencies of cancer stem cells. We also review the current knowledge of targeting these metabolic factors that regulate CSC maintenance and PDAC progression.
Construction of a mini-RNA replicon inEscherichia coli
Authors: Kashiwagi Akiko , Yomo Tetsuya 
Published: March 2023

AbstractHow the ribonucleic acid (RNA) world transited to the deoxyribonucleic acid (DNA) world has remained controversial in evolutionary biology. At a certain time point in the transition from the RNA world to the DNA world, ‘RNA replicons’, in which RNAs produce proteins to replicate their coding RNA, and ‘DNA replicons’, in which DNAs produce RNA to synthesize proteins that replicate their coding DNA, can be assumed to coexist. The coexistent state of RNA replicons and DNA replicons is desired for experimental approaches to determine how the DNA world overtook the RNA world. We constructed a mini-RNA replicon in Escherichia coli. This mini-RNA replicon encoded the β subunit, one of the subunits of the Qβ replicase derived from the positive-sense single-stranded Qβ RNA phage and is replicated by the replicase in E. coli. To maintain the mini-RNA replicon persistently in E. coli cells, we employed a system of α complementation of LacZ that was dependent on the Qβ replicase, allowing the cells carrying the RNA replicon to grow in the lactose minimal medium selectively. The coexistent state of the mini-RNA replicon and DNA replicon (E. coli genome) was successively synthesized. The coexistent state can be used as a starting system to experimentally demonstrate the transition from the RNA–protein world to the DNA world, which will contribute to progress in the research field of the origin of life.
Effect of dietary cation-anion difference on dry matter intake, digestibility, body weight gain, blood parameters, and carcass traits in Zandi lambs
Authors: Khani M , Fattah A , Ebrahimi-Mahmoudabad S R , Joezy-Shekalgorabi S 
Published: March 2023

Abstract
The dietary cation-anion difference (DCAD) has gotten much attention recently; however, there is not much evidence on organic matter digestibility, blood parameters, dry matter intake, body weight, and carcass features of male sheep fed with different DCAD diets. The effects of dietary cation-anion difference (DCAD) on these traits in male lambs under the environmental high temperatures were investigated in this study. Forty male lambs (average body weight of 39 kg) were randomly assigned to one of five treatments with eight replicates. Lambs were fed diets with DCAD levels ranging from 150 (control group) to 300, 450, 600, and 750 mEq/kg dry matter. This study lasted 100 days and used a 21-day adaptation. The results showed that the control group had the highest dry matter intake, dry matter digestibility, and crude protein digestibility (p= 0.02). Also, the lowest amount of average body weight was observed in the control group (p= 0.01). The results showed the different DCAD levels affected the statistically significant in terms of live weight, carcass weight, length and width of muscle cross section, lung weight, spleen weight, and abdominal fat (p= 0.04). As well, the highest ruminal pH was observed in the control group (p= 0.4). The results of the blood glucose parameter showed that control group had a significant effect on the blood glucose level (p= 0.04). Furthermore, the highest abdominal fat weight was observed in the control group (p= 0.04). There was no statistically significant difference between other traits, including skin weight, head weight, leg weight, carcass length, liver weight, kidney weight, heart weight, testicle weight, tail weight, rumen weight, and lactation weight. In summary, increasing DCAD in the diet could improve the production and carcass quality in lambs under environmental high temperatures.
A model template approach for rapid evaluation and application of physiologically based pharmacokinetic models: extension to volatile organic compounds
Authors: Bernstein Amanda S , Prasad Bidya , Schlosser Paul M , Kapraun Dustin F 
Published: March 2023

AbstractChemical risk assessors use physiologically based pharmacokinetic (PBPK) models to perform dosimetric calculations, including extrapolations between exposure scenarios, species, and populations of interest. Assessors should complete a thorough quality assurance (QA) review to ensure biological accuracy and correct implementation prior to using these models. This process can be time-consuming, and we developed a PBPK model template that allows for faster, more efficient QA review. The model template consists of a single model “superstructure” with equations and logic commonly found in PBPK models, allowing users to implement a wide variety of chemical-specific PBPK models. QA review can be completed more quickly than for conventional PBPK model implementations because the general model equations have already been reviewed and only parameters describing chemical-specific model and exposure scenarios need review for any given model implementation. We have expanded a previous version of the PBPK model template by adding features commonly included in PBPK models for volatile organic compounds (VOCs). We included multiple options for representing concentrations in blood, describing metabolism, and modeling gas exchange processes to allow for inhalation exposures. We created PBPK model template implementations of published models for seven VOCs: dichloromethane, methanol, chloroform, styrene, vinyl chloride, trichloroethylene, and carbon tetrachloride. Simulations performed using our template implementations matched published simulation results to a high degree of accuracy (maximum observed percent error: 1%). Thus, the model template approach can now be applied to a broader class of chemical-specific PBPK models while continuing to bolster efficiency of QA processes that should be conducted prior to using models for risk assessment applications.
No-Test Medication Abortion: A Systematic Review
Authors: Shapiro Marit Pearlman , Dethier Divya , Kahili-Heede Melissa , Kaneshiro Bliss 
Published: March 2023

ABSTRACT
The use of medication abortion has increased significantly in the past several years, in part due to the increased adoption of telemedicine during the COVID-19 pandemic. Several leading organizations have established recommendations for the practice of providing a medication abortion without a prior pelvic examination or ultrasonogram (no-test medication abortion). Evidence demonstrates that gestational age can be accurately measured with patient screening questions and the risk of ectopic pregnancy among women seeking medication abortion is very low. Given this paradigm shift in abortion access, increasing numbers of health care professionals worldwide have adopted these practices and published their results.
This systematic review aimed to summarize the efficacy and safety outcomes of medication abortion performed without prior pelvic examination or ultrasound. Ongoing and published clinical trials were identified, and randomized control trials and comparative cohort trials discussing the provision of no-test medication abortion were eligible. The primary study outcome was successful medication abortion, defined as complete abortion without the need for surgical management. Failure was thus defined as the need for surgical intervention to complete the abortion. Medication regimens, efficacy rates, complication rates, and adverse events were abstracted from eligible studies.
A total of 21 studies were included in this review, including cases performed in over 24 countries. Ultimately, 15 studies were sufficiently homogenous in terms of design and comparator to create aggregate data with summary statistics for the primary outcome. The overall efficacy rate of no-test medication abortion was found to be 96.4% (95% confidence interval [CI], 96.0–96.7) in the 10,693 patients included in this review. Among pregnancies at less than 70 days' gestation (n = 8166), the efficacy rate was 95.2% (95% CI, 94.7–95.7). The rate of surgical intervention was 4.4% (95% CI, 4.0–4.9), and at less than 70 days' gestation was 3.8% (95% CI, 3.3–4.3). The ectopic pregnancy rate was 0.06% (95% CI, 0.02–0.15), blood transfusion rate ranged from 0% to 0.7%, and there were no deaths reported.
The results of this systematic review encompassing data on 10,693 patients showed demonstrate that no-test medication abortion is likely effective and safe. The rates of surgical evacuation and complication were comparable with the rate among those undergoing medication abortion with pretreatment ultrasound, and significantly lower than the rates seen with unsafe methods of abortion.
Spontaneous Hemoperitoneum in Pregnancy and Endometriosis: A New Challenge in a Known Disease
Authors: Zilberman Sharon Nataly , Shiber Yair , Vaknin Zvi , Betser Moshe , Copel Laurian , Maymon Ron 
Published: March 2023

ABSTRACT

Importance
Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare life-threatening event previously associated with endometriosis. Although pregnancy is thought to improve the symptoms of endometriosis, abrupt intraperitoneal bleeding can occur, jeopardizing both maternal and fetal outcomes.

Objective
The aim of this study was to review the published information regarding SHiP pathophysiology, presentation, diagnosis, and management in a flowchart approach.

Evidence Acquisition
A descriptive review of published articles in the English-language was carried out.

Results
SHiP most commonly presents in the second half of pregnancy with a combination of abdominal pain, hypovolemia, a decline in hemoglobin level, and fetal distress. Nonspecific gastrointestinal symptoms are not uncommon. Surgical management is suitable in most scenarios and avoids complications such as recurrent bleeding and infected hematoma. Maternal outcome has improved greatly, whereas perinatal mortality remained unchanged. In addition to physical strain, SHiP was reported to have a psychosocial sequela.

Conclusions and Relevance
A high index of suspicion is required when patients present with acute abdominal pain and signs of hypovolemia. Early use of sonography contributes to narrowing down the diagnosis. Health care providers should be familiar with the SHiP diagnosis because early identification is crucial when attempting to safeguard maternal and fetal outcomes. Maternal and fetal requirements are often contradictory, creating a greater challenge in decision-making and treatment. A multidisciplinary team approach should coordinate the treatment, whenever a SHiP diagnosis is suspected.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After completing this activity, the learner should be better able to identify SHiP symptoms and contributing factors; propose recommendations for diagnosis and differential diagnosis; and describe the treatment options, emphasizing multidisciplinary approach.
The Role of Lung Ultrasound in Systemic Sclerosis
Authors: Gomes Guerra Miguel , Machado Pinto Tânia , Águeda Ana , Rodrigues Joana , Marona José , Violante António , Oliveira Margarida 
Published: March 2023

Background
In systemic sclerosis (SSc), high-resolution computed tomography (HRCT) of the chest is the standard criterion for the diagnosis of interstitial lung disease (ILD). However, recent evidence suggests that lung ultrasound (LUS) can also detect ILD, without radiation exposure. Thus, our goal was to perform a systematic review, aiming to clarify the role of LUS in the detection of ILD in SSc.

Methods
A systematic review was carried out in PubMed and EMBASE (PROSPERO register number CRD42022293132), to identify studies that compared LUS with HRCT in the detection of ILD in patients with SSc. Risk of bias was assessed with the QUADAS-2 () tool.

Results
Three hundred seventy-five publications were identified. After screening, 13 were included in the final analysis. No study presented high risk of bias. Lung ultrasound protocol was highly heterogeneous between authors, specifically concerning transducer, intercostal spaces evaluated, exclusion criteria, and definition of positive LUS. Most authors evaluated the presence of B-lines as a surrogate of ILD, with only 4 focusing on pleural changes. A positive correlation between LUS findings and ILD detected by HRCT was reported. Results also revealed high sensitivity (74.3%–100%) but variable specificity (16%–99%). Positive predictive value varied between 16% and 95.1%, and negative predictive value between 51.7% and 100%.

Conclusion
Lung ultrasound is sensitive in the detection of ILD, but specificity must be optimized. The value of pleural evaluation also requires further investigation. Moreover, a consensus is needed to define a uniform LUS protocol to implement in future investigations.
Glucagon-Like Peptide 1 Receptor Agonists in Patients With Inflammatory Arthritis or Psoriasis
Authors: Karacabeyli Derin , Lacaille Diane 
Published: March 2023

Abstract
Obesity is a proinflammatory state associated with increased disease severity in various types of inflammatory arthritis. Weight loss is associated with improved disease activity in certain forms of inflammatory arthritis such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We conducted a scoping review summarizing the literature evaluating the effect of glucagon-like peptide 1 (GLP-1) receptor agonists on weight and disease activity in patients with inflammatory arthritis or psoriasis. MEDLINE, PubMed, Scopus, and Embase were searched for publications evaluating the role of GLP-1 analogs in RA, PsA, psoriasis, axial spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, gout, and calcium pyrophosphate deposition disease. Nineteen studies were included: 1 gout study, 5 RA studies (3 basic science, 1 case report, and 1 longitudinal cohort), and 13 psoriasis studies (2 basic science, 4 case reports, 2 combined basic science/clinical studies, 3 longitudinal cohorts, and 2 randomized controlled trials). No psoriasis study reported on PsA outcomes. Basic science experiments demonstrated weight-independent immunomodulatory effects of GLP-1 analogs through inhibition of the NF-κB pathway (via AMP-activated protein kinase phosphorylation in psoriasis and prevention of IκBα phosphorylation in RA). In RA, improved disease activity was reported. In psoriasis, 4 of 5 clinical studies demonstrated significant improvements in Psoriasis Area Severity Index and weight/body mass index with no major adverse events. Common limitations included small sample sizes, short follow-up periods, and lack of control groups. GLP-1 analogs safely cause weight loss and have potential weight-independent anti-inflammatory effects. Their role as an adjunct in patients with inflammatory arthritis and obesity or diabetes is understudied, warranting future research.
Genotype-Phenotype Associations of Children With Familial Mediterranean Fever in a Cohort Consisting of M694V Mutation and Implications for Colchicine-Resistant Disease
Authors: Kisaoglu Hakan , Baba Ozge , Kalyoncu Mukaddes 
Published: March 2023

Objectives
The aim of this study was to investigate the clinical associations of the second allele mutations and the effect of genotype and presenting features on colchicine resistance in children with familial Mediterranean fever (FMF), carrying at least one M694V variant.

Methods
The medical records of the patients diagnosed with FMF, in whom at least one allele M694V mutation was detected, were reviewed. Patients were grouped according to the genotype as M694V homozygotes, compound heterozygote M694V with an exon 10 mutation, compound heterozygote M694V with a variant of unknown significance (VUS), and M694V heterozygotes. Disease severity was assessed with the International Severity Scoring System for FMF.

Results
Among the 141 patients included, homozygote M694V (43.3%) was the most frequent MEFV genotype. Clinical manifestations of FMF at diagnosis were not significantly different according to genotypic alterations except homozygote M694V. Besides, homozygous M694V was associated with a more severe disease, with more frequent comorbidities and colchicine-resistant disease. A lower disease severity score was observed in compound heterozygotes with VUS than in M694V heterozygotes (median 1 vs 2, p = 0.006). Regression analysis revealed that homozygous M694V, arthritis, and frequency of attacks were associated with an increased risk of colchicine-resistant disease.

Conclusions
Clinical manifestations of FMF at diagnosis with a M694V allele were predominantly influenced by the M694V rather than the second allele mutations. Although homozygous M694V was associated with the most severe form, the presence of compound heterozygosity with a VUS did not affect disease severity or clinical features. Homozygous M694V confers the highest risk of colchicine-resistant disease.
CIRC_0012535 CONTRIBUTES TO LIPOPOLYSACCHARIDE-INDUCED FETAL LUNG FIBROBLAST APOPTOSIS AND INFLAMMATION TO REGULATE INFANTILE PNEUMONIA DEVELOPMENT BY MODULATING THE MIR-338-3P/IL6R SIGNALING
Authors: Fang Xing , Mei Wenjing , Zeng Rihua , Zou Li , Zeng Xuefei , Tang Shanghong 
Published: March 2023

ABSTRACT

Background: Infantile pneumonia is a respiratory infection disease, seriously threatening the life of neonatal patients. Circular RNA (circRNA) dysregulation is reported to be involved in pneumonia pathogenesis. Circ_0012535 was previously displayed to be upregulated in blood samples of patients with community-acquired pneumonia. However, circ_0012535’s role in this disorder remains unclear. We thus aim to unveil the functions of circ_0012535 in infantile pneumonia. Methods: Fetal lung fibroblasts (WI38) treated with LPS were used as pneumonia cell models. Expression analysis for circ_0012535, miR-338-3p and IL6R was performed using quantitative real-time polymerase chain reaction. Cell counting kit 88), 5-ethynyl-2′-deoxyuridine, and flow cytometry assays were implemented for cell function detection. The release of inflammatory factors, and superoxide dismutase activity and malonaldehyde content were ascertained using commercial kits. The putative binding between miR-338-3p and circ_0012535 or IL6R was validated by dual-luciferase analysis, RIP analysis, and pull-down analysis. Results: Circ_0012535 was highly expressed in LPS-treated WI38 cells. Knockdown of circ_0012535 recovered LPS-inhibited cell viability and proliferation and attenuated LPS-induced cell apoptosis, cell cycle arrest, inflammation, and oxidative stress. Circ_0012535 bound to miR-338-3p and negatively regulated miR-338-3p expression. Inhibition of miR-338-3p reversed the role of circ_0012535 knockdown, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. MiR-338-3p bound to IL6R 3′UTR, and circ_0012535 shared miR-338-3p binding site with IL6R. IL6R overexpression reversed the role of miR-338-3p, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. Conclusion: Circ_0012535 supported LPS-induced WI38 cell apoptosis and inflammation to promote the progression of infantile pneumonia, and circ_0012535 functioned partly by targeting the miR-338-3p/IL6R signaling.