bluuebunny/crossref_metadata_2025 huggingface dataset:
Humans as inverted bats: A comparative approach to the obstetric conundrum
Authors: Grunstra Nicole D. S. , Zachos Frank E. , Herdina Anna Nele , Fischer Barbara , Pavličev Mihaela , Mitteroecker Philipp
Published: February 2019

Objectives

The narrow human birth canal evolved in response to multiple opposing selective forces on the pelvis. These factors cannot be sufficiently disentangled in humans because of the limited range of relevant variation. Here, we outline a comparative strategy to study the evolution of human childbirth and to test existing hypotheses in primates and other mammals.

Methods

We combined a literature review with comparative analyses of neonatal and female body and brain mass, using three existing datasets. We also present images of bony pelves of a diverse sample of taxa.

Results

Bats, certain non‐human primates, seals, and most ungulates, including whales, have much larger relative neonatal masses than humans, and they all differ in their anatomical adaptations for childbirth. Bats, as a group, are particularly interesting in this context as they give birth to the relatively largest neonates, and their pelvis is highly dimorphic: Whereas males have a fused symphysis, a ligament bridges a large pubic gap in females. The resulting strong demands on the widened and vulnerable pelvic floor likely are relaxed by roosting head‐down.

Conclusions

Parturition has constituted a strong selective force in many non‐human placentals. We illustrated how the demands on pelvic morphology resulting from locomotion, pelvic floor stability, childbirth, and perhaps also erectile function in males have been traded off differently in mammals, depending on their locomotion and environment. Exploiting the power of a comparative approach, we present new hypotheses and research directions for resolving the obstetric conundrum in humans.
Sex hormone replacement therapy for individuals with Turner syndrome
Authors: Backeljauw Philippe , Klein Karen
Published: February 2019

Turner syndrome is a relatively common genetic condition resulting from absence of all or part of the second sex chromosome. Individuals with Turner syndrome commonly exhibit cardiovascular, endocrine, renal, reproductive, and/or psychosocial abnormalities, among other conditions. Most girls with Turner syndrome have hypergonadotropic hypogonadism and therefore need sex steroid hormonal replacement therapy. The optimal estrogen replacement treatment regimen to induce pubertal development is still being determined. The goals of the estrogen replacement are to mimic the normal physical and social development for timing and progression of puberty. Treatment should begin at 11–12 years of age, with dose increases every 6 months over a 2–3 year period. Initiation with low doses of estrogen is crucial to preserve growth potential. On the other hand, delaying estrogen replacement may be deleterious to bone and uterine health.
Unraveling the dispersal patterns and the social drivers of natal emigration of a cooperative breeding mammal, the golden lion tamarin
Authors: Romano Valéria , Martins Andreia F. , Ruiz‐Miranda Carlos R.
Published: February 2019

The study of the social drivers of animal dispersal is key to understanding the evolution of social systems. Among the social drivers of natal emigration, the conspecific attraction, aggressive eviction, and reduced social integration hypotheses predict that sexually mature individuals who receive more aggressive behavior and are engaged in less affiliative interactions are more likely to disperse. Few reports have explored these proximate factors affecting emigration in cooperatively breeding species, particularly of Neotropical primates. In this study, we investigated the dispersal patterns and tested the social drivers of natal emigration in the golden lion tamarin (Leontopithecus rosalia) — an endangered species inhabiting Atlantic rainforests fragments in Brazil. We used behavioral and demographic data collected during 7 years from 68 groups of tamarins inhabiting 20 forest fragments. Our analyses from the 160 dispersing individuals showed that dispersal success is higher for males and for those engaged in parallel dispersal, but that males and females use different strategies to enhance their dispersal success, males immigrate into established groups while females form new groups. We did not find high levels of agonistic behavior among group members before natal emigration. Instead we found that conspecific attraction drives natal emigration in both sexes, while additionally the low level of affiliative interactions within the natal group triggers male emigration. We discuss natal emigration in the broader perspective of the cooperative breeding system and the implications of these findings for the conservation of the species.
A SERS Optophysiological Probe for the Real‐Time Mapping and Simultaneous Determination of the Carbonate Concentration and pH Value in a Live Mouse Brain
Authors: Wang Weikang , Zhao Fan , Li Mingzhi , Zhang Chuanping , Shao Yuanhua , Tian Yang
Published: February 2019

To have a profound understanding of the physiological and pathological processes in a brain, both chemical and electrical signals need to be recorded, but this is still very challenging. Herein, micrometer‐ to nanometer‐sized SERS optophysiological probes were created to determine both the CO32− concentration and the pH in live brains and neurons because both species play important roles in regulating the acid–base balance in the brain. A ratiometric SERS microarray of eight microprobes with tip sizes of 5 μm was established and used for the first time for real‐time mapping and simultaneous quantification of CO32− and pH in a live brain. We found that both the CO32− concentration and the pH value dramatically decreased under ischemic conditions. The present SERS technique can be combined with electrophysiology without cross‐talk to record both electrical and chemical signals in brains. To deepen our understanding of the mechanism of ischemia on the single‐cell level, a SERS nanoprobe with a tip size of 200 nm was developed for use in a single neuron.
Harnessing Intramolecular Rotation To Enhance Two‐photon Imaging of Aβ Plaques through Minimizing Background Fluorescence
Authors: Shin Jinwoo , Verwilst Peter , Choi Hayoung , Kang Sangrim , Han Jiyou , Kim Na Hee , Choi Jin Gyu , Oh Myung Sook , Hwang Ji Sun , Kim Dokyoung , Mook‐Jung Inhee , Kim Jong Seung
Published: February 2019

The aggregation of amyloid beta (Aβ) proteins in senile plaques is a critical event during the development of Alzheimer's disease, and the postmortem detection of Aβ‐rich proteinaceous deposits through fluorescent staining remains one of the most robust diagnostic tools. In animal models, fluorescence imaging can be employed to follow the progression of the disease, and among the different imaging methods, two‐photon microscopy (TPM) has emerged as one of the most powerful. To date, several near‐infrared‐emissive two‐photon dyes with a high affinity for Aβ fibrils have been developed, but there has often been a tradeoff between excellent two‐photon cross‐sections and large fluorescence signal‐to‐background ratios. In the current work, we introduced a twisted intramolecular charge state (TICT)‐based de‐excitation pathway, which results in a remarkable fluorescence increase of around 167‐fold in the presence of Aβ fibrils, while maintaining an excellent two‐photon cross section, thereby enabling high‐contrast ex vivo and in vivo TPM imaging. Overall, the results suggest that adopting TICT de‐excitation in two‐photon fluorophores may represent a general method to overcome the tradeoff between probe brightness and signal‐to‐background ratio.
Wider Perspectives in Family Mediation: An Ecosystemic Approach
Authors: Parkinson Lisa
Published: February 2019

All mediation processes are constrained by their theoretical frameworks. A wider ecosystemic framework extends perspectives and can open new windows on family systems, interdisciplinary connections, and links between past, present, and future that shape decisions. While showing some similarities to family therapy, ecosystemic family mediation is a discrete process with clearly defined principles and boundaries. In practice, it needs to be tailored to the needs of the particular family, with special attention to the importance of listening and talking with children who are experiencing parental separation and major changes in their lives. Family mediators help family members to manage change. Mediators need to look for change within themselves too, remaining open to new ideas and the development of their thinking and practice.
Effects of the matrix crystallinity, dispersed phase, and processing type on the morphological, thermal, and mechanical properties of polylactide‐based binary blends with poly[(butylene adipate)‐co‐terephthalate] and poly[(butylene succinate)‐co‐adipate]
Authors: Nofar Mohammadreza , Oguz Hazal , Ovalı Didem
Published: February 2019

In this study, we prepared immiscible blends of 75 wt % polylactide (PLA) with 25 wt % poly[(butylene adipate)‐co‐terephthalate] (PBAT) through an injection‐molding (IM) process and a twin‐screw extruder (TSE) followed by IM. An amorphous polylactide (A‐PLA) and a semicrystalline polylactide (SC‐PLA) were used as the matrixes to investigate the matrix crystallization effect on the morphology and property development of the blends with only IM. A blend of A‐PLA with 25 wt % poly[(butylene succinate)‐co‐adipate] (PBSA) was also prepared through IM to compare its properties with those of the A‐PLA–PBAT blends. The morphological, thermal, solid viscoelastic, tensile, and flexural properties of the blends were compared, and their dependency on the evolution of the blend morphology was analyzed. The tensile results show that when IM was used as the sole processing technique, the ductility and toughness were significantly improved only when SC‐PLA was used as the matrix. Preprocessing through TSE also resulted in the enhancement of the blend ductility. In A‐PLA–PBSA, the vitrification of PLA hindered the crystallization of PBSA to very low temperatures (<0°C) and resulted in a very nonuniform structure with weak intermolecular bonding between phases. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47636.
Evaluation of Cilia Function in Rat Trachea Reconstructed Using Collagen Sponge Scaffold Seeded with Adipose Tissue‐Derived Stem Cells
Authors: Nakamura Ryosuke , Katsuno Tatsuya , Tateya Ichiro , Omori Koichi
Published: February 2019

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue‐derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC‐seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471–477, 2020. © 2019 American Association for Anatomy
An improved sum‐of‐squares based approach to fuzzy tracking control design of nonlinear systems
Authors: Pakkhesal Sajjad , Mohammadzaman Iman
Published: February 2019

In this paper, using a more general Lyapunov function, less conservative sum‐of‐squares (SOS) stability conditions for polynomial‐fuzzy‐model‐based tracking control systems are derived. In tracking control problems the objective is to drive the system states of a nonlinear plant to follow the system states of a given reference model. A state feedback polynomial fuzzy controller is employed to achieve this goal. The tracking control design is formulated as an SOS optimization problem. Here, unlike previous SOS‐based tracking control approaches, a full‐state‐dependent Lyapunov matrix is used, which reduces the conservatism of the stability criteria. Furthermore, the SOS conditions are derived to guarantee the system stability subject to a given H∞ performance. The proposed method is applied to the pitch‐axis autopilot design problem of a high‐agile tail‐controlled pursuit and another numerical example to demonstrate the effectiveness and benefits of the proposed method.
Multicentre study of non-surgical management of diverticulitis with abscess formation
Authors: Lambrichts D P V , Bolkenstein H E , van der Does D C H E , Dieleman D , Crolla R M P H , Dekker J W T , van Duijvendijk P , Gerhards M F , Nienhuijs S W , Menon A G , de Graaf E J R , Consten E C J , Draaisma W A , Broeders I A M J , Bemelman W A , Lange J F
Published: February 2019

Background

Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non-surgical management (antibiotics with or without percutaneous drainage (PCD)). The aim was to assess outcomes of non-surgical treatment and to identify risk factors for adverse outcomes.

Methods

Patients with a first episode of CT-diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non-surgically. Baseline characteristics, short-term (within 30 days) and long-term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no-PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery.

Results

Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow-up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74·3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short-term treatment failure (Hinchey I: 22·3 versus 33 per cent, P = 0·359; Hinchey II: 25·9 versus 36 per cent, P = 0·149) or emergency surgery (Hinchey I: 5·1 versus 6 per cent, P = 0·693; Hinchey II: 10·4 versus 15 per cent, P = 0·117), but significantly more complications were found in patients with Hinchey II disease undergoing PCD (12 versus 3·7 per cent; P = 0·032). Multivariable analyses showed that treatment strategy (PCD versus no PCD) was not independently associated with short-term treatment failure (odds ratio (OR) 1·47, 95 per cent c.i. 0·81 to 2·68), emergency surgery (OR 1·29, 0·56 to 2·99) or long-term surgery (hazard ratio 1·08, 95 per cent c.i. 0·69 to 1·69). Abscesses of at least 3 cm in diameter were associated with short-term treatment failure (OR 2·05, 1·09 to 3·86), and abscesses of 5 cm or larger with the need for surgery during short-term follow-up (OR 2·96, 1·03 to 8·13).

Conclusion

The choice between PCD with antibiotics or antibiotics alone as initial non-surgical treatment of Hinchey Ib and II diverticulitis does not seem to influence outcomes.
Understanding cognitive functioning in glioma patients: The relevance of IDH‐mutation status and functional connectivity
Authors: Derks Jolanda , Kulik Shanna , Wesseling Pieter , Numan Tianne , Hillebrand Arjan , van Dellen Edwin , de Witt Hamer Philip C. , Geurts Jeroen J. G. , Reijneveld Jaap C. , Stam Cornelis J. , Klein Martin , Douw Linda
Published: February 2019

Introduction

Cognitive deficits occur frequently in diffuse glioma patients, but are limitedly understood. An important marker for survival in these patients is isocitrate dehydrogenase (IDH) mutation (IDH‐mut). Patients with IDH‐mut glioma have a better prognosis but more often suffer from epilepsy than patients with IDH‐wildtype (IDH‐wt) glioma, who are generally older and more often have cognitive deficits. We investigated whether global brain functional connectivity differs between patients with IDH‐mut and IDH‐wt glioma, and whether this measure reflects variations in cognitive functioning in these subpopulations beyond the associated differences in age and presence of epilepsy.

Methods

We recorded magnetoencephalography and tested cognitive functioning in 54 diffuse glioma patients (31 IDH‐mut, 23 IDH‐wt). Global functional connectivity between 78 atlas regions spanning the entire cortex was calculated in two frequency bands (theta and alpha). Group differences in global functional connectivity were tested, as was their association with cognitive functioning, controlling for age, education, and presence of epilepsy.

Results

Patients with IDH‐wt glioma had lower functional connectivity in the alpha band than patients with IDH‐mut glioma (p = 0.040, corrected for age and presence of epilepsy). Lower alpha band functional connectivity was associated with poorer cognitive performance (p < 0.034), corrected for age, education, and presence of epilepsy.

Conclusion

Global functional connectivity is lower in patients with IDH‐wt diffuse glioma compared to patients with IDH‐mut diffuse glioma. Moreover, having lower functional alpha connectivity relates to poorer cognitive performance in patients with diffuse glioma, regardless of age, education, and presence of epilepsy.
Human immunodeficiency virus in cadavers: A review
Authors: Cilliers Karen , Muller Christo J.F. , Page Benedict J.
Published: February 2019

Millions of people are infected with human immunodeficiency virus (HIV); however, limited research focuses on post‐mortem HIV detection. Post‐mortem HIV testing is vital because medical records are not always available, and the HIV status can be unknown. The aims of this study were to review the available literature and determine the most efficient HIV test for post‐mortem samples, the optimal tissue or bodily fluid to be tested, and the duration that HIV remains reliably detectable. A literature search was conducted using PubMed and Google Scholar. Terms were related to HIV (HIV detection, HIV testing, HIV prevalence) and deceased individuals (post‐mortem, cadaver, deceased, organ donor). Inclusion criteria included English studies, or articles with at least an English abstract, while review articles were excluded. From this literature search, 43 studies were applicable. These studies most commonly used enzyme‐linked immunosorbent assay and Western blot as screening and confirmation tests, respectively. As for the optimal tissue or bodily fluid, serum remained the golden standard, while testing skin seemed promising. HIV remains detectable in the body up to 58 days after death, although few studies tested samples after 48 h. Knowledge of the HIV status can be beneficial in the case of accidental exposure and can create a range of possible research opportunities on the effects of HIV in different organ systems. This review outlined several gaps in the current literature and future studies should investigate these gaps because this information can be relevant to numerous professions. Clin. Anat. 32:603–610, 2019. © 2019 Wiley Periodicals, Inc.
The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin
Authors: Liu Qiang , Wang Kunzheng
Published: February 2019

Recent studies have indicated that promoting ferroptosis is a promising approach to attenuate drug resistance of cancer cells. Hence, this study aimed to induce ferroptosis in osteosarcoma cells, thereby increasing the sensitivity to cisplatin. Osteosarcoma cells MG63 and Saos‐2 were incubated with increasing doses of cisplatin to generate cisplatin‐resistant strains, MG63/DDP and Saos‐2/DDP. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate cell proliferation and cell death, respectively. Malondialdehyde (MDA), reactive oxygen species (ROS), and lipid oxidation in cells were measured to evaluate the degree of cell ferroptosis. MG63/DDP and Saos‐2/DDP cells showed increased viability and decreased death rate compared with MG63 and Saos‐2 cells, respectively, upon cisplatin treatment. Western blotting analysis indicated that protein levels of p‐STAT3 (Ser727), nuclear factor erythroid 2‐related factor 2 (Nrf2), and glutathione peroxidase 4 (GPx4) in drug‐resistant strains increased significantly in response to cisplatin. Co‐treatment with cisplatin and agonists of ferroptosis, Erastin, and RSL3, remarkably increased MDA, ROS, lipid oxidation, and sensitivity to cisplatin, in MG63/DDP and Saos‐2/DDP cells. Similar results were observed by co‐treatment of cells with cisplatin and a STAT3 inhibitor. The reduction of protein levels of p‐STAT3 (Ser727), Nrf2, and GPx4 in MG63/DDP and Saos‐2/DDP cells resulted in increased ferroptosis and sensitivity to cisplatin. These results indicate that cisplatin‐resistant osteosarcoma cells inhibited ferroptosis after exposure to low doses of cisplatin. However, ferroptosis agonists and STAT3 inhibitor reactivated ferroptosis in the cells and consequently increased sensitivity to cisplatin. This study demonstrates a new approach to attenuate resistance of osteosarcoma to cisplatin in vitro
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The Importance of Detail: How Differences in Ligand Structures Determine Distinct Functional Responses in Integrin αvβ3
Authors: Paladino Antonella , Civera Monica , Curnis Flavio , Paolillo Mayra , Gennari Cesare , Piarulli Umberto , Corti Angelo , Belvisi Laura , Colombo Giorgio
Published: February 2019

Ligand‐based control of protein functional motions can provide novel opportunities in the study of fundamental biological mechanisms and in the development of novel therapeutics. In this work we addressed the ligand‐based modulation of integrin functions. Inhibitors of integrin αvβ3 are interesting anticancer agents but their molecular mechanisms are still unclear: Peptides and peptidomimetics characterized by the Arg‐Gly‐Asp (RGD) or isoAsp‐Gly‐Arg (isoDGR) binding motifs have shown controversial agonist/antagonist effects. We have investigated the differential mechanisms of integrin activation/deactivation by three distinct ligands (cyclo‐RGDf(NMe)V (Cilengitide), cyclo[DKP3‐RGD], cyclo[DKP3‐isoDGR]; DKP=diketopiperazine) through a comparative analysis of ligand‐controlled protein internal dynamics: Although RGD facilitates the onset of dynamic states leading to activation, isoDGR induces a diffuse rigidification of the complex consistent with antagonist activities. Computational predictions have been experimentally probed by showing that the antibody AP5, which is capable of recognizing the active form of integrin, binds specifically to the RGD complexes and not to the isoDGR complex, which supports opposite functional roles of the two motifs targeting the same binding site.
Double Cu‐Catalyzed Direct Csp3−H Azidation/ CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates
Authors: Brandhofer Tobias , Özdemir Aysegül , Gini Andrea , García Mancheño Olga
Published: February 2019

Invited for the cover of this issue are Olga García Mancheño and Andrea Gini, previously at Regensburg University and currently at Münster University and Geneva University, respectively. The image depicts a dinosaur with its spines covered by the Cu‐catalyst to symbolize the one‐pot cascade reaction. Read the full text of the article at 10.1002/chem.201806288.
Model Experiments on Redox Flow Batteries
Authors: Rosenberg Dominique , Busker Maike , Jansen Walter
Published: February 2019

Redox‐Flow‐Batteries werden derzeit als eine mögliche Technologie zur Energiespeicherung im Rahmen der Energiewende diskutiert. Neben einem einfachen Laboraufbau für die Schule und das Hochschulpraktikum kann das Prinzip von Redox‐Flow‐Batteries mit verschiedenen Modellversuchen dargestellt werden. Durch diese Modellversuche werden der Aufbau und die Funktionsweise von Redox‐Flow‐Batteries simpel demonstriert.
Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors
Authors: Vojacek Steffen , Schulig Lukas , Wössner Nathalie , Geist Norman , Langel Walter , Jung Manfred , Schade Dennis , Link Andreas
Published: February 2019

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less‐well‐explored areas of chemical space. Thus, we synthesized fragment‐like tetrahydroindoles suitable for fragment‐based drug discovery as well as a well‐characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6‐trimethyl‐4‐oxo‐4,5,6,7‐tetrahydro‐1H‐indole‐3‐carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit‐to‐lead profiling.
A Phase I Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Adults With Severe Renal Impairment and Healthy Matched Control Participants
Authors: Parasrampuria Ridhi , Ford Susan L. , Lou Yu , Fu Caifeng , Bakshi Kalpana K. , Tenorio Allan R. , Trezza Christine , Spreen William R. , Patel Parul
Published: February 2019

This study investigates the impact of severe renal impairment on the pharmacokinetics of cabotegravir, an investigational HIV‐1 integrase inhibitor. This was a phase I, open‐label, parallel‐group, multicenter study conducted in 8 participants with severe renal impairment (creatinine clearance <30 mL/min; no renal replacement therapy) and 8 healthy participants (creatinine clearance >90 mL/min; 2 women/group; 6 men/group) matched for sex, age (±10 years), and body mass index (±25%). Participants received a single 30‐mg oral cabotegravir tablet to determine total and unbound plasma cabotegravir concentrations. Arithmetic and geometric least squares means were calculated, and cabotegravir noncompartmental pharmacokinetic parameters were compared using geometric least squares mean ratios with 90% confidence intervals. Safety was assessed throughout the study. Geometric least squares mean ratios (90% confidence intervals) were 0.97 (0.84–1.14) for area under the plasma concentration‐time curve extrapolated to infinity, 1.01 (0.87–1.17) for maximum observed plasma concentration, 1.31 (0.84–2.03) for unbound cabotegravir 2 hours after dosing, and 1.51 (1.19–1.92) for unbound cabotegravir 24 hours after dosing. All adverse events were grade 1, except grade 3 lipase elevation in a participant with renal impairment. Severe renal impairment did not impact plasma cabotegravir exposure, and cabotegravir may be administered without dose adjustment in renal impairment among patients not receiving renal replacement.
Visualisation of Electronic Excited‐State Correlation in Real Space
Authors: Plasser Felix
Published: February 2019

A method for the visualisation of excited‐state electron correlation is introduced and shown to address two notorious problems in excited‐state electronic structure theory, the analysis of excitonic correlation and the distinction between covalent and ionic wavefunction character. The method operates by representing the excited state in terms of electron and hole quasiparticles, fixing the hole on a fragment of the system and observing the resulting conditional electron density in real space. The application of this approach to oligothiophene, an exemplary conjugated polymer, illuminates excitonic correlation effects of its excited states in unprecedented clarity and detail. A study of naphthalene shows that the distinction between the ionic and covalent states of this molecule, which has so far only been achieved using elaborate valence‐bond theory protocols, arises naturally in terms of electron‐hole avoidance and enhanced overlap, respectively. More generally, the method is relevant for any excited state that cannot be described by a single electronic configuration.
Effect of the non‐linear screening on a modification of the Debye–Hückel plus hole approximation in complex plasma
Authors: Martynova Inna A. , Iosilevskiy Igor L.
Published: February 2019

The authors analyse two‐component electroneutral systems of classical macroions of finite size and point‐like oppositely charged microions. This article deals with the modification of the Debye–Hückel plus hole approximation when a non‐linear screening effect is taken into account in a complex plasma. Parameters of non‐linear screening of the macroions by surrounding microions are calculated within the framework of the Poisson–Boltzmann approximation. Two effects are found as a result of such calculations: (a) subdivision of all microions into two subclasses, free microions and bound microions and (b) a significant reduction of an effective charge Z* of the macroion in comparison with its true value Z due to the non‐linear screening by a thin high‐density envelope of the bound microions. We show that the value of a non‐ideal portion of an internal energy differs considerably in the case when the non‐linear screening effect is taken into account in the vicinity of the macroion.
Evolution of population structure in an estuarine‐dependent marine fish
Authors: Hollenbeck Christopher M. , Portnoy David S. , Gold John R.
Published: February 2019

Restriction site‐associated DNA (RAD) sequencing was used to characterize neutral and adaptive genetic variation among geographic samples of red drum, Sciaenops ocellatus, an estuarine‐dependent fish found in coastal waters along the southeastern coast of the United States (Atlantic) and the northern Gulf of Mexico (Gulf). Analyses of neutral and outlier loci revealed three genetically distinct regional clusters: one in the Atlantic and two in the northern Gulf. Divergence in neutral loci indicated gradual genetic change and followed a linear pattern of isolation by distance. Divergence in outlier loci was at least an order of magnitude greater than divergence in neutral loci, and divergence between the regions in the Gulf was twice that of divergence between other regions. Discordance in patterns of genetic divergence between outlier and neutral loci is consistent with the hypothesis that the former reflects adaptive responses to environmental factors that vary on regional scales, while the latter largely reflects drift processes. Differences in basic habitat, initiated by glacial retreat and perpetuated by contemporary oceanic and atmospheric forces interacting with the geomorphology of the northern Gulf, followed by selection, appear to have led to reduced gene flow among red drum across the northern Gulf, reinforcing differences accrued during isolation and resulting in continued divergence across the genome. This same dynamic also may pertain to other coastal or nearshore fishes (18 species in 14 families) where genetically or morphologically defined sister taxa occur in the three regions.
Three‐dimensional imaging of subsurface delamination in carbon fiber reinforced plastic using photoacoustic wave method
Authors: Nakahata Kazuyuki , Ogi Keiji , Mizukami Koichi , Ohira Katsumi , Maruyama Masayuki , Wada Satoshi , Namita Takeshi , Shiina Tsuyoshi
Published: February 2019

Ultrasonic wave generated by interaction of the material with pulsed lasers is known as photoacoustic (PA) wave. In this study, the PA imaging is applied to the nondestructive testing for carbon fiber reinforced plastic (CFRP). When subsurface flaws are in CFRP, the detection of the flaws is sometimes challenging because the trailing signal from the surface interferes with the scattered signal from the flaws. Here, we developed a PA microscopy (PAM) to reconstruct the location and shape of the subsurface flaws. The PAM employs a confocal arrangement of optical and acoustic lens to maximize the intensity of generated PA waves. To enhance the lateral resolution of the image, we introduced the synthetic aperture focusing technique (SAFT). In the SAFT, it is necessary to consider direction‐dependent group velocities due to the strong anisotropy in CFRP. The performance of the PA imaging combined with the SAFT was checked with artificial delaminations in a cross‐ply CFRP specimen. It was shown that the PA wave had a wide frequency band and our method offered a high spatial resolution image.
Spatial variability in beach biogeomorphology in a tropical archipelago
Authors: Gore Shannon , Cooper J. Andrew G. , Jackson Derek W.T. , Jarecki Lianna
Published: February 2019

Beaches of tropical island coasts exhibit high levels of diversity in composition and form in comparison with their continental counterparts. To investigate the nature and origin of this diversity, individual beach morphology and sedimentology was investigated in the British Virgin Islands (BVI), a Caribbean archipelago of > 60 high volcanic and low reef islands. The islands exhibit a diversity of orientations (some facing the Atlantic and some the Caribbean), elevation and gradient, rock type and wave energy. An examination of 100 beaches in the archipelago revealed a first‐order division into sand (70 beaches) and coral rubble (30 beaches). These beaches occur in seven planform types (determined by the antecedent geological framework) and are further subdivided according to shoreface type (seagrass, sandy shoreface, or reef). Mainland‐attached headland‐embayment beaches are the most common form of sand beach while coral rubble beaches usually occur as barriers that enclose salt ponds and wetlands.

Among sand beaches, carbonate content is greatest on Atlantic‐facing beaches, and coral rubble beaches are more common on Caribbean‐facing beaches. Grain size characteristics on sandy beaches are highly variable and range from fine to very coarse sands while coral rubble beaches range up to boulder‐sized clasts. The local source material is a primary determinant of sediment composition.

The local factors such as the underlying geology, source and availability of sediments are the primary determinants of beach form, composition and texture in the BVI. Oceanographic and climatic conditions such as the prevailing easterly trade winds and waves which seasonally range in direction from east‐northeast to southeast as well as beach orientation to Atlantic‐ or Caribbean‐facing waves also contribute to the variability, but in a secondary role. © 2019 John Wiley & Sons, Ltd.
Inverse association between statin use and head and neck cancer: Population‐based case‐control study in Han population
Authors: Kao Li‐Ting , Hung Shih‐Han , Kao Pai‐Feng , Liu Ju‐Chi , Lin Herng‐Ching
Published: February 2019

Background

This case‐control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population‐based database.

Methods

This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score‐matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure.

Results

Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77‐0.95) compared to propensity score‐matched controls.

Conclusion

This study found an inverse association between statin usage and head and neck cancer occurrence.
MCPIP1 regulates RORα expression to protect against liver injury induced by lipopolysaccharide via modulation of miR‐155
Authors: Li Zhenzhen , Han Shichao , Jia Yanhui , Yang Yunshu , Han Fu , Wu Gaofeng , Li Xiaoqiang , Zhang Wei , Jia Wenbin , He Xiang , Han Juntao , Hu Dahai
Published: February 2019

Liver injury plays vital roles in the development of inflammation and organ dysfunction during sepsis. MCP‐1‐induced protein 1 (MCPIP1), as an endoribonuclease, is a critical regulator for the maintenance of immune homeostasis. However, whether MCPIP1 participates in the septic liver injury remains unknown. The aim of this study was to investigate the role of MCPIP1 in lipopolysaccharides‐induced liver injury and the underlying modulatory mechanisms. Quantitative real‐time polymerase chain reaction and immunoblotting were used to determine proinflammatory cytokines, MCPIP1, retinoid‐related orphan receptor α (RORα), miR‐155, and related protein from nuclear factor‐κB (NF‐κB) pathway expression. Dual luciferase reporter assay was used to analyze whether miR‐155 regulates RORα transcription. Secretion of inflammatory cytokines into sera in mice were measured by enzyme‐linked immunosorbent assay. Hematoxylin and eosin staining, alanine aminotransferase, and aspartate transaminase, assay were used to evaluate liver function. We found that MCPIP1 expression was notably upregulated and significantly downregulated inflammatory cytokine secretion and NF‐κB signaling activation in macrophages following exposure to lipopolysaccharide. Moreover, miR‐155, lowered by MCPIP1, directly targeted on 3′‐untranslated region of RORα to activate an inflammatory response. Importantly, MCPIP1 overexpression in mice alleviated septic liver injury symptoms following lipopolysaccharides stimulation. Collectively, these data highlight MCPIP1/miR‐155/RORα axis as a novel modulation of inflammation in liver injury and potential therapeutic target for future research.
Gene therapy in rheumatoid arthritis: Strategies to select therapeutic genes
Authors: Zavvar Mahdi , Assadiasl Sara , Soleimanifar Narjes , Pakdel Fatemeh Dadgar , Abdolmohammadi Kamal , Fatahi Yousef , Abdolmaleki Mohsen , Baghdadi Hamed , Tayebi Lobat , Nicknam Mohammad H.
Published: February 2019

Significant advances have been achieved in recent years to ameliorate rheumatoid arthritis (RA) in animal models using gene therapy approaches rather than biological treatments. Although biological agents serve as antirheumatic drugs with suppressing proinflammatory cytokine activities, they are usually accompanied by systemic immune suppression resulting from continuous or high systemic dose injections of biological agents. Therefore, gene transfer approaches have opened an interesting perspective to deliver one or multiple genes in a target‐specific or inducible manner for the sustained intra‐articular expression of therapeutic products. Accordingly, many studies have focused on gene transferring methods in animal models by using one of the available approaches. In this study, the important strategies used to select effective genes for RA gene therapy have been outlined. Given the work done in this field, the future looks bright for gene therapy as a new method in the clinical treatment of autoimmune diseases such as RA, and by ongoing efforts in this field, we hope to achieve feasible, safe, and effective treatment methods.
Invasive aspergillosis causing gastric necrosis and perforation: A case report
Authors: Kulkarni Aditya Atul , Aruni Amaresh , Rastogi Pulkit , Rana Surinder , Gupta Rajesh
Published: February 2019

Aspergillosis is an opportunistic infection commonly seen in immunocompromised patients. Patients with hematological malignancies, postorgan transplantation, or those with comorbid conditions are susceptible to the development of invasive aspergillosis. Lungs are the main portal of entry and are thus most commonly involved. Aspergillosis can involve the gut, causing vascular thrombosis leading to ischemia and necrosis of the gut wall, resulting in perforation. Primary gastric involvement has been rarely seen, with few case reports in the literature. We report a rare case of primary invasive gastric aspergillosis in a 60‐year‐old diabetic and cirrhotic woman, who presented with clinical features of perforation peritonitis. Exploratory laparotomy was performed, and a 6 cm × 6 cm perforation with necrotizing inflammation was found in the distal stomach, pylorus, and duodenum. Distal gastrectomy with Billroth II reconstruction was performed. Pathology demonstrated septate fungal hyphae invading the gastric wall transmurally. The morphology was compatible with those of Aspergillus spp. Liposomal amphotericin B was started immediately after surgery based on the presence of unusually large areas of necrosis and perforation with blackish exudate covering the ulcer base. Unfortunately, the patient succumbed to rapidly progressive fungal septicemia despite early surgical intervention and critical care management. We recommend that any large confluent areas of gastric ulceration and necrosis with blackish exudates in an appropriate setting should evoke suspicion of invasive fungal infection. These patients should be started on prophylactic broadspectrum antifungal therapy immediately, which may be switched over to specific therapy once the diagnosis is confirmed.
Surgical management of colorectal lung metastases
Authors: Phillips Joseph D. , Hasson Rian M.
Published: February 2019

Pulmonary metastasectomy for colorectal cancer is an established means of treatment for select patients. This article will highlight the recent evidence published in the literature related to current practices for the surgical management of colorectal lung metastases and propose a diagnostic algorithm for use in clinical practice. It will also discuss controversies related to pulmonary metastasectomy, including the optimal timing of surgery, the extent of lymph node sampling/dissection, and the extent of surgical resection.
Submicellar liquid chromatography with fluorescence detection improves the analysis of naproxen in plasma and brain tissue
Authors: García‐Herrero Víctor , Torrado‐Salmerón Carlos , García‐Rodríguez Juan José , Torrado Guillermo , Torrado‐Santiago Santiago
Published: February 2019

Rapid, simple, and sensitive submicellar liquid chromatography with fluorescence detection was developed and validated to quantify naproxen in plasma and brain samples after oral administration of Naproxen formulations. The method used tramadol as an internal standard. Different submicellar mobile phases with organic phases ranging from 40 to 60% were studied to improve the native fluorescence of the Naproxen and decrease retention times. Separation was done in a Zorbax SB C8 column (250 × 4.6 mm, 5 μm) with a mobile phase containing acidic 0.007 M sodium dodecyl sulfate/acetonitrile (50:50, v/v) at a flow rate of 1 mL/min. Detection was performed with an excitation wavelength of 280 nm and emission of 310 nm and 360 nm for internal standard and Naproxen, respectively. The method was validated by International Conference of Harmonization standards. The method is specific, accurate, and precise (relative standard deviation <3%). Limits of detection and quantification were 0.08 and 0.25 μg/mL, respectively, for biological samples. This method was applied to analyze brain/plasma ratios in mice that had received oral administrations of Naproxen micellar formulations containing 10% w/w of sodium dodecyl sulfate, Cremophor RH 40, or Tween 80. The sodium dodecyl sulfate micelles were faster and more widely distributed in the mouse brains.
Improvement in nasal obstruction and quality of life after septorhinoplasty and turbinate surgery
Authors: Yamasaki Alisa , Levesque Patricia A. , Bleier Benjamin S. , Busaba Nicolas Y. , Gray Stacey T. , Holbrook Eric H. , Sedaghat Ahmad R. , Lindsay Robin W.
Published: February 2019

Objectives

To evaluate the long‐term impact of functional septorhinoplasty (SRP) with and without inferior turbinate reduction (ITR) on disease‐specific symptom severity and general health‐related quality of life (QOL).

Study Design

Prospective cohort study at a tertiary referral center.

Methods

Patients undergoing functional SRP with and without ITR were administered the Nasal Obstruction Symptom Evaluation (NOSE) scale to assess severity of nasal obstruction and the EuroQol‐5 Dimension Questionnaire Visual Analog Scale (EQ‐5D VAS) to assess general health‐related QOL preoperatively and at 2, 4, 6, 12, 24, and 36 months postoperatively. Patient demographics, surgical technique, symptom severity, and QOL outcomes were analyzed.

Results

A total of 567 patients were included, with 391 patients undergoing functional SRP alone (54.0% female; mean age 36.0 years [standard deviation (SD):16.2]) and 176 patients undergoing functional SRP with ITR (50.0% female; mean age 35.6 years [SD:13.6]). There was a significant decrease in NOSE and increase in EQ‐5D VAS scores in both groups through at least 24 months postoperatively. Change in NOSE scores was negatively correlated with change in EQ‐5D VAS (r = −0.38, P < 0.01). Compared to patients undergoing SRP, patients also undergoing ITR had a statistically but nonclinically significant improvement in NOSE, with similar trends for EQ‐5D VAS that were not significant.

Conclusion

SRP results in a sustained, long‐term improvement in nasal obstruction based on disease‐specific and general health‐related QOL measures, with incremental improvement in outcomes with addition of ITR. This study provides the foundation for defining health outcomes and the health utility value of surgical interventions that address nasal obstruction.

Level of Evidence

2c

Laryngoscope, 129:1554–1560, 2019