bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat flux effect of thermal metamaterials
Authors: Lim Taekyung , Jeong Sang-Mi , Mun Ju–Hyun , Yang Keun–Hyeok , Park Sang Yoon , Yoo Young Joon , Ju Sanghyun
Published: October 2018

In this study, we investigated the heat flux effect of thermal metamaterials, which can effectively suppress heat propagation, through the three-dimensional finite-difference time-domain techniques. When a concrete block was heated or cooled, different heat propagation characteristics were demonstrated according to the plate-shaped meta-structure embedded in the concrete block. Under the assumption that the overall thickness of the plate-shaped meta-structure is constant, separating the plate-shaped meta-structure into two or more layers has a better heat blocking effect than using a single plate-shaped meta-structure. In addition, the thermal blocking efficiency varies depending on the thermal metamaterial used as the plate-shaped meta-structure. The thermal blocking efficiency of the thermal metamaterials was better in the order of air, aerogel, Styrofoam, and paraffin. The result indicated that the heat transfer in a concrete block can be manipulated by controlling the material, number, and spacing of the plate-shaped meta-structures, and the proposed plate-shaped meta-structures can be applied to reduce the thickness of a concrete block containing an insulating layer used in buildings.
Pseudorandom number generator uses true chaos to generate sequences with random behavior
Authors: Fellet Melissae
Published: October 2018

Pseudorandom number algorithms often produce sequences that eventually repeat. On the basis of chaos and number theories, a new approach generates nonrepeating sequences that behave as if truly random.
New photodetector offers sensitive broadband detection and low power consumption
Authors: Liebendorfer Adam
Published: October 2018

A germanium quantum dot approach yields high performance across visible and near-infrared wavelengths at significantly lower voltages than commercially available products.
Feedback control in optical tweezers enables thermodynamic experiments for biological molecules
Authors: DeJarnette Drew
Published: October 2018

Adding feedback capabilities to standard optical tweezers greatly enhances the control of trapped particle motion at small length and time scales by actively changing the forces induced by a focused laser.
Ninety years of change on the TGB Osborn Vegetation Reserve, Koonamore: a unique research opportunity
Authors: Sinclair R. , Facelli Jose M.
Published: October 2018

The TGB Osborn Vegetation Reserve, on Koonamore station in the NE pastoral area of South Australia, is the longest-running vegetation monitoring project of its type in Australia. In 1925, a 4-km2 rectangle in a heavily overgrazed area was fenced to exclude rabbits and sheep, and permanent quadrats and photo-points set up to record changes. The area is predominantly chenopod shrubland, with an open woodland tree layer. After the initial elimination of rabbits, control slackened and rabbit numbers increased until the 1970s, when intense elimination efforts resumed, together with the arrival of myxomatosis and rabbit haemorrhagic disease viruses. Consequently, the reserve has had 50 years without sheep, followed by 40 years virtually without either sheep or rabbits. Changes over that time have been very striking, and they have been recorded regularly via mapped quadrats and photopoints.
The objective of this paper is to highlight opportunities for making use of this database for researching several interesting ecological questions.
A response to ‘Clarifying the meaning of mantras in wildland fire behaviour modelling: reply to Cruz et al. (2017)'
Authors: Cruz Miguel G. , Alexander Martin E. , Sullivan Andrew L.
Published: October 2018

This paper represents our response to the questioning by Mell et al. (2018) of our interpretation (Cruz et al. 2017) of five generalised statements or mantras commonly repeated in the wildland fire behaviour modelling literature. We provide further clarity on key subjects and objectively point out, using examples from relevant scientific findings, that our discussion of the identified mantras presented in Cruz et al. (2017) was indeed not ill-conceived as suggested by Mell et al. (2018).
Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis
Authors: Li Yuwei , Junge Jason A. , Arnesano Cosimo , Gross Garrett G. , Miner Jeffrey H. , Moats Rex , Roberts Richard W. , Arnold Don B. , Fraser Scott E.
Published: October 2018

Significance

An integrative approach is presented for studying cell biology in vivo, assessing protein dynamics and cell behavior, and offering in situ analyses of cytokinesis, daughter-cell polarity, and stereotyped tissue morphogenesis. Tagging endogenous Discs Large 1 (Dlg1) in cartilage using intrabody technology permits in situ 3D time-lapse imaging and reveals Dlg1 enrichment at the midbody during cytokinesis. Functional significance is tested by disrupting Dlg1 multimerization and its midbody localization by using an ablating intrabody, DLGE3. Building on prior work on Dlg1 in epithelia, our work reveals that Dlg1 propagates cell polarity in proliferative mesenchymal tissues and suggests that multiple mechanisms act in concert at distinct phases of the cell cycle to transmit and maintain cell polarity.
KDM3A histone demethylase functions as an essential factor for activation of JAK2−STAT3 signaling pathway
Authors: Kim Hyunkyung , Kim Dongha , Choi Seon Ah , Kim Chang Rok , Oh Se Kyu , Pyo Ki Eun , Kim Joomyung , Lee Seung-Hoon , Yoon Jong-Bok , Zhang Yi , Baek Sung Hee
Published: October 2018

Significance

An aberrant covalent histone modification which drives dysregulation of transcriptional program is related to human diseases such as cancer. Thus, identifying signaling pathways modulating transcription factors and epigenetic enzymes are coming into view as attractive therapeutic targets. In this study, we provide evidence that KDM3A is tyrosine-phosphorylated by JAK2, and tyrosine-phosphorylated KDM3A acts as a coactivator for STAT3, thereby exerting increased cancer cell growth and motility. We propose that JAK2-dependent tyrosine phosphorylation of KDM3A could be a potential therapeutic target for epigenetic control of oncogenic effect governed by JAK2−STAT3 signaling pathway.
Population-level rhythms in human skin with implications for circadian medicine
Authors: Wu Gang , Ruben Marc D. , Schmidt Robert E. , Francey Lauren J. , Smith David F. , Anafi Ron C. , Hughey Jacob J. , Tasseff Ryan , Sherrill Joseph D. , Oblong John E. , Mills Kevin J. , Hogenesch John B.
Published: October 2018

Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. The epidermal layer shows rhythmic physiological responses to daily environmental variation (e.g., DNA repair). We investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, in which a limited set of human subjects (
n
= 20) were sampled throughout the 24-h cycle and a larger population (
n
= 219) were sampled once. We found a robust circadian oscillator in human epidermis at the population level using pairwise correlations of clock and clock-associated genes in 298 epidermis samples. We then used CYCLOPS to reconstruct the temporal order of all samples, and identified hundreds of rhythmically expressed genes at the population level in human epidermis. We compared these results with published time-series skin data from mice and found a strong concordance in circadian phase across species for both transcripts and pathways. Furthermore, like blood, epidermis is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human epidermis that is capable of reporting circadian phase to within 3 hours from a single sample. In summary, we show rhythms in human epidermis that persist at the population scale and describe a path to develop robust single-sample circadian biomarkers.
Study on optimization of low carbon renewal system for residential area
Authors: Zhao G C , Yu X F , Fan J S
Published: October 2018

Global climate change has been an impending cosmopolitan issue. As the basic part of the city, urban residential area is the basic space for the use of sustainable ideas to promote the construction of low carbon city. Along with urban expansion, social polarization and significant change of social space in China, the decline tendency of central city become significantly faster. Faced with the double test between climate change and residential area recession, traditional renewal methods no longer meet the needs of urban sustainable development. The urban renewal modes need a major transformation, and Low carbon renewal is an effective way not only to slow down the decline of residential areas but also promote sustainable development of the city. To put forward an analysis and optimization methods for low carbon renewal, we proposed a low carbon renewal system from six aspects: layout planning, road and traffic, architecture planning and design, environment engineering, municipal engineering and construction management. Moreover, we used Analytic Network Process (ANP) to analyse the internal feedback of the system. At last, the optimization process of residential low carbon renewal was proposed.
Sex and death: from cell fate specification to dynamic control of X-chromosome structure and gene expression
Authors: Meyer Barbara J.
Published: October 2018

Determining sex is a binary developmental decision that most metazoans must make. Like many organisms, Caenorhabditis elegans specifies sex (XO male or XX hermaphrodite) by tallying X-chromosome number. We dissected this precise counting mechanism to determine how tiny differences in concentrations of signals are translated into dramatically different developmental fates. Determining sex by counting chromosomes solved one problem but created another—an imbalance in X gene products. We found that nematodes compensate for the difference in X-chromosome dose between sexes by reducing transcription from both hermaphrodite X chromosomes. In a surprising feat of evolution, X-chromosome regulation is functionally related to a structural problem of all mitotic and meiotic chromosomes: achieving ordered compaction of chromosomes before segregation. We showed the dosage compensation complex is a condensin complex that imposes a specific three-­dimensional architecture onto hermaphrodite X chromosomes. It also triggers enrichment of histone modification H4K20me1. We discovered the machinery and mechanism underlying H4K20me1 enrichment and demonstrated its pivotal role in regulating higher-order X-chromosome structure and gene expression.
CBE—Life Sciences Education: the story of a “great journal scientists might be caught reading”
Authors: Dolan Erin L.
Published: October 2018

How did a moderately sized scientific society create what many consider to be the leading journal in biology education? As Editor-in-Chief of the education journal of the American Society for Cell Biology (ASCB), CBE—Life Sciences Education ( LSE) and recipient of the 2018 Bruce Alberts Award for Excellence in Science Education, I tell the story of the establishment, growth, and impact of ASCB’s “other journal.”
Let curiosity lead you
Authors: Chen Elizabeth H.
Published: October 2018

It is an incredible honor to receive the Woman in Cell Biology Mid-Career Award for Excellence in Research. My lab works on cell–cell fusion, an indispensable process in the conception, development, and physiology of multicellular organisms. In this essay, I reflect on my curiosity-led journey, which uncovered some unexpected mechanisms underlying cell–cell fusion.
A New Mechanism of Resistance of Human Immunodeficiency Virus Type 2 to Integrase Inhibitors: A 5-Amino-Acid Insertion in the Integrase C-Terminal Domain
Authors: Le Hingrat Quentin , Collin Gilles , Lê Minh , Peytavin Gilles , Visseaux Benoit , Bertine Mélanie , Tubiana Roland , Karmochkine Marina , Valin Nadia , Collin Fidéline , Lemaignen Adrien , Bernard Louis , Damond Florence , Matheron Sophie , Descamps Diane , Charpentier Charlotte ,   French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO5 HIV-2 Cohort
Published: October 2018

Background

Integrase strand transfer inhibitors (INSTIs) are crucial for the treatment of human immunodeficiency virus (HIV) type 2 infection, due to limited available therapeutic options. Recently, bictegravir has been approved for HIV-1, but no data are currently available for HIV-2.

Methods

We assessed the phenotypic susceptibility of 12 HIV-2 clinical isolates, obtained from 2 antiretroviral-naive and 10 antiretroviral-experienced patients, to 5 INSTIs (bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir) at the virological failure of an INSTI-based regimen. The 50% inhibitory concentrations (IC50s) were determined. Phenotypic inhibitory quotients were determined using trough INSTI plasma concentrations.

Results

Wild-type viruses were susceptible to the 5 INSTIs, with IC50s in the nanomolar range. Bictegravir had a lower IC50 than the other INSTIs on those HIV-2 isolates bearing major, resistance-associated mutations (codons 143, 148, and 155). We identified a new resistance profile—a 5–amino-acid insertion at codon 231 of the HIV-2 integrase (231INS)—in 6 patients at the virological failure of a raltegravir-based regimen. Those patients had adequate raltegravir concentrations, but harbored multiresistant viruses with low genotypic susceptibility scores (median = 1.5). This insertion rendered isolates highly resistant to raltegravir and elvitegravir, and moderately resistant to dolutegravir and cabotegravir. Regarding bictegravir, 2 isolates remained susceptible and 2 had a slight increase in IC50 (3- to 5-fold change).

Conclusions

Our results confirm the potency of INSTI on HIV-2 clinical isolates with wild-type integrase. In addition, we identified a new resistance pathway, 231INS, selected in antiretroviral-experienced patients with multiresistant HIV-2 viruses. This highlights the need of close follow-up of those patients initiating an INSTI-based regimen.
A sentiment analysis system for social media using machine learning techniques: Social enablement
Authors: Rani Sujata , Kumar Parteek
Published: October 2018

In this article, an innovative approach to perform the sentiment analysis (SA) has been presented. The proposed system handles the issues of Romanized or abbreviated text and spelling variations in the text to perform the sentiment analysis. The training data set of 3,000 movie reviews and tweets has been manually labeled by native speakers of Hindi in three classes, i.e. positive, negative, and neutral. The system uses WEKA (Waikato Environment for Knowledge Analysis) tool to convert these string data into numerical matrices and applies three machine learning techniques, i.e. Naive Bayes (NB), J48, and support vector machine (SVM). The proposed system has been tested on 100 movie reviews and tweets, and it has been observed that SVM has performed best in comparison to other classifiers, and it has an accuracy of 68% for movie reviews and 82% in case of tweets. The results of the proposed system are very promising and can be used in emerging applications like SA of product reviews and social media analysis. Additionally, the proposed system can be used in other cultural/social benefits like predicting/fighting human riots.
Beyond biomarkers: How enhanced CT imaging can improve the diagnostic-driven management of invasive mould disease
Authors: Stanzani Marta , Sassi Claudia , Battista Giuseppe , Lewis Russell E
Published: October 2018

CT imaging remains an essential diagnostic test for identification, staging and management of invasive mould infection (IMI) in patients with hematological malignancies. Yet the limited specificity of standard CT imaging can drive excessive antifungal use in patients, especially when more definitive diagnosis cannot be established through microbiology or invasive diagnostic procedures. CT pulmonary angiography (CTPA) is a complimentary, non-invasive approach to standard CT that allows for direct visualization of pulmonary arteries inside infiltrates for signs of angioinvasion, vessel destruction and vessel occlusion. Experience from several centers that are using CTPA as part of a standard diagnostic protocol for IMI suggests that a positive vessel occlusion sign (VOS) is the most sensitive and a specific sign of IMI in both neutropenic and non-neutropenic patients. CTPA is particularly useful in patients who develop suspected breakthrough IMI during antifungal prophylaxis because, unlike serum and/or BAL galactomannan and polymerase chain reaction (PCR) testing, the sensitivity is not reduced by antifungal therapy. A negative VOS may also largely rule-out the presence of IMI, supporting earlier discontinuation of empirical therapy. Future imaging protocols for IMI in patients with hematological malignancies will likely replace standard chest X-rays in favor of early low radiation dose CT exams for screening, with characterization of the lesions by CTPA and routine follow-up using functional/metabolic imaging such as 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) to assess treatment response. Hence, enhanced CT imaging techniques can improve the diagnostic-driven management of IMI management in high-risk patients with hematological malignancies.
Reaching rural veterans: a new mechanism to connect rural, low-income US Veterans with resources and improve food security
Authors: Wright B N , MacDermid Wadsworth S , Wellnitz A , Eicher-Miller H A
Published: October 2018

Background

Rural, low-income US veterans face additional barriers to accessing food and resources compared to urban veterans. Based on both social-ecological and cultural competence approaches, the Reaching Rural Veterans (RRV) pilot intervention built on the existing infrastructure of food pantries to improve food security and connect rural, low-income veterans with resources. This article describes the process of implementing and evaluating RRV.

Methods

Five rural food pantries within each of two states, Indiana and Kentucky, received training in cultural competence and held monthly outreach events where food and services were offered to veterans. Veteran adult participants completed an assessment at baseline and 3-month follow-up that measured food security using the US Household Food Security Survey Module and self-reported resource enrollment. Repeated measures logistic regression models evaluated the odds of improving food security and resource enrollment from baseline to follow-up (significance P < 0.05).

Results

RRV recruited 234 participants; 53% completed the follow-up assessment. At follow-up, the odds of household (P = 0.009) and adult (P = 0.01) food security increased, as did enrollment in one or more of the following resources: Temporary Assistance for Needy Families, Supplemental Security Income, General Assistance or Assistance from the Township Trustee (P = 0.005).

Conclusions

RRV yielded promising preliminary results of improved food security and resource use.
Correlation between Empirical Antibiotic Therapy and Bone Culture Results in Patients with Osteomyelitis
Authors: Tardáguila-García Aroa , Lázaro-Martínez José Luis , Sanz-Corbalán Irene , García-Álvarez Yolanda , Álvaro-Afonso Francisco Javier , García-Morales Esther
Published: October 2018

OBJECTIVE:

To analyze the correlation between empirical antibiotic therapies prescribed in primary care centers by general practitioners and the microbiology results of bone culture in patients with diabetic foot–related osteomyelitis.

METHODS:

This observational study involved 80 patients with diabetic foot ulcers and clinically suspected osteomyelitis. The patients were taking antibiotics prescribed by general practitioners to treat diabetic foot infections. Bone samples were taken from every patient for microbiology analysis in a specialized diabetic foot unit.

MAIN OUTCOME MEASURE:

The sensitivity of the bone cultures to antibiotics was compared with the patient’s previous antibiotic therapy, and antibiotic and bacterial resistance were analyzed.

MAIN RESULTS:

The bone cultures from only 16 patients (22.3%) showed sensitivity to the antibiotics that the patient had been prescribed. Fifty-six patients (77.8%) displayed bacterial resistance to the antibiotic that they were taking.

CONCLUSIONS:

Awareness and implementation of international antibiotic stewardship guidelines are poor in primary care centers. It is important to establish strategies that foster a better understanding of treatment management standards and ensure the proper implementation of guidelines.
Drug updates and approvals
Authors: Mospan Cortney , Mospan Geoffrey , Byland Emily , Whitaker William Blake , Xiong Linda , Dunlap Jordan , Canupp Katherine
Published: October 2018

In 2018, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy); doxylamine succinate and pyridoxine hydrochloride (Bonjesta); erenumab-aooe (Aimovig); lofexidine hydrochloride (Lucemyra); tezacaftor and ivacaftor (Symdeko); and tildrakizumab-asmn (Ilumya).
Increased Hip Intracapsular Pressure Decreases Perfusion of the Capital Femoral Epiphysis in a Skeletally Immature Porcine Model
Authors: Upasani Vidyadhar V. , Badrinath Raghav , Farnsworth Christine L. , Jeffords Megan E. , Hallare Jericho A. , Ahmed Syed I. , Schrader Tim
Published: October 2018

Background:

Increased intracapsular hip pressure is thought to be one of the possible etiologies of femoral head avascular necrosis after intra-articular proximal femoral fractures or acute slipped capital femoral epiphysis. The purpose of this study was to evaluate the relationship between intra-articular hip pressure (IAP) and epiphyseal perfusion pressure (EPP), and its dependency on skeletal maturity using a porcine model.

Methods:

Seven female Yorkshire-hybrid pigs were used to study the direct relationship between IAP and EPP. A needle inserted into the capsule provided both IAP monitoring and saline infiltration until IAP was above mean arterial pressure (MAP). Video simultaneously documented IAP, EPP, MAP. Parameters for all trials in each hip were averaged and compared between the 2 age groups. Significance was P<0.05.

Results:

Four young hips (in pigs 10.3±1.0 wk, 27.4±2.0 kg) and 5 older hips (21.1±0.1 wk, 89.4±7.1 kg) were studied. There was no significant difference in the MAP (50.0±11.8 and 55.5±7.0 mm Hg respectively, P=0.411) between the 2 age groups. In the older hips, biphasic EPP persisted despite increasing IAP to an average of 177 mm Hg over MAP. In the young pigs, the biphasic EPP waveform ceased with increased IAP to an average of 28 mm Hg over MAP. Biphasic waveforms returned once IAP fell to an average of 5 mm Hg over MAP.

Conclusions:

Increased IAP resulted in tamponade of epiphyseal perfusion in the young, but not in the older hips. An intact physis may preclude intraosseous metaphyseal vessels from penetrating the epiphysis, leaving it vulnerable to retinacular artery tamponade.

Clinical Relevance:

The IAP and EPP relationship has direct clinical practice implications. Hip capsulotomy and decompression in young patients with intra-articular proximal femoral fractures and increased intracapsular pressure may decrease avascular necrosis risk.
Risk Factors for Cerebrospinal Fluid Leak Following Anterior Cervical Discectomy and Fusion
Authors: Kapadia Bhaveen H. , Decker Samuel I. , Boylan Matthew R. , Shah Neil V. , Paulino Carl B.
Published: October 2018

Study Design/Setting:

This was a retrospective cohort study.

Purpose:

The purpose of this study was to examine the association between postoperative cerebrospinal fluid (CSF) leak and anterior cervical discectomy and fusion (ACDF). Specifically, we evaluated: (1) demographic risk factors; (2) comorbid risk factors; (3) indications for surgery; and (4) lengths of stay.

Summary of Background Data:

CSF leak is a rare but serious complication of ACDF. Currently, there is a paucity of literature describing the risk factors for CSF leak following ACDF.

Methods:

The Nationwide Inpatient Sample was used to identify all patients who underwent cervical fusion using the anterior approach with excision of intervertebral disc between 1998 and 2010. Patients who had a diagnosis of ossification of the posterior longitudinal ligament in the cervical region were excluded. All patients who had a CSF leak were identified. Demographics and comorbidities were compared via χ2 analysis, and logistic regression to calculate the odds of having a CSF leak.

Results:

Of the 1,261,140 patients identified, 3048 patients (0.24%) had a postoperative CSF leak. Patients who were between the ages of 55 and 69 years (P=0.038) and 70 years or older (P=0.001) were at an increased risk of CSF leak compared with patients who were aged 40–54 years. Non-white race (P=0.021), obesity, (P<0.001) and hypertension (P=0.025) were associated with an increased risk of CSF leak, but diabetes (P=0.966) and hyperlipidemia (P=0.226) were not. Herniated disc diagnosis was associated with decreased risk of CSF leak (P=0.032), but cervical spondylosis with myelopathy patients had an increased risk (P<0.001). Patients with CSF leak had a mean length of stay of 6.0 days compared with 2.1 days among controls.

Conclusions:

Surgical candidates who are older and non-white should be counseled of their increased risk for CSF leak in preoperative planning. Patients who are obese and have hypertension may benefit from medical optimization before surgery.

Level of Evidence:

Level III.
Relationship Between Midface Volume Deficits and the Appearance of Tear Troughs and Nasolabial Folds
Authors: Glaser Dee Anna , Lambros Val , Kolodziejczyk Julia , Magyar Andrew , Dorries Kathleen , Gallagher Conor J.
Published: October 2018

BACKGROUND

Understanding interrelationships among aging facial features is important in facial aesthetics as a global treatment approach becomes standard.

OBJECTIVE

Examine empirical relationships between midface volume deficit and severity of tear troughs (TTs) and nasolabial folds (NLFs) in women and men of different racial/ethnic groups.

METHODS

A web-based study was administered to health panel members (aged 18–75 years). Participants compared their midface volume, TTs, and NLFs against photonumeric scales depicting degrees of severity. Linear regressions were conducted to assess the relationship of midface volume on severity of TTs and NLFs, controlling for demographic factors.

RESULTS

Of 4,086 participants (80.0% female), 3,553 had complete data. Increasing severity of midface volume deficit was associated with increasing severity of TTs and NLFs in both sexes (all p < .001). Race/ethnicity was associated with differences in severity in all 3 facial areas, although specific differences between races/ethnicities varied for women and men. Progression rates of severity differed between racial/ethnic groups. Correlations between midface volume deficit, TTs, and NLFs were positive and significant (all p < .001).

CONCLUSION

Midface volume deficit was associated with severity of TT deformity and NLFs after controlling for age and other demographic variables.
Efficacy of Amphotericin B Against Fusarium and Aspergillus in Corneal Storage Medium
Authors: Duncan Katherine , Parker Jeff , Hoover Caroline , Lindquist Thomas D. , Jeng Bennie H.
Published: October 2018

Purpose:

The incidence of postkeratoplasty fungal infection is increasing in the United States, and our most commonly used corneal storage medium, Optisol-GS, contains antibiotics but no antifungal agents. We previously demonstrated the efficacy of amphotericin B additives in eliminating Candida albicans contaminants in Optisol-GS. The purpose of this study was to determine whether amphotericin B would also be efficacious against Fusarium solani and Aspergillus fumigatus.

Methods:

Vials of Optisol-GS were supplemented with 0.255 μg/mL of amphotericin B. Half of the vials were inoculated with F. solani and half with A. fumigatus. Positive control vials were inoculated with the fungi but no amphotericin B. The vials were refrigerated, sampled, and plated at different time points. The plates were then incubated at 36°C for 48 hr after which fungal colony counts were performed.

Results:

There was an average reduction in the growth of F. solani in the amphotericin B–supplemented vials of 44% on day 2, 79% on day 7, and 80% on day 14 when compared with the positive control vials. There was an average reduction in the growth of A. fumigatus in the amphotericin B–supplemented vials of 40% on day 2 and 14% on day 7 when compared with the positive control vials. Both amphotericin B–supplemented and control vials grew less than 2 colonies of A. fumigatus on day 14.

Conclusions:

This study suggests that amphotericin B additives in Optisol-GS reduce the growth of F. solani and A. fumigatus.
Trainee Performance in Loop Electrosurgical Excision Procedure (LEEP) After Simulation Training
Authors: Wilson Erin , Janssens Sarah , Ng Dora , Jolly Brian , Hewett David G. , Beckmann Michael
Published: October 2018

Objective

The aim of the study was to review the performance of trainees in loop electrosurgical excision procedure (LEEP) procedures after the introduction of a simulation training program.

Materials and Method

A simulation training program was introduced in September 2016 for gynecology trainees at the study institution. Trainees were encouraged to perform at least 3 simulated LEEP procedures before operating. For a 12-month period after the introduction of training, data on operating time and specimen quality measures of clear margin status, adequate depth, and absence of fragmentation were reviewed. This was compared with a 12-month period before simulation training (from September 2014–September 2015). Trainees were surveyed for feedback on the training.

Results

In total, 135 LEEP procedures were reviewed: 68 before and 67 after simulator training. Trainee specimens after training were more likely to be nonfragmented (89.2% vs 55.9%, p = .003), have clear margins (72.2% vs 41.9%, p = .015), and meet “all criteria” (46% vs 20.6%, p = .043) than trainee specimens before training. There was no change in depth adequacy (70.3% vs 67.7%, p = .99). Median trainee procedure time reduced from 18 minutes (interquartile range = 11–24) before training to 8 minutes after training (interquartile range = 6–11) (p = <0.001). There was no significant change in operating time or specimen quality from LEEP procedures performed by attendings (who did not use the simulator). Trainee and attending procedural outcomes were similar after training. Trainees had mostly positive views on the training, though reported time constraints as a barrier to simulation.

Conclusions

After the introduction of an LEEP simulation training program, operative time and specimen quality from trainee procedures seemed to improve.
Passive Leg Raising After Left Ventricular Assist Device Implantation
Authors: Ram Eilon , Dourov Daniil , Berkenstadt Haim , Lavee Jacob , Kassif Yigal , Peled-Potashnik Yael , Kogan Dina , Preisman Sergey , Raanani Ehud , Kogan Alexander
Published: October 2018

Left ventricular assist device (LVAD) implantation is a common procedure in patients with end-stage heart failure. Although optimal fluid management is essential for acceptable postoperative treatment, it is critical to identify which patients will benefit from fluid administration. Passive leg raising (PLR) is a validated dynamic method that predicts fluid responsiveness in patients with heart failure by inducing a transient increase in cardiac preload. We performed a prospective study on 20 consecutive patients who underwent PLR maneuvers after LVAD implantation. Left ventricular assist device flow, end-tidal carbon dioxide, central venous pressure (CVP), and mean arterial pressure (MAP) were measured before and after PLR. Passive leg raising responsiveness was defined as at least a 15% increase in LVAD flow: (11 were responders and 9 nonresponders). Of the responders, 7 had right ventricular dysfunction (≥3). Passive leg raising responsiveness was associated with an increase of 19% in the LVAD flow, the mean CVP was raised from 11.3 to 14.4 mm Hg and the MAP from 82.6 to 86.7 mm Hg. After PLR, end-tidal carbon dioxide was increased by 4.6 mm Hg in the responders and 1.1 mm Hg in the nonresponders. The PLR maneuver is a noninvasive and easy to perform method that uses LVAD flow to assess fluid responsiveness in patients with heart failure after LVAD implantation.
Direct-acting antiviral hepatitis C virus treatment perturbation of the metabolic milieu
Authors: Driedger Matt , Galanakis Chrissi , Doyle Mary-Anne , Cooper Curtis L.
Published: October 2018

Objective

Hepatitis C virus (HCV), cirrhosis, and HCV medications including direct-acting antivirals (DAAs) ±ribavirin may all influence the metabolic milieu. While interferon-based regimens improve glucose tolerance, evidence is limited on DAAs. Cases of elevated lactate have recently been reported in patients treated with DAAs, and lactic acidosis is a known complication of antivirals used to treat hepatitis B virus and HIV.

Patients and methods

Measures were evaluated at baseline, week 4, end of treatment, and 12–24 weeks after treatment. Mixed-effects modeling was used to determine factors influencing glucose and lactate over time.

Results

In total, 442 patients were treated (mean age 56, 65% male, 72% genotype 1, 48% cirrhotic). Glucose did not change on or after DAA treatment from baseline (P=0.51) aside from those with untreated diabetes, which declined (P=0.02). Overall, there was a decline in lactate following HCV treatment (mean 2.4–2.1 mmol/l; P<0.001). Lactate initially increased on treatment and then decreased after treatment completion in male patients treated with ribavirin. This pattern was not observed in other groups. There was no evidence of lactic acidosis with HCV nucleotide use.

Conclusion

Distinct glucose and lactate trajectories were identified without evidence of DAA metabolic toxicity. HCV treatment does not improve random glucose levels aside from perhaps in untreated diabetic patients.
Xenotransplantation tolerance: applications for recent advances in modified swine
Authors: Llore Nathaly P. , Bruestle Karina A. , Griesemer Adam
Published: October 2018

Purpose of review

The aim of this study was to review the recent progress in xenotransplantation achieved through genetic engineering and discuss the potential of tolerance induction to overcome remaining barriers to extended xenograft survival.

Recent findings

The success of life-saving allotransplantation has created a demand for organ transplantation that cannot be met by the supply of human organs. Xenotransplantation is one possible solution that would allow for a nearly unlimited supply of organs. Recent genetic engineering of swine has decreased the reactivity of preformed antibodies to some, but not all, potential human recipients. Experiments using genetically modified swine organs have now resulted in survival of life-supporting kidneys for over a year. However, the grafts show evidence of antibody-mediated rejection on histology, suggesting additional measures will be required for further extension of graft survival. Tolerance induction through mixed chimerism or thymic transplantation across xenogeneic barriers would be well suited for patients with a positive crossmatch to genetically modified swine or relatively negative crossmatches to genetically modified swine, respectively.

This review highlights the current understanding of the immunologic processes in xenotransplantation and describes the development and application of strategies designed to overcome them from the genetic modification of the source animal to the induction of tolerance to xenografts.
Anti-aquaporin-4 Antibody Positive Optic Neuritis Following Scrub Typhus in an Elderly Female
Authors: Bae Dae Woong , An Jae Young
Published: October 2018

Introduction:

Aquaporin-4 antibody (AQP4-Ab) is specific for neuromyelitis optica spectrum disorder (NMOSD) and so is helpful to distinguish NMOSD from other autoimmune diseases. Several viral infections may play a role in the onset of NMOSD.

Case Report:

We describe a case of a previous healthy 82-year-old woman who presented with acute visual loss occurring 3 weeks after scrub typhus. Physical examination showed a relatively afferent pupillary defect in the right eye and ophthalmoscopy revealed edema of the right optic disc. Enhanced magnetic resonance imaging revealed enhancement of the right optic nerve. Serological testing showed AQP4-Ab. After methylprednisolone pulse therapy followed by oral tapering of prednisolone, visual dysfunction was improved. Subsequently she experienced no attacks for 5 years.

Conclusions:

Optic neuritis (ON) associated with scrub typhus is extremely rare. Our case support that scrub typhus could trigger ON in a lifelong asymptomatic patient with AQP4-Ab and AQP4-Ab should be considered in a very old age patient with suspected postinfectious inflammatory ON.
Thrombolysis After Protamine Reversal of Heparin for Acute Ischemic Stroke After Cardiac Catheterization
Authors: Warner Danielle S. , Schwartz Bryan G. , Babygirija Reji , Rovin Richard A. , Kassam Amin B. , Biddick Lindsay , Sajjad Rehan , Chohan Adil , Panichpisal Kessarin
Published: October 2018

Background:

Patients with an acute ischemic stroke (AIS) following cardiac catheterization (CC) generally do not receive intravenous thrombolysis [intravenous tissue plasminogen activator (IV-tPA)] as it is contraindicated due to the coagulopathy related to the heparin used during the procedure. We report a case of AIS successfully treated with IV thrombolysis following protamine reversal of heparin effect.

Case report:

An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent elective transradial CC following an abnormal stress test. He had 2 drug-eluting stents for severe stenosis of mid-circumflex and right coronary arteries and received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. Computed tomographic scan of the brain and computed tomographic angiogram of head and neck were unremarkable. Bedside activated clotting time was 181. Protamine 40 mg was administered and 30 minutes later, the activated clotting time level was normalized. IV-tPA was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Magnetic resonance imaging of brain showed no acute infarction 24 hours after stroke.

Conclusions:

There are limited reports of protamine reversal of heparin before IV-tPA administration. To our knowledge, there are only 6 AIS cases including ours. Three cases received 0.6 mg/kg of tPA dose. All have favorable outcomes and no intracranial hemorrhage was reported. Protamine reversal of heparin for AIS after CC seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy.
Moana: A robust and scalable cell type classification framework for single-cell RNA-Seq data
Authors: Wagner Florian , Yanai Itai
Published: October 2018

Single-cell RNA-Seq (scRNA-Seq) enables the systematic molecular characterization of heterogeneous tissues at an unprecedented resolution and scale. However, it is currently unclear how to establish formal cell type definitions, which impedes the systematic analysis of scRNA-Seq data across experiments and studies. To address this challenge, we have developed Moana, a hierarchical machine learning framework that enables the construction of robust cell type classifiers from heterogeneous scRNA-Seq datasets. To demonstrate Moana’s capabilities, we construct cell type classifiers for human immune cells that accurately distinguish between closely related cell types in the presence of experimental perturbations and systematic differences between scRNA-Seq protocols. We show that Moana is generally applicable and scales to datasets with more than ten thousand cells, thus enabling the construction of tissue-specific cell type atlases that can be directly applied to analyze new scRNASeq datasets. A Python implementation of Moana can be found at https://github.com/yanailab/moana.
Intersubject MVPD: Empirical Comparison of fMRI Denoising Methods for Connectivity Analysis
Authors: Li Yichen , Saxe Rebecca , Anzellotti Stefano
Published: October 2018

Noise is a major challenge for the analysis of fMRI data in general and for connectivity analyses in particular. As researchers develop increasingly sophisticated tools to model statistical dependence between the fMRI signal in different brain regions, there is a risk that these models may increasingly capture artifactual relationships between regions, that are the result of noise. Thus, choosing optimal denoising methods is a crucial step to maximize the accuracy and reproducibility of connectivity models. Most comparisons between denoising methods require knowledge of the ground truth: of what is the ‘real signal’. For this reason, they are usually based on simulated fMRI data. However, simulated data may not match the statistical properties of real data, limiting the generalizability of the conclusions. In this article, we propose an approach to evaluate denoising methods using real (non-simulated) fMRI data. First, we introduce an intersubject version of multivariate pattern dependence (iMVPD) that computes the statistical dependence between a brain region in one participant, and another brain region in a different participant. iMVPD has the following advantages: 1) it is multivariate, 2) it trains and tests models on independent folds of the real fMRI data, and 3) it generates predictions that are both between subjects and between regions. Since whole-brain sources of noise are more strongly correlated within subject than between subjects, we can use the difference between standard MVPD and iMVPD as a ‘discrepancy metric’ to evaluate denoising techniques (where more effective techniques should yield smaller differences). As predicted, the difference is the greatest in the absence of denoising methods. Furthermore, a combination of removal of the global signal and CompCorr optimizes denoising (among the set of denoising options tested).
JHU-2545 Selectively Shields Salivary Glands and Kidneys during PSMA-Targeted Radiotherapy
Authors: Nedelcovych Michael T. , Dash Ranjeet P. , Wu Ying , Choi Eun Yong , Lapidus Rena S. , Majer Pavel , Abou Diane , Penet Marie-France , Nikolopoulou Anastasia , Amor-Coarasa Alex , Babich John , Thorek Daniel L. , Rais Rana , Kratochwil Clemens , Slusher Barbara S.
Published: October 2018

PURPOSE

Prostate-specific membrane antigen (PSMA) radiotherapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) with several beta or alpha particle-emitting radionuclide-conjugated small molecules showing efficacy in late stage patients. However, PSMA is also expressed in kidneys and salivary glands where specific uptake causes dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2- (phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Selective delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radiotherapy.

EXPERIMENTAL DESIGN

A tri-alkoxycarbonyloxy alkyl (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Preclinical pharmacokinetic and imaging experiments were conducted prior to assessment in 3 mCRPC patients receiving PSMA PET and radiotherapy.

RESULTS

JHU-2545 resulted in 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers 68Ga-PSMA-11 and 18F-DCFPyL by up to 85% without effect on tumor. In a mCRPC patient, JHU-2545 treatment prior to 68Ga-PSMA-617 administration reduced kidney SUVmax by 76% without effect on metastatic lesions. When administered prior to injection of the beta emitter 177Lu-PSMA-617, JHU-2545 shielded both the salivary glands (72% Gy reduction) and kidneys (45% Gy reduction) without effect on metastases’ dose.

CONCLUSIONS

JHU-2545 pre-treatment raises the cumulative dose limit and improves the safety and efficacy profile of PSMA radiotherapy.

STATEMENT OF TRANSLATIONAL RELEVANCE

Prostate Specific Membrane Antigen (PSMA) molecular radiotherapy has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), but endogenous expression of PSMA in kidneys and salivary glands causes uptake into these organs resulting in dose-limiting toxicities. We describe the discovery of JHU-2545, a PSMA inhibitor prodrug that selectively blocks kidney and salivary gland uptake of PSMA theranostics without altering tumor uptake in both preclinical models and in mCRPC patients. Pretreatment of JHU-2545 thereby improves the safety and efficacy profile of the multiple PSMA radiotherapies in development.
Deep reinforcement learning for the control of microbial co-cultures in bioreactors
Authors: Treloar Neythen J. , Fedorec Alexander J.H. , Ingalls Brian P. , Barnes Chris P.
Published: October 2018

Multi-species microbial communities are widespread in natural ecosystems. When employed for biomanufacturing, engineered synthetic communities have shown increased productivity (in comparison with pure cultures) and allow for the reduction of metabolic load by compartmentalising bioprocesses between multiple sub-populations. Despite these benefits, co-cultures are rarely used in practice because control over the constituent species of an assembled community has proven challenging. Here we demonstrate,in silico, the efficacy of an approach from artificial intelligence – reinforcement learning – in the control of co-cultures within continuous bioreactors. We confirm that feedback via reinforcement learning can be used to maintain populations at target levels, and that model-free performance with bang-bang control can outperform traditional proportional integral controller with continuous control, when faced with infrequent sampling. Further, we demonstrate that a satisfactory control policy can be learned in one twenty-four hour experiment, by running five bioreactors in parallel. Finally, we show that reinforcement learning can directly optimise the output of a co-culture bioprocess. Overall, reinforcement learning is a promising technique for the control of microbial communities.
Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector. Corrigendum
Authors: van Genderen E. , Clabbers M. T. B. , Das P. P. , Stewart A. , Nederlof I. , Barentsen K. C. , Portillo Q. , Pannu N. S. , Nicolopoulos S. , Gruene T. , Abrahams J. P.
Published: October 2018

Corrections are made to Table 1 in the article by van Genderen et al. [Acta Cryst. (2016), A72, 236–242].