bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement
Authors:   US Preventive Services Task Force
Published: September 2020

(Abstracted from JAMA 2020;323(13):1286–1292)
Bacterial vaginosis (BV) is a common vaginal condition, occurring in 5.8% to 19.3% of pregnant women. It is also associated with a 2-fold higher risk for preterm delivery, although it is unclear whether the condition is a cause of preterm birth.
Neonatal Mortality After Interhospital Transfer of Pregnant Women for Imminent Very Preterm Birth in Illinois
Authors: Shah Kshama P. , deRegnier Raye-Ann O. , Grobman William A. , Bennett Amanda C. 
Published: September 2020

(Abstracted from JAMA Pediatr 2020;174(4):358–365)
In the United States, prematurity is a major contributor to mortality in children younger than 5 years. To reduce infant mortality, preterm newborns should be delivered or transferred to a hospital that can meet their medical care needs.
High Prevalence of Falls Independent of Age in Adults Living With Chronic Pain
Authors: Bisson Etienne J. , Gemmell Jen , Kelly Sarah , Marsala Adam , Brown Elizabeth , Good Mary Anne , Wilson Rosemary , Duggan Scott 
Published: September 2020

Objectives:
High risks of falls have been reported in older adults with chronic pain but chronic pain similarly affects adults of all ages. This cross-sectional study aimed to determine the prevalence of falls and associated risk factors in adults of all ages living with chronic pain.

Materials and Methods:
Patient-reported data were analyzed from 591 adults with chronic pain enrolled in a local pain clinic between November 2017 and April 2019. Sociodemographic, history of falls, and biopsychosocial measures of pain were examined to identify and describe adults with chronic pain who fell in the previous year. Factors associated with falls were examined using logistic regression.

Results:
A total of 268 (45%) reported at least 1 fall in the previous year (fallers) where 194 (33%) fell in the previous 3 months, and 185 (31%) had multiple falls. The prevalence of falls in the previous year was over 37% across age groups. Overall, fallers were older, had greater pain severity and interference, lower physical function and pain self-efficacy, greater depression, more reported neuropathic pain, and had more pain sites compared with nonfallers. Number of pain sites reported (odds ratio=1.12; 95% confidence interval, 1.02-1.22) and lower physical function (odds ratio=0.96; 95% confidence interval, 0.94-0.99) were independently associated with falls.

Discussion:
A high prevalence of falls was found independent of age for adults with chronic pain. Although the risk of falls may increase with age, lower physical function and more pain sites are better indicators for falls. A better understanding of circumstances and consequences of falls in all adults with chronic pain is warranted.
Perioperative Pregabalin for Preventive Analgesia in Breast Cancer Surgery
Authors: Chang Chun-Chia , Yen Wei-Ting , Lin Yao-Tsung , Wang Li-Kai , Hung Kuo-Chuan , Wu Zhi-Fu , Chen Jen-Yin 
Published: September 2020

Objectives:Pregabalin is a drug for neuropathic pain. Antipronociceptive properties of pregabalin have led to its recent use as an adjuvant to the multimodal postoperative pain regimen. This meta-analysis was conducted to evaluate the efficacy of perioperative pregabalin on acute and chronic postsurgical pain (CPSP) after breast cancer surgery.Methods:A meta-analysis including 8 randomized controlled trials searched from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted. Subgroup analysis was performed according to doses and timecourse of pregabalin administration. Review Manager 5.3 was selected to conduct the meta-analysis.Results:Preoperative pregabalin in breast cancer surgery alleviated acute postoperative pain at rest 24 hours after surgery by 0.31 points on an 0 to 10 Numerical Rating Scale (95% confidence interval [CI] −0.57 to −0.05). Morphine consumption showed a decrease in postoperative use by 1.09 mg (95% CI: −1.61 to −0.57). The incidence of CPSP 3 months after surgery was reduced to 46% (95% CI: 0.25-0.85). Postoperative nausea and vomiting, dizziness, and sedation showed no overall significant reductions. However, a decrease in the incidence of postoperative nausea and vomiting and an increase in the incidence of dizziness were noted when patients received 300 mg of pregabalin before surgery.Discussion:This study demonstrated that pregabalin showed more efficacy on chronic pain than acute pain after a breast cancer surgery. Further study based on doses and treatment course of pregabalin should be conducted to establish stronger evidence of treatment effects.
Synthetic Bone Graft Substitute for Treatment of Unicameral Bone Cysts
Authors: Nunziato Carl , Williams John , Williams Ronald 
Published: September 2020

Background:
Treatments for unicameral bone cysts (UBCs) have high documented failure rates (27% to 63%) because of recurrence or persistence of the cyst, similar to nonoperative management. Recent evidence suggests that filling of the defect with a synthetic bone graft substitute (SBGS) supports the weakened cortex and promotes new bone growth. A calcium sulfate, brushite, calcium phosphate, composite graft material (PRODENSE, Wright Medical, Memphis, TN) has been evaluated as a substitute for autogenous or allogenous graft in animal and human studies. The purpose of this study was to compare the rates of revision surgery in patients treated for UBCs with an SBGS compared with historical treatments with allograft or autologous bone marrow aspirate.

Methods:
The authors reviewed 27 of 33 patients (age, 6 months to 21 years) an average of 121 months (range, 32 to 228) after filling of a UBC with an injection of SBGS (n=18) versus allograft or autologous bone marrow aspirate (n=9) between June 2008 and December 2017. Six patients with no follow-up were excluded. Groups did not differ in age at surgery, sex (19/27 male), history of pathologic fracture (22/27), or previous treatments (11/27). The primary outcome was the rate of revision surgery. Secondary outcomes included revision surgery-free survival as evaluated by the log-rank test, rate of postoperative fracture, persistent cysts, continued pain, and/or growth disturbance at the final follow-up.

Results:
Seven of 9 patients treated with allograft or autograft underwent revision surgery for postoperative pathologic fracture (n=2) or resorption of the graft (n=5) compared with 2 of 18 patients injected with the SBGS, both treated for graft resorption. The use of SBGS was associated with a decreased need for revision surgery over all time periods (hazard ratio, 0.14; 95% confidence interval, 0.03-0.05). There was no significant difference between postoperative fracture (2/18 vs. 2/9), persistent cyst (7/18 vs. 5/9), pain (0/18 vs. 2/9), or growth disturbance (1/18 vs. 3/9).

Conclusions:
Treatment of UBCs with SBGS may decrease reoperation rates. Initial radiographic appearance after SBGS treatment shows solid structural support, followed by new bone formation. This appearance may lead to a less aggressive approach in considering revision surgery.

Level of Evidence:
Level III—retrospective comparative study investigating the results of treatment.
Biomarkers or factors for predicting the efficacy and adverse effects of immune checkpoint inhibitors in lung cancer: achievements and prospective
Authors: Shi Wen-Jia , Zhao Wei 
Published: September 2020

Abstract
Immune checkpoint inhibitors (ICIs) are widely used in lung cancer therapy due to their effectiveness and minimal side effects. However, only a few lung cancer patients benefit from ICI therapy, driving the need to develop alternative biomarkers. Programmed death-ligand 1 (PD-L1) molecules expressed in tumor cells and immune cells play a key role in the immune checkpoint pathway. Therefore, PD-L1 expression is a prognostic biomarker in evaluating the effectiveness of programmed death-1 (PD-1)/PD-L1 inhibitors. Nevertheless, adverse predictive outcomes suggest that other factors are implicated in the response. In this review, we present a detailed introduction of existing biomarkers concerning tumor abnormality and host immunity. PD-L1 expression, tumor mutation burden, neoantigens, specific gene mutations, circulating tumor DNA, human leukocyte antigen class I, tumor microenvironment, peripheral inflammatory cells, and microbiome are discussed in detail. To sum up, this review provides information on the current application and future prospects of ICI biomarkers.
Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes
Authors: Zhao Huan-Huan , Han Qiu-Xia , Ding Xiao-Nan , Yan Jing-Yao , Li Qi , Zhang Dong , Zhu Han-Yu 
Published: September 2020

Abstract
Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.
Population Pharmacokinetics of Voriconazole in Patients With Invasive Aspergillosis: Serum Albumin Level as a Novel Marker for Clearance and Dosage Optimization
Authors: Chantharit Prawat , Tantasawat Montira , Kasai Hidefumi , Tanigawara Yusuke 
Published: September 2020

Background:
Voriconazole (VRCZ) is an antifungal triazole recommended as an effective first-line agent for treating invasive aspergillosis.

Objectives:
To develop a population pharmacokinetic model of VRCZ and trough concentration-based dosing simulation for dynamic patient conditions.

Methods:
The authors combined plasma VRCZ data from intensive sampling, and retrospective trough concentration monitoring for analysis. Nonlinear mixed-effects modeling with subsequent model validation was performed. The recommended dosage regimens were simulated based on the developed model.

Results:
The study participants included 106 patients taking oral VRCZ. A linear one-compartment model with first-order elimination and absorption best described the observed data. The CYP2C19 phenotypes did not influence the pharmacokinetic parameters. Serum albumin (SA) levels and gamma-glutamyl transferase significantly correlated with the VRCZ clearance rate, whereas the actual body weight influenced the volume. A visual predictive check showed good consistency with the observed data, whereas SA levels across the treatment course correlated with linear clearance, irrespective of the CYP2C19 phenotype. Patients with SA levels ≤30 g/L had lower linear clearance than that in patients with SA levels >30 g/L. Dosing simulation based on the developed model indicated that patients with SA levels of ≤30 g/L required a lower daily maintenance dose to attain the therapeutic trough level.

Conclusions:
SA level was identified as a novel marker associated with VRCZ clearance. This marker may be a practical choice for physicians to perform therapeutic drug monitoring and optimize VRCZ dosage.
Population Pharmacokinetic Modeling of Vancomycin in Thai Patients With Heterogeneous and Unstable Renal Function
Authors: Jaisue Siriluk , Pongsakul Cholatip , D'Argenio David Z. , Sermsappasuk Pakawadee 
Published: September 2020

Background:
Vancomycin is widely used to treat gram-positive bacterial infections. However, given significant interpatient variability in its pharmacokinetics, maintaining plasma concentrations is difficult within its characteristically narrow therapeutic window. This is especially challenging in patients with unstable renal function. Thus, the aim of this study was to develop a population pharmacokinetic model for vancomycin that is suitable for Thai patients with variable renal functions, including those with unstable renal function.

Methods:
Data from 213 patients, including 564 blood samples, were retrospectively collected; approximately 70% patients exhibited unstable renal function during vancomycin treatment. The model building group was randomly assigned 108 patients and the remaining 33 patients comprised the validation group. A population pharmacokinetic model was developed that incorporated drug clearance (CL) as a function of time-varying creatine clearance (CrCL). The predictive ability of the resulting population model was evaluated using the validation data set, including its ability to forecast serum concentrations within a Bayesian feedback algorithm.

Results:
A 2-compartment model with drug CL values that changed with time-varying CrCL adequately described vancomycin pharmacokinetics in the evaluated heterogeneous patient population with unstable renal function. Vancomycin CL was related to time-varying CrCL as follows: CL (t) = 0.11 + 0.021 × CrCL (t) (CrCL <120 mL/min. Using the population model, Bayesian estimation with at least one measured serum concentration resulted in a forecasting error of small bias (−2.4%) and adequate precision (31.5%).

Conclusions:
In hospitals with a high incidence of unstable renal function, incorporating time-varying CrCL with Bayesian estimation and at least one measured drug concentration, along with frequent CrCL monitoring, improves the predictive performance of therapeutic drug monitoring of vancomycin.
Dried Plasma Spots and Oral Fluid as Alternative Matrices for Therapeutic Drug Monitoring of Busulfan: Analytical Method Development and Clinical Evaluation
Authors: Granzotto Fabiana C. N. , da Silva Anne C. C. , Lizot Lilian F. , Antunes Marina V. , Linden Rafael 
Published: September 2020

Background:
Busulfan (BU) is an alkylating agent with a narrow therapeutic index and high intraindividual pharmacokinetic variability used in conditioning therapy for hematopoietic stem cell transplantation. Monitoring BU exposure during high-dose conditioning regimens is recommended and positively impacts outcomes. We aimed to develop, validate, and apply a ultra–high-performance liquid chromatography–mass spectrometry (MS)/MS assay to measure BU concentrations in oral fluid and dried plasma spots (DPS) as alternative matrices to plasma.

Methods:
We prepared plasma and oral fluid samples by protein precipitation and DPS after liquid extraction. We analyzed extracts using an LC-MS/MS system with an Acquity HSS T3 column in the positive electrospray ionization mode. The method was validated and applied to 79 paired plasma and oral fluid samples from 7 patients on BU conditioning treatment. DPS were prepared by pipetting plasma onto Whatman 903 paper. The correlation between BU in plasma, oral fluid, and DPS samples was evaluated.

Results:
Run time was 4.0 minutes. The assay was linear at 50–5000 ng mL−1 (r > 0.99), precise (1.9%–5.3% oral fluid and 1.8%–5.9% DPS), and accurate (98.1%–108.9% oral fluid and 93%–103.1% DPS). BU was stable in DPS at 23°C for 24 hours. BU levels in oral fluid (r = 0.927) and DPS (r = 0.982) were significantly correlated with plasma. Despite the good correlation, we found a wide variation between oral fluid and plasma levels. The area under curves (AUCs) calculated with oral fluid concentrations were 79.1%–167.1% of plasma AUCs. Bland–Altman plots found a better agreement for DPS, with AUCs estimated from corrected DPS levels at 83.1%–114.1% of plasma values.

Conclusions:
We developed and validated a simple and fast ultra–high-performance liquid chromatography–MS/MS assay to measure BU in oral fluid and DPS. The results do not support the use of oral fluid as a matrix for routine therapeutic drug monitoring of BU. The AUC estimated from BU measurements in DPS was comparable to that in plasma, supporting the use of DPS in BU therapeutic drug monitoring as an alternative matrix, with adequate short-term stability and logistic advantages.
Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Quantitation of Total and Free Aprepitant and Its Active N-Dealkylated Metabolites in Human Plasma
Authors: Naito Takafumi , Suzuki Yusuke , Shibata Kaito , Kawakami Junichi 
Published: September 2020

Background:
Aprepitant, an antiemetic selective neurokinin-1 receptor antagonist, is primarily metabolized to the active N-dealkylated form (ND-AP) and then converted to its carbonyl form (ND-CAP) in humans. This study developed a simple liquid chromatography–tandem mass spectrometry method using electrospray ionization for the quantitation of plasma total and free aprepitant and its N-dealkylated metabolites and used them to analyze patient plasma.

Methods:
Free aprepitant and ND-AP in plasma were fractionated using centrifugal ultrafiltration. The analytes in plasma or their ultrafiltered specimens treated with triethylamine/acetonitrile were isocratically separated using a 3-μm octadecylsilyl column with a total run time of 10 minutes and scanned using positive ion electrospray ionization.

Results:
The calibration curves of total aprepitant, ND-AP, and ND-CAP were prepared at concentration ranges of 50–2500, 20–1000, and 5–250 ng/mL, respectively, whereas that of free aprepitant and ND-AP were at a concentration range of 2–150 ng/mL. The intraassay and interassay accuracy and imprecision values were 93.5%–107.7% and 94.6%–103.3%, and 2.1%–7.5% and 1.0%–8.9%, respectively. Aprepitant and its metabolites did not exhibit any matrix effects or instabilities in the plasma specimens. In cancer patients receiving oral aprepitant, the plasma concentration ranges of total aprepitant, ND-AP, and ND-CAP, and free aprepitant and ND-AP were 137–2170, 104–928, 22.4–97.6, 8.11–60.0, and 3.53–56.0 ng/mL, respectively. The median plasma free fraction proportion of aprepitant and ND-AP was 4.14% and 4.90%, respectively.

Conclusions:
The present developed method showed an acceptable analytical performance and can be used to evaluate total and free aprepitant and its N-dealkylated metabolites in patient plasma.
lncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer
Authors: Si Lihui , Chen Jun , Yang Shuli , Liu Ziwei , Chen Yuying , Peng Minhua , Jia Yan 
Published: September 2020

Abstract

Objective:
Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown.

Methods:
Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, β-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ± standard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant.

Results:
Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05).

Conclusions:
In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.
Fat‐soluble Vitamin Deficiency is Common in Children With Chronic Pancreatitis Undergoing Total Pancreatectomy With Islet Autotransplantation
Authors: McEachron Kendall R. , Downs Elissa M. , Schwarzenberg Sarah J. , Chinnakotla Srinath , Bellin Melena D. 
Published: September 2020

ABSTRACTThe prevalence of fat‐soluble vitamin (FSV) deficiency in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis (CP) is unknown. We quantified FSV deficiency in 100 children (age ≤18) undergoing TPIAT. FSV levels (vitamins A, E, D) and clinical history were abstracted from medical records. Vitamin A was low in 4% before and 7% at 1 year after TPIAT, vitamin E in 17% and 18%, and vitamin D in 22% and 24%, respectively, regardless of pancreatic enzyme or vitamin supplement dosing. Longer duration of CP was associated with pre‐TPIAT vitamin D insufficiency (P = 0.0002). This remained significant in a multivariate regression model (adjusted P = 0.01). On multivariate analysis, there were no significant predictors of low FSV levels post‐TPIAT. FSV deficiencies are common among children undergoing TPIAT and patients who have had longer disease duration may be at increased risk. All children should be monitored for FSV deficiency after TPIAT.
Babies in Occiput Posterior Position Are Significantly More Likely to Require an Emergency Cesarean Birth Compared With Babies in Occiput Transverse Position in the Second Stage of Labor: A Prospective Observational Study
Authors: Tempest Nicola , Lane Steven , Hapangama Dharani 
Published: September 2020

(Abstracted from Acta Obstet Gynecol Scand 2020;99:537–545)
A fetus in the occiput posterior (OP) or occiput transverse (OT) position at delivery increases the risk for cesarean delivery up to 6-fold and instrumental delivery by up to 4-fold. Although there are a number of methods to assist with the delivery of the fetus in these malpositions, limited data are available on the rates of obstetric intervention in this patient population and the subsequent neonatal and maternal outcomes.