bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic values of the femoral pulse palpation test
Authors: Khammari Nystrom Fatine , Petersson Gunnar , Stephansson Olof , Johansson Stefan , Altman Maria
Published: October 2019

Objectives

To calculate diagnostic values of the femoral pulse palpation to detect coarctation of the aorta or other left-sided obstructive heart anomalies in newborn infants.

Design

Population-based cohort study.

Setting

Stockholm-Gotland County 2008–2012.

Patients

All singleton live-born infants without chromosomal trisomies, at ≥35 gestational weeks, followed-up until 1–2 years of age.

Main outcome measures

Diagnostic values and ORs for the femoral pulse test and subsequent diagnosis of coarctation of the aorta or left-sided obstructive heart malformation.

Results

Among the 118 592 included infants, 432 had weak or absent femoral pulses at the newborn examination. Seventy-eight infants were diagnosed with coarcation of the aorta and 48 with other left-sided obstructive heart malformations. The diagnostic values for the femoral pulse palpation test to detect coarctation of the aorta were: sensitivity: 19.2%, specificity: 99.6, positive predictive value: 3.5% and negative predictive value: 99.9%. For left-sided heart malformations: sensitivity: 8.3%, specificity: 99.6%, positive predictive value: 0.9% and negative predictive value: 100%. Sensitivity for coarctation of the aorta increased from 16.7% when examined at <12 hours of age to 30.0% at ≥96 hours of age.

Conclusions

The femoral pulse test to detect coarctation of the aorta and left-sided heart malformations has limited sensitivity, whereas specificity is high. As many infants with life-threatening cardiac malformations leave the maternity ward undiagnosed, further efforts are necessary to improve the diagnostic yield of the routine newborn examination.
Satisfaction of 30 402 callers to a medical helpline of the Emergency Medical Services Copenhagen: a retrospective cohort study
Authors: Zinger Nienke Doreen , Blomberg Stig Nikolaj , Lippert Freddy , Collatz Christensen Helle
Published: October 2019

Objectives

To keep healthcare systems sustainable for future demands, many countries are developing a centralised telephone line for out-of-hours primary care services. To increase the quality of such services, more information is needed on factors that influence caller satisfaction. The aim of this study was to identify demographic and call-related characteristics that are associated with the patient satisfaction of callers to a medical helpline in Denmark.

Design

Retrospective cohort study on patient registry data and questionnaire results.

Setting

Non-emergency medical helpline in the Capital Region of Denmark.

Participants

A random sample of 30 402 callers to the medical helpline between May 2016 and May 2018.

Primary and secondary outcome measures

Responses of a satisfaction questionnaire were linked to demographic and call-related dispatch data. Associations between the characteristics were analysed with multivariable logistic regression analysis with satisfaction as the dependent variable. A subgroup analysis was performed on callers for children aged between 0 and 4 years.

Results

Of the 30 402 analysed callers, 73.0% were satisfied with the medical helpline. Satisfaction was associated with calling for a somatic injury (OR: 1.96, 95% CI: 1.72 to 2.23), receiving a face-to-face consultation (OR: 2.27, 95% CI: 2.04 to 2.50) and a waiting time less than 10 min (OR: 1.82, 95% CI: 1.56 to 2.08). Callers for a 0-year to 4-year-old patient were more likely to be satisfied when they called for a somatic illness or received a telephone consultation, compared with the rest of the population (p<0.0001).

Conclusion

Callers were in general satisfied with the medical helpline. Satisfaction was associated with reason for encounter, triage response and waiting time. People calling for 0-year to 4-year-old patients were, compared with the rest of the population, more frequently satisfied when they called for a somatic illness or received a telephone consultation.
Implementation of digital pathology into diagnostic practice: perceptions and opinions of histopathology trainees and implications for training
Authors: Browning Lisa , Colling Richard , Rittscher Jens , Winter Lucinda , McEntyre Nicholas , Verrill Clare
Published: October 2019

There is increasing interest in the utility of digital pathology in the diagnostic setting. Successful transition requires guidance and training, but additionally an understanding of opinions and attitudes of histopathologists to ensure that potential barriers are addressed. Histopathology trainees as a group are likely to be at the forefront of this revolution, and have specific and as yet largely neglected training needs in this context. We designed an online survey for trainees within our region to capture their opinions and attitudes to digital pathology in the diagnostic setting, and to assess their perceived training needs. This survey indicates overall that these trainees have similar aspirations with regard to the predicted utility of digital pathology and the challenges faced as have been recognised among consultant histopathologists. While their training needs are also largely similar, there are specific additional considerations based around training in multiple centres with varying exposure to digital pathology.
Analysis of physically realizable stellar models in embedded class one spacetime manifold
Authors: Tamta Ritu , Fuloria Pratibha
Published: October 2019

In this paper, we searched two new exact solutions of Einstein’s field equations for modeling of compact cold stars using embedded class one spacetime continuum. We find out the expressions for pressure, density, anisotropy, redshift, metric potentials and other physical variables in terms of algebraic and trigonometric expressions and observe that all variables show well-behaved trends inside the compact stellar configurations. The causality condition is well maintained by our stellar models, i.e. the radial velocity and transverse velocity are less than l. The stability of our models is assessed via different stability criteria. The Buchdahl condition holds good for our solution. Herrera’s cracking method is applied to check the stability of stellar models. We generate anisotropic compact star models, whose masses and radii are in close agreement with the observed values for compact stars 4U 1538-52, LMCX-4, PSRJ1614-2230. A comparative analysis of the proposed models is carried out based on two different solutions reported in the paper. The appropriate graphical analysis is provided to authenticate the viability of the models.
Mass spectrum of exotic X(5568) state via artificial neural network
Authors: Mutuk Halil
Published: October 2019

In this paper, we assume [Formula: see text] exist and study mass spectrum of [Formula: see text] resonance and its hypothetical charmed partner, [Formula: see text], by artificial neural network method. The obtained predictions are compared with the experimental data and results of other theoretical works.
Chiral edge states in (2+1)-dimensional topological phases
Authors: Hernaski Carlos A. , Gomes Pedro R. S.
Published: October 2019

Chiral edge states of [Formula: see text]-dimensional Abelian and non-Abelian topological phases can be represented by chiral conformal field theories with integer and noninteger values of central charge, respectively. In this work we describe certain edge states in terms of constrained fermionic fields that realize chiral coset CFT structures. This construction arises naturally in the so-called quantum wires approach for topological phases and allows for representing fractionalized edge states directly in terms of fermionic degrees of freedom. At the same time, the constrained fermions description introduces some subtleties concerning gauge anomalies since it involves the coupling of chiral fermions to gauge fields. We describe in this paper how to handle these issues.
Towards microbe-targeted photosensitizers: Synthesis, characterization and in vitro photodynamic inactivation of the tuberculosis model pathogen M. smegmatis by porphyrin-peptide conjugates
Authors: Feese Elke , Gracz Hanna S. , Boyle Paul D. , Ghiladi Reza A.
Published: October 2019

Porphyrin-peptide conjugates have a breadth of potential applications, including use in photodynamic therapy, boron neutron capture therapy, as fluorescence imaging tags for tracking subcellular localization, as magnetic resonance imaging (MRI) positive-contrast reagents and as biomimetic catalysts. Here, we have explored three general routes to porphyrin-peptide conjugates using the Cu(I)-catalyzed Huisgen-Medal-Sharpless 1,3-dipolar cycloaddition of peptide-containing azides with a terminal alkyne-containing porphyrin, thereby generating porphyrin-peptide conjugates (PPCs) comprised of a cationic porphyrin coupled to short antimicrobial peptides. In addition to characterizing the PPCs using a variety of spectroscopic (UV-vis, [Formula: see text]H- and [Formula: see text]C-NMR) and mass spectrometric methods, we evaluated their efficacy as photosensitizers for the in vitro photodynamic inactivation of Mycobacterium smegmatis as a model for the pathogen Mycobacterium tuberculosis. Difficulties that needed to be overcome for the efficient synthesis of PPCs were the limited solubility of the quaternized pyridyl porphyrin in common solvents, undesired (de)metallation and transmetallation, and chromatographic purification. Photodynamic inactivation studies of a small library of PPCs against Mycobacterium smegmatis confirmed our hypothesis that the porphyrin-based photosensitizer maintains its ability to efficiently inactivate bacteria when conjugated to a small peptide by upwards of 5–6 log units (99.999[Formula: see text]%) using white light illumination (400–700 nm, 60 mW/cm[Formula: see text], 30 min). Further, hemolysis assays revealed the lack of toxicity of the PPCs against sheep blood at concentrations employed for in vitro photodynamic inactivation. Taken together, the results demonstrated the ability of PPCs to maintain their antimicrobial photodynamic inactivation efficacy when possessing a short cationic peptides for enabling the potential targeting of pathogens in vivo.
Obsessive-Compulsive Behavior Isn't Necessarily a Bad Thing
Authors: Marrack Philippa
Published: October 2019

It is difficult to believe that in about 1960 practically nothing was known about the thymus and some of its products, T cells bearing αβ receptors for antigen. Thus I was lucky to join the field of T cell biology almost at its beginning, when knowledge about the cells was just getting off the ground and there was so much to discover. This article describes findings about these cells made by others and myself that led us all from ignorance, via complete confusion, to our current state of knowledge. I believe I was fortunate to practice science in very supportive institutions and with very collaborative colleagues in two countries that both encourage independent research by independent scientists, while simultaneously ignoring or somehow being able to avoid some of the difficulties of being a woman in what was, at the time, a male-dominated profession.
Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia
Authors: Lignelli Ettore , Palumbo Francesco , Myti Despoina , Morty Rory E.
Published: October 2019

Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process of alveolarization—the generation of alveolar gas exchange units—is impeded, through mechanisms that remain largely unclear. As such, there is interest in the clarification both of the pathomechanisms at play in affected lungs, and the mechanisms of de novo alveoli generation in healthy, developing lungs. A better understanding of normal and pathological alveolarization might reveal opportunities for improved medical management of affected infants. Furthermore, disturbances to the alveolar architecture are a key histopathological feature of several adult chronic lung diseases, including emphysema and fibrosis, and it is envisaged that knowledge about the mechanisms of alveologenesis might facilitate regeneration of healthy lung parenchyma in affected patients. To this end, recent efforts have interrogated clinical data, developed new—and refined existing—in vivo and in vitro models of BPD, have applied new microscopic and radiographic approaches, and have developed advanced cell-culture approaches, including organoid generation. Advances have also been made in the development of other methodologies, including single-cell analysis, metabolomics, lipidomics, and proteomics, as well as the generation and use of complex mouse genetics tools. The objective of this review is to present advances made in our understanding of the mechanisms of lung alveolarization and BPD over the period 1 January 2017–30 June 2019, a period that spans the 50th anniversary of the original clinical description of BPD in preterm infants.
Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation
Authors: Capcha José Manuel Cóndor , Rodrigues Camila Eleutério , Moreira Roberto de Souza , Silveira Marcelo Duarte , Dourado Paulo , dos Santos Fernando , Irigoyen Maria Claudia , Jensen Leonardo , Garnica Margoth Ramos , Noronha Irene L , Andrade Lúcia , Gomes Samirah Abreu
Published: October 2019

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 106 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 106 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.
Delayed access to feed alters expression of genes associated with carbohydrate and amino acid utilization in newly hatched broiler chicks
Authors: Payne Jason A. , Proszkowiec-Weglarz Monika , Ellestad Laura E.
Published: October 2019

Newly hatched chicks must transition from lipid-rich yolk to carbohydrate-rich feed as their primary nutrient source, and posthatch delays in access to feed can have long-term negative consequences on growth and metabolism. In this study, impacts of delayed access to feed at hatch on expression of genes related to nutrient uptake and utilization in two metabolically important tissues, liver and muscle, were determined in broiler (meat-type) chickens. Hatched chicks were given access to feed within 3 h (fed) or delayed access to feed for 48 h (delayed fed), and liver and breast muscle were collected from males at hatch and 4 h, 1 day, 2 days, 4 days, and 8 days posthatch for analysis of gene expression. Differential expression of carbohydrate response element-binding protein and peroxisome proliferator-activated receptor-γ in muscle and liver was observed, with results indicating a transitional delay from lipid to carbohydrate metabolism when hatched chicks were not given immediate access to feed. Extended upregulation of insulin receptor mRNA was observed in both tissues in delayed fed birds, suggesting increased sensitivity to circulating levels of the hormone. Developmental delays in expression patterns of cationic amino acid transporters 1 and 2 in both tissues and large neutral amino acid transporter 1 in muscle were also apparent when immediate feed access was prevented. These data suggest that delayed transition to carbohydrate use and altered nutrient transport and utilization within liver and breast muscle are key factors negatively affecting growth and metabolism following delayed feed access in broiler chickens.
Evidence that hindbrain astrocytes in the rat detect low glucose with a glucose transporter 2-phospholipase C-calcium release mechanism
Authors: Rogers Richard C. , Burke Susan J. , Collier J. Jason , Ritter Sue , Hermann Gerlinda E.
Published: October 2019

Astrocytes generate robust cytoplasmic calcium signals in response to reductions in extracellular glucose. This calcium signal, in turn, drives purinergic gliotransmission, which controls the activity of catecholaminergic (CA) neurons in the hindbrain. These CA neurons are critical to triggering glucose counter-regulatory responses (CRRs) that, ultimately, restore glucose homeostasis via endocrine and behavioral means. Although the astrocyte low-glucose sensor involvement in CRR has been accepted, it is not clear how astrocytes produce an increase in intracellular calcium in response to a decrease in glucose. Our ex vivo calcium imaging studies of hindbrain astrocytes show that the glucose type 2 transporter (GLUT2) is an essential feature of the astrocyte glucosensor mechanism. Coimmunoprecipitation assays reveal that the recombinant GLUT2 binds directly with the recombinant Gq protein subunit that activates phospholipase C (PLC). Additional calcium imaging studies suggest that GLUT2 may be connected to a PLC-endoplasmic reticular-calcium release mechanism, which is amplified by calcium-induced calcium release (CICR). Collectively, these data help outline a potential mechanism used by astrocytes to convert information regarding low-glucose levels into intracellular changes that ultimately regulate the CRR.
Kinematics of forward and backward locomotion performed in different environmental conditions
Authors: Vemula Manideep G. , Deliagina Tatiana G. , Zelenin Pavel V.
Published: October 2019

Mice are frequently used in analyses of the locomotor system. Although forward locomotion (FWL) in intact mice has been studied previously, backward locomotion (BWL) in mice has never been analyzed. The aim of the present study was to compare kinematics of FWL and BWL performed in different environmental conditions (i.e., in a tunnel, on a treadmill, and on an air-ball). In all setups, the average speed and step amplitude during BWL were significantly reduced compared with FWL. The cycle duration varied greatly during both FWL and BWL. The average swing duration during BWL was twice shorter than during FWL on each setup. Mice exhibited different interlimb coordinations (trot and walk with lateral or diagonal sequence) during BWL but only one gait (walk with lateral sequence) during FWL. Location of the rostro-caudal paw trajectory in relation to the hip projection to the surface (HP) depended on hip height. With low hip height, the trajectory was displaced either rostrally (anterior steps) or caudally (posterior steps) to HP. With high hip height, HP was near the middle of the trajectory (middle steps). During FWL, all three forms of steps were observed in the tunnel and predominantly anterior and posterior steps on the treadmill and air-ball, respectively. During BWL, only anterior steps were observed. Intralimb coordination depended on the form of stepping. Limb joints were coordinated to keep the hip at approximately constant height during stance and to have the smallest functional limb length during swing when the limb passed under the hip.

NEW & NOTEWORTHY Mice are extensively used for the analysis of the locomotor system. This study is the first examination of the kinematics of forward and backward locomotor movements in different environmental conditions in mice. Obtained results represent a benchmark for studies based on manipulations of activity of specific populations of neurons to reveal their roles in control of specific aspects of locomotion.
Experimental Study on the Creep Behavior of Red Sandstone under Low Temperatures
Authors: Song Yongjun , Zhang Leitao , Yang Huimin , Ren Jianxi , Che Yongxin
Published: October 2019

In cold regions, the deformation characteristics and long‐term mechanical properties of rocks under low‐temperature conditions are considerably different from those in other regions. To study the deformation characteristics and long‐term mechanical properties of rocks in a low‐temperature environment and the effect of different temperatures, we perform a multilevel loading‐unloading uniaxial creep test on red sandstone samples and obtain the creep curves at different temperatures (20°C, −10°C, and −20°C). The results demonstrate that the total strain at each temperature can be divided into instantaneous and creep strains; the instantaneous strain includes instantaneous elastic and plastic strains, and the creep strain includes viscoelastic and viscoplastic strains. Temperature has a significant effect on the deformation properties of red sandstone. A decrease in temperature reduces the instantaneous and creep deformations of the rocks at all levels of stress. In addition, a decrease in temperature exponentially attenuates the total creep and viscoplastic strains of the rocks. 0°C is a critical point for the reduction of the total creep and viscoplastic strains of the rocks. When the temperature is greater than 0°C, the total creep and viscoplastic strains of the rocks decrease rapidly and linearly with decrease in temperature; however, when the temperature is less than 0°C, the decrease in the total creep and viscoplastic strains of the rocks is slow. The steady‐state creep rate of the rock samples decreases with decrease in temperature, whereas the creep duration increases with decrease in temperature, especially in the case of the accelerated creep stage. The accelerated creep durations of the rock samples S4 (20°C) and S7 (–10°C) are 0.07 h and 0.23 h, respectively.
Spatiotemporal Differences in Dominants of Dryness/Wetness Changes in Southwest China
Authors: Zhou Shujia , Sun Shanlei , Shi Wanrong , Wang Jiazhi , Li Jinjian , Wang Guojie , Lou Weiping
Published: October 2019

A full analysis of 3-month Standardized Precipitation-Evapotranspiration index (SPEI-3) changes and attribution analyses are of significance for deeply understanding dryness/wetness evolutions and thus formulating specific measures to sustain regional development. In this study, we analyze monthly and annual SPEI-3 changes over Southwest China (SWC; including Sichuan (SC), Chongqing (CQ), Guizhou (GZ), Yunnan (YN), and west Guangxi (wGX)) during 1961–2012, using the SPEI model and routine meteorological measurements at 269 weather sites. For SWC and each subregion (excluding wGX), annual SPEI-3 during 1961–2012 tends to decrease, and drying is at most of months in January and September–December, but wetting is in February–August (excluding March for wGX). Additionally, more than 50% of sites show declined and increased SPEI-3 in January, April, June, and August–December and the remaining months, respectively. Except for wGX with dominant of ET0, annual SPEI-3 changes in SWC and other four subregions have dominant of precipitation. Spatially, annual SPEI-3 changes at 59% of sites are because of precipitation, generally located in southeast SC, south YN, CQ, GZ, and south and northeast wGX. Nevertheless, dominants at regional and site scales vary among months, e.g., SWC, SC, CQ, and GZ, having dominant of precipitation (ET0) during September–December (most of months during January–August), YN always with dominant of precipitation, and wGX with dominant of precipitation (ET0) in February–April and July–December (January, May, and June). Importantly, this study provides a reference for quantitatively evaluating spatiotemporal dryness/wetness variations with climate change, especially for regions with significant drying/wetting.
A Comprehensive Review of the Mechanical Behavior of Suspension Bridge Tunnel-Type Anchorage
Authors: Han Yafeng , Liu Xinrong , Wei Ning , Li Dongliang , Deng Zhiyun , Wu Xiangchao , Liu Dongshuang
Published: October 2019

The recent surge of interest towards the mechanical response of rock mass produced by tunnel-type anchorage (TTA) has generated a handful of theories and an array of empirical explorations on the topic. However, none of these have attempted to arrange the existing achievements in a systematic way. The present work puts forward an integrative framework laid out over three levels of explanation and practical approach, mechanical behavior, and calculation method of the ultimate pullout force to compare and integrate the existing findings in a meaningful way. First, it reviews the application of TTA in China and analyzes its future development trend. Then, it summarizes the research results of TTA in terms of load transfer characteristics, deformation characteristics, failure modes, and calculation of ultimate uplift resistance. Finally, it introduces four field model tests in soft rock (mainly mudstone formations), and some research results are obtained. Furthermore, it compares the mechanical behavior of TTA in hard rock strata and soft rock strata, highlighting the main factors affecting the stability of TTA in soft rock formation. This paper proposes a series of focused topics for future investigation that would allow deconstruction of the drivers and constraints of the development of TTA.
Heparin-Induced Pituitary Apoplexy Presenting as Isolated Unilateral Oculomotor Nerve Palsy: A Case Report and Literature Review
Authors: Swaid Bakr , Kalaba Frank , Bachuwa Ghassan , Sullivan Stephen E.
Published: October 2019

Introduction. Pituitary apoplexy (PA) is a rare and potentially life-threatening clinical syndrome resulting from pituitary gland hemorrhage and/or infarction. Anticoagulation is a risk factor for triggering PA. Isolated oculomotor nerve palsy is an atypical presentation of PA. Case Presentation. A 65-year-old African American female with no past medical history of pituitary disease presented to the emergency department (ED) with nonspecific abdominal pain that was thought to be secondary to fecal stasis and subsequently improved with laxatives. She also reported atypical chest pain that was concerning for unstable angina. She was started on aspirin, clopidogrel, and intravenous (IV) heparin. Later, coronary catheterization showed no significant coronary artery disease (CAD). Twelve hours after the procedure, the patient developed acute complete left oculomotor nerve palsy with a severe headache. Magnetic resonance imaging (MRI) of the head showed a large pituitary mass. Pituitary apoplexy was suspected and the patient eventually underwent a successful trans-sphenoidal pituitary resection. Discussion. We report a case of PA manifesting as isolated left oculomotor nerve palsy without visual field defects in the setting of using dual antiplatelet therapy (DAPT) and IV heparin for acute coronary syndrome. To the best of our knowledge, this unique combination has not been previously reported.
Femtosecond Laser Implantation of a 355-Degree Intrastromal Corneal Ring Segment in Keratoconus: A Three-Year Follow-Up
Authors: Abdellah Marwa Mahmoud , Ammar Hatem Gamal
Published: October 2019

Purpose. To evaluate the outcomes of femtosecond laser-assisted implantation of a 355-degree intracorneal ring (ICR) (Keraring) in patients with keratoconus in the three-year follow-up. Setting. Future Femtolaser Center, Sohag, Egypt. Design. Prospective interventional case series. Patients and Methods. A prospective case series of 38 eyes of 26 patients with keratoconus had implantation of the 355-degree ICR keraring after tunnel creation with a femtosecond laser. The uncorrected visual acuities (UCVA) and best-corrected visual acuities (BCVA), sphere, cylinder, and manifest refraction spherical equivalent (SE), and mean keratometry (K), K max, and K min were evaluated preoperatively and 3, 6, 12, 24, and 36 months postoperatively, and all complications were reported. Results. 38 eyes of 26 patients with mean age 25.92 ± 5.44 years were enrolled in the study, 11 were males (42.3%). The mean UCVA improved from 0.93 ± 0.21 to 0.63 ± 0.21 logMAR (P≤0.001) and the mean BCVA from 0.67 ± 0.22 to 0.43 ± 0.26 logMAR (P<0.001). The mean sphere, cylinder, and spherical equivalent have been changed dramatically from preoperative to 3 month postoperative, which is statistically significant (P≤0.001), and the changes between 1 and 2 years and 2 and 3 years are also considerable and statistically significant; the K max and K min and K mean improved and the changes were statistically significant (P≤0.001), and the changes between one, two, and three years were also statistically significant. The safety and efficacy indices were changed through the three-year follow-up. The complications were corneal neovascularization (36.84%), corneal melting (26.3%), and ring extrusion (31.5%) at the end of the study. Conclusions. Implantation of a 355-degree intracorneal keraring using femtosecond laser improved the visual, refractive, and topographic parameters in keratoconus patients, with a high rate of ICR extrusion and instability. The study has been registered for the Pan African Clinical Trial Registry (http://www.pactr.org) database within No: PACTR201810796878908 on 29 October 2018.
Clinical Features of Combined Central Retinal Artery and Vein Occlusion
Authors: Wang Hao , Chang Yongye , Zhang Fen , Yang Rong , Yan Suxia , Dong Jieying , Zhang Minglian , Peng Shaomin
Published: October 2019

Purpose. To describe the clinical features of combined central retinal artery and vein occlusion (CCRAVO).Methods. This retrospective study included 33 admitted patients (33 eyes) who had CCRAVO. Clinical data, such as age, gender, best-corrected visual acuity (BCVA), intraocular pressure (IOP), findings on fundus color photography and fundus fluorescein angiography (FFA), and information about follow-up, were collected and analyzed.Results. The age of the patients with CCRAVO ranged from 22 to 78 years, with a mean of 48.8 ± 14.1 years. At presentation, BCVA of the involved eyes ranged from no light perception (NLP) to 20/20. In addition, 45.5% (15/33) of the eyes had BCVA of finger counting (FC) or below, whereas 12.1% (4/33) had BCVA of 20/60 or above. The IOP was lower in the involved eyes than in the fellow eyes (15.0 ± 3.0 mmHg vs. 16.4 ± 2.3 mmHg,p=0.03). Ophthalmoscopic examination showed changes in both central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO), including retinal hemorrhage, retinal ischemic whitening, optic disc hyperemia and/or edema, venous dilation and tortuosity, cotton wool spot (CWS), and Roth’s spot. FFA showed prolonged arm-to-retina time (ART) and retinal arteriovenous passage time (RAP) (17.1 ± 4.9 s and 12.1 ± 8.8 s, respectively). Capillary nonperfusion (CNP) was seen in 21 eyes (63.6%), and in 14 (42.2%) of these, CNP was larger than 10 disc areas. At 2 to 3 weeks after presentation, BCVA improved in 23 eyes (71.9%) and further deteriorated in 5 eyes (15.6%). Retinal ischemic whitening improved in more than half of the eyes, whereas retinal hemorrhage increased in nearly half of the eyes. Follow-up ranged from 6 to 56 months. Seven patients were lost to follow-up. At final follow-up, six eyes had a visual acuity of 20/60 or greater, but 6 eyes had FC or worse. Four eyes developed neovascularization on follow-up.Conclusion. CCRAVO is a sight-threatening entity. Manifestations of CRAO and CRVO can be seen simultaneously in the early stage of disease, and CRVO may play a more important role in the development of CCRAVO.
Agricultural and Forest Residues towards Renewable Chemicals and Materials Using Microwave Liquefaction
Authors: Shao Huijuan , Zhao Hongli , Xie Jiulong , Qi Jinqiu , Shupe Todd F.
Published: October 2019

Microwave-assisted liquefaction is regarded as a promising thermochemical approach to produce renewable and sustainable chemicals and materials from lignocellulosic biomass. Agricultural and forest residues as sources of lignocellulosic biomass have great potential in this regard. With process optimizations, several biomass types have been subjected to liquefaction in different solvents with various catalysts. The products from recent microwave liquefaction with and without further fractionation have been thoroughly analyzed and used for the synthesis of biomaterials. Renewable chemicals, polyurethane foams with partial use of renewable raw materials, and phenolic resins have been the main products from microwave-liquefied products. Further research on microwave liquefaction mechanisms and scalable production should be enhanced to fully evaluate the economic and environmental benefits. This work presents an overview on achievements using liquefaction in combination with microwave energy to convert lignocellulosic biomass into value-added products and chemicals.
Risk of Anal Cancer Following Benign Anal Disease and Anal Cancer Precursor Lesions: A Danish Nationwide Cohort Study
Authors: Faber Mette T. , Frederiksen Kirsten , Palefsky Joel M. , Kjaer Susanne K.
Published: October 2019

Background:

Human papillomavirus (HPV) is associated with the majority of anal high-grade intraepithelial neoplasia (AIN) and anal cancers. Little is known about the risk of anal cancer following a diagnosis of benign anal disease and AIN.

Methods:

Using data from nationwide, population-based Danish registries, a cohort of 126,174 individuals with either non-neoplastic anal disease or AIN 1 to 3 during 1970 to 2016 was followed until first occasion of anal cancer. Information on HIV status was obtained from the Danish HIV Cohort Study. The absolute risk of anal cancer was estimated using the Aalen-Johansen estimator taking into account censoring at emigration and end of follow-up and competing risk at time of death. Standardized incidence ratios (SIR) for anal cancer among individuals with non-neoplastic anal disease, including inflammatory lesions, hemorrhoids, and polyps, were estimated in Poisson models. Sex-, age-, and calendar period-specific national population rates were estimated using the Danish National Pathology Registry.

Results:

Anal cancer risk increased with increasing severity of lesions, reaching 4% 5 years after diagnosis of AIN3. Even among those with non-neoplastic anal lesions, particularly inflammatory lesions, anal cancer risk was significantly higher than expected from Danish national anal cancer rates (SIR = 2.8; 95% confidence intervals, 2.3–3.2). The absolute 5-year risk of anal cancer following AIN3 was considerably higher among HIV-positive (14.1%) than HIV-negative (3.2%) individuals.

Conclusions:

Anal cancer risk increases with increasing severity of lesions and is especially high among HIV-positive individuals.

Impact:

Vaccination against HPV is important in the prevention of both high-grade AIN and anal cancer.
Precision Chemoradiotherapy for HER2 Tumors Using Antibody Conjugates of an Auristatin Derivative with Reduced Cell Permeability
Authors: Hingorani Dina V. , Doan Matthew K. , Camargo Maria F. , Aguilera Joseph , Song Seung M. , Pizzo Donald , Scanderbeg Daniel J. , Cohen Ezra E.W. , Lowy Andrew M. , Adams Stephen R. , Advani Sunil J.
Published: October 2019

The most successful therapeutic strategies for locally advanced cancers continue to combine decades-old classical radiosensitizing chemotherapies with radiotherapy. Molecular targeted radiosensitizers offer the potential to improve the therapeutic ratio by increasing tumor-specific kill while minimizing drug delivery and toxicity to surrounding normal tissue. Auristatins are a potent class of anti-tubulins that sensitize cells to ionizing radiation damage and are chemically amenable to antibody conjugation. To achieve tumor-selective radiosensitization, we synthesized and tested anti-HER2 antibody–drug conjugates of two auristatin derivatives with ionizing radiation. Monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) were attached to the anti-HER2 antibodies trastuzumab and pertuzumab through a cleavable linker. While MMAE is cell permeable, MMAF has limited cell permeability as free drug resulting in diminished cytotoxicity and radiosensitization. However, when attached to trastuzumab or pertuzumab, MMAF was as efficacious as MMAE in blocking HER2-expressing tumor cells in G2–M. Moreover, MMAF anti-HER2 conjugates selectively killed and radiosensitized HER2-rich tumor cells. Importantly, when conjugated to targeting antibody, MMAF had the advantage of decreased bystander and off-target effects compared with MMAE. In murine xenograft models, MMAF anti-HER2 antibody conjugates had less drug accumulated in the normal tissue surrounding tumors compared with MMAE. Therapeutically, systemically injected MMAF anti-HER2 conjugates combined with focal ionizing radiation increased tumor control and improved survival of mice with HER2-rich tumor xenografts. In summary, our results demonstrate the potential of cell-impermeable radiosensitizing warheads to improve the therapeutic ratio of radiotherapy by leveraging antibody–drug conjugate technology.
Interferon-Gamma and Tumor Necrosis Factor-Related Weak Inducer of Apoptosis Expression in Neoangiogenesis in Colorectal Polypoid Lesions
Authors: Ruffolo Cesare , Toffolatti Luisa , Massani Marco , Pozza Anna , Campo Dell'Orto Marta , Saadeh Luca M. , Ferrara Francesco , Benvenuti Stefano , Dei Tos Angelo P. , Bassi Nicolò , Kotsafti Andromachi , Scarpa Marco
Published: October 2019

Background: Interferon gamma (IFNγ) and tumor necrosis factor-related weak inducer of apoptosis (TWEAK) molecules seem to have a potential effect on angiogenic factors such as vascular endothelial growth factor (VEGF). The aim of this study was to assess a possible interplay between IFNγ and TWEAK cytokines and VEGF machinery in the different steps of colorectal carcinogenesis. Methods: A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Polypoid lesion tissue samples were collected and frozen. Real-time reverse transcription polymerase chain reaction for IFNγ, TWEAK, and VEGF-A mRNA expression was performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Nonparametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. Results: IFNγ and TWEAK mRNA expression was higher in patients with T2 or more advanced colorectal cancer than in those with adenomas or T1 cancer (p < 0.001 and p = 0.01, respectively). IFNγ and TWEAK mRNA expression levels directly correlated with VEGF-A mRNA expression levels (rho = 0.44, p < 0.001 and rho = 0.29, p = 0.004, respectively). On the contrary, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGF-C protein levels (rho = –0.29, p = 0.04 and rho = –0.31, p = 0.03, respectively). Similarly, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGFR2 protein levels (rho = –0.38, p = 0.033 and rho = –0.40, p = 0.025, respectively). Conclusion: This study showed that in colorectal polypoid lesions, IFNγ and TWEAK expressions are directly correlated to VEGF-A expression but inversely correlated with VEGFR2 levels, suggesting a possible feedback mechanism in the regulation of VEGF-A expression.
Migratory and Dancing Macrophage Subsets in Atherosclerotic Lesions
Authors: McArdle Sara , Buscher Konrad , Ghosheh Yanal , Pramod Akula Bala , Miller Jacqueline , Winkels Holger , Wolf Dennis , Ley Klaus
Published: October 2019

Rationale:

Macrophages are essential regulators of atherosclerosis. They secrete cytokines, process lipoproteins and cholesterol, and take up apoptotic cells. Multiple subsets of plaque macrophages exist and their differential roles are emerging.

Objective:

Here, we explore macrophage heterogeneity in atherosclerosis plaques using transgenic fluorescent mice in which subsets of macrophages are labeled by GFP (green fluorescent protein), YFP (yellow fluorescent protein), neither, or both. The objective was to define migration patterns of the visible subsets and relate them to their phenotypes and transcriptomes.

Methods and Results:

Apoe
−/−
Cx3cr1

GFP

Cd11c

YFP

mice have 4 groups of macrophages in their aortas. The 3 visible subsets show varying movement characteristics. GFP and GFP+YFP+ macrophages extend and retract dendritic processes, dancing on the spot with little net movement while YFP macrophages have a more rounded shape and migrate along the arteries. RNA sequencing of sorted cells revealed significant differences in the gene expression patterns of the 4 subsets defined by GFP and YFP expression, especially concerning chemokine and cytokine expression, matrix remodeling, and cell shape dynamics. Gene set enrichment analysis showed that GFP+ cells have similar transcriptomes to cells found in arteries with tertiary lymphoid organs and regressing plaques while YFP+ cells were associated with progressing and stable plaques.

Conclusions:

The combination of quantitative intravital imaging with deep transcriptomes identified 4 subsets of vascular macrophages in atherosclerosis that have unique transcriptomic profiles. Our data link vascular macrophage transcriptomes to their in vivo migratory function. Future work on the functional significance of the change in gene expression and motility characteristics will be needed to fully understand how these subsets contribute to disease progression.
Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1‐Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial
Authors: Berger Samantha E. , Huggins Gordon S. , McCaffery Jeanne M. , Jacques Paul F. , Lichtenstein Alice H.
Published: October 2019

Background

Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established.

Methods and Results

Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1‐year intensive lifestyle intervention and with year 4 follow‐up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1–4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers.

Conclusions

Maintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00017953.
Stimulation of Collateral Vessel Growth by Inhibition of Galectin 2 in Mice Using a Single‐Domain Llama‐Derived Antibody
Authors: Hollander Maurits R. , Jansen Matthijs F. , Hopman Luuk H. G. A. , Dolk Edward , van de Ven Peter M. , Knaapen Paul , Horrevoets Anton J. , Lutgens Esther , van Royen Niels
Published: October 2019

Background

In the presence of arterial stenosis, collateral artery growth (arteriogenesis) can alleviate ischemia and preserve tissue function. In patients with poorly developed collateral arteries, Gal‐2 (galectin 2) expression is increased. In vivo administration of Gal‐2 inhibits arteriogenesis. Blocking of Gal‐2 potentially stimulates arteriogenesis. This study aims to investigate the effect of Gal‐2 inhibition on arteriogenesis and macrophage polarization using specific single‐domain antibodies.

Methods and Results

Llamas were immunized with Gal‐2 to develop anti–Gal‐2 antibodies. Binding of Gal‐2 to monocytes and binding inhibition of antibodies were quantified. To test arteriogenesis in vivo, Western diet‐fed
LDLR
.(low‐density lipoprotein receptor)–null Leiden mice underwent femoral artery ligation and received treatment with llama antibodies 2H8 or 2C10 or with vehicle. Perfusion restoration was measured with laser Doppler imaging. In the hind limb, arterioles and macrophage subtypes were characterized by histology, together with aortic atherosclerosis. Llama‐derived antibodies 2H8 and 2C10 strongly inhibited the binding of Gal‐2 to monocytes (93% and 99%, respectively). Treatment with these antibodies significantly increased perfusion restoration at 14 days (relative to sham, vehicle: 41.3±2.7%; 2H8: 53.1±3.4%,
P
=0.016; 2C10: 52.0±3.8%,
P
=0.049). In mice treated with 2H8 or 2C10, the mean arteriolar diameter was larger compared with control (vehicle: 17.25±4.97 μm; 2H8: 17.71±5.01 μm; 2C10: 17.84±4.98 μm;
P
<0.001). Perivascular macrophages showed a higher fraction of the M2 phenotype in both antibody‐treated animals (vehicle: 0.49±0.24; 2H8: 0.73±0.15,
P
=0.007; 2C10: 0.75±0.18,
P
=0.006). In vitro antibody treatment decreased the expression of M1‐associated cytokines compared with control (
P
<0.05 for each). Atherosclerotic lesion size was comparable between groups (overall
P
=0.59).

Conclusions

Inhibition of Gal‐2 induces a proarteriogenic M2 phenotype in macrophages, improves collateral artery growth, and increases perfusion restoration in a murine hind limb model.