bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Function of Uterine Glands in Domestic Animals
Authors: Spencer Thomas E. , Kelleher Andrew M. , Bartol Frank F.
Published: September 2018

All mammalian uteri contain glands that synthesize or transport and secrete substances into the uterine lumen. Uterine gland development, or adenogenesis, is uniquely a postnatal event in sheep and pigs and involves differentiation of glandular epithelium from luminal epithelium, followed by invagination and coiling morphogenesis throughout the stroma. Intrinsic transcription factors and extrinsic factors from the ovary and pituitary as well as the mammary gland (lactocrine) regulate uterine adenogenesis. Recurrent pregnancy loss is observed in the ovine uterine gland knockout sheep, providing unequivocal evidence that glands and their products are essential for fertility. Uterine gland hyperplasia and hypertrophy during pregnancy are controlled by sequential actions of hormones from the ovary and/or pituitary as well as the placenta. Gland-derived histotroph is transported by placental areolae for fetal growth. Increased knowledge of uterine gland biology is expected to improve pregnancy outcomes, as well as the health and productivity of mothers and their offspring.
Direct Numerical Simulation of Turbulent Flows Laden with Droplets or Bubbles
Authors: Elghobashi Said
Published: September 2018

This review focuses on direct numerical simulations (DNS) of turbulent flows laden with droplets or bubbles. DNS of these flows are more challenging than those of flows laden with solid particles due to the surface deformation in the former. The numerical methods discussed are classified by whether the initial diameter of the bubble/droplet is smaller or larger than the Kolmogorov length scale and whether the instantaneous surface deformation is fully resolved or obtained via a phenomenological model. Also discussed are numerical methods that account for the breakup of a single droplet or bubble, as well as multiple droplets or bubbles in canonical turbulent flows.
Three Mathematical Foundations for Syntax
Authors: Stabler Edward P.
Published: September 2018

Three different foundational ideas can be identified in recent syntactic theory: structure from substitution classes, structure from dependencies among heads, and structure as the result of optimizing preferences. As formulated in this review, it is easy to see that these three ideas are completely independent. Each has a different mathematical foundation, each suggests a different natural connection to meaning, and each implies something different about how language acquisition could work. Since they are all well supported by the evidence, these three ideas are found in various mixtures in the prominent syntactic traditions. From this perspective, if syntax springs fundamentally from a single basic human ability, it is an ability that exploits a coincidence of a number of very different things.
Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma
Authors: Nie Xin-Gang , Fan Dong-Sheng , Huang Yan-Xia , He Ying-Ying , Dong Bo-Li , Gao Feng
Published: September 2018

Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected and subsequently treated with 60 mmHg pressure and transfected with a series of plasmids aiding in the regulation of the expression of miR-149 and betacellulin (BTC). The levels of miR-149, BTC, phosphatidylinositol 3-kinase (PI3K), and Akt were subsequently determined. Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase reporter gene assay provided validation, highlighting BTC was indeed a target gene of miR-149. The downregulation of miR-149 is accompanied by an increased number of RGCs and decreased ultrastructural RGC alterations. Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.
Superior colliculus signals decisions rather than confidence: analysis of single neurons
Authors: Grimaldi Piercesare , Cho Seong Hah , Lau Hakwan , Basso Michele A.
Published: September 2018

Recent findings indicate that monkeys can report their confidence in perceptual decisions and that this information is encoded in neurons involved in making decisions, including the lateral intraparietal area (LIP) and the supplementary eye field (SEF). A key issue to consider when studying confidence is that decision accuracy often correlates with confidence reports; when we are performing well, we generally feel more confident. Expanding on work performed in humans, we designed a novel task for monkeys that dissociates perceptual information leading to decisions from perceptual information leading to confidence reports. Using this task, we recently showed that decoded ensemble activity recorded from the superior colliculus (SC) reflected decisions rather than confidence reports. However, our previous population level analysis collapsed over multiple SC neuronal types and therefore left open the possibility that first, individual discharge rates might encode information related to decision confidence, and second, different neuronal cell types within the SC might signal decision confidence independently of decision accuracy. We found that when decision accuracy and decision confidence covaried, modulation occurred primarily in neurons with prelude activity (buildup neurons). However, isolating decision confidence from decision accuracy uncovered that only a few, primarily buildup neurons showed signals correlating uniquely with decision confidence and the effect sizes were very small. Based on this work and our previous work using decoding methods, we conclude that neuronal signals for decision confidence, independent of decision accuracy, are unlikely to exist at the level of single or populations of neurons in the SC. Our results together with other recent work call into question normative models of confidence based on the optimal readout of decision signals.

NEW & NOTEWORTHY Models of decision confidence suggest that our sense of confidence is an optimal readout of perceptual decision signals. Here, we report that a subcortical area, the superior colliculus (SC), contains neurons with activity that signal decisions and confidence in a task in which decision accuracy and confidence covary, similar to area lateral intraparietal area in cortex. The signals from SC occur primarily in the neurons with prelude activity (buildup neurons). However, in a task that dissociates decision accuracy from decision confidence, we find that only a few individual neurons express unique signals of confidence. These results call into question normative models of confidence based on optimal readout of perceptual decision signals.
Movement and perception recalibrate differently across multiple days of locomotor learning
Authors: Leech Kristan A. , Day Kevin A. , Roemmich Ryan T. , Bastian Amy J.
Published: September 2018

Learning a new movement through error-based adaptation leads to recalibration of movement and altered perception of that movement. Although presumed to be closely related, the relationship between adaptation-based motor and perceptual changes is not well understood. Here we investigated the changes in motor behavior and leg speed perception over 5 days of split-belt treadmill adaptation. We specifically wanted to know if changes in the perceptual domain would demonstrate savings-like behavior (i.e., less recalibration with more practice) and if these changes would parallel the savings observed in the motor domain. We found that the recalibration of leg speed perception decreased across days of training, indicating savings-like behavior in this domain. However, we observed that the magnitude of savings across days was different between motor and perceptual domains. These findings suggest a degree of independence between the motor and perceptual processes that occur with locomotor adaptation.

NEW & NOTEWORTHY Error-based adaptation learning drives changes in movement and perception of movement. Are these changes across domains linked or simply coincidental? Here, we studied changes in movement and perception across 5 days of repeated locomotor adaptation. Savings-like behavior in the motor and perceptual domains developed with different magnitudes and over different timescales, leading us to conclude that motor and perceptual processes operate at least somewhat independently during locomotor adaptation.
Opposing mechanisms underlying differential changes in brain oxygen and temperature induced by intravenous morphine
Authors: Solis Ernesto , Afzal Anum , Kiyatkin Eugene A.
Published: September 2018

Morphine remains widely used in clinical settings due to its potent analgesic properties. However, one of the gravest risks of all opioids is their ability to induce respiratory depression and subsequent brain hypoxia that can lead to coma and death. Due to these life-threatening effects, our goal was to examine the effects of intravenous morphine at a wide range of doses (0.1–6.4 mg/kg) on changes in brain oxygen levels in freely moving rats. We used oxygen sensors coupled with high-speed amperometry and conducted measurements in the nucleus accumbens (NAc) and subcutaneous (SC) space, the latter serving as a proxy for blood oxygen levels that depend on respiratory activity. We also examined the effects of morphine on NAc, muscle, and skin temperature. Morphine induced dose-dependent decreases in SC oxygen levels, suggesting respiratory depression, but differential effects on NAc oxygen: increases at low and moderate doses (0.1–1.6 mg/kg) and decreases at the highest dose tested (6.4 mg/kg). Morphine also increased brain temperature at low and moderate doses but induced a biphasic, down-up change at high doses. The oxygen increases appear to result from a neurovascular coupling mechanism via local vasodilation and enhanced oxygen entry into brain tissue to compensate for blood oxygen drops caused by modest respiratory depression. At high morphine doses, this adaptive mechanism is unable to compensate for the enhanced respiratory depression, resulting in brain hypoxia. Hence, morphine appears to be safe when used as an analgesic at clinically relevant doses but poses great risks at high doses, likely to be abused by drug users.

NEW & NOTEWORTHY With the use of oxygen sensors coupled with amperometry, we show that morphine induces differential effects on brain oxygen levels, slightly increasing them at low doses and strongly decreasing them at high doses. In contrast, morphine dose dependently decreases oxygen levels in the SC space. Therefore, morphine engages opposing mechanisms affecting brain oxygen levels, enhancing them through neurovascular coupling at low, clinically relevant doses and decreasing them due to dramatic respiratory depression at high doses, likely to be abused.
Survey of Octylphenol, Nonylphenol, and Bisphenol A in Infant Milk Powders by Solid-Phase Extraction Combined GC/MS Method
Authors: Cai Chenggang , Ying Yibin , Wu Pinggu , Tang Jun , Wang Liyuan , Ying Tan
Published: September 2018

A detection method for 3 kinds of phenolic compounds of endocrine disruptors (4-nonylphenol, 4-octylphenol, and bisphenol A) in infant milk powders by solid-phase extraction combined GC-MS was established. This method can effectively remove interference materials from infant milk powder products. The limit of detection and the limit of quantitation of the 3 kinds of compounds were 0.8 μg/kg and 2.5 μg/kg, respectively, with the relative standard deviations of 4.3–12.1%. The recovery rates of 4-nonylphenol, 4-octylphenol, and bisphenol A were of 68.5–89.2%, 64.8–87.0%, and 97.8–110.0%, respectively. Concentrations of the bisphenol A were from 0.8 to 14 μg/kg in 35 samples of the total 60 samples. And the other two compounds of 4-nonylphenol and 4-octylphenol were not found in all the 60 samples tested. The established method is simple, rapid, accurate, and highly sensitive, and the pollution of endocrine disruptors in some infant milk powders products was detectable in trace amounts.
Renal Dysfunction and Recovery following Initial Treatment of Newly Diagnosed Multiple Myeloma
Authors: Derman Benjamin A. , Reiser Jochen , Basu Sanjib , Paner Agne
Published: September 2018

Introduction. Renal insufficiency (RI) in Multiple Myeloma (MM) portends a higher tumor burden and worse prognosis. Reversal of RI in newly diagnosed MM (NDMM) improves patient outcomes, but it is unknown if there is a disparity in renal recovery in NDMM between African Americans (AA) and non-African Americans. Methods. A retrospective chart review was conducted of 690 patients with NDMM at Rush University Medical Center from 2005 to 2016. 118 patients (59 AA and 59 non-AA) with NDMM and an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 at the time of diagnosis were identified and analyzed. The time to best renal response and best eGFR achieved during initial myeloma therapy were tabulated. Results. Median eGFR at the time of diagnosis was similar between the AA and non-AA groups (47.89 versus 51.95, p=0.56). Median absolute change in eGFR after initial therapy was significantly higher in the AA (+33.64) versus the non-AA group (+21.07, p=0.00183). This difference remained whether the baseline eGFR at diagnosis was <90 or <60 mL/min/1.73 m2. Discussion. AA patients with NDMM treated in the era of novel agents have greater improvement in renal function in comparison to non-AA patients, regardless of myeloma response. The biological underpinnings for this disparity require further investigation.
Analysis and Evaluation of SafeDroid v2.0, a Framework for Detecting Malicious Android Applications
Authors: Argyriou Marios , Dragoni Nicola , Spognardi Angelo
Published: September 2018

Android smartphones have become a vital component of the daily routine of millions of people, running a plethora of applications available in the official and alternative marketplaces. Although there are many security mechanisms to scan and filter malicious applications, malware is still able to reach the devices of many end-users. In this paper, we introduce the SafeDroid v2.0 framework, that is a flexible, robust, and versatile open-source solution for statically analysing Android applications, based on machine learning techniques. The main goal of our work, besides the automated production of fully sufficient prediction and classification models in terms of maximum accuracy scores and minimum negative errors, is to offer an out-of-the-box framework that can be employed by the Android security researchers to efficiently experiment to find effective solutions: the SafeDroid v2.0 framework makes it possible to test many different combinations of machine learning classifiers, with a high degree of freedom and flexibility in the choice of features to consider, such as dataset balance and dataset selection. The framework also provides a server, for generating experiment reports, and an Android application, for the verification of the produced models in real-life scenarios. An extensive campaign of experiments is also presented to show how it is possible to efficiently find competitive solutions: the results of our experiments confirm that SafeDroid v2.0 can reach very good performances, even with highly unbalanced dataset inputs and always with a very limited overhead.
Evaluation of Quality of Life and Satisfaction of Patients with Neuropathic Pain and Breakthrough Pain: Economic Impact Based on Quality of Life
Authors: Madariaga Muñoz María Candelas , Villegas Estévez Francisco , Jiménez López Antonio Javier , Cabezón Álvarez Ana , Soler López Begoña
Published: September 2018

Objective. The study objective was to assess the quality of life and satisfaction with treatment of patients with chronic neuropathic pain (CNP) who experience breakthrough pain (BTP) and to assess its economic impact. Design. Cross-sectional observational study. Setting. Fifteen pain units from Spanish hospitals completed the study. Participants. A total of 124 patients with adequately controlled CNP who experienced BTP were enrolled into the study. Intervention. No interventions were required. Main Outcome Measures. Quality of life was assessed using the SF12 v2 questionnaire, the results of which were used to calculate the estimated costs per patient and month and the SF-6D Health Utility Index. Patient satisfaction with treatment received for CNP and for BTP was assessed using a 10-point visual analogue scale. Other associated symptoms were analyzed using the ESAS (Edmonton Symptom Assessment System). Results. Patients had a mean age of 60.2 years (95% CI 58.4-63.3), and 46.8% (58) were males. 18.9% (23) experienced their first episode of BTP. A severe impairment of the physical component of SF12v2 was noted, with 94% of patients below the mean score of the population, while 88% had values lower than normal for the mental component. Mean cost per patient and month was $679 and was significantly greater in males ($763 versus $606), 4.96 times greater than in healthy population, and approximately double the cost of patients with CNP in Spain. Conclusions. Occurrence of BTP in patients with CNP causes a substantial increase in healthcare costs which is significantly greater in older males.
A Novel Model and ADMM Algorithm for MR Image Reconstruction
Authors: Zhou Bo , Yang Yu-Fei , Xie Wei-Si
Published: September 2018

Motivated by the ideas from the LOT model and its deformations, we propose a coupling model for the MR image reconstruction and apply the split Bregman iterative method on the proposed model by utilizing the augmented Lagrangian technique. The related minimization problem is then divided into four subproblems by means of the alternating minimization method. And on this basis, by combining the Barzilai-Borwein step size selection scheme, generalized shrinkage formulas, and the shrink operator, we propose an ADMM type algorithm to solve the proposed model. Several numerical examples are implemented; the experimental results demonstrate the feasibility and effectiveness of the proposed model and algorithm.
Regeneration of Pancreatic β-Islet Cells in a Type-II Diabetic
Authors: Jones Edwin C. , Rylands J. Craig , Jardet Cortney L.
Published: September 2018

A case report is presented in which a type-II diabetic patient significantly improved his dysfunctional β-islet cells using a combination of a strenuous exercise program, cyclical ketogenic diet, and oral GABA/probiotic supplementation. The patient was diagnosed with type-II diabetes at the age of 41 which then progressed through a typical series of treatment changes over 14 years. Treatment periods consisted of metformin therapy alone for 4 years followed by a metformin/glyburide combination therapy for 6 years, and eventually an insulin/metformin combination therapy for 4 years. One year after the initiation of insulin, the patient increased the level of strenuous physical activity (hiking and weight lifting) and adopted a ketogenic diet. Oral GABA and probiotic supplementation were also initiated at the age of 52.7. By the age of 55, the patient no longer required any insulin and is currently being managed with metformin alone. C-peptide values indicate a functional improvement of the β-islet cells during the time of insulin/GABA/probiotic treatment.
Optimization of Vacuum Microwave-Mediated Extraction of Syringoside and Oleuropein from Twigs of Syringa oblata
Authors: Liu Xiangping , Jing Xuemin , Li Guoliang
Published: September 2018

A vacuum microwave-mediated method was used to extract syringoside and oleuropein from Syringa oblata twigs. The optimal extraction conditions were an ethanol volume fraction of 40%, a liquid-solid ratio of 17 mL/g, 1 h of soaking time, −0.08 MPa of vacuum, a microwave irradiation power of 524 W, and a microwave irradiation time of 8 min. Under optimal parameters, the maximum yields of syringoside (5.92 ± 0.24 mg/g) and oleuropein (4.02 ± 0.18 mg/g) were obtained. The proposed method is more efficient than conventional methods for extracting syringoside and oleuropein from Syringa oblata. Moreover, less energy and time were required. The results implied that vacuum microwave-mediated extraction is a suitable method for the extraction of thermosensitive glycosides such as syringoside and oleuropein.
A Systematic Method to Evaluate the Shear Properties of Soil‐Rock Mixture considering the Rock Size Effect
Authors: Ren Minghui , Zhao Guangsi , Qiu Xianhao , Xue Qinghua , Chen Meiting
Published: September 2018

The soil‐rock mixture (S‐RM) is widely applied in the geotechnical engineering due to its better mechanical properties. The shear strength, an essential aspect of S‐RM which governs the stability and the deformation, is rather necessary to be revealed properly. The extraordinary issue of S‐RM compared to fine‐grained soils is the grain size effect on the strength analysis. This paper proposes a systematic method to obtain the realistic shear strength of S‐RM by detecting the rock size effect. Firstly, based on fractal theory, the rock size was determined as 5 mm by the multifractal property of granular size distribution. Then, based on 2 selected specimen sizes combining the engineering dimension, shear gaps (T) effect and specimen size effect on the shear strength of S‐RM have been investigated. It is shown that the gap of the direct shear test decides the physical mechanism of particles forming the shear resistance of S‐RM based on the variation of apparent cohesion and mobilized internal friction angle. Specimen size effect is weakened by the gap effect considering the boundary effect. Realistic and stable shear strength parameters of S‐RM have been researched by a reasonable gap (0.2–0.4D, where D is the largest particle size).
CDK8 Selectively Promotes the Growth of Colon Cancer Metastases in the Liver by Regulating Gene Expression of TIMP3 and Matrix Metalloproteinases
Authors: Liang Jiaxin , Chen Mengqian , Hughes Daniel , Chumanevich Alexander A. , Altilia Serena , Kaza Vimala , Lim Chang-Uk , Kiaris Hippokratis , Mythreye Karthikeyan , Pena Maria Marjorette , Broude Eugenia V. , Roninson Igor B.
Published: September 2018

Unresectable hepatic metastases of colon cancer respond poorly to existing therapies and are a major cause of colon cancer lethality. In this study, we evaluated the therapeutic viability of targeting the mediator kinase CDK8, an early clinical stage drug target, as a means to suppress metastasis of colon cancer. CDK8 was amplified or overexpressed in many colon cancers and CDK8 expression correlated with shorter patient survival. Knockdown or inhibition of CDK8 had little effect on colon cancer cell growth but suppressed metastatic growth of mouse and human colon cancer cells in the liver. This effect was due in part to inhibition of already established hepatic metastases, indicating therapeutic potential of CDK8 inhibitors in the metastatic setting. In contrast, knockdown or inhibition of CDK8 had no significant effect on the growth of tumors implanted subcutaneously, intrasplenically, or orthotopically in the cecum. CDK8 mediated colon cancer growth in the liver through downregulation of matrix metalloproteinase (MMP) inhibitor TIMP3 via TGFβ/SMAD-driven expression of a TIMP3-targeting microRNA, miR-181b, along with induction of Mmp3 in murine or MMP9 in human colon cancer cells via Wnt/β-catenin-driven transcription. These findings reveal a new mechanism for negative regulation of gene expression by CDK8 and a site-specific role for CDK8 in colon cancer hepatic metastasis. Our results indicate the utility of CDK8 inhibitors for the treatment of colon cancer metastases in the liver and suggest that CDK8 inhibitors may be considered in other therapeutic settings involving TGFβ/SMAD or Wnt/β-catenin pathway activation.

Significance:

These findings demonstrate that inhibition of the transcription-regulating kinase CDK8 exerts a site-specific tumor-suppressive effect on colon cancer growth in the liver, representing a unique therapeutic opportunity for the treatment of advanced colon cancer.
Strategy for Tumor-Selective Disruption of Androgen Receptor Function in the Spectrum of Prostate Cancer
Authors: Rosati Rayna , Polin Lisa , Ducker Charles , Li Jing , Bao Xun , Selvakumar Dakshnamurthy , Kim Seongho , Xhabija Besa , Larsen Martha , McFall Thomas , Huang Yanfang , Kidder Benjamin L. , Fribley Andrew , Saxton Janice , Kakuta Hiroki , Shaw Peter , Ratnam Manohar
Published: September 2018

Purpose:

Testosterone suppression in prostate cancer is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 is required for AR-dependent growth in various hormone-dependent and castration-resistant prostate cancer models. The amino-terminal domain of AR docks at two sites on ELK1 to coactivate essential growth genes. This study explores the ability of small molecules to disrupt the ELK1–AR interaction in the spectrum of prostate cancer, inhibiting AR activity in a manner that would predict functional tumor selectivity.

Experimental Design:

Small-molecule drug discovery and extensive biological characterization of a lead compound.

Results:

We have discovered a lead molecule (KCI807) that selectively disrupts ELK1-dependent promoter activation by wild-type and variant ARs without interfering with ELK1 activation by ERK. KCI807 has an obligatory flavone scaffold and functional hydroxyl groups on C5 and C3′. KCI807 binds to AR, blocking ELK1 binding, and selectively blocks recruitment of AR to chromatin by ELK1. KCI807 primarily affects a subset of AR target growth genes selectively suppressing AR-dependent growth of prostate cancer cell lines with a better inhibitory profile than enzalutamide. KCI807 also inhibits in vivo growth of castration/enzalutamide-resistant cell line–derived and patient-derived tumor xenografts. In the rodent model, KCI807 has a plasma half-life of 6 hours, and maintenance of its antitumor effect is limited by self-induced metabolism at its 3′-hydroxyl.

Conclusions:

The results offer a mechanism-based therapeutic paradigm for disrupting the AR growth-promoting axis in the spectrum of prostate tumors while reducing global suppression of testosterone actions. KCI807 offers a good lead molecule for drug development.
Automated Quantification of Fragmented Red Blood Cells: Neonatal Reference Intervals and Clinical Disorders of Neonatal Intensive Care Unit Patients with High Values
Authors: Judkins Allison J. , MacQueen Brianna C. , Christensen Robert D. , Henry Erick , Snow Gregory L. , Bennett Sterling T.
Published: September 2018

Background: Schistocytes are circulating erythrocyte fragments. They can be identified microscopically from a blood smear; but automated systems evaluate more cells and avoid inconsistencies in microscopy. Studies using adult subjects indicate that automated quantification of schistocytes can be clinically useful. However, reference intervals for automated schistocyte counts of neonates have not been published, and the relevance of a high automated schistocyte count from neonates has not been reported. Objectives: Using retrospective automated neonatal complete blood count (CBC) data, we created reference intervals for fragmented red cells (FRCs) and sought to discover the clinical conditions of neonates with high FRCs (above the upper reference interval). Results: We created reference intervals based on 39,949 CBCs from 15,655 neonates 0–90 days old. The lower reference interval was 0 FRC/µL and the upper interval was 100,000/µL. The highest FRCs (96 CBCs from 44 neonates) were > 250,000/µL. These neonates clustered into the following groups: 37% had sepsis, 29% had disseminated intravascular coagulation (DIC), 17% had a genetic syndrome, 14% necrotizing enterocolitis (NEC), and 7% had iron deficiency (some had more than one diagnosis). Based on the reference intervals, we divided the 39,949 FRC values into 3 groups: (1) < 100,000/µL (“normal”), (2) 100,000–200,000/µL (“moderately elevated”), and (3) > 200,000/µL (“extremely elevated”). The odds that a microangiopathic condition (DIC, sepsis, NEC) or a microcytic disorder (iron deficiency) were present were significantly higher in the moderately elevated, and more so in the extremely elevated group. Conclusions: Our study suggests that a high FRC could prompt investigation into, or inform follow-up of, a neonatal microangiopathic or extremely microcytic disorder.
A Systematic Review of the Outcome of Hair Transplantation in Primary Scarring Alopecia
Authors: Ekelem Chloe , Pham Christine , Atanaskova Mesinkovska Natasha
Published: September 2018

Importance: Hair loss, or alopecia, is one of the most commonly presented problems in dermatology. Scarring alopecias are considered particularly damaging due to limited success in slowing permanent disease progression, and current treatment methods, such as intralesional and topical steroids and topical minoxidil, are largely ineffective. Objective: Hair transplantation is a debated treatment option for advanced cases of primary scarring alopecia. This study reviews the efficacy of hair transplantation as a treatment option for primary scarring alopecia. Evidence Review: A primary literature search was conducted using PubMed to identify articles in scarring alopecia and hair transplants published from 1960 to the present time. Findings: Fifteen reports with 34 patients were included in this review. Twenty six patients experienced moderate to positive results, while 8 patients experienced negative results or recurrence of disease. Positive hair transplantation results have been reported in patients with central centrifugal cicatricial alopecia, en coup de sabre, discoid lupus erythematous, pseudopelade de brocq, and folliculitis decalvans. Positive and ­negative results were observed in patients with lichen planopilaris and frontal fibrosing alopecia. Conclusion and Relevance: Findings show that hair transplant surgery can be considered as a treatment option for certain primary scarring alopecias. However, data must be interpreted with caution due to concern for positive-result publication bias.
Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies
Authors: Suwanwela Nijasri C. , Chen Christopher L.H. , Lee Chun Fan , Young Sherry H. , Tay San San , Umapathi Thirugnanam , Lao Annabelle Y. , Gan Herminigildo H. , Baroque II Alejandro C. , Navarro Jose C. , Chang Hui Meng , Advincula Joel M. , Muengtaweepongsa Sombat , Chan Bernard P.L. , Chua Carlos L. , Wijekoon Nirmala , de Silva H. Asita , Hiyadan John Harold B. , Wong Ka Sing Lawrence , Poungvarin Niphon , Eow Gaik Bee , Venketasubramanian Narayanaswamy ,   CHIMES-E Study Investigators
Published: September 2018

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.
Sunitinib or Sorafenib as Neoadjuvant Therapy May not Improve the Survival Outcomes of Renal Cell Carcinoma with Tumor Thrombus
Authors: Cai Wen , Huang Jiwei , Yuan Yichu , Hu Xiaoyi , Li Mingyang , Kong Wen , Zhang Jin , Guo Jianming , Chen Yonghui , Huang Yiran
Published: September 2018

Objectives: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. Methods: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. Results: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17–39 months) and 42 months (95% CI 30–54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. Conclusions: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.
MicroRNA High Throughput Loss-of-Function Screening Reveals an Oncogenic Role for miR-21-5p in Hodgkin Lymphoma
Authors: Yuan Ye , Niu Fubiao , Nolte Ilja M. , Koerts Jasper , de Jong Debora , Rutgers Bea , Osinga Jan , Azkanaz Maria , Terpstra Martijn , Bystrykh Leonid , Diepstra Arjan , Visser Lydia , Dzikiewicz-Krawczyk Agnieszka , Kok Klaas , Kluiver Joost  , van den Berg Anke
Published: September 2018

Background/Aims: Classical Hodgkin lymphoma (cHL) is among the most frequent lymphoma subtypes. The tumor cells originate from crippled germinal center (GC)-B cells that escaped from apoptosis. MicroRNAs (miRNAs) play important roles in B-cell maturation and aberrant expression of miRNAs contributes to the pathogenesis of cHL. Our aim was to identify oncogenic miRNAs relevant for growth of cHL using a high-throughput screening approach. Methods: A lentiviral pool of 63 miRNA inhibition constructs was used to identify miRNAs essential to cell growth in three cHL cell lines in duplicate. As a negative control we also infected cHL cell lines with a lentiviral barcoded empty vector pool consisting of 222 constructs. The abundance of individual constructs was followed over time by a next generation sequencing approach. The effect on growth was confirmed using individual GFP competition assays and on apoptosis using Annexin-V staining. Our previously published Argonaute 2 (Ago2) immunoprecipitation (IP) data were used to identify target genes relevant for cell growth / apoptosis. Luciferase assays and western blotting were performed to confirm targeting by miRNAs. Results: Four miRNA inhibition constructs, i.e. miR-449a-5p, miR-625-5p, let-7f-2-3p and miR-21-5p, showed a significant decrease in abundance in at least 4 of 6 infections. In contrast, none of the empty vector constructs showed a significant decrease in abundance in 3 or more of the 6 infections. The most abundantly expressed miRNA, i.e. miR-21-5p, showed significantly higher expression levels in cHL compared to GC-B cells. GFP competition assays confirmed the negative effect of miR-21-5p inhibition on HL cell growth. Annexin-V staining of cells infected with miR-21-5p inhibitor indicated a significant increase in apoptosis at day 7 and 9 after viral infection, consistent with the decrease in growth. Four miR-21-5p cell growth- and apoptosis-associated targets were AGO2-IP enriched in cHL cell lines and showed a significant decrease in expression in cHL cell lines in comparison to normal GC-B cells. For the two most abundantly expressed, i.e. BTG2 and PELI1, we confirmed targeting by miR-21-5p using luciferase assays and for PELI1 we also confirmed this at the protein level by western blotting. Conclusion: Using a miRNA loss-of-function high-throughput screen we identified four miRNAs with oncogenic effects in cHL and validated the results for the in cHL abundantly expressed miR-21-5p. MiR-21-5p is upregulated in cHL compared to GC-B cells and protects cHL cells from apoptosis possibly via targeting BTG2 and PELI1.
Diplomats' Mystery Illness and Pulsed Radiofrequency/Microwave Radiation
Authors: Golomb Beatrice Alexandra
Published: September 2018

Importance: A mystery illness striking U.S. and Canadian diplomats to Cuba (and now China) “has confounded the FBI, the State Department and US intelligence agencies” (Lederman, Weissenstein, & Lee, 2017). Sonic explanations for the so-called health attacks have long dominated media reports, propelled by peculiar sounds heard and auditory symptoms experienced. Sonic mediation was justly rejected by experts. We assessed whether pulsed radiofrequency/microwave radiation (RF/MW) exposure can accommodate reported facts in diplomats, including unusual ones.

Observations: (1) Noises: Many diplomats heard chirping, ringing or grinding noises at night during episodes reportedly triggering health problems. Some reported that noises were localized with laser-like precision or said the sounds seemed to follow them (within the territory in which they were perceived). Pulsed RF/MW engenders just these apparent “sounds” via the Frey effect. Perceived “sounds” differ by head dimensions and pulse characteristics and can be perceived as located behind in or above the head. Ability to hear the “sounds” depends on high-frequency hearing and low ambient noise. (2) Signs/symptoms: Hearing loss and tinnitus are prominent in affected diplomats and in RF/MW-affected individuals. Each of the protean symptoms that diplomats report also affect persons reporting symptoms from RF/MW: sleep problems, headaches, and cognitive problems dominate in both groups. Sensations of pressure or vibration figure in each. Both encompass vision, balance, and speech problems and nosebleeds. Brain injury and brain swelling are reported in both. (3) Mechanisms: Oxidative stress provides a documented mechanism of RF/MW injury compatible with reported signs and symptoms; sequelae of endothelial dysfunction (yielding blood flow compromise), membrane damage, blood-brain barrier disruption, mitochondrial injury, apoptosis, and autoimmune triggering afford downstream mechanisms, of varying persistence, that merit investigation. (4) Of note, microwaving of the U.S. embassy in Moscow is historically documented.

Conclusions and relevance: Reported facts appear consistent with pulsed RF/MW as the source of injury in affected diplomats. Nondiplomats citing symptoms from RF/MW, often with an inciting pulsed-RF/MW exposure, report compatible health conditions. Under the RF/MW hypothesis, lessons learned for diplomats and for RF/MW-affected civilians may each aid the other.
Rediscovery of the bopyrid isopod Parabopyrella thomasi (Nierstrasz & Brender à Brandis, 1929), parasite of the arrow shrimp Tozeuma carolinense Kingsley, 1878 (Decapoda, Caridea) in the Caribbean region
Authors: Romero-Rodríguez Jesús , Martínez-Mayén Mario
Published: September 2018

This is only the second report of the bopyrid isopodParabopyrella thomasi(Nierstrasz & Brender à Brandis, 1929) since it was described. The species infests the arrow shrimpTozeuma carolinenseKingsley, 1878, and this report of new material extends its known geographic distribution to the Caribbean coasts of Mexico. We provide data on some morphological variations in both sexes of this species as well as on the fecundity of this ectoparasite.
Abundance of Boeckella gracilis (Daday, 1902) (Copepoda, Calanoida) in seasonal coastal pools in the Araucania region (38°S, Chile)
Authors: De los Ríos Patricio
Published: September 2018

The presence of the calanoid copepod Boeckella gracilis (Daday, 1902) in Chilean seasonal pools has been only poorly studied as yet. The aim of the present study thus is to investigate the role of conductivity and temperature on the relative and absolute abundance of B. gracilis in seasonal coastal pools in the Araucania region (38°S, Chile). The results of correlation analysis revealed the presence of a significant inverse correlation between conductivity and relative abundance, whereas no significant correlations were found between conductivity and absolute abundance, between temperature and absolute abundance, and between temperature and relative abundance. These results agree partially with similar observations for mountain pools in the same region, but they would not agree with observations for calanoids of saline and subsaline inland waters in the northern and southern extremes of Chile. Considering this scenario, the species would show different populational responses to environmental stress in different situations, which phenomenon deserves to be studied more extensively and in more detail.
Claw regeneration, waving display and burrow characteristics of Austruca perplexa (H. Milne Edwards, 1852) (Brachyura, Ocypodidae) from southern Thailand
Authors: Tina Fahmida Wazed , Jaroensutasinee Mullica , Jaroensutasinee Krisanadej
Published: September 2018

We studied the effects of claw regeneration on male waving rate and burrow characteristics (i.e., important mate choice criteria) by examining the waving rates and burrow characteristics (diameter, total and horizontal lengths, depth, volume, maximum width, entry and burrow angles, and presence and location of chambers) of large-sized original-clawed males (OCMs) and regenerated-clawed males (RCMs) of Austruca perplexa (H. Milne Edwards, 1852). Female burrows were also examined. The results showed that female burrows were smaller than male burrows, with no chamber and, thus, female burrows are not used for breeding; however, 80% of RCM burrows, and 65% of OCM burrows, had chambers. Other characteristics were not different between RCM and OCM burrows, except for maximum width, which was larger in RCM burrows. The waving rates of OCMs and RCMs were not different. Our results indicate that claw regeneration do not have detrimental effects on male waving rate and burrow characteristics.
Effects of the Number of Muscle-Nerve-Muscle Grafts on Rat Facial Nerve Functional Recovery
Authors: Foecking Eileen M. , Burgess Bridget D. , Fridrici Zachary C. , Bialek Samantha E. , Low Christopher , Charous Steven J.
Published: September 2018

Introduction:

Facial nerve denervation can be devastating for patients. Primary neurorrhaphy and interposition (IP) nerve grafting are common reinnervation techniques. Muscle-nerve-muscle (MNM) grafting is a lesser known alternative. After previously demonstrating significant return of function using MNM grafting in a rat facial nerve model, the authors compare the use of multiple MNM nerve grafts with that of single MNM and IP nerve grafts.

Methods:

Thirty-six male rats were randomized into 4 groups: (1) repair with IP grafts, (2) 1 MNM graft, (3) 3 MNM grafts, and (4) control with no intervention. All groups had the lower zygomatic, buccal, and marginal mandibular branches of the right facial nerve removed. Return of movement and snout symmetry was measured over 16 weeks. Axonal regeneration and muscle atrophy were assessed and quantified.

Results:

All intervention groups had significantly improved movement and snout symmetry compared with control. Rats in the IP group had significantly increased axon density compared with those in the MNM groups but with smaller axonal diameter than control rats. No difference in axon density or diameter was observed between MNM groups. Use of 3 MNM grafts and IP grafts resulted in preservation of similar muscle mass compared with the control and 1-MNM groups.

Conclusion:

MNM grafting may be an alternative when other reanimation techniques are not possible.

Level of Evidence:

NA
The North Atlantic anchor: Canada and the Pacific Century
Authors: Nossal Kim Richard
Published: September 2018

This paper surveys Canada’s ambivalence towards the Asia Pacific, and seeks to put that ambivalence into the broader context of the dominant strategic perspective in Canada that has privileged, and continues to privilege, a North Atlantic focus for Canadian foreign and defence policy. It argues that Canada’s laggardly approach to Asia Pacific diplomacy can be best explained by the widespread perception among Canadians—and their government—that the North Atlantic alliance should remain the key driver of Canadian foreign and defence policy. Indeed, this geostrategic outlook has actually intensified with the election of Donald J. Trump and his unorthodox approach to the transatlantic alliance and the liberal international order. I argue that this North Atlantic outlook, so dominant for so much of Canada’s history, will continue to anchor Canadian foreign and defence policy, making Canada’s engagement in the Asia Pacific more problematic.
Collective suffering and the possibility of empathy in Karan Mahajan’s The Association of Small Bombs and Kiran Desai’s The Inheritance of Loss
Authors: Sinha Babli
Published: September 2018

This article argues that Karan Mahajan’s The Association of Small Bombs and Kiran Desai’s The Inheritance of Loss depart from conventional literary representations of the suffering of neoliberal subjects because they focus on collective rather than individual experiences of abjection. Emphasizing the breakdown in state services, the rise in insurgent groups, and the monetization of human life, the novels consider the possibility of empathy in a society structured by self-preoccupation and extreme inequality. The article compares how the two novels imagine coping with the condition of abjection, and focuses on their shared narrative technique of free indirect discourse as a means of encouraging empathy with characters.