bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual Presentation of an Esophagopleural Fistula in a Patient With Severe Esophagitis: Blunt Trauma or Iatrogenic?
Authors: Wang Yanting , Rivas Chicas Oscar A. , Basu Anupam
Published: November 2019

Esophagopleural fistula (EPF) is rare despite the anatomical proximity of the esophagus and the pleural space. A 64-year-old man presented with a pneumothorax after a fall requiring chest tube placement. An esophagogastroduodenoscopy revealed severe LA grade D esophagitis and a large EPF in the distal esophagus. Computed tomography scan revealed that subtle tracking of air extending from the distal esophagus into the right pleural space was noted. The patient was treated with placement of a fully covered esophageal metal stent, and he recovered uneventfully. Interpreting key subtle clues in pleural fluid analysis and imaging can lead to a timely diagnosis and thus improves morbidity and mortality of EPF.
La etnoedafología como instrumento para la caracterización de agroecosistemas a nivel local, el caso de un ejido cafetalero del centro de Veracruz
Authors: Aguilar-Orea Geovanni Fidel , Ruiz Rosado Octavio , Ortiz Solorio Carlos Alberto , Armida Alcudia Liliana
Published: November 2019

En la actualidad se necesita contar con instrumentos que consideren el conocimiento local para la caracterización de agroecosistemas (AES). Ante tal contexto, la clasificación campesina de tierras de Ortiz et al. (1991), como parte de la disciplina etnoedafológica, complementa el conocimiento local con el conocimiento técnico, esta combinación suministra información detallada para la cartografía, clasificación, descripción de uso, manejo y aprovechamiento no solo de tierras, sino de los componentes de cualquier AES. A partir de esto, se pueden obtener insumos para describir a nivel de ejido y de finca la estructura de AES con información actualizada y de primera mano. Se aplicó este método en el ejido de Mafafas, ubicado en el municipio de Tepetlán, Veracruz, este presenta problemas de disminución de la productividad de café. Se realizó una clasificación campesina de tierras y también se empleó el método etnoedafológico para recopilar información y caracterizar la estructura de agroecosistemas cafetaleros. Se obtuvo un mapa con escala 1:10 000 y en total se identificaron 8 clases de tierra con 4 tipos predominantes de uso del suelo. Además, se analizaron 11 fincas que mostraron distintas estructuras, sin embargo, muestran patrones en común. Se mostrará una alternativa para caracterizar AES con un método sistémico que se vale del conocimiento local y que resulta de fácil aplicación, los resultados obtenidos de este procedimiento respaldan la idea de que todos los ejidos requieren un estudio con este enfoque, que sirva como base para la planeación local y el desarrollo del campo mexicano.
Challenges for Research on Reading, Writing, Interpreting, and Translation
Authors: Da Silva Igor Antonio Lourenço , Ferreira Aline , Schwieter John W.
Published: November 2019

Introduction
Pengembangan Potensi Wisata Desa Buluhcina Kabupaten Kampar
Authors: Salmiah Neneng
Published: November 2019

Program pengabdian kepada masyarakat ini bertujuan untuk meningkatkan wawasan masyarakat Desa Buluhcina tentang potensi wisata yang dapat dikembangkan serta peningkatan pengetahuan mempromosikan Desa Wisata Buluhcina melalui media sosial sehingga Desa tersebut menjadi maju dan mandiri serta kesejahteraan masyarakat meningkat. Permasalahan mitra adalah belum dikembangkannya potensi wisata yang dimiliki serta belum mempromosikan desa wisata secara optimal. Hal ini tentu saja berdampak pada rendahnya minat wisatawan berkunjung ke Desa Wisata Buluhcina. Khalayak sasaran adalah perangkat desa beserta masyarakat Desa Buluhcina. Solusi yang dilakukan adalah dengan memberikan penyuluhan dalam rangka peningkatan wawasan terkait pengembangan potensi wisata yang ada di Desa Buluhcina dan meningkatkan pengetahuan dalam mempromosikan wisata Desa Buluhcina melalui media sosial. Hasil yang dicapai adalah peningkatan wawasan peserta terhadap potensi wisata yang dapat dikembangkan di Desa Buluhcina dan peningkatan pengetahuan dalam mempromosikan wisata Desa Buluhcina melalui sosial media. Hal ini dapat dilihat dari antusiasme peserta pada saat pelaksanaan serta peningkatan hasil pre-test.[This program of community service aims to improve the insight of the community of Buluhcina Village about the potential of tourism that can be developed as well as increased knowledge of promoting the Village of Buluhcina through social media so that the village becomes advanced and independent and the welfare of society increases. Partner problems are not yet developed the tourism potential that is owned and has not promoted the tourist village optimally. This of course affects the low interest of tourists visiting the Tourism Village Buluhcina. The target audience is a village device along with the people of Buluhcina Village. The solution is to provide counseling in order to increase the insight related to the development of tourism potential in Buluhcina Village and increase the knowledge in promoting Buluhcina Village tourism through social media. The results achieved are increasing participants' insight into tourism potentials that can be developed in Buluhcina Village and increased knowledge in promoting the tourism of Buluhcina Village through social media. This can be seen from the enthusiasm of participants at the time of execution and improvement of pre-test results.]
Go Organic-Gerakan Kelompok Petani Pesanggem Dalam Biokonversi Kulit Kopi Menjadi Kompos dan Pupuk Organik Granule
Authors: Kurniawan Syahrul , Riyanto Sugeng , Gutama Wisynu Ari , Kusumarini Novalia , Adieb Noval , Azizah Nur , Nugroho Gabryna Auliya
Published: November 2019

Sejak tahun 2016, Universitas Brawijaya memperoleh mandat dari Kementerian Lingkungan Hidup dan Kehutanan untuk mengelola hutan seluas 544 ha di lereng Gunung Arjuno menjadi hutan Pendidikan dan Pelatihan, yang diberi nama UB Forest. Di dalam UB forest terdapat petani penggarap yang menanam kopi dibawah tegakan pinus. Setiap tahun, produksi kopi di UB Forest mencapai 600 kg ha-1, dengan potensi limbah sisa panen kulit kopi antara 50–60%. Limbah sisa panen kulit kopi tersebut hanya ditumpuk saja dan berpotensi menimbulkan pencemaran. Kegiatan ini ditujukan untuk meningkatkan pengetahuan dan keterampilan kelompok tani hutan UB Forest di dalam mengolah sisa panen kulit kopi menjadi pupuk kompos dan pupuk organik granul (POG). Kegiatan yang dilakukan meliputi: 1) Penyuluhan; 2) Pembuatan rumah produksi kompos; 3) Introduksi mesin granulator; 4) Pelatihan pembuatan kompos dan POG; 5) Pengemasan produk, dan 6) analisa kualitas kompos dari kulit kopi. Hasil kegiatan meliputi 1) tersedianya rumah produksi pupuk organik granul beserta alat pembuat pupuk organik granule (granulator); 2) 85% dari petani hutan peserta penyuluhan dan pelatihan mengalami peningkatan pengetahuan dan keterampilan di dalam mengolah sisa panen kulit kopi menjadi kompos dan pupuk organik granul; 3) kelompok tani hutan memiliki modul dan SOP pembuatan kompos dan pupuk organik granul.[Since 2016, Brawijaya University received a mandate from the Indonesian Ministry of Environment and Forestry to manage 544 hectares (ha) of forest, located in the slopes of Mount Arjuno, as a forest for Education and Training, which is named UB Forest. In UB forest, there are forest farmer who planted coffee under the pine trees. Every year, coffee production in UB Forest reaches 600 kg ha-1, with 50-60% of them is coffee peel. The waste of the remaining coffee peel is only stacked and potentially cause pollution. This activity is aimed to increase the knowledge and skills of forest farmer groups (UB Forest) in processing the remaining coffee peel into compost and granular organic fertilizer (POG). The activities included: 1) Counseling; 2) Creating compost production houses; 3) Introducing of granulator machines; 4) Training in composting and POG; 5) Product packaging, and 6) analysis of the quality of compost. The results of the activities included: 1) the availability of houses for the production of compost and POG along with the tools for processing granule organic fertilizers (granulators); 2) 85% of forest farmers participating in counseling and training experience increased knowledge and skills in processing the remaining coffee peel into compost and granule organic fertilizer; 3) forest farmer groups have modules and SOPs for composting and granule organic fertilizer.]
Inquiry at the Botanical Gardens: Practicing Science Processes during a Field Trip to the  Zoo
Authors: McConnell Tom J. , Foster Tolly , Schilten Michele
Published: November 2019

Field trips offer excellent learning opportunities, but teachers often think of them as informal experiences to teach concepts and content. But it is possible to structure science lessons at sites like zoos, aquariums and museums as an inquiry activity. Using the NRC (2000) definition of inquiry and the Indiana Academic Standards list of process standards (IDOE 2016), facilitators at the BLINDED ACADEMY developed the Plant Adaptations Inquiry lesson.  This activity lets learners hypothesize, observe, analyze data and construct conclusions about the types of plant adaptations seen in plants from different ecosystems. The observations, including the use of technology to use photographs, were recorded on the grounds of the BLINDED Gardens and the BLINDED Zoo. This article explains the design of the lesson and alignment with state and national standards. Readers can download a version of the lesson and rubric.
Perbedaan Metode Mutilasi Terhadap Lama Waktu Molting Scylla serrata
Authors: Ario Raden , Djunaedi Ali , Pratikto Ibnu , Subardjo Petrus , Farida Fauzia
Published: November 2019

Kepiting bakau (Scylla serrata) memiliki nilai ekonomis tinggi. Kebutuhan kepiting bakau selalu meningkat sehingga perlu diupayakan budidaya kepiting bakau secara intensif. Salah satu perkembangan teknologi dalam budidaya perikanan untuk meningkatkan produksi kepiting bakau adalah produksi kepiting cangkang lunak. Kepiting cangkang lunak merupakan kepiting fase ganti kulit (molting) yang mempunyai keunggulan cangkangnya lunak sehingga dapat dikonsumsi secara utuh. Untuk mempercepat kepiting molting diperlukan berbagai rangsangan yang salah satunya adalah menggunakan metode mutilasi. Tujuan penelitian untuk mengetahui perbedaan lama waktu molting dan pertumbuhan berat kepiting bakau dengan menggunakan metode mutilasi pada kaki jalan dan capit. Metode penelitian yang digunakan yaitu metode eksperimental dengan rancangan acak lengkap (RAL) yang terdiri dari empat perlakuan, yaitu mutilasi kaki jalan dan capit, semua kaki jalan, capit, dan alami. Biota yang digunakan berjumlah 40 ekor dengan 10 kali ulangan tiap perlakuan. Data yang diperoleh berupa lama waktu molting serta pertambahan berat mutlak kepiting bakau yang dianalisis menggunakan uji statistik parametrik. Hasil penelitian menunjukkan metode mutilasi berpengaruh terhadap lama waktu molting dengan waktu molting tercepat pada perlakuan mutilasi kaki jalan dan capit rata-rata 13 hari. Metode mutilasi tidak berpengaruh terhadap pertumbuhan berat mutlak dengan nilai tertinggi pada kepiting perlakuan alami sebesar 53,30 gram. Mud crabs (Scylla serrata) are known to have a high economic value. The increasing demand of mud crabs for consumption rxcequires higher production. Therefore, mud crabs need to be cultivated intensively. One of the methods to improve the values of mud crabs’ aquaculture is by producing soft-shell crabs. Soft-shell crabs are produced during molting phase in which the crab shed it’s exoskeleton in order to grow. In the fisheries industry, the soft-shell crabs are considered to be more valuable as it can be consumed as a whole. Accelerating the production of molting crabs, requires stimulus. One of the methods is mutilation. The aim of this study is to estimate the periods required for molting under different treatments, as well as calculating the increase of total weight of molting crabs.. The method used was an experimental method which contained four treatments. The treatments are mutilation of walking legs and claws, all of walking legs, claws, and no mutilation. The number of crabs used was 40 with 10 replications per treatment. The data obtained in the period of molting and the increase of total weight of the mud crabs were analyzed using ANOVA. The result shows that mutilation affects the period of crab’s molting in which the fastest molting (13 days on average) occurred after mutilation of walking legs and claws. This mutilation method does not influence the increase of total weight and the highest value is showed in non-treated group with the increase of 53,30 grams in weight.
Data Mining Menggunakan Algoritma Apriori untuk Rekomendasi Produk bagi Pelanggan
Authors: Riszky Ariefana Ria , Sadikin Mujiono
Published: November 2019

The implementation of a marketing strategy requires a reference so that promotion can be on target, such as by looking for similarities between product items. This study examines the application of the association rule method and apriori algorithm to the purchase transaction dataset to assist in forming candidate combinations among product items for customer recommended product promotion. The purchase transaction dataset was collected in October and November 2018 with a total data of 1027. In the experiment, the minimum value of support is 85%, and the minimum confidence value is 90% by processing data using the Weka software 3.9 version. Apriori algorithm can form association rules as a reference in the promotion of company products and decision support in providing product recommendations to customers based on defined minimum support and confidence values.
Modifikasi Algoritme Bellman-Ford Untuk Pencarian Rute Terpendek Berdasarkan Kondisi Jalan
Authors: Yaddarabullah Yaddarabullah
Published: November 2019

The application of the Bellman-ford algorithm for finding the shortest path both weighted and unweighted graph has a weakness in determining the shortest path based on road conditions. This study modified the Bellman-Ford algorithm by adding the Technique for Order of Preference by Similarity to the Ideal Solution method to provide alternative road assessments based on its condition criteria including road density, road width, travel time, and distance. This modified Bellman-Ford has better performance in finding the alternative shortest path by choosing a road with smoother conditions, even though distance and travel time increase.
Precision medicine applications for severe asthma
Authors: Hacohen Orit Gourgy , Cohen Shai
Published: November 2019

Asthma is a heterogeneous condition in which multiple pathological pathways manifest with similar symptoms. Severe asthma (SA) is challenging to manage and comprises a significant health and economic burden. Many studies have been conducted in an attempt to define different clinical phenotypes that translate into biological endotypes, with the goal of tailoring treatment based on precision medicine. This review summarizes the current evidence for the treatments of SA, and in particular, the biologic treatments that are currently available: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. We found only limited high-quality direct evidence regarding treatment with anti-IgE (omalizumab) in SA patients. Data regarding anti-interleukin (IL)-5 (mepolizumab, reslizumab and benralizumab) showed beneficial effects in severe eosinophilic asthma (SEA) with different levels of blood eosinophils used in clinical trials. Dupilumab, anti-IL-4/IL-13, was shown to be effective in SEA and is the only agent currently FDA-approved for the indication of oral corticosteroid dependent asthma, regardless of the blood eosinophil level. This review also summarizes the existing knowledge regarding the characteristics of the patient who may respond to the different therapies. As of today, more studies are needed to better understand the diverse mechanisms that underlie SA phenotypes. We have not yet adequately reached the goal of precision medicine. Additional studies are necessary in order to find novel surrogate markers that can predict the response to a specific biologic therapy, especially in patients who are oral corticosteroid dependent. In addition, efforts must be invested into research looking for new treatment options for patients with non-type-2 inflammation SA.

Statement of novelty: we review the current evidence regarding tailored treatment therapies in SA, with a particular focus on the knowledge regarding patient selection for specific biologic treatments.
Elements of X
Authors: Öhrström Lars
Published: November 2019

We are moving into the last part of the 2019 International Year of the Periodic Table and one wonders: Is there anything left to say? Has the equation Elements of X, not been thoroughly investigated? Not quite we think, and an amazing set of authors from around the globe** who accepted the challenge adequately proves the point in this special issue of Chemistry international.
Elements of Stars
Authors: Lugaro Maria , Dishoeck Ewine van
Published: November 2019

What are stars made of? Less than 200 years ago this basic, simple question was deemed impossible to answer. As Auguste Comte put it in 1835: “On the subject of stars…While we can conceive of the possibility of determining their shapes, their sizes, and their motions, we shall never be able by any means to study their chemical composition or their mineralogical structure.” Today, we have a broad, clear answer to the question: “What are stars made of?” We also understand its far-reaching implications in relation to the evolution of the cosmos. Satellites and many ground-based spectroscopic surveys routinely provide new discoveries on the chemical composition of astronomical objects. In parallel, the nuclear processes that produce the elements inside stars are investigated in increasingly sophisticated nuclear physics experimental facilities across the world. At the same time, supercomputers allow us to calculate detailed models of the evolution of stars and galaxies: how much of which element is produced where? Finally, the presence of tiny amounts of extra-solar material can be found within meteorites, whose analysis is reaching unparalleled precisions with uncertainties down to parts per million. How have we managed to travel from an impossible question to such broad knowledge filled with discoveries?
Elements of Technology
Authors: Droescher Michael
Published: November 2019

There are many ways to look at the periodic table. When Mendeleev established the table, he arranged the elements according to atomic number and chemical properties. Here, we try a different look. We discuss the influence and links of elements on the development of cultures and technologies. Some of the elements have a direct impact on our life: carbon, nitrogen, hydrogen, oxygen and phosphorous are the main building blocks of our organism, besides small amounts of other elements. Many other elements, especially metals, are the base of the development of our social and technological world, due to the availability and/or innovative use of new or already known elements. We will have a look on the relevance and importance of these elements for the development of technologies over the last 10 millennia.
In Memoriam: René Dybkaer
Authors: Hibbert Brynn
Published: November 2019

I first met René when the IUPAC General Assembly came to Brisbane Australia in 2001. IUPAC was not an organization I (then) knew much about, but I found myself confronted by Paul De Bièvre demanding that I join a task group on metrological traceability. At the time I would not have called myself a metrologist in chemistry (MiC) or in any other field. The great minds assembled for the project were Paul De Bièvre, René Dybkaer, Ales Fajgelj, and me. I had no idea that our task would take ten years (finally published as De Bièvre, P.; Dybkaer, R.; Fajgelj, A.; Hibbert, D. B.: Metrological traceability of measurement results in chemistry: Concepts and implementation (IUPAC Technical report) Pure Appl. Chem. 2011, 83, 1873-1935), and that during the time I would come to form strong friendships with my comrades in the “Gang of Four.” Paul is no longer with us and now René has left the stage.
The application of a phosphorus nitrogen flame retardant curing agent in epoxy resin
Authors: Li Anxin , Mao Pingli , Liang Bing
Published: November 2019

In order to improve the compatibility of flame retardant and epoxy resin, a phosphorus nitrogen flame retardant curing agent poly(p-xylylenediamine spirocyclic pentaerythritol bisphosphonate) (PPXSPB) was synthesized. FTIR,1HNMR, and mass spectroscopy were used to identify the chemical structure of PPXSPB. Epoxy resin (E-44) and PPXSPB as the raw material, a series of thermosetting systems were prepared. The effects of PPXSPB on flame retardancy, water resistance, thermal degradation behavior, mechanical properties and the adhesive strength of EP/PPXSPB thermosets were investigated. The results show that with the increase of phosphorus content, the oxygen index and carbon residue of the system both increased significantly, and the heat release rate gradually decreased, which is of great significance in delaying the occurrence of fire. When the phosphorus content is 3.24% in EP/PPXSPB thermosets, EP-2 can successfully pass the UL94 V-0 flammability rating, the LOI value of EP-2 can reach 31.4%, the impact strength and tensile strength was 6.58 kJ/m2and 47.10 MPa respectively, and the adhesive strength was 13.79 MPa, the system presents a good overall performance.
Effect of salt and temperature on molecular aggregation behavior of acrylamide polymer
Authors: Ma Jingyuan , Yu Peizhi , Xia Boru , An Yuxiu
Published: November 2019

Three kinds of acrylamide copolymers were synthesized in this paper, acrylamide (AM) homopolymer, acrylamide/acrylic acid (AA) copolymer and acrylamide/2-acrylamide-2-methylpropanesulfonic acid (AMPS) copolymer by free radical polymerization. The aggregation behaviours of these polymers in salts water solution were studied. The molecular chains of homopolymer were stretched in salt water solutions, since it did not undergo hydrolysis and there were no charges in the backbone and side chains. Therefore, the conformation of homopolymer was hard to be attacked by salt ions. However, the copolymers synthesized from these monomers had large number of anionic groups. These anions were easily attracted by cations from salt solutions forming ionic bonds, which led to changes in molecular conformation. The viscosity of copolymer decreased since the molecular chains were crimped. The viscosity of copolymer decreased distinctly according to the temperature of different salt solutions, as temperature had great impact on the viscosity of copolymer. The interaction mechanism of polymers exhibited great difference in salts solutions, comparing to temperature. High temperature reduced the entanglement between molecular chains, whereas salt ions neutralized the negative charges on the molecular chains causing curling of molecular chains.
Positive Affect Is Associated With Decreased Symptom Severity in the Daily Lives of Individuals With Borderline Personality Disorder
Authors: Harp⊘th Tine S. D. , Hepp Johanna , Trull Timothy J. , Bateman Anthony W. , Kongerslev Mickey T. , Simonsen Erik
Published: November 2019

Previous research has repeatedly demonstrated positive associations between negative affect (NA) and borderline personality disorder (BPD) symptoms in daily life, but studies have rarely addressed potential effects of positive affect (PA). Consequently, little is known about how PA in daily life covaries with symptoms of BPD. The authors assessed the effects of both PA and NA levels on BPD symptom severity in a sample of 81 treatment-seeking women diagnosed with BPD over a period of 21 days, employing a daily diary design. Using multivariate multilevel modeling, the authors obtained negative associations between PA levels and daily BPD severity in total and at the level of the individual symptoms inappropriate anger, affective instability, emptiness, identity disturbance, and paranoid ideation/dissociation. Moreover, the authors replicated previously reported positive associations between NA and BPD severity for all nine symptoms. Future research can address whether increasing PA in the treatment of BPD may potentially help reduce symptom burden.
Long-Term Exposure to PFE-360 in the AAV-α-Synuclein Rat Model: Findings and Implications
Authors: Andersen Michael Aagaard , Sotty Florence , Jensen Poul Henning , Badolo Lassina , Jeggo Ross , Smith Garrick Paul , Christensen Kenneth Vielsted
Published: November 2019

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with impaired motor function and several non-motor symptoms, with no available disease modifying treatment. Intracellular accumulation of pathological α-synuclein inclusions is a hallmark of idiopathic PD, whereas, dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial PD that is clinically indistinguishable from idiopathic PD. Recent evidence supports the hypothesis that an increase in LRRK2 kinase activity is associated with the development of not only familial LRRK2 PD, but also idiopathic PD. Previous reports have shown preclinical effects of LRRK2 modulation on α-synuclein-induced neuropathology. Increased subthalamic nucleus (STN) burst firing in preclinical neurotoxin models and PD patients is hypothesized to be causally involved in the development of the motor deficit in PD. To study a potential pathophysiological relationship between α-synuclein pathology and LRRK2 kinase activity in PD, we investigated the effect of chronic LRRK2 inhibition in an AAV-α-synuclein overexpression rat model. In this study, we report that chronic LRRK2 inhibition using PFE-360 only induced a marginal effect on motor function. In addition, the aberrant STN burst firing and associated neurodegenerative processes induced by α-synuclein overexpression model remained unaffected by chronic LRRK2 inhibition. Our findings do not strongly support LRRK2 inhibition for the treatment of PD. Therefore, the reported beneficial effects of LRRK2 inhibition in similar α-synuclein overexpression rodent models must be considered with prudence and additional studies are warranted in alternative α-synuclein-based models.
Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat
Authors: Toor Rahat Ul Ain Summan , Sun Qi-Jian , Kumar Natasha N. , Le Sheng , Hildreth Cara M. , Phillips Jacqueline K. , McMullan Simon
Published: November 2019

Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.

SIGNIFICANCE STATEMENTInteractions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.
Audiogenic Seizures in theFmr1Knock-Out Mouse Are Induced byFmr1Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus
Authors: Gonzalez Darya , Tomasek Madison , Hays Seth , Sridhar Vinay , Ammanuel Simon , Chang Chia-wei , Pawlowski Karen , Huber Kimberly M. , Gibson Jay R.
Published: November 2019

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model—theFmr1knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Hyperactive circuits are hypothesized to underlie dysfunction in a number of brain regions in patients with FXS andFmr1KO mice, and the AGS may be a result of this. But the specific cell types and brain regions underlying AGSs in theFmr1KO are unknown. We used conditional deletion or expression ofFmr1in different cell populations to determine whetherFmr1deletion in those cells was sufficient or necessary, respectively, for the AGS phenotype in males. Our data indicate thatFmr1deletion in glutamatergic neurons that express vesicular glutamate transporter 2 (VGlut2) and are located in subcortical brain regions is sufficient and necessary to cause AGSs. Furthermore, the deletion ofFmr1in glutamatergic neurons of the inferior colliculus is necessary for AGSs. When we demonstrate necessity, we show thatFmr1expression in either the larger population of VGlut2-expressing glutamatergic neurons or the smaller population of inferior collicular glutamatergic neurons—in an otherwiseFmr1KO mouse—eliminates AGSs. Therefore, targeting these neuronal populations in FXS and autism may be part of a therapeutic strategy to alleviate sensory hypersensitivity.

SIGNIFICANCE STATEMENTSensory hypersensitivity in fragile X syndrome (FXS) and autism patients significantly interferes with quality of life. Audiogenic seizures (AGSs) are arguably the most robust behavioral phenotype in the FXS mouse model—theFmr1knockout—and may be considered a model of sensory hypersensitivity in FXS. We provide the clearest and most precise genetic evidence to date for the cell types and brain regions involved in causing AGSs in theFmr1knockout and, more broadly, for any mouse mutant. The expression ofFmr1in these same cell types in an otherwiseFmr1knockout eliminates AGSs indicating possible cellular targets for alleviating sensory hypersensitivity in FXS and other forms of autism.
Developmental Pathogenicity of 4-Repeat Human Tau Is Lost with the P301L Mutation in Genetically Matched Tau-Transgenic Mice
Authors: Gamache Julia E. , Kemper Lisa , Steuer Elizabeth , Leinonen-Wright Kailee , Choquette Jessica M. , Hlynialuk Chris , Benzow Kellie , Vossel Keith A. , Xia Weiming , Koob Michael D. , Ashe Karen H.
Published: November 2019

Tau is a microtubule-associated protein that becomes dysregulated in a group of neurodegenerative diseases called tauopathies. Differential tau isoforms, expression levels, promoters, and disruption of endogenous genes in transgenic mouse models of tauopathy make it difficult to draw definitive conclusions about the biological role of tau in these models. We addressed this shortcoming by characterizing the molecular and cognitive phenotypes associated with the pathogenic P301L tau mutation (rT2 mice) in relation to a genetically matched transgenic mouse overexpressing nonmutant (NM) 4-repeat (4R) human tau (rT1 mice). Both male and female mice were included in this study. Unexpectedly, we found that 4R NM human tau (hTau) exhibited abnormal dynamics in young mice that were lost with the P301L mutation, including elevated protein stability and hyperphosphorylation, which were associated with cognitive impairment in 5-month-old rT1 mice. Hyperphosphorylation of NM hTau was observed as early as 4 weeks of age, and transgene suppression for the first 4 or 12 weeks of life prevented abnormal molecular and cognitive phenotypes in rT1, demonstrating that NM hTau pathogenicity is specific to postnatal development. We also show that NM hTau exhibits stronger binding to microtubules than P301L hTau, and is associated with mitochondrial abnormalities. Overall, our genetically matched mice have revealed that 4R NM hTau overexpression is pathogenic in a manner distinct from classical aging-related tauopathy, underlining the importance of assaying the effects of transgenic disease-related proteins at appropriate stages in life.

SIGNIFICANCE STATEMENTDue to differences in creation of transgenic lines, the pathological properties of the P301L mutation confers to the tau proteinin vivohave remained elusive, perhaps contributing to the lack of disease-modifying therapies for tauopathies. In an attempt to characterize P301L-specific effects on tau biology and cognition in novel genetically matched transgenic mouse models, we surprisingly found that nonmutant human tau has development-specific pathogenic properties of its own. Our findings indicate that overexpression of 4-repeat human tau during postnatal development is associated with excessive microtubule binding, which may disrupt important cellular processes, such as mitochondrial dynamics, leading to elevated stability and hyperphosphorylation of tau, and eventual cognitive impairments.
Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm
Authors: Bergmann Til Ole , Lieb Anne , Zrenner Christoph , Ziemann Ulf
Published: November 2019

Alpha oscillations (8–14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor μ-alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor μ-alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single- and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude μ-alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) μ-alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor μ-alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the μ-alpha cycle further reveals that voltage differences alone cannot explain the impact of phase.

SIGNIFICANCE STATEMENTThe pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor μ-alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor μ-alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.
Activation of PPARγ Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission
Authors: Domi Esi , Caputi Francesca Felicia , Romualdi Patrizia , Domi Ana , Scuppa Giulia , Candeletti Sanzio , Atkins Alison , Heilig Markus , Demopulos Gregory , Gaitanaris George , Ciccocioppo Roberto , Ubaldi Massimo
Published: November 2019

An isoform of peroxisome proliferator-activated receptors (PPARs), PPARγ, is the receptor for the thiazolidinedione class of anti-diabetic medications including pioglitazone. Neuroanatomical data indicate PPARγ localization in brain areas involved in drug addiction. Preclinical and clinical data have shown that pioglitazone reduces alcohol and opioid self-administration, relapse to drug seeking, and plays a role in emotional responses. Here, we investigated the behavioral effect of PPARγ manipulation on nicotine withdrawal in male Wistar rats and in male mice with neuron-specific PPARγ deletion (PPARγ(−/−)) and their littermate wild-type (PPARγ(+/+)) controls. Real-time quantitative RT-PCR and RNAscopein situhybridization assays were used for assessing the levels of expression and cell-type localization of PPARγ during nicotine withdrawal. Brain site-specific microinjections of the PPARγ agonist pioglitazone were performed to explore the role of this system on nicotine withdrawal at a neurocircuitry level. Results showed that activation of PPARγ by pioglitazone abolished the expression of somatic and affective nicotine withdrawal signs in rats and in (PPARγ(+/+)) mice. This effect was blocked by the PPARγ antagonist GW9662. During early withdrawal and protracted abstinence, the expression of PPARγ increased in GABAergic and glutamatergic cells of the amygdala and hippocampus, respectively. Hippocampal microinjections of pioglitazone reduced the expression of the physical signs of withdrawal, whereas excessive anxiety associated with protracted abstinence was prevented by pioglitazone microinjection into the amygdala. Our results demonstrate the implication of the neuronal PPARγ in nicotine withdrawal and indicates that activation of PPARγ may offer an interesting strategy for smoking cessation.

SIGNIFICANCE STATEMENTSmoking cessation leads the occurrence of physical and affective withdrawal symptoms representing a major burden to quit tobacco use. Here, we show that activation of PPARγ prevents the expression of both somatic and affective signs of nicotine withdrawal. At molecular levels results show that PPARγ expression increases in GABAergic cells in the hippocampus and in GABA- and glutamate-positive cells in the basolateral amygdala. Hippocampal microinjections of pioglitazone reduce the insurgence of the physical withdrawal signs, whereas anxiety linked to protracted abstinence is attenuated by pioglitazone injected into the amygdala. Our results demonstrate the implication of neuronal PPARγ in nicotine withdrawal and suggest that PPARγ agonism may represent a promising treatment to aid smoking cessation.
Functional Connectome of the Fetal Brain
Authors: Turk Elise , van den Heuvel Marion I. , Benders Manon J. , de Heus Roel , Franx Arie , Manning Janessa H. , Hect Jasmine L. , Hernandez-Andrade Edgar , Hassan Sonia S. , Romero Roberto , Kahn René S. , Thomason Moriah E. , van den Heuvel Martijn P.
Published: November 2019

Large-scale functional connectome formation and reorganization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated before birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules, and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function.

SIGNIFICANCE STATEMENTThe fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesisin utero. Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.
Developmental Plasticity and Cellular Reprogramming in Caenorhabditis elegans
Authors: Rothman Joel , Jarriault Sophie
Published: November 2019

While Caenorhabditis elegans was originally regarded as a model for investigating determinate developmental programs, landmark studies have subsequently shown that the largely invariant pattern of development in the animal does not reflect irreversibility in rigidly fixed cell fates. Rather, cells at all stages of development, in both the soma and germline, have been shown to be capable of changing their fates through mutation or forced expression of fate-determining factors, as well as during the normal course of development. In this chapter, we review the basis for natural and induced cellular plasticity in C. elegans. We describe the events that progressively restrict cellular differentiation during embryogenesis, starting with the multipotency-to-commitment transition (MCT) and subsequently through postembryonic development of the animal, and consider the range of molecular processes, including transcriptional and translational control systems, that contribute to cellular plasticity. These findings in the worm are discussed in the context of both classical and recent studies of cellular plasticity in vertebrate systems.
Development of a Short Pulse Broadband and Narrow Linewidth Ultraviolet Laser Using Ce:LiCAF Crystal
Authors: Duong Pham Van , Tu Nguyen Xuan , Diep Nguyen Van , Pham Minh Hong , Sarukura Nobuhiko , Cadatal-Raduban Marilou
Published: November 2019

We report the successful development of an all-solid state laser based on a Czochralski method-grown cerium-doped lithium calcium aluminum fluoride (Ce3+:LiCaAlF6 or Ce:LiCAF) crystal as the gain medium. Results for the broadband, narrow linewidth and short pulse laser emission are obtained by pumping the crystal with 7 ns pulses from the fourth harmonics (266 nm) of a Nd:YAG laser operating at 10 Hz. The effects of output coupler reflectivity, resonator length and pump energy on the laser pulse duration were explored. With broadband configuration, a maximum output pulse energy of 3.4 mJ and a slope efficiency of about 33% were achieved. By optimizing the parameters of the resonator and pump laser energy, 450 ps UV laser pulses were generated from resonator transient conditions of low-Q and short resonator under a near threshold pump energy. With narrow linewidth configuration, where the end mirror is replaced by a grating, tunability from 281 nm to 299 nm is also achieved with a linewidth of about 0.2 nm.
Sparking interest in public health amongst future doctors to tackle our NHS sustainability crisis
Authors: Beetham Hannah , Cole Duncan , Phillips Rhiannon , Wood Fiona , Broughton Hannah , Ariti Cono , Behbod Behrooz
Published: November 2019

This article was migrated. The article was marked as recommended. The new NHS 'Long Term Plan' has a particular focus on the public health issues of disease prevention and reducing health inequalities. However, medical students often perceive public health as abstract and irrelevant to clinical practice. We believe students need to be encouraged to appreciate wider public health issues and ultimately be able to apply clinical and public health tools to achieve change for patients and populations. Our aim is for all medical graduates to be able to apply public health and evidence-based principles to their chosen specialties. In the undergraduate curriculum, we hope to extend problem-, case-, and simulation-based learning into public health education, emphasise the context around statistics and epidemiology teaching, and make the teaching more relevant, tangible and enjoyable. Intercalated BSc students will gain an interdisciplinary perspective by joining Master of Public Health (MPH) students to learn about the prevention and control of disease and the promotion of health and wellbeing. They will also have opportunities to join the new Health Intelligence Team (H.I.T.), on a voluntary reserve list to support Public Health Wales in the event of real investigations. We will evaluate these strategies, and we hope that medical educators worldwide will share their experience of innovative approaches to public health and evidence-based medicine teaching in response to this article, so that public health teaching may be improved.