bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence of FOX AmpC gene among Pseudomonas aeruginosa isolates in abattoir samples from south-eastern Nigeria
Authors: Ejikeugwu Chika , Hasson Shaimaa O. , Al-Mosawi Reham M. , Alkhudhairy Miaad K. , Saki Morteza , Ezeador Chika , Eze Peter , Ugwu Malachy , Duru Carissa , Ujam Nonye Treasure , Edeh Chijioke , Udu-Ibiam Onyinyechi , Iroha Ifeanyichukwu , Michael Adikwu
Published: January 2020

In Nigeria, several investigations have been done about the prevalence of the AmpC enzyme in clinical isolates of Gram-negative bacteria; however, little information is available on the occurrence rate of this important enzyme in abattoir specimens that play a major role in the environmental pollution in Nigeria. This study aimed to evaluate the presence of FOX AmpC-producing Pseudomonas aeruginosa isolates from abattoir samples by both phenotypic method and polymerase chain reaction (PCR). In this study, 360 abattoir samples were analyzed for the isolation of P. aeruginosa strains. Antibiogram was carried out using the disk diffusion technique. The production of AmpC enzymes was phenotypically screened and confirmed using the cefoxitin--cloxacillin double-disk synergy test (CC-DDST). Finally, gene responsible for FOX AmpC enzyme production was investigated using PCR. A total of 147 (40.8%) isolates of P. aeruginosa was recovered from the abattoir samples. Ceftazidime and ciprofloxacin with 45.6 and 19% of susceptibility rates were the most and the less effective antibiotics, respectively. A total of 24 (16.3%) P. aeruginosa isolates were confirmed to phenotypically produce AmpC enzyme. However, the PCR result showed that only three (12.5%) of P. aeruginosa isolates harbored the FOX AmpC gene suggesting the attendance of other AmpC resistance genes. This study reported the first occurrence of P. aeruginosa isolates harboring the FOX AmpC gene in abattoir samples from south-eastern Nigeria. This incident requires the adoption of new policies and measures to prevent the further spread of strains carrying the AmpC gene.
Brief Report: Linking Depressive Symptoms to Viral Nonsuppression Among Women With HIV Through Adherence Self-Efficacy and ART Adherence
Authors: Crockett Kaylee B. , Entler Kristin J. , Brodie Emilee , Kempf Mirjam-Colette , Konkle-Parker Deborah , Wilson Tracey E. , Tien Phyllis C. , Wingood Gina , Neilands Torsten B. , Johnson Mallory O. , Weiser Sheri D. , Turan Janet M. , Turan Bulent
Published: January 2020

Background:

Depression plays a key role in suboptimal HIV outcomes, possibly mediated by adherence self-efficacy beliefs and antiretroviral treatment (ART) adherence behavior. Applying social-cognitive theory, we examined a longitudinal sequential path model of the association between depressive symptoms and viral nonsuppression in women with HIV (WWH) through these mediating mechanisms.

Methods:

This was an observational longitudinal study using data from the Women's Adherence and Visit Engagement substudy of the Women's Interagency HIV Study. WWH (N = 375) completed measures of depressive symptoms, adherence self-efficacy, and ART adherence. Viral load was measured through blood draw. We examined a longitudinal sequential path model spanning 3 time points at least 6 months apart between 2015 and 2017. Indirect effects were assessed of depressive symptoms at time 1 (T1) on viral nonsuppression at T3 through adherence self-efficacy at T2 and ART adherence at T3. Covariates included age, income, recreational drug use, race, and months on ART.

Results:

Depressive symptoms were associated with subsequent viral nonsuppression through its association with adherence self-efficacy and ART adherence [indirect effect: adjusted odds ratio = 1.004, 95% confidence interval: (1.001 to 1.008)]. Months on ART and recreational drug use were also significantly associated with viral nonsuppression at T3.

Conclusions:

Our findings support depressive symptoms' association with adherence self-efficacy that in turn lead to suboptimal ART adherence and ultimately to viral nonsuppression for WWH. Tailoring of interventions aimed at addressing depressive symptoms, substance use, and adherence self-efficacy among WWH is needed to help close the gap between ART prescription and viral suppression on the HIV care continuum.
Point-of-Care Ultrasound Predictors for the Diagnosis of Tuberculosis in HIV-Positive Patients Presenting to an Emergency Center
Authors: Van Hoving Daniël Jacobus , Kenge Andre P. , Maartens Gary , Meintjes Graeme
Published: January 2020

Background:

The performance of point-of-care ultrasound (PoCUS) to diagnose HIV-associated tuberculosis has not been evaluated in large prospective studies. We determined the diagnostic accuracy of individual PoCUS features, performed an external validation of the focused assessment with sonography for HIV/TB (FASH) protocol, and determined independent PoCUS predictors of HIV-associated tuberculosis appropriate for use by emergency center practitioners.

Setting:

A cross-sectional diagnostic study was performed at the emergency center of Khayelitsha Hospital (Cape Town, South Africa).

Methods:

HIV-positive adults with the suspicion of having tuberculosis were prospectively enrolled. PoCUS was performed according to a standardized protocol. Reference standard was the detection of Mycobacterium tuberculosis using Xpert MTB/RIF or culture.

Results:

We enrolled 414 participants: 243 female, median age 36 years, median CD4 cell count 86/mm3, and 172 (42%) had tuberculosis. Sensitivity and specificity were ≥1 individual PoCUS feature [73% (95% CI: 65 to 79), 54% (95% CI: 47 to 60)], FASH protocol [71% (95% CI: 64 to 78), 57% (95% CI: 50 to 63)]. Independent PoCUS predictors identified were intra-abdominal lymphadenopathy of any size (aDOR 3.7 (95% CI: 2.0 to 6.7)], ascites [aDOR 3.0 (95% CI: 1.5 to 5.7)], and pericardial effusion of any size [aDOR 1.9 (95% CI: 1.2 to 3.0)]. The c-statistic for the derivation model was 0.680 (95% CI: 0.631 to 0.729), compared with 0.630 (95% CI: 0.576 to 0.684) of the FASH protocol. Two or more independent PoCUS predictors had 91% (95% CI: 86 to 94) specificity.

Conclusion:

The presence of 2 or more independent PoCUS predictors (intra-abdominal lymphadenopathy, ascites, and pericardial effusion) had moderate discrimination for HIV-associated tuberculosis in patients presenting to the emergency center.
Higher Acuity Resource Utilization With Older Age and Poorer HIV Control in Adolescents and Young Adults in the HIV Research Network
Authors: Neilan Anne M. , Lu Frances , Gebo Kelly A. , Diaz-Reyes Rebeca , Huang Mingshu , Parker Robert A. , Karalius Brad , Patel Kunjal , Voss Cindy , Ciaranello Andrea L. , Agwu Allison L.
Published: January 2020

Background:

Adolescents and young adults (AYA) with HIV experience poorer health outcomes compared with adults. To improve care for AYA with HIV, information about patterns of costly health care resource utilization is needed.

Methods:

Among 13–30 year olds in the US HIV Research Network, we stratified outpatient visits, emergency department (ED) visits, and inpatient days/person-year (PY) by HIV acquisition model [perinatal (PHIVY) and nonperinatal (NPHIVY)], age (13–17, 18–23, and 24–30 years), CD4 strata (<200, 200–499, and ≥500 cells/µL), and viral load (VL) suppression (<, ≥400 copies/mL [c/mL]) combined with antiretroviral (ARV) use.

Results:

Among 4540 AYA (PHIVY: 15%; NPHIVY: 85%), mean follow-up was 2.8 years. Among PHIVY, most person-time (PT) was spent between ages 13 and 23 years (13–17 years: 43%; 18–23 years: 45%), CD4 ≥500/µL (61%), and VL <400 c/mL (69%). Among NPHIVY, most PT was spent between ages 24 and 30 years (56%), with CD4 ≥500/µL (54%), and with VL <400 c/mL (67%). PT spent while prescribed ARVs and with VL ≥400 c/mL was 29% (PHIVY) and 24% (NPHIVY). For PHIVY and NPHIVY, outpatient visit rates were higher at younger ages (13–17 years and 18–23 years), lower CD4 (<200 and 200–499/µL), and among those prescribed ARVs. Rates of ED visits and inpatient days were higher during PT spent at older ages (18–23 years and 24–30 years), lower CD4 (<200 and 200–499/µL), and VL ≥400 c/mL. Utilization was higher among PHIVY than NPHIVY (outpatient: 12.1 vs. 6.0/PY; ED: 0.4 vs. 0.3/PY; inpatient: 1.5 vs. 0.8/PY).

Conclusions:

More ED visits and inpatient days were observed during time spent at older ages, lower CD4 count, and VL ≥400 c/mL. Interventions to improve virologic suppression and immune response may improve outcomes, and thus decrease costly resource utilization, for AYA with HIV.
A Classifier to Predict Viral Control After Antiretroviral Treatment Interruption in Chronic HIV-1–Infected Patients
Authors: Fehér Csaba , Plana Montserrat , Crespo Guardo Alberto , Climent Nuria , Leal Lorna , Ugarte Ainoa , Fernández Irene , Etcheverry María F. , Gatell Josep M. , Sánchez-Palomino Sonsoles , García Felipe , Aloy Patrick
Published: January 2020

Objectives:

To construct a classifier that predicts the probability of viral control after analytical treatment interruptions (ATI) in HIV research trials.

Methods:

Participants of a dendritic cell–based therapeutic vaccine trial (DCV2) constituted the derivation cohort. One of the primary endpoints of DCV2 was the drop of viral load (VL) set point after 12 weeks of ATI (delta VL12). We classified cases as “controllers” (delta VL12 > 1 log10 copies/mL, n = 12) or “noncontrollers” (delta VL12 < 0.5 log10 copies/mL, n = 10) and compared 190 variables (clinical data, lymphocyte subsets, inflammatory markers, viral reservoir, ELISPOT, and lymphoproliferative responses) between the 2 groups. Naive Bayes classifiers were built from combinations of significant variables. The best model was subsequently validated on an independent cohort.

Results:

Controllers had significantly higher pre–antiretroviral treatment VL [110,250 (IQR 71,968–275,750) vs. 28,600 (IQR 18737–39365) copies/mL, P = 0.003] and significantly lower proportion of some T-lymphocyte subsets than noncontrollers: prevaccination CD4+CD45RA+RO+ (1.72% vs. 7.47%, P = 0.036), CD8+CD45RA+RO+ (7.92% vs. 15.69%, P = 0.017), CD4+CCR5+ (4.25% vs. 7.40%, P = 0.011), and CD8+CCR5+ (14.53% vs. 27.30%, P = 0.043), and postvaccination CD4+CXCR4+ (12.44% vs. 22.80%, P = 0.021). The classifier based on pre–antiretroviral treatment VL and prevaccine CD8+CD45RA+RO+ T cells was the best predictive model (overall accuracy: 91%). In an independent validation cohort of 107 ATI episodes, the model correctly identified nonresponders (negative predictive value = 94%), while it failed to identify responders (positive predictive value = 20%).

Conclusions:

Our simple classifier could correctly classify those patients with low probability of control of VL after ATI. These data could be helpful for HIV research trial design.
Immediate Reconstruction After Colorectal Cancer Resection
Authors: Crystal Dustin T. , Zwierstra Myrthe J. , Blankensteijn Louise L. , Ibrahim Ahmed M. S. , Sieber Brady A. , Lee Bernard T. , Lin Samuel J.
Published: January 2020

Background

Colorectal cancer is one of the most common and fatal malignancies in the United States. When localized to the distal gastrointestinal tract, surgical therapy includes abdominoperineal resection (APR) or pelvic exenteration (PEX). Subsequent ablative defects are considerable, impart concerning morbidity, and often necessitate autologous reconstruction. The aim of this study was to assess postoperative outcomes after reconstruction of APR and PEX defects.

Methods

The American College of Surgeons National Surgical Quality Improvement Program (2005–2017) was queried for patients undergoing APR for lower gastrointestinal malignancies with concurrent autologous reconstructions. Cases of disseminated cancer were excluded. Postoperative adverse event profiles, including rates of wound and systemic complications, were evaluated. Multivariate regression analysis controlling for age, sex, body mass index, and operative time was performed to calculate adjusted odds ratios (ORs).

Results

A total of 1309 patients were identified as undergoing APR/PEX with concomitant reconstruction. The majority (96.9%) of reconstructions consisted of muscle, myocutaneous, fasciocutaneous, or omental pedicled flaps. Of the cohort, 45.7% experienced at least 1 all-cause complication within 30-days of the procedure. Having a limited or moderate frailty (frailty index of “1” or “2”) was identified as a predictor of all-cause complications [OR, 1.556; 95% confidence interval (CI), 1.187–2.040, P = 0.001; and OR, 1.741; 95% CI, 1.193–2.541, P = 0.004, respectively], whereas smoking was a predictor of wound complications (OR, 1.462; 95% CI, 1.070–1.996, P = 0.017) and steroid use was a predictor of mild systemic complications (OR, 2.006; 95% CI, 1.058–3.805, P = 0.033).

Conclusion

Anorectal cancer resection often necessitates reconstruction secondary to postexenteration perineal defects. The incidence of postoperative complications is relatively high, and several risk factors are identified to help refine patient optimization.
A Comparison of Case Volume in Craniofacial Surgery by Plastic Surgery Residency Training Model
Authors: Silvestre Jason , Doss Linden R. , Hernandez Jade M. , Serletti Joseph M. , Chang Benjamin
Published: January 2020

Background

Plastic surgeons in the United States are trained under 2 residency training models: integrated and independent. This study analyzes the variability of craniofacial surgery cases performed both between and within training models.

Methods

Case volume data from national data reports of 5 plastic surgery resident cohorts were analyzed (2011–2015). Craniofacial surgery case volumes across 4 major categories and 23 subcategories were compared between training models via t tests. Differences in intramodel variability were compared with F tests. Fold differences were calculated between mean case volumes and minimum requirements in craniofacial surgery.

Results

A total of 526 independent/combined (64%) and 292 integrated (36%) plastic surgery residents were included. Integrated residents reported more cases classified as congenital defect (118.8 ± 49.3 vs 110.3 ± 42.9, P = 0.013), neoplasm (202.0 ± 79.7 vs 163.2 ± 60.8, P < 0.001), and trauma (149.0 ± 61.8 vs 127.0 ± 52.0, P < 0.001), but not aesthetic (122.3 ± 68.6 vs 116.5 ± 50.5, P = 0.201). Integrated residents reported more case volume in 12 case subcategories, whereas independent/combined residents reported more cases in 3 case subcategories. Integrated residents had greater intramodel variability in 12 case subcategories, whereas independent/combined residents had greater intramodel variability in 2 case subcategories. Fold differences between mean case volumes and minimum requirements ranged from 1.8 times to 6.0 times.

Conclusions

Integrated residents tended to report significantly more craniofacial surgery cases and exhibit greater intrapathway variability. More research is needed to understand the impact of disparate case volume on core competency training in craniofacial surgery during plastic surgery residency.
Inferiorly Based Preauricular Flap for Anterior Ear Reconstruction
Authors: Sorkin Alex , Heller Lior , Landau Geva , Sherf Matan , Hartstein Morris E. , Hadad Eran
Published: January 2020

Background

The anterior aspect of the auricle is a complex 3-dimensional structure. Each anatomical component in this region has an essential role in the aesthetic appearance of the ear and face. The reconstruction of defects in this region is challenging because of the lack of mobile, excess skin for primary closure, and the inability to skin graft overexposed cartilage.

Objective

The aim of the study was to present the planning and surgical technique of a simple, reproducible, 1-stage flap, for the reconstruction of the anterior aspect of the auricle.

Patients and Methods

A series of 11 patients, who underwent reconstruction of the anterior aspect of the auricle with 1-stage, inferiorly based, preauricular, cutaneous flap. All reconstructions were conducted under local anesthesia, and the defects were mainly due to tumor resections or skin necrosis after otoplasty. The average defect size was 1.5 cm. The flap was applied to different sites of the anterior auricle.

Results

All flaps survived except one, where there was partial flap loss. The aesthetic results were excellent, with no auricular deformity.

Conclusions

The inferiorly based, preauricular flap is a versatile flap for a safe, simple, and reproducible, 1-stage reconstruction for almost every region of anterior ear defect, with excellent aesthetic results.
Mass Spectrometric Characterization of Metabolites in Ear Cartilage
Authors: Yang Jinxiu , He Leren
Published: January 2020

Objective

The aims of the study were to perform mass spectrometric characterization of metabolites in microtic and healthy ear auricular cartilage tissue, to screen the differential metabolites and pathways in these tissues, and to find a connection between the changes in the metabolic pathways and the biochemical properties of the cartilage tissue.

Methods

According to the inclusion criteria, patients with simple microtia admitted to the hospital between June 2017 and January 2018 were selected upon admission. During ear reconstruction surgery, residual auricle cartilage tissues of the patients were harvested as the case group (18 cases), and normal auricle cartilage tissues (18 cases) were taken as the control group. The mass spectrometry technique gas chromatography time-of-flight mass spectrometry and the XploreMET platform were used to identify and characterize the metabolites in the ear cartilage samples. Then, differential metabolites and key pathways were identified and analyzed.

Results

In total, 277 metabolites were detected, but only 132 metabolites were annotated in the JiaLib (one of the largest metabolomics libraries in the world). Of those, 14 differential metabolites and 3 metabolic pathways were identified between microtia and healthy ear cartilage, including the pathways of arginine metabolism, taurine metabolism, and pantothenate and CoA metabolism, P < 0.05.

Conclusions

Arginine, taurine, and l-cysteine may have an association with the development of microtia ear cartilage, and arginine succinate synthase and argininosuccinate lyase may be the key enzyme in microtia. This new direction on microtia can help us understand the pathogenesis of microtia and propose some new ideas for its etiology.
Dermal Autografts in Breast Reconstruction
Authors: Davis Claire , Boyd Carter , Mateo de Acosta Andino David A. , Kumbla Pallavi A. , Sanchez Ruston J. , Kurapati Srikanth , King Timothy W. , de la Torre Jorge I.
Published: January 2020

Breast cancer affects 1 in 8 women. As the treatment of breast cancer evolves, breast reconstruction does as well. Implant-based reconstructions are increasing, leading to increased use of acellular dermal matrix (ADM) for better implant positioning. Acellular dermal matrices are derived from cadaveric skin and are processed to be immunologically inert. However, ADM can be costly and can have complications such as seroma and infection. This has led to the development of dermal autografts. These were first used in postmastectomy breast reconstruction in women with redundant breast skin that was deepithelialized and used for lower pole coverage of tissue expanders and implants. This evolved into harvesting dermal autografts from the abdomen. Later studies evaluated the use of meshed dermal autografts. Histological analysis of ADM versus dermal autografts shows that there are increased vessels within dermal autografts compared with ADM. This potentially contributes to the decreased complication rate seen with autografts. In addition, one study showed equivalent results in aesthetic outcomes and capsular contracture between ADM and dermal autograft. Analysis of cost has shown that ADM is significantly more costly than harvesting a dermal autograft. Physician reimbursement is also higher for dermal autografts. This review article seeks to summarize key studies that highlight the feasibility of using dermal autografts in breast reconstruction.
Versatility of Pedicled Perforator-Based V-Y Advancement Flaps for Reconstruction of the Upper Limb
Authors: Kennedy Anne-Marie , Lloyd Mark Sheldon , Niranjan Niri S.
Published: January 2020

Introduction

The aim of any reconstruction is to provide a robust and cosmetically pleasing result that does not significantly alter function. We describe our experience of using the V-Y principle in advancement flaps designed around a distinct perforator to reconstruct soft tissue defects of the upper limb. The shortcomings of fasciocutaneous and fascial flaps requiring skin grafting can be eliminated.

Methods

This was a 10-year retrospective review of patients who had V-Y flaps based on a distinct perforator for defects of the shoulder, axilla, arm, elbow, forearm, wrist, and hand. Defects of the digits and thumb were excluded.

Results

There were 59 flaps in 52 patients with an average age of 44 years (18–72 years). Skin malignancy was the most common primary etiology. The average defect size was 35 cm2 (9–80 cm2). There were no total flap failures; however, there were 4 partial losses, which healed by secondary intention. Seven flaps had to be explored for the hematoma evacuation.

Conclusions

The use of V-Y flaps based on distinct perforators in the upper limb retains limb aesthetics, allows early mobility and is a safe and reliable technique.
The Effects of Dextran on Postoperative Thrombosis and Hemodilution in Microvascular Head and Neck Reconstruction
Authors: Filipan Dorotea , Dediol Emil , Blivajs Igor , Milic Morena
Published: January 2020

Background

Free tissue transfer is an integral part of reconstructive head and neck surgery today. Although increased experience and refinements in techniques have minimized flap loss, pharmacological agents have been used to prevent thrombus formation and flap failures, despite their questionable effectiveness. The aim of this study is to investigate the use of dextran 40 in thrombosis prophylaxis, as well as its effects on blood coagulability and flap survival.

Methods

This is a retrospective analysis of 176 free flaps performed at University Hospital Dubrava, Zagreb, Croatia, during a 4-year period. A comparison was made between 2 patient groups, based on their respective postoperative prophylaxis protocols. All patients were treated with low-molecular-weight heparin as deep vein thrombosis prevention, until patient mobilization. Group 1 was on dextran 40 protocol, whereas group 2 did not receive additional treatment. Primary outcome of the study was determined as flap loss rate, whereas secondary outcome was evaluated as the rate of thrombosis or hemorrhage. The hemodilution potential of dextran 40 was examined through blood count laboratory values.

Results

Total flap survival rate was 90.34%. There were 16 free flap losses and 1 partial loss overall. Anastomoses were re-explored in a total of 27 cases, of which 17 were salvaged. There were 29 events of hemorrhage or arterial or venous thrombosis: 17 in group 1 and 12 in group 2. A sum of 26 incidences of other postoperative complications was recorded, 13 in each group. Hemodilution status showed a statistically significant reduction in erythrocyte count and hemoglobin and hematocrit levels in the group receiving dextran 40, on postoperative days 1 and 3, but no such effect was observed on postoperative platelet count.

Conclusions

Although dextran 40 has been shown to have a valuable effect on hemodilution, which is beneficial in microsurgery, it did not demonstrate better outcomes in terms of flap survival. Because it can cause serious systemic complications, it is better not to administer it routinely. However, its important influence on reduction in erythrocyte count and hemoglobin and hematocrit levels should be further investigated.
Integrated physical and mental healthcare: an overview of models and their evaluation findings
Authors: Coates Dominiek , Coppleson Danielle , Schmied Virginia
Published: January 2020

Background:

Comorbid physical and mental health problems are common across the age spectrum. However, services addressing these health concerns are typically siloed and disconnected. Over the past 2 decades efforts have been made to design integrated services to address the physical and mental health needs of the population but little is known about the characteristics of effective integrated care models. The aim of the review was to map the design of integrated care initiatives/models and to describe how the models were evaluated and their evaluation findings.

Method:

Using a scoping review methodology, quantitative and qualitative evidence was systematically considered. To identify studies, Medline, PubMed, PsychINFO, CINAHL were searched for the period from 2003 to 2018, and reference lists of included studies and review articles were examined.

Results:

The current review identified 43 studies, describing 37 models of integrated physical and mental healthcare. Although modest in terms of evaluation design, it is evident that models are well received by consumers and providers, increase service access, and improve physical and mental health outcomes. Key characteristics of models include shared information technology, financial integration, a single-entry point, colocated care, multidisciplinary teams, multidisciplinary meetings, care coordination, joint treatment plan, joint treatment, joint assessment/joint assessment document, agreed referral criteria and person-centred care. Although mostly modest in term of research design, models were well received by consumers and providers, increased service access and improved physical and mental health outcomes. There was no clear evidence regarding whether models of integrated care are cost neutral, increase or reduce costs.

Conclusion:

Future research is needed to identify the elements of integrated care that are associated with outcomes, measure cost implications and identify the experiences and priorities of consumers and clinicians.
Accucopy: Accurate and Fast Inference of Allele-specific Copy Number Alterations from Low-coverage Low-purity Tumor Sequencing Data
Authors: Fan Xinping , Luo Guanghao , Huang Yu S.
Published: January 2020

Background

Copy number alterations (CNAs), due to their large impact on the genome, have been an important contributing factor to oncogenesis and metastasis. Detecting genomic alterations from the shallow-sequencing data of a low-purity tumor sample remains a challenging task.

Results

We introduce Accucopy, a method to infer total copy numbers (TCNs) and allele-specific copy numbers (ASCNs) from challenging low-purity and low-coverage tumor samples. Accucopy adopts many robust statistical techniques such as kernel smoothing of coverage differentiation information to discern signals from noise and combines ideas from time-series analysis and the signal-processing field to derive a range of estimates for the period in a histogram of coverage differentiation information. Statistical learning models such as the tiered Gaussian mixture model, the Expectation-Maximization (EM) algorithm, and Sparse Bayesian Learning (SBL) were customized and built into the model. Accucopy is implemented in C++/Rust, packaged in a docker image, and supports non-human samples, more athttp://www.yfish.org/software/.

Conclusions

We describe Accucopy, a method that can predict both TCNs and ASCNs from low-coverage low-purity tumor sequencing data. Through comparative analyses in both simulated and real-sequencing samples, we demonstrate that Accucopy is more accurate than Sclust, ABSOLUTE, and Sequenza.
Programmable and portable CRISPR-Cas transcriptional activation in bacteria
Authors: Ho Hsing-I , Fang Jennifer , Cheung Jacky , Wang Harris H.
Published: January 2020

Programmable gene activation enables fine-tuned regulation of endogenous and synthetic gene circuits to control cellular behavior. While CRISPR-Cas-mediated gene activation have been extensively developed for eukaryotic systems, similar strategies have been difficult to implement in bacteria. Here, we present a generalizable platform for screening and selection of functional bacterial CRISPR-Cas transcription activators. Using this platform, we identified a novel CRISPR activator, dCas9-AsiA, that could activate gene expression by up to 200-fold across genomic and plasmid targets with diverse promoters after directed evolution. The evolved dCas9-AsiA can simultaneously mediate activation and repression of bacterial regulons inE. coli. We further identified hundreds of promoters with varying basal expression that could be induced by dCas9-AsiA, which provides a rich resource of genetic parts for inducible gene activation. Finally, we show that dCas9-AsiA can be ported to other bacteria of clinical and bioindustrial relevance, thus enabling bacterial CRISPRa in more application areas. This work expands the toolbox for programmable gene regulation in bacteria and provides a useful resource for future engineering of other bacterial CRISPR-based gene regulators.
Cytotoxic and mutagenic capacity of TTO and terpinen-4-ol in oral squamous cell carcinoma
Authors: Casalle Nicole , de Andrade Cleverton Roberto
Published: January 2020

The essential oil of Melaleuca Alternifolia (tea tree oil - TTO) consists of about 100 components, and the highest concentration are terpinen-4-ol. Studies of their cytotoxic capacity have shown effect on malignant neoplastic lineages. The aim of this study was to evaluate the cytotoxic and mutagenic capacity of TTO and main soluble components, terpinen-4-ol and gama-terpinene in cell cultures. Two lineages of oral squamous cell carcinoma and a keratinocyte cell were analyzed: (1) colorimetric analysis Metiltetrazolium (MTT); (2) Micronucleus assay. The results were expressed as susceptibility tests and degree of mutagenicity. The statistical test used in the analysis was one-way ANOVA (Tukey test). The IC50values obtained from the MTT analysis of cells exposed to TTO were 0.2% for HaCaT, 0.14% for HSC-3, and 0.17% for SCC-25. For exposure to terpinen-4ol, IC50values were 0.5%, 0.3% and 0.45% for HaCaT, HSC-3 and SCC-25, respectively. The gamma-terpinene didn’t show significant cytotoxic activity, therefore it was impossible to calculate the IC50. TTO and terpinen-4-ol was unable to produce mutagenicity in all the lineages. In conclusion, both the TTO and terpinen-4-ol had cytotoxic capacity on HaCaT, HSC-3 and SCC-25. TTO and terpinen-4-ol wasn’t mutagenic. In this sense, our study provides new perspectives on the potential use of TTO and terpinen-4-ol for the development of new alternative therapies to treat topically locally oral squamous cell carcinoma.
A suppressor of axillary meristem maturation promotes longevity in flowering plants
Authors: Karami Omid , Rahimi Arezoo , Khan Majid , Bemer Marian , Hazarika Rashmi R. , Mak Patrick , Compier Monique , van Noort Vera , Offringa Remko
Published: January 2020

Post embryonic development and growth of flowering plants are for a large part determined by the activity and maturation state of stem cell niches formed in the axils of leaves, the so-called axillary meristems (AMs)1,2. Here we identify a new role for the ArabidopsisAT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED 15(AHL15) gene as a suppressor of AM maturation. Loss ofAHL15function accelerates AM maturation, whereas ectopic expression ofAHL15suppresses AM maturation and promotes longevity in Arabidopsis and tobacco. Together our results indicate thatAHL15expression acts as a key molecular switch, directly downstream of flowering genes (SOC1, FUL) and upstream of GA biosynthesis, in extending the plant’s lifespan by suppressing AM maturation.
The stability flexibility tradeoff and the dark side of detail
Authors: Nassar Matthew R. , Troiani Vanessa
Published: January 2020

Learning in dynamic environments requires integrating over stable fluctuations to minimize the impact of noise (stability) but rapidly responding in the face of fundamental changes (flexibility). Achieving one of these goals often requires sacrificing the other to some degree, producing a stability-flexibility tradeoff. Individuals navigate this tradeoff in different ways, with some people learning rapidly (emphasizing flexibility) and others relying more heavily on historical information (emphasizing stability). Despite the prominence of such individual differences in learning tasks, the degree to which they relate to broader characteristics of real-world behavior or pathologies has not been well explored. Here we relate individual differences in learning behavior to self-report measures thought to collectively capture characteristics of the Autism spectrum. We show that that young adults who learn most slowly tend to integrate more effective samples into their beliefs about the world making them more robust to noise (more stability), but are more likely to integrate information from previous contexts (less flexibility). We show that individuals who report paying moreattention to detailtend to use high flexibility and low stability information processing strategies. We demonstrate the robustness of this inverse relationship betweenattention to detailand formation of stable beliefs in a heterogeneous population of children that includes a high proportion of Autism diagnoses. Together, our results highlight thatattention to detailreflects an information processing policy that comes with a substantial downside, namely the ability to integrate data to overcome environmental noise.
A semi-automated machine learning-aided approach to quantitative analysis of centrosomes and microtubule organization
Authors: Sankaran Divya Ganapathi , Hariharan Bharath , Pearson Chad G.
Published: January 2020

Microtubules (MTs) perform important cellular functions including migration, intracellular trafficking, and chromosome segregation. The centrosome, comprised of two centrioles surrounded by the pericentriolar material (PCM), is the cell’s central MT organizing center. The PCM proteins, includingγ-tubulin and Pericentrin, promote MT nucleation and organization. Centrosomes in cancer cells are commonly numerically amplified. However, the question of how amplification of centrosomes alters the MT organization capacity is not well-studied. We developed a quantitative image-processing and machine learning-aided approach for the automated analysis of MT organization. We designed a convolutional neural network-based approach for detecting centrosomes and an automated pipeline for analyzing MT organization around centrosomes, encapsulated in a semi-automatic graphical tool. Using this tool, we analyzed the spatial distribution of PCM proteins, the growing ends of MTs and the total MT density in breast cancer cells. We find that breast cancer cells with supernumerary centrosomes not only have increased PCM protein but also exhibit expansion in PCM size. Moreover, centrosome amplified cells have a greater MT density and more growing MT ends near centrosomes than unamplified cells. The semi-automated approach developed here enables facile, unbiased and quantitative measurements of centrosome aberrations. We show that these aberrations increase MT nucleation and promote changes to MT density and the spatial distribution of MTs around amplified centrosomes.
Neural evidence for recognition of naturalistic videos in monkey hippocampus
Authors: Sakon John J. , Suzuki Wendy A.
Published: January 2020

The role of the hippocampus in recognition memory has long been a source of debate. Tasks used to study recognition that typically require an explicit probe, where the participant must make a response to prove they remember, yield mixed results on hippocampal involvement. Here, we tasked monkeys to freely view naturalistic videos, and only tested their memory via looking times for two separate novel v. repeat video conditions on each trial. Notably, a large proportion of hippocampal neurons differentiated these videos via changes in firing rates time-locked to the duration of their presentation on screen, and not during the delay period between them as would be expected for working memory. Single neurons often contributed to both retrieval conditions, and did so across many trials with trial-unique video content, suggesting they detect familiarity. The majority of neurons contributing to the classifier showed an enhancement in firing rate on repeat compared to novel videos, a pattern which has not previously been shown in hippocampus. These results suggest the hippocampus contributes to recognition memory via familiarity during free-viewing.

Significance Statement

Recognition memory enables distinction of new from previously encountered stimuli. In the majority of recognition memory work, humans or animals are tasked to explicitly identify whether a stimulus is old or new. In some of these studies—but for unknown reasons not others—there is evidence of hippocampal involvement. Here, when we present trial-unique, naturalistic videos to monkeys, firing rates from many single hippocampal neurons surprisingly differentiate new from repeated videos. The ability of these hippocampal neurons to detect recently-viewed stimuli, despite the videos’ unfamiliar content, suggests they contribute to memory. These results are consistent with hippocampal involvement in the familiarity aspect of recognition memory during free-viewing.
Diagnosing uncertainty, producing neonatal abstinence syndrome
Authors: Chandler Amy , Whittaker Anne , Cunningham‐Burley Sarah , Elliott Lawrie , Midgley Paula , Cooper Sarah
Published: January 2020

The use of alcohol and other drugs during pregnancy is understood to be an important public health problem. One way in which this problem is expressed and responded to is via the identification and treatment of neonatal abstinence syndrome (NAS). In this article, we demonstrate how the processes of anticipating, identifying and responding to NAS are characterised by significant uncertainty among parents and health and social care practitioners. We draw on interviews with 16 parents who had recently had a baby at risk of NAS, and multidisciplinary focus groups with 27 health and social care professionals, held in Scotland, UK. NAS, and drug use in pregnancy, is a fraught and complex arena. Parents in the UK who use opioids risk losing custody of children, and must navigate a high degree of surveillance, governance and marginalisation. We suggest that considering NAS as a social diagnosis, further informed by Mol's political ontology of ‘multiple’ bodies/diseases, may help to produce clinical and social responses to uncertainty which avoid, rather than promote, further marginalisation of parents who use drugs. One such response is to develop a culture of relationship‐based care which empowers both service providers and service users to challenge existing practice and decision‐making.
Knockdown of long noncoding RNA TP73‐AS1 suppresses the malignant progression of breast cancer cells in vitro through targeting miRNA‐125a‐3p/metadherin axis
Authors: Liu Yuxiong , Wei Guangqing , Ma Qian , Han Yanyan
Published: January 2020

Background

TP73 antisense RNA 1 (TP73‐AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73‐AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis.

Methods

Expression of TP63‐AS1, miRNA‐125a‐3p (miR‐125a) and metadherin (MTDH) was detected by real‐time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK‐8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo.

Results

Expression of TP73‐AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC‐70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N‐cadherin and Vimentin level. Moreover, TP73‐AS1 downregulation restrained the tumor growth of HCC‐70 cells in vivo. Mechanically, TP73‐AS1 functioned as a molecular “sponge” for miR‐125a to modulate MTDH, a downstream target of miR‐125a. Intriguingly, both miR‐125a overexpression and MTDH silencing exerted a tumor‐suppressive effect in the malignant progression of HCC‐70 and MB231 cells, which was counteracted by TP73‐AS1 upregulation and miR‐125a downregulation, respectively.

Conclusion

Knockdown of TP73‐AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR‐125a and upregulating MTDH, suggesting a novel TP73‐AS1/miR‐125a/MTDH pathway in the malignant progression of breast cancer.
Automated tracheal intubation in an airway manikin using a robotic endoscope: a proof of concept study
Authors: Biro P. , Hofmann P. , Gage D. , Boehler Q. , Chautems C. , Braun J. , Spahn D. R. , Nelson B. J.
Published: January 2020

Robotic endoscope‐automated via laryngeal imaging for tracheal intubation (REALITI) has been developed to enable automated tracheal intubation. This proof‐of‐concept study using a convenience sample of participants, comprised of trained anaesthetists and lay participants with no medical training, assessed the performance of a robotic device for the insertion of a tracheal tube into a manikin. A prototype robotic endoscope device was inserted into the trachea of an airway manikin by seven anaesthetists and seven participants with no medical training. Each individual performed six device insertions into the trachea in manual mode and six in automated mode. The anaesthetists succeeded with 40/42 (95%) manual insertions (median (IQR [range]) 17 (12–26 [4–132]) s) and 40/42 (95%) automated insertions (15 (13–18 [7–25]) s). The non‐trained participants succeeded in 41/42 (98%) manual insertions (median (IQR [range]) 18 (13–21 [8–133]) s) and 42/42 (100%) automated insertions (16 (13–23 [10–58])] s). The duration of insertion did not differ between groups. An effect of increasing experience was observed in both groups in manual mode. A Likert scale for ‘ease of use’ (0 = very difficult to 10 = very easy) showed similar results within the two groups; the mean (SD) was 5.9 (2.1) for the anaesthetists and 6.9 (1.3) for the non‐trained participants. We have successfully performed the first automated tracheal device insertion in a manikin with comparable results in a convenience sample of anaesthetists and lay participants with no medical training.
Transfusion rates after 800 Aquablation procedures using various haemostasis methods
Authors: Elterman Dean , Bach Thorsten , Rijo Enrique , Misrai Vincent , Anderson Paul , Zorn Kevin C. , Bhojani Naeem , El Hajj Albert , Chughtai Bilal , Desai Mihir
Published: January 2020

Objective

To determine if athermal methods are as effective in preventing blood transfusions as the use of cautery across various prostate volumes following prostate tissue resection for benign prostatic hyperplasia using Aquablation.

Patients and methods

The current commercial AQUABEAM robot that performs Aquablation therapy was first used in 2014. Since then numerous clinical studies have been conducted in various countries; Australia, Canada, Germany, India, Lebanon, Spain, New Zealand, United Kingdom, and the United States. All of the clinical trial data since 2014 were pooled with the early commercial procedures from France, Germany, and Spain to determine the effectiveness of haemostatic techniques in reducing the transfusion rate in patients after Aquablation.

Results

In all, 801 patients were treated with Aquablation therapy from 2014 to early 2019. The mean (SD, range) prostate volume was 67 (33, 20–280) mL and 31 (3.9%) transfusions were reported. The largest contributing factor to transfusion risk was prostate size and method of traction. There was an increasing risk of transfusions in larger prostates when robust traction using a catheter‐tensioning device (CTD) without cautery was used, ranging from 0.8% to 7.8% in prostates ranging from 20 to 280 mL. However, when standard traction (taping the catheter to the leg, gauze knot synched up to the meatus, or no traction at all) was used and where the surgeon performed bladder neck cautery only when necessary, the risk of transfusion was 1.4–2.5% in prostates ranging from 20 to 280 mL.

Conclusions

While the athermal subgroup with robust traction with a CTD had comparable transfusion rates for smaller prostates, the risk increased significantly as prostate volume increased. With standard traction methods and selective bladder neck cautery, the risk of transfusion was reduced to 1.9% across all prostate sizes.
Metastatic leiomyosarcoma to the pancreas diagnosed on endoscopic ultrasound‐guided fine needle aspiration – A report of two cases with review of spindle cell lesions of pancreas
Authors: Thakur Abha , Choudhary Narendra S. , Sarin Haimanti
Published: January 2020

Metastatic pancreatic leiomyosarcoma is a rare entity. EUS FNA supplemented with cell block and IHC can accurately diagnose metastatic deposits in pancreas and guide patient management. Spindle cell lesions of pancreas are reviewed.
How green is your packaging—A comparative international study of cues consumers use to recognize environmentally friendly packaging
Authors: Herbes Carsten , Beuthner Christoph , Ramme Iris
Published: January 2020

Consumers have grown increasingly aware of the impact of packaging on the environment. Therefore, interest has grown in more environmentally friendly packaging, but we wondered how consumers recognize ‘green’ as distinct from ‘grey’ when evaluating packaging. We asked over 3,000 respondents from Germany, France and the United States how they recognize environmentally friendly packaging. To solicit responses that we may not have anticipated, we used an open‐ended format, which we then followed with a closed‐ended format so that we could compare the two sets of responses. Not surprisingly, in both sets of responses, we found labelling to be the attribute consumers rely upon most, as well as evidence of misleading labels. We also found consumers in Germany and the United States relied on information on the packaging and named searching for information as one of their preferred ways to decide whether packaging is environmentally friendly. French consumers seemed less trusting of published information and more trusting of the look and feel, especially the material, of the package. Our results point to the importance of cultural influences in the acquisition of perceptual cues by the consumer.