bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer
Authors: Miyashita Hirotaka , Mikami Takahisa , Satoi Sera , Cruz Christina , Galsky Matthew D.
Published: September 2020

Colitis is a major immune-related adverse event associated with programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, but the risk of colitis with PD-1 versus PD-L1 inhibitors is not well characterized. We performed a meta-analysis for the incidence of all grade and grade 3–4 colitis with PD-1 inhibitor (nivolumab, pembrolizumab, and cemiplimab) or PD-L1 inhibitor (atezolizumab, avelumab, and durvalumab) monotherapy using a fixed effects model. We also conducted subgroup meta-analyses of non–small cell lung cancer (NSCLC) or urothelial carcinoma (UC) trials, and a network meta-analysis of randomized trials comparing PD-1 or PD-L1 inhibitors with docetaxel for NSCLC. We also analyzed the Food and Drug Administration Adverse Event Reporting System database to estimate the reporting odds ratio of each medication. PD-1 inhibitors were associated with a higher incidence of all grade and grade 3–4 colitis compared with PD-L1 inhibitors in the analysis of all cancer types [1.49% vs. 0.83%, relative risk; 1.80, 95% confidence interval (CI); 1.22–2.67 for all grade colitis, and 0.85% vs. 0.34%, relative risk; 2.52, 95% CI; 1.46–4.37 for grade 3–4 colitis]. The meta-analyses of NSCLC and UC trials, and the network meta-analysis of NSCLC trials were also suggestive of a higher risk of colitis with PD-1 versus PD-L1 inhibitors. The reporting odds ratio of colitis with PD-1 versus PD-L1 inhibitors was 1.80 (95% CI; 1.53–2.14). In this meta-analysis of clinical trials exploring PD-1 and PD-L1 inhibitors in solid tumors, PD-1 inhibitors were associated with a higher risk of colitis.
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

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

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

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

The 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.
The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes and New Entities
Authors: Choi Joon Hyuk , Ro Jae Y.
Published: September 2020

Soft tissue tumors are a relatively rare and diagnostically challenging group of neoplasms that can have varying lines of differentiation. Accurate diagnosis is important for appropriate treatment and prognostication. In the 8 years since the publication of the 4th Edition of World Health Organization (WHO) classification of soft tissue tumors, significant advances have been made in our understanding of soft tissue tumor molecular biology and diagnostic criteria. The 5th Edition of the 2020 WHO classification of tumors of soft tissue and bone incorporated these changes. Classification of tumors, in general, but particularly in soft tissue tumors, is increasingly based on the molecular characteristics of tumor types. Understanding tumor molecular genetics improves diagnostic accuracy for tumors that have been difficult to classify on the basis of morphology alone, or that have overlapping morphologic features. In many large hospitals in the United States and Europe, molecular tests on soft tissue tumors are a routine part of diagnosis. Therefore, surgical pathologists should be familiar with newly emerging molecular genetic techniques in clinical settings. In the near future, molecular tests, particularly in soft tissue tumor diagnosis, will become as routine during diagnosis as immunohistochemistry is currently. This new edition provides an updated classification scheme and essential diagnostic criteria for soft tissue tumors. Newly recognized entities and subtypes of existing tumor types, several reclassified tumors, and newly defined molecular and genetic data have been incorporated. Herein, we summarize the updates in the WHO 5th Edition, focusing on major changes in each category of soft tissue tumor, and the newly described tumor entities and subtypes.
Clear Cell Adenocarcinoma in Men
Authors: Grosser Daniel , Matoso Andres , Epstein Jonathan I.
Published: September 2020

Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The mean time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle.
Community Care Facility—A Novel Concept to Deal With the COVID-19 Pandemic: A Singaporean Institutionʼs Experience
Authors: Goei Anne
Published: September 2020

Context:

The coronavirus disease 2019 (COVID-19) pandemic has placed a strain on health care systems worldwide. Many hospitals experienced severe bed shortages; some had to turn patients away. In Singapore, the widespread outbreak, especially among the dormitory-based population, created a pressing need for alternative care sites.

Program:

The first massive-scale community care facility (CCF) was started in Singapore to address the pandemic. It served as a low-acuity primary care center that could isolate and treat COVID-19–positive patients with mild disease. This allowed decompression of the patient load in hospitals, ensuring that those with more severe disease could receive timely medical attention.

Implementation:

Various groups from the private and public sectors, including health care, construction, security, hotel management, and project coordination, were involved in the setup and operations of the CCF. A large exhibition center was converted into the care facility and segregated into zones to reduce cross-contamination. State-of-the-art technological infrastructure for health management was used. Several paraclinical services were made available.

Evaluation:

The CCF was a timely and robust response that fulfilled several crucial functions, including cohort isolation, triage, basic medical care, and timely reviews and escalation of patients. It placed a unique focus on promoting patient ownership, responsibility, and mental well-being. It was largely successful, with a low hospital transfer rate of 0.37%.

Discussion:

The success of the CCF could be attributed to the use of a facility of opportunity, strong interorganizational and cross-sector cooperation, an integrated and robust clinical system, and clear communication channels. It allows for efficient resource utilization and is valuable in future pandemics with similar disease characteristics.
Modeling Tissue Expansion with Isogeometric Analysis: Skin Growth and Tissue Level Changes in the Porcine Model
Authors: Janes Lindsay E. , Ledwon Joanna K. , Vaca Elbert E. , Turin Sergey Y. , Lee Taeksang , Tepole Adrian B. , Bae Hanah , Gosain Arun K.
Published: September 2020

Background:

Tissue expansion relies on the ability of skin to grow in response to sustained mechanical strain. This study focuses on correlation of cellular and histologic changes with skin growth and deformation during tissue expansion.

Methods:

Tissue expanders were placed underneath the skin of five Yucatan minipigs and inflated with one fill of 60 cc of saline 1 hour, 24 hours, 3 days, and 7 days before the animals were killed, or two fills of either 30 cc or 60 cc at 10 and 3 days or 14 and 7 days before the animals were killed. Skin biopsy specimens and three-dimensional photographs were used to calculate skin growth and stretch according to the authors’ novel finite element analysis model.

Results:

The mitotic index of keratinocytes in the basal layer increased 1 hour after stimulus was applied (4 percent) (p = 0.022), peaked at approximately day 3 (26 percent) (p < 0.0001), and tapered by day 7 (12.5 percent) (p = 0.012) after tissue expansion. The authors demonstrated that it is the volume per fill rather than the total volume in the expander that scales the magnitude of response. Lastly, the authors demonstrated that the ratio of deformation attributable to growth versus stretch (Fgrowth/Fstretch) after 60 cc of tissue expansion fill was 1.03 at 1 hour, 0.82 at 1 day, 0.85 at day 3, and 0.95 at 7 days.

Conclusions:

Peak cell proliferation occurred 3 days after tissue expansion fill and is scaled in response to stimulus magnitude. The growth component of deformation equilibrates to the stretch component at day 7, as cell proliferation has started to translate to skin growth.
Ambulatory Access: Improving Scheduling Increases Patient Satisfaction and Revenue
Authors: Volk Angela S. , Davis Matthew J. , Abu-Ghname Amjed , Warfield Rachel G. , Ibrahim Ramzey , Karon Grace , Hollier Larry H.
Published: September 2020

Background:

Even before seeing a physician, patients must first gain access to the hospital system. At large hospitals with high patient volumes, access to specialty care can pose a particular challenge. This study examines the effects of specific initiatives to increase clinic capacity, appointment use, and ease of scheduling on both patient satisfaction and hospital revenue.

Methods:

In 2017, a task force at a large, multidisciplinary pediatric hospital instituted a number of initiatives to increase patient access to ambulatory specialty clinics. Clinic sessions were standardized to a 4-hour template, and unscheduled, “held” appointment slots were required to be made available (“flipped”) 72 hours before the appointment. A patient-centered electronic scheduling platform was also implemented. Patient satisfaction was assessed using Press Ganey scores. Revenue estimates were calculated for increases in “new” and “return” patient appointments.

Results:

Total new appointment slots increased by over 44 percent, with over 53,000 appointments added annually. The number of held appointment slots declined by 93 percent. A total of 17,996 annual appointments were added in surgical subspecialties, and an additional 14,756 more surgical appointments were completed. Over 2000 appointments were scheduled by means of the online patient portal. Press Ganey “ease-of-scheduling” scores increased from 57 percent to 72 percent over the intervention period. Hospitalwide, these initiatives generated an estimated $8.3 million in revenue opportunity.

Conclusion:

Standardizing clinic sessions and optimizing clinic availability generates new appointment opportunities, improves patient experience, and increases hospital revenue.
Radiologic Manifestations of Pulmonary Vein Ablation Complications: A Pictorial Review
Authors: Saad Hannan , Myers Daniel T. , Song Thomas K. , Nadig Jeffrey
Published: September 2020

In patients with atrial fibrillation refractory to drug therapy and cardioversion, pulmonary vein ablation is an alternative treatment that eradicates arrhythmogenic activity originating in the muscles of the pulmonary veins. While this procedure has a low incidence of significant complications, iatrogenic injuries are possible. Through multimodality pictorial examples utilizing computed tomography, nuclear medicine, fluoroscopy, and chest radiographs, the complications associated with pulmonary vein ablation will be reviewed. Examples of pulmonary vein stenosis, right phrenic nerve injury with associated diaphragmatic paralysis, atrioesophageal fistula, and pericardioesophageal fistula will be illustrated.
Exercise and the Risk of Mild Cognitive Impairment
Authors: Hughes Tiffany F. , Liu Anran , Jacobsen Erin , Rosano Caterina , Berman Sarah B. , Chang Chung-Chou H. , Ganguli Mary
Published: September 2020

Introduction:

Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors.

Methods:

In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics.

Results:

Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors.

Conclusions:

Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.
Androgen Deprivation Therapy Use and Risk of Mild Cognitive Impairment in Prostate Cancer Patients
Authors: Alonso-Quiñones Hector , Stish Bradley J. , Aakre Jeremiah A. , Hagen Clinton E. , Petersen Ronald C. , Mielke Michelle M.
Published: September 2020

Introduction:

We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients.

Methods:

We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted. Follow-up visits occurred every 15 months and MCI diagnoses were made based on clinical consensus. Cox proportional hazards models, with age as the timescale, were used to examine the association between ADT use (yes/no) and length of exposure with the risk of MCI adjusting for education, apolipoprotein E, depression, and the Charlson Index score.

Results:

There was no association between any ADT use (27.8% of participants) and the risk of MCI in the multivariable model [hazard ratio (HR), 1.25; 95% confidence interval (CI), 0.75-2.10]. Although not significant, there was an ADT dose-response relationship for risk of MCI: <5 years versus no use (HR, 1.08; 95% CI, 0.60-1.96) and ≥5 years versus not use (HR, 1.89; 95% CI, 0.83-4.27).

Conclusion:

ADT use among prostate cancer patients was not associated with an increased risk of developing MCI.
Telehealth, Telemedicine, and Related Technologic Platforms
Authors: Mahoney Mary F.
Published: September 2020

BACKGROUND:

Providing health care at a distance has evolved over the past decades, resulting in a myriad of terms and styles of care delivery. Telehealth is defined as any health care service delivered at a distance. Nursing services have been delivered by a wide range of specialty nurses for many years using various technological formats. Clinical experience suggests that few WOC nurses had extensively adopted these technologies and principles into their practice as recently as 2019. However, the COVID-19 pandemic of 2020 has forced both administrators and clinicians to rapidly adapt or introduce telemedicine technologies to deliver specialty care including WOC nurse services.

CASES:

Three WOC nurses were chosen to describe the use of telehealth technologies to illustrate opportunities for WOC nurses to integrate telehealth nursing into a health care setting. Two adapted telehealth technology into their practice before the pandemic, and one started telehealth practice as a means to provide care after the onset of the pandemic. Disadvantages and advantages are discussed to provide further information regarding WOC patient care using these technologies.

CONCLUSION:

The pandemic crisis has accelerated the need for health care to reimagine the delivery of care to patients. Telehealth technologies and principles have emerged as essential for WOC nurses to deliver safe and effective care.
Generational shift in the migratory common noctule bat: first-year males lead the way to hibernacula at higher latitudes
Authors: Kravchenko K. A. , Vlaschenko A. S. , Lehnert L. S. , Courtiol A. , Voigt C.C.
Published: September 2020

Many migratory species have shifted their geographic distribution in response to climate change, yet the underlying mechanisms are poorly understood, particularly for mammals. We hypothesized that generational shifts are underlying the observed colonization of hibernation sites further north in a migratory bat, the common noctule (
Nyctalus noctula)
. To evaluate our hypothesis, we collected long-term data on the migratory status and demography of common noctules in a recently colonized hibernation area. Based on isotopic data of 413 individuals, we observed a significant decline in the proportion of long-distance migrants from 2004 to 2015 for both sexes and across all age groups. Demographic data collected between 2007 and 2016 from 3394 individuals demonstrated that subadult males were more abundant during the early colonization stage, followed by a gradual shift to a more balanced age and sex composition. Our results suggest that the colonization of hibernacula at higher latitudes is promoted by generational shifts, involving mostly first-year males. Generational shifts seem to be a likely mechanism for distribution changes in other bats and potentially also in other mammals.
Vape flavourants dull sensory perception and cause hyperactivity in developing zebrafish embryos
Authors: Gauthier Patrick T. , Holloway Alison C. , Vijayan Mathilakath M.
Published: September 2020

E-cigarette use (vaping) during pregnancy has been increasing, and the potential exists for the developing brainin uteroto be exposed to chemical constituents in the vape. Vapes come in over 7000 unique flavours with and without nicotine, and while nicotine is a known neurotoxicant, the effects of vape flavouring alone, in the absence of nicotine, on brain function are not well understood. Here, we performed a screen of vape aerosol extracts (VAEs) to determine the potential for prenatal neurotoxicity using the zebrafish embryo photomotor response (PMR)—a translational biosensor of neurobehavioural effects. We screened three commonly used aerosolized vape liquids (flavoured and flavourless) either with or without nicotine. No neurobehavioural effects were detected in flavourless, nicotine-free VAEs, while the addition of nicotine to this VAE dulled sensory perception. Flavoured nicotine-free VAEs also dulled sensory perception and caused hyperactivity in zebrafish embryos. The combination of flavour and nicotine produced largely additive effects. Flavoured VAEs without nicotine had similar neuroactive potency to nicotine. Together, using zebrafish PMR as a high throughput translational behavioural model for prenatal exposure, our results demonstrate that e-cigarette flavourants that we screened elicit neurobehavioural effects worthy of further investigation for long-term neurotoxic potential and also have the potential to modulate nicotine impact on the developing brain.
The link between selection for function and human-directed play behaviour in dogs
Authors: Kolm Niclas , Temrin Hans , Miklósi Ádám , Kubinyi Enikő , Garamszegi László Zsolt
Published: September 2020

Human-directed play behaviour is a distinct behavioural feature of domestic dogs. But the role that artificial selection for contemporary dog breeds has played for human-directed play behaviour remains elusive. Here, we investigate how human-directed play behaviour has evolved in relation to the selection for different functions, considering processes of shared ancestry and gene flow among the different breeds. We use the American Kennel Club (AKC) breed group categorization to reflect the major functional differences and combine this with observational data on human-directed play behaviour for over 132 breeds across 89 352 individuals from the Swedish Dog Mentality Assessment project. Our analyses demonstrate that ancestor dogs already showed intermediate levels of human-directed play behaviour, levels that are shared with several modern breed types. Herding and Sporting breeds display higher levels of human-directed play behaviour, statistically distinguishable from Non-sporting and Toy breeds. Our results suggest that human-directed play behaviour played a role in the early domestication of dogs and that subsequent artificial selection for function has been important for contemporary variation in a behavioural phenotype mediating the social bond with humans.
Treefrogs exploit temporal coherence to form perceptual objects of communication signals
Authors: Gupta Saumya , Bee Mark A.
Published: September 2020

For many animals, navigating their environment requires an ability to organize continuous streams of sensory input into discrete ‘perceptual objects’ that correspond to physical entities in visual and auditory scenes. The human visual and auditory systems follow several Gestalt laws of perceptual organization to bind constituent features into coherent perceptual objects. A largely unexplored question is whether nonhuman animals follow similar Gestalt laws in perceiving behaviourally relevant stimuli, such as communication signals. We used females of Cope's grey treefrog (
Hyla chrysoscelis
) to test the hypothesis that temporal coherence—a powerful Gestalt principle in human auditory scene analysis—promotes perceptual binding in forming auditory objects of species-typical vocalizations. According to the principle of temporal coherence, sound elements that start and stop at the same time or that modulate coherently over time are likely to become bound together into the same auditory object. We found that the natural temporal coherence between two spectral components of advertisement calls promotes their perceptual binding into auditory objects of advertisement calls. Our findings confirm the broad ecological validity of temporal coherence as a Gestalt law of auditory perceptual organization guiding the formation of biologically relevant perceptual objects in animal behaviour.
Spatio-temporal reconstruction of emergent flash synchronization in firefly swarms via stereoscopic 360-degree cameras
Authors: Sarfati Raphaël , Hayes Julie C. , Sarfati Élie , Peleg Orit
Published: September 2020

During mating season, males of synchronous firefly species flash in unison within swarms of thousands of individuals. These strongly correlated collective displays have inspired numerous mathematical models to explain how global synchronous patterns emerge from local interactions. Yet, experimental data to validate these models remain sparse. To address this gap, we develop a method for three-dimensional tracking of firefly flashes, using a stereoscopic set-up of 360-degree cameras. We apply this method to record flashing displays of the North American synchronous speciesPhotinus carolinusin its natural habitat as well as within controlled environments, and obtain the three-dimensional reconstruction of flash occurrences in the swarm. Our results show that even a small number of interacting males synchronize their flashes; however, periodic flash bursts only occur in groups larger than 15 males. Moreover, flash occurrences are correlated over several metres, indicating long-range interactions. While this suggests emergent collective behaviour and cooperation, we identify distinct individual trajectories that hint at additional competitive mechanisms. These reveal possible behavioural differentiation with early flashers being more mobile and flashing longer than late followers. Our experimental technique is inexpensive and easily implemented. It is extensible to tracking light communication in various firefly species and flight trajectories in other insect swarms.
Exact solutions of the harmonic oscillator plus non-polynomial interaction
Authors: Dong Qian , Iván García Hernández H. , Sun Guo-Hua , Toutounji Mohamad , Dong Shi-Hai
Published: September 2020

The exact solutions to a one-dimensional harmonic oscillator plus a non-polynomial interactiona x2 + b x2/(1 + c x2) (a > 0,c > 0) are given by the confluent Heun functionsHc(α,β,γ,δ,η;z). The minimum value of the potential well is calculated asVmin(x)=−(a+|b|−2a |b|)/catx=±[(|b|/a−1)/c]1/2(|b| > a) for the double-well case (b < 0). We illustrate the wave functions through varying the potential parametersa,b,cand show that they are pulled back to the origin when the potential parameterbincreases for given values ofaandc. However, we find that the wave peaks are concave to the origin as the parameter |b| is increased.
Proposal of Bifidobacterium saeculare Biavati et al. 1992 as a later heterotypic synonym of Bifidobacterium gallinarum Watabe et al. 1983 and Bifidobacterium gallinarum subsp. saeculare subsp. nov.
Authors: Liu Dan Dan , Wang Hao , Gu Chun Tao
Published: September 2020

In 2018, Nouioui et al. transferred

Bifidobacterium gallinarum

and

Bifidobacterium saeculare

to

Bifidobacterium pullorum

as

B. pullorum

subsp.

gallinarum

and

B. pullorum

subsp.

saeculare

on the basis of digital DNA–DNA hybridization (dDDH) values. These two new subspecies were validated in the same year. However, we found that the genome (GenBank/ENA/DDBJ accession number JGZJ01000000) of

B. pullorum

used by Nouioui et al. in the dDDH analysis cannot represent

B. pullorum

. So, the taxonomic relationship between

B. gallinarum

,

B. saeculare

and

B. pullorum

should be re-examined.

B. pullorum

DSM 20433T had 88.7–89.0 % average nucleotide identity (ANI) values and 37.5–38.0 % dDDH values to the type strains of

B. gallinarum

and

B. saeculare

, respectively, less than the threshold for species demarcation, confirming that

B. pullorum

represents a different species from

B. gallinarum

and

B. saeculare

. The ANI values and dDDH values between the type strains of

B. gallinarum

and

B. saeculare

were 96.7–96.9 % and 73.0–73.3 %, respectively, greater than the threshold for species demarcation, confirming that they represent the same species. Relatively low dDDH values (less than the 79–80 % threshold for subspecies demarcation) between the type strains of

B. gallinarum

and

B. saeculare

indicated that

B. saeculare

can be considered as a subspecies of

B. gallinarum

. On the basis of the results presented here, (i)

B. gallinarum

and

B. saeculare

should not be transferred to

B. pullorum

; (ii) we propose

B. saeculare

Biavati et al. 1992 as a later heterotypic synonym of

B. gallinarum

Watabe et al. 1983 and as a new subspecies of

B. gallinarum

, for which the name

B. gallinarum

subsp. saeculare subsp. nov. is proposed.