bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Catch-Up Growth in Very Low Birth Weight Infants (<1500 g)
Authors: Durá-Travé Teodoro , San Martín-García Isabel , Gallinas-Victoriano Fidel , Malumbres-Chacón María , Moreno-González Paula , Urretavizcaya-Martinez María
Published: March 2021

Features of catch-up growth are not well established in very low birth weight infants (VLBW). The aim of this study is to analyze the catch-up growth in height and some factors associated in a cohort of VLBW (<1500 g) from birth to age 14 years. Retrospective registration of weight and height at birth and ages 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 14 years in a cohort of 170 VLBW have been recorded Anthropometric variables were compared with those from a control group. Sixty-nine (40.6%) were small for gestational age (SGA subgroup) and 101 (59.4%) were appropriate for gestational age (AGA subgroup). Thirty-seven (21.8%) were extremely low birth weight (ELBW), and 32 (18.8%) extremely preterm (EPT). At age 2, 4 and 10 years, 49.4%, 78.9% and 87.1% VLBW, respectively, did reach normal height. Between 4 and 10 years of age, only 8.2% of VLBW reached normal height. At 10 years of age, 7% of VLBW (1000–1500 g) and 35% of ELBW (<1500 g) showed short stature (p = 0.001). Almost the entire sample of VLBW with normal height at age 2, 4 and 10 have reached an adequate catch-up growth in weight in the previous evaluations. ELBW, SGA and EPT were found to be independent predictors for inadequate catch-up growth in height at 2, 4, and 10 years of age. The growth pattern of children born preterm has particular features: they have a lower rate and/or slowness in the catch-up growth in height with respect to that described in full-term small-for-gestational-age infants. Catch-up in weight appears to be a decisive factor for catch-up in height, and, on this basis, we recommend a rigorous nutritional follow-up in these individuals. If these measures do not help improve catch-up in height, they may be eligible for the establishment of rhGH therapy.
Insights from Systematic DFT Calculations on Superconductors
Authors: D.R. Mackinnon Ian , Almutairi Alanoud , A. Alarco Jose
Published: March 2021

We present three systematic approaches to use of Density Functional Theory (DFT) for interpretation and prediction of superconductivity in new or existing materials. These approaches do not require estimates of free parameters but utilize standard input values that significantly influence computational resolution of reciprocal space Fermi surfaces and that reduce the meV-scale energy variability of calculated values. Systematic calculations on conventional superconductors show that to attain a level of resolution comparable to the energy gap, two key parameters, Δk and the cut-off energy, must be optimized for a specific compound. The optimal level of resolution is achieved with k-grids smaller than the minimum reciprocal space separation between key parallel Fermi surfaces. These approaches enable estimates of superconducting properties including the transition temperature (Tc) via (i) measurement of the equivalent thermal energy of a phonon anomaly (if present), (ii) the distribution of electrons and effect on Fermi energy (EF) when subjected to a deformation potential and (iii) use of parabolic, or higher order quartic, approximations for key electronic bands implicated in electron–phonon interactions. We demonstrate these approaches for the conventional superconductors MgB2, metal substituted MgB2 and boron-doped diamond.
Oral Versus Intravenous Medications for Treatment of Patent Ductus Arteriosus in Preterm Neonates: A Cost-Saving Initiative
Authors: Godin Robert , Rodriguez Juan Carlos , Kahn Doron J.
Published: March 2021

OBJECTIVE

The purpose of the study was to quantify cost savings after promoting oral pharmacotherapy for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA).

METHODS

This was a retrospective before-and-after time series quality improvement study. Oral ibuprofen and acetaminophen use criteria were developed and recommended, rather than the more costly intravenous equivalents. There were 24-month medication use reports generated for both the pre-criteria (Era-1) and the post-criteria (Era-2) implementation phases to identify neonates prescribed hsPDA medications in order to assess cost differences.

RESULTS

Era-1 had 190 treatment courses in 110 neonates for a total medication cost of $171,260.70. Era-2 had 210 courses in 109 patients for a total medication cost of $47,461.49, yielding savings of $123,799.21 ($61,899.61 annually) after criteria implementation. The reduction in intravenous ibuprofen use in Era-2 accounted for all the savings.

CONCLUSION

Preferentially prescribing lower-cost oral medications to treat hsPDA led to significant cost savings.
Pulmonary thromboembolism and pericardial effusion as cardiovascular complications of COVID-19 infection
Authors: Đenić Aleksandar
Published: March 2021

Systemic activation of coagulation and pulmonary thrombo-inflammation with local vascular damage caused by SARS-CoV-2 infection increases the risk of developing thromboembolic complications: stroke, pulmonary arterial thrombosis (pulmonary thromboembolism) and deep vein thrombosis. Myopericarditis may occurs in COVID-19 patients as part of or after the onset of respiratory symptoms. Minor pericardial effusions up to 1 cm that accompany pericardial involvement are common. In our patient during hospitalization due to bilateral pneumonia caused by SARS-Cov-2 virus during a routine control of D-dimer, elevated values 2.3 fold higher than the reference range were observed, with elevated biomarkers of inflammation. She had symptoms of a respiratory infection and no pronounced clinical symptoms that would indicate pulmonary thromboembolism. MSCT pulmonary angiography was performed and low-risk thromboembolism was confirmed. Anticoagulant therapy was started - therapeutic doses of low molecular weight heparin (enoxaparin), which was extended after discharge from the hospital with DOAC (Rivaroxaban) according to the protocol for the treatment of pulmonary thromboembolism. At the control examination after 3 weeks, pericarditis with moderate pericardial effusion was determined. Anticoagulant therapy (DOAC) was extended with the inclusion of colchicine in the therapy according to the protocol for the treatment of pericarditis with effusion. After 3 months of hospitalization in our patient with mild respiratory symptoms, bronchopneumonia of the right lung developed with slightly elevated biomarkers of inflammation and normal values of D-dimer. With prescribed antibiotic therapy and current therapy (DOAC and colchicine), there was a withdrawal of symptoms and regression of pericardial effusion and a reduction in right ventricular overload. At the follow-up examination 5 months after hospitalization, complete regression of pericardial effusion was confirmed with normal biomarkers of inflammation and D-dimer values. It is advisable to exclude anticoagulant therapy (DOAC) with continued low-dose aspirin therapy.
Advantages of arbitration over court resolution of employment disputes
Authors: Stanojević Sanja
Published: March 2021

An employment dispute is a dispute between a single worker and the employer, or between a trade union and employer or association of employers. The division of employment disputes is important because it indicates the method of the settlement of labour disputes. According to Serbian legal system, employment disputes can be settled in court or using one of the alternative labour dispute resolution methods (arbitration, conciliation, mediation). Based on the Law on the Amicable Settlement of Employment Disputes, an institution for the peaceful settlement of labour disputes was established - State Agency for Amicable Settlement of Employment Disputes. Arbitration is always voluntary. The Agency is to be in charge only if both parties accept to solve the dispute using arbitration. An individual employment dispute can be solved using arbitration only if that is allowed by work contract or a general employer act. A collective dispute can also be solved using arbitration. If one of the parties does not want to use an alternative method for solving the problem, arbitration cannot be an option. In that case, the only way to protect its rights is in court. The process of settling a dispute in court before a judge is an extremely strict and formal procedure required by law. The court is obligated to determine relevant facts and make a decision based on them. The judgment is binding for the parties and can be forcedly executed. Protection of rights is accomplished when the judgment or arbitration decision is made and executed. The arbitration decision can be voluntarily executed, unlike the judgment that can be forcedly executed. The arbitration decision cannot be forcedly executed and that is the main disadvantage of the arbitration. The arbitration procedure needs to be improved in order to guarantee the protection of rights.
Influence of socio-demographic factors and length of disease on adherence of patients with arterial hypertension
Authors: Jandrić-Kočič Marijana , Knežević Snežana
Published: March 2021

INTRODUCTION: The World Health Organization defines patient adherence as the willingness to adapt its behavior (in terms of therapy, diet, lifestyle, and diagnostic procedures) to the recommendations agreed with the healthcare provider. Objective. The study aimed to determine the impact of socio-demographic factors and length of elevated blood pressure on the adherence of patients with arterial hypertension. METHOD: The study was performed as a cross-sectional study. The sample consisted of 170 patients, 88 (51.8%) women and 82 (48.2%) men, with a mean age of 58 ± 7.9 years. In addition to the general questionnaire, the study used the Adherence in Chronic Diseases Scale. RESULTS: Statistically significantly higher adherence was found in subjects aged 60-69 years and participants in the study with arterial hypertension for more than 15 years (p<0.05). Subjects with completed primary school had statistically significantly lower adherence (p<0.05). Place of residence, employment status and gender of the respondents did not show a statistically significant influence on the adherence of the respondents (NS). CONCLUSION: It uses the age, educational status and duration of arterial hypertension in the adherence of examination statistics. Place of residence, employee status and gender of respondents do not show a statistically significant impact.
Importance of haemodynamic stability and adjuvant therapy in the treatment of patients with sepsis and septic shock
Authors: Marjanović Vesna , Budić Ivana , Ignjatijević Saša , Stević Marija , Simić Dušica
Published: March 2021

Sepsis represents a life-threatening condition that requires prompt recognition, detailed initial assessment and energetic administration of therapy. Guidelines published in 2016 emphasized the importance of early fluids replacement and infection control together with assessment based on laboratory parameters and precise monitoring of hemodynamic status of septic patients within the first 3-6 hours after diagnosis. Revision that followed in 2018 stressed that all therapeutic actions should be initiated within the first hour after diagnosis. Urgent administration of isotonic saline and balanced crystalloids in a dose of 30ml/kg should provide adequate hemodynamic stability of septic patients. If the fluid replacement fails to achieve hemodynamic stability and mean arterial pressure >65 mmHg, addition of vasopressors is mandatory. The vasopressor of choice for septic patients is norepinephrine. It may be used alone or in combination with other vasopressors such as epinephrine, vasopressin, terlipresine or phenylephrine. Septic patients with inadequate cardiac output after fluid replacement, and cardiomyopathy induced by sepsis or those with combined shock may need treatment with inotropic medication such as epinephrine or dobutamine. Adjuvant therapy with steroids, immunoglobulins, anticoagulants, statins, vitamin C and Bl, may be useful, but no benefit regarding the overall outcome was observed. In conclusion, early detection of sepsis and septic shock within the first hour and immediate adequate fluid administration with vasoactive medications to maintain hemodynamic stability, are crucial for achievement of better outcome of these patients.
From Louis Braille to the first Serbian spelling book for the blind
Authors: Stanković-Babić Gordana , Babić Rade
Published: March 2021

INTRODUCTION. Blindness is a multiple problem of a psychological-economic-social nature, viewed from different points through the centuries. Louis Braille is the creator of the letter that enabled blind people around the world to become literate and educated. THE LIFE and WORK of Louis BRAILLE. Blind from the age of three after an eye injury with an awl, Louis Braille (1809-1852) had the opportunity to learn about the possibilities of educating blind people early on. However, his talent, recognized in time and a desire to acquire new knowledge, will enable him to attend the "Royal Institute for Blind Youth" in Paris, where young Braille continues his education, creation, living, and later became a lecturer. A PRECURSOR to BRAILLE. Until the creation of the Braille script, a relief linear script was used to educate the blind. THE ORIGIN of BRAILLE. The meeting with the French captain Charles Barbie (1821), the introduction to the communication system for the needs of soldiers "night writing", was the starting point for the future Braille (1825), a dotted alphabet method for the blind, which the author adapted later for writing music and mathematical symbols (1837). The Braille alphabet was chosen as the official method of reading and writing intended for blind people only in 1878 at the World Congress in Paris, and later on adapted to more than two hundred languages and dialects. IN 1917, BRAILLE "SPOKE" IN CYRILLIC. The beginnings of the education of the blind in Serbia are related to 1917 and Bizerte, where, as part of the rehabilitation of the blind Serb soldiers with disabilities, for the first time in the "Printing House of Serbian Disabled People", the Braille "spoke" in Cyrillic. "my first joy" is the name of the first Serbian spelling book by Veljko Ramadanović (1874-1943), who at that time was the only one who knew pedagogical work with the blind, and was also their first teacher and future school principal. CONCLUSION. Louis Braille is one of the most inventive personalities in history, the creator of the letter that enabled blind people around the world to become literate and educated, as well as our brave Serbian army during the First World War.
The effect of brief anxiety interventions on reported anxiety and math test performance
Authors: Ganley Colleen M. , Conlon Rachel A. , McGraw Amanda L. , Barroso Connie , Geer Elyssa A.
Published: March 2021

Research suggests that math and test anxiety have detrimental impacts on performance in math. To prevent these effects, a number of interventions have been developed, but these interventions have not been extensively tested. In the current study, we examine whether four brief anxiety interventions reduce state anxiety and/or increase math performance. We also examine whether any of the interventions weaken the relation between math or test anxiety and math performance. Participants were 300 college students varying in math and test anxiety levels. Participants were randomly assigned to one of four single-session interventions, which each took 5 minutes or less (reappraisal as challenge, reappraisal as excitement, expressive writing, and look ahead), or a no intervention control group. Results generally show that none of the interventions had an effect on reports of state anxiety or performance on a difficult math assessment, with the exception that students in the expressive writing condition reported higher levels of state anxiety. None of the interventions served to attenuate the relation between math or test anxiety and math performance. These findings were not consistent with results of previous work, and suggest that interventions may need to be more extensive in order to have an effect on state anxiety and math performance.
El devenir-animal. La filosofía de Gilles Deleuze aplicada a la obra artística de Francis Bacon.
Authors: Biondi Valeria
Published: March 2021

Este artículo expone el concepto del devenir-animal de Gilles Deleuze en el arte te Francis Bacon. Se trata de un pasaje peculiar que no termina y no empieza nunca, es una particular condición del ser humano, algo que pasa a través de nuestro propio cuerpo y expresa la deformación de este. Analizaremos el idioma filosófico que Deleuze emplea para describir este arte, un arte hecho de sensación y no de imitación. El extranjero, el intruso es alguien que parece vivir en los protagonistas que viven en las pinturas de Bacon; pronto descubrimos que, según la filosofía del pintor, solo podemos ver una zona indiscernible, esta es la sensación que vive entre el hombre y el animal.

This text wants to expose the Gilles Deleuze’s concept of becoming-animal in Francis Bacon’s art. This peculiar passage, that never ends and never begins, is a special condition of human being, something that pass through is own body and express itself as a deformation. We will analyze the philosophical language that Deleuze uses to describe this art, something that is made of sensation and not of imitation. The stranger, the intruder is someone who seems to live within the characters that inhabit Bacon’s paintings; soon we will discover that, as per the philosopher’s theory, what we only can see is an indiscernibility zone, that is the sensation lived between man and animal.
"Un montón de imágenes rotas”: Estudio comparativo de "Respiración artificial", de Ricardo Piglia, y "Ansay o los infortunios", de la gloria, de Martín Caparrós
Authors: Snoey Christian
Published: March 2021

El objetivo de este trabajo es reflexionar sobre las cercanías que existen entre Respiración artificial(1980), de Ricardo Piglia, y Ansay o los infortunios de la gloria(1984), de Martín Caparrós. Ambas novelas parten de la misma pregunta: cómo narrar la historia; por tanto, me centro en analizar la manera en que cada una da respuesta narrativa a este interrogante. Para ello, me detengo en cuatro aspectos: la relectura que ambos autores efectúan con ánimo desmitificador del legado del siglo XIX, el recurso al pasado para decir el presente, la elección de personajes periféricos para crear una contrahistoria y la manera en que cada autor adapta y expande el legado de Borges. El fin último es reflexionar sobre un gesto común: el de intentar recuperar la historia.

The objective of this work is to study the closeness that exists between Respiración artificial(1980), by Ricardo Piglia, and Ansay o los infortunios de la gloria(1984), by Martín Caparrós. Both novels start from the same question: how to tell the history. Therefore, I focus on analyzing how each author gives a narrative answer to this question. To do this, I focus on four aspects: the rereading that both authors do with a demystifying spirit of the legacy of the 19th century, the use of the past to say the present, the choice of peripherical characters to create a counter-history and how each author adapts and expands Borges’s legacy. The ultimate goal is to reflect on a common gesture: the intention to recover history.
El mono filósofo. Presentación de El mono de Heidelberg, cuento de Michael von Albrecht
Authors: Lobe Michael
Published: March 2021

Michael von Albrecht, el gran catedrático emérito de Filología Latina y autor, entre otras obras pioneras, de la monumental Historia de la literatura romana, publicó en 1989 un cuento en latín con el título de De simia Heidelbergensi (El mono de Heidelberg). El objetivo de esta presentación es proporcionar al lector un breve panorama sobre esta preciada joya de la literatura neolatina y presentarle, al mismo tiempo, la actualidad que lo recorre, capaz de trascender la ficción cuentística.

Michael von Albrecht, great Emeritus Professor of Latin Philology and author, among other pioneering works, of the monumental History of Roman Literature, published in 1989 a short story in Latin under the title De simia Heidelbergensi (Heidelberg's Monkey). The objective of this presentation is to provide the reader with a brief overview of this precious jewel of Neo-Latin literature and reveal, at the same time, current events that run through it, capable of transcending short story fiction.
El mono de Heidelberg o la antorcha del latín
Authors: Mauriz Antonio
Published: March 2021

El mono de Heidelberg, la obra que aquí nos complace presentar, no contiene simplemente un cuento. El mono de Heidelberg es, además, portador de una llama. Al igual que, hoy en día, durante la celebración de los Juegos Olímpicos, el portador de la llama olímpica se encarga de llevar la antorcha que reúne en sí algunos de los valores más representativos de la humanidad, el presente cuento porta, en pleno siglo XXI, la antorcha de la lengua latina y de todos los valores asociados tanto a ella como a su milenaria literatura. Se halla, por tanto, al cabo de la tradición de la literatura escrita en latín, que en él se condensa.
Italia en los textos de Ramón Gaya: epistolario y escritos
Authors: Ladrón de Guevara Mellado Pedro Luis
Published: March 2021

Ramón Gaya fijó su residencia en Italia tras un viaje a Europa en el verano de 1952. El deslumbramiento por Venecia, la presencia creciente de escritores españoles que volvían del exilio americano y la acogida en Roma de los círculos literarios italianos propició que Italia fuese el país de elección para el pintor. En este artículo se recorre la huella de   Italia en el epistolario y los escritos de Gaya.

Ramón Gaya settled in Italy after a trip to Europe in the summer of 1952. The dazzling of Venice, the growing presence of Spanish writers returning from American exile and the reception in Rome of Italian literary circles led to Italy being the country of choice for the painter. This article traces the footprint of Italy in Gaya's letters and writings.
La música y Ramón Gaya
Authors: Sanz Ayala Pedro
Published: March 2021

El presente artículo trata de la importancia que tuvo la música en la vida y en la obra de Ramón Gaya: cómo influyó en la creación de su obra y cómo se refleja en ella, en su pintura, en su literatura, en su poesía. Veremos la admiración y el entusiasmo que Gaya sentía hacia la música y hacia algunas de sus principales figuras, la influencia que tuvo en su obra y la gran cantidad de escritos y pinturas con temática musical que Gaya nos legó. Gaya fue un creador y un artista completo. Pintor, escritor, ensayista, poeta…Y la música siempre estuvo presente en su vida y en su obra.   

This article deals with the importance that music had in the life and work of Ramón Gaya: how it influenced the creation of his work and how it is reflected in it, in his painting, in his literature, in his poetry. We will study the admiration and enthusiasm that Gaya felt towards music and towards some of its main figures, the influence of the music on his work and the large amount of music-themed writings and paintings that Gaya left us. Gaya was a complete creator and artist. Painter, writer, essayist, poet ... And music was always present in his life and in his work.
L’enseignement critique du droit du travail : essai
Authors: Tremblay Potvin Charles
Published: March 2021

L’enseignement critique du droit ne doit pas avoir pour objet la transmission d’un savoir encyclopédique. Il n’est pas question non plus d’amener les étudiants à adhérer à une vision particulière de l’ordre juridique. Il importe plutôt de leur transmettre, en plus des connaissances classiques qu’ils doivent acquérir au fil de leur parcours universitaire, le désir de s’approprier et d’ajouter à leurs connaissances de base différentes visions du droit, de la société et du monde. Il semble peu réaliste de demander aux étudiants déjà submergés de lectures de lire en entier ne serait-ce qu’une seule grande oeuvre critique dans le contexte d’une session universitaire. Si l’enseignement critique du droit impose une certaine modestie quant à ses objectifs, il exige également du réalisme dans le choix des moyens employés pour les atteindre. À partir d’un auteur bien choisi, il conviendra de s’appuyer sur des textes accessibles qui permettront de vulgariser les concepts de base de ses analyses. L’objectif est d’offrir des clés d’accès à sa pensée pour faciliter une lecture ultérieure de son oeuvre. Il sera également de mise de rattacher constamment la pensée de l’auteur choisi à la matière étudiée et de montrer en quoi elle permet d’approfondir l’étude du droit actuel. Dans le présent texte, l’auteur tentera d’illustrer la manière dont l’affaire Walmart de Jonquière en droit du travail peut être enseignée à partir de la pensée critique de Marx, qui offre un éclairage particulièrement fécond pour en comprendre les enjeux. À cet égard, le bref texte intitulé Salaire, prix et profit offre une excellente introduction à la pensée de cet auteur.
La comunicación de los Objetivos de Desarrollo Sostenible en las organizaciones de la Economía Social
Authors: Herranz de la Casa José María , García Caballero Sara
Published: March 2021

La agenda 2030 y los Objetivos de Desarrollo Sostenible se han convertido en la referencia que marca la acción de los gobiernos, las naciones, las empresas, las ciudades y los ciudadanos. Cinco años después de su lanzamiento, los datos sobre el cumplimiento de las metas para el año 2030 encuentran áreas críticas y tendencias favorables, lo que hace necesario acelerar el proceso. Las organizaciones de la economía social tienen una oportunidad para posicionarse preferentemente por su filosofía y valores que abarcan la sostenibilidad, la responsabilidad social y la persona. En este artículo se analiza el modelo de comunicación que están desarrollando las principales organizaciones de la economía social en España. Un modelo de comunicación de tres niveles -declarativo, informativo y participativo- que supone un mayor o menor compromiso en la implantación de los ODS dentro de la organización con sus miembros y fuera de ella para visibilizarlos. Se han analizado distintas iniciativas donde la participación de los miembros de organizaciones ha generado reconocimiento en este ámbito. La comunicación no es solo un proceso informativo, sino que supone diálogo y puntos de encuentro para sensibilizar, concienciar y ejercer influencia. Las organizaciones de la economía social no han destacado especialmente por la gestión de la comunicación, pero potenciar la implantación de los ODS puede ser una apuesta firme por diferenciarse en los próximos 10 años.
El arte a través del tratamiento del ruido en imágenes digitales
Authors: Mora Peralta Joan
Published: March 2021

El ruido en las imágenes es un problema ineludible para cualquier fotógrafo y a menudo se combate con unos pocos –y sencillos– algoritmos, pero ¿son todos iguales?, ¿cuáles son y cómo logran sus objetivos? y ¿qué efectos colaterales causan en las imágenes? Estas y otras cuestiones son la raíz del Trabajo de Final de Grado que desarrolló la autora en la modalidad de creación gráfica.

El planteamiento, una vez definido, le permitió esbozar las fases del cronograma e identificar el propósito del trabajo, su utilidad y su valor para el público, aportando conocimiento sobre dichos algoritmos. Su pensamiento analítico y su afecto por la divulgación científica me llevaron a tratarlo como un estudio, valorando mucho la objetividad y la ponderación de cada variable y explicando sus causas con un estilo dirigido al público general.
An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization
Authors: Park Bo-yong , Bethlehem Richard AI , Paquola Casey , Larivière Sara , Rodríguez-Cruces Raul , Vos de Wael Reinder ,   Neuroscience in Psychiatry Network (NSPN) Consortium, Bullmore Edward , Dolan Raymond , Goodyer Ian , Fonagy Peter , Jones Peter , Moutoussis Michael , Hauser Tobias , Neufeld Sharon , Romero-Garcia Rafael , St Clair Michelle , Vértes Petra , Whitaker Kirstie , Inkster Becky , Prabhu Gita , Ooi Cinly , Toseeb Umar , Widmer Barry , Bhatti Junaid , Villis Laura , Alrumaithi Ayesha , Birt Sarah , Bowler Aislinn , Cleridou Kalia , Dadabhoy Hina , Davies Emma , Firkins Ashlyn , Granville Sian , Harding Elizabeth , Hopkins Alexandra , Isaacs Daniel , King Janchai , Kokorikou Danae , Maurice Christina , McIntosh Cleo , Memarzia Jessica , Mills Harriet , O’Donnell Ciara , Pantaleone Sara , Scott Jenny , Kiddle Beatrice , Polek Ela , Fearon Pasco , Suckling John , van Harmelen Anne-Laura , Kievit Rogier , Chamberlain Sam , Bullmore Edward T , Bernhardt Boris C
Published: March 2021

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes, with strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.
Neural network of social interaction observation in marmosets
Authors: Cléry Justine C , Hori Yuki , Schaeffer David J , Menon Ravi S , Everling Stefan
Published: March 2021

A crucial component of social cognition is to observe and understand the social interactions of other individuals. A promising nonhuman primate model for investigating the neural basis of social interaction observation is the common marmoset (Callithrix jacchus), a small New World primate that shares a rich social repertoire with humans. Here, we used functional magnetic resonance imaging acquired at 9.4 T to map the brain areas activated by social interaction observation in awake marmosets. We discovered a network of subcortical and cortical areas, predominately in the anterior lateral frontal and medial frontal cortex, that was specifically activated by social interaction observation. This network resembled that recently identified in Old World macaque monkeys. Our findings suggest that this network is largely conserved between New and Old World primates and support the use of marmosets for studying the neural basis of social cognition.
Complementary biosensors reveal different G-protein signaling modes triggered by GPCRs and non-receptor activators
Authors: Garcia-Marcos Mikel
Published: March 2021

It has become evident that activation of heterotrimeric G-proteins by cytoplasmic proteins that are not G-protein-coupled receptors (GPCRs) plays a role in physiology and disease. Despite sharing the same biochemical guanine nucleotide exchange factor (GEF) activity as GPCRs in vitro, the mechanisms by which these cytoplasmic proteins trigger G-protein-dependent signaling in cells have not been elucidated. Heterotrimeric G-proteins can give rise to two active signaling species, Gα-GTP and dissociated Gβγ, with different downstream effectors, but how non-receptor GEFs affect the levels of these two species in cells is not known. Here, a systematic comparison of GPCRs and three unrelated non-receptor proteins with GEF activity in vitro (GIV/Girdin, AGS1/Dexras1, and Ric-8A) revealed high divergence in their contribution to generating Gα-GTP and free Gβγ in cells directly measured with live-cell biosensors. These findings demonstrate fundamental differences in how receptor and non-receptor G-protein activators promote signaling in cells despite sharing similar biochemical activities in vitro.
Transient kinetic studies of the antiviral Drosophila Dicer-2 reveal roles of ATP in self–nonself discrimination
Authors: Singh Raushan K , Jonely McKenzie , Leslie Evan , Rejali Nick A , Noriega Rodrigo , Bass Brenda L
Published: March 2021

Some RIG-I-like receptors (RLRs) discriminate viral and cellular dsRNA by their termini, and Drosophila melanogaster Dicer-2 (dmDcr-2) differentially processes dsRNA with blunt or 2 nucleotide 3’-overhanging termini. We investigated the transient kinetic mechanism of the dmDcr-2 reaction using a rapid reaction stopped-flow technique and time-resolved fluorescence spectroscopy. Indeed, we found that ATP binding to dmDcr-2’s helicase domain impacts association and dissociation kinetics of dsRNA in a termini-dependent manner, revealing termini-dependent discrimination of dsRNA on a biologically relevant time scale (seconds). ATP hydrolysis promotes transient unwinding of dsRNA termini followed by slow rewinding, and directional translocation of the enzyme to the cleavage site. Time-resolved fluorescence anisotropy reveals a nucleotide-dependent modulation in conformational fluctuations (nanoseconds) of the helicase and Platform–PAZ domains that is correlated with termini-dependent dsRNA cleavage. Our study offers a kinetic framework for comparison to other Dicers, as well as all members of the RLRs involved in innate immunity.
Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex
Authors: de Filippo Roberto , Rost Benjamin R , Stumpf Alexander , Cooper Claire , Tukker John J , Harms Christoph , Beed Prateep , Schmitz Dietmar
Published: March 2021

Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations with in vitro electrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT2A receptor (5-HT2AR) play an important role in the suppression of SOs. Since 5-HT2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics.
Bioinformatic strategies for the analysis of genomic aberrations detected by targeted NGS panels with clinical application
Authors: Hynst Jakub , Navrkalova Veronika , Pal Karol , Pospisilova Sarka
Published: March 2021

Molecular profiling of tumor samples has acquired importance in cancer research, but currently also plays an important role in the clinical management of cancer patients. Rapid identification of genomic aberrations improves diagnosis, prognosis and effective therapy selection. This can be attributed mainly to the development of next-generation sequencing (NGS) methods, especially targeted DNA panels. Such panels enable a relatively inexpensive and rapid analysis of various aberrations with clinical impact specific to particular diagnoses. In this review, we discuss the experimental approaches and bioinformatic strategies available for the development of an NGS panel for a reliable analysis of selected biomarkers. Compliance with defined analytical steps is crucial to ensure accurate and reproducible results. In addition, a careful validation procedure has to be performed before the application of NGS targeted assays in routine clinical practice. With more focus on bioinformatics, we emphasize the need for thorough pipeline validation and management in relation to the particular experimental setting as an integral part of the NGS method establishment. A robust and reproducible bioinformatic analysis running on powerful machines is essential for proper detection of genomic variants in clinical settings since distinguishing between experimental noise and real biological variants is fundamental. This review summarizes state-of-the-art bioinformatic solutions for careful detection of the SNV/Indels and CNVs for targeted sequencing resulting in translation of sequencing data into clinically relevant information. Finally, we share our experience with the development of a custom targeted NGS panel for an integrated analysis of biomarkers in lymphoproliferative disorders.
New alignment-based sequence extraction software (ALiBaSeq) and its utility for deep level phylogenetics
Authors: Knyshov Alexander , Gordon Eric R.L. , Weirauch Christiane
Published: March 2021

Despite many bioinformatic solutions for analyzing sequencing data, few options exist for targeted sequence retrieval from whole genomic sequencing (WGS) data with the ultimate goal of generating a phylogeny. Available tools especially struggle at deep phylogenetic levels and necessitate amino-acid space searches, which may increase rates of false positive results. Many tools are also difficult to install and may lack adequate user resources. Here, we describe a program that uses freely available similarity search tools to find homologs in assembled WGS data with unparalleled freedom to modify parameters. We evaluate its performance compared to other commonly used bioinformatics tools on two divergent insect species (>200 My) for which annotated genomes exist, and on one large set each of highly conserved and more variable loci. Our software is capable of retrieving orthologs from well-curated or unannotated, low or high depth shotgun, and target capture assemblies as well or better than other software as assessed by recovering the most genes with maximal coverage and with a low rate of false positives throughout all datasets. When assessing this combination of criteria, ALiBaSeq is frequently the best evaluated tool for gathering the most comprehensive and accurate phylogenetic alignments on all types of data tested. The software (implemented in Python), tutorials, and manual are freely available at https://github.com/AlexKnyshov/alibaseq.
Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status
Authors: Xu Zhengquan , Ding Yanhong , Lu Wei , Zhang Ke , Wang Fei , Ding Guanxiong , Wang Jianqing
Published: March 2021

Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.
Unusual Thoracic Tumours- A Concise Imaging Approach
Authors: Goyal Alka , Bagarhatta Meenu , Mangalhara Naresh Kumar , Jhanwar Vikas , Tiwari Raghav , Kumari Sunita
Published: March 2021

Introduction: There are certain uncommon large thoracic masses sharing overlapping radiological features with commoner ones except few salient characteristic features. Diagnosing these uncommon tumours has practical implications for patient management and prognosis including obviating unnecessary surgeries. Aim: To demonstrate characteristic Computed Tomography (CT) features of large common and certain uncommon intra-thoracic masses Materials and Methods: A retrospective cross-sectional search was done in January 2020, from the archives of patients record in Radiology Department from December 2017 to January 2019 for intra-thoracic tumours. Those tumors or masses meeting inclusion criteria were analysed by two radiologists who were blinded about the histopathologic reports. A probable radiological diagnosis was made and it was later matched-up with the histopathologic reports to reach to a confirmed diagnosis. The unique CT features were separately tabulated and their p-value for a particular diagnosis was calculated using Fisher’s-exact test. Results: Out of total 23 cases studied, 12 bronchogenic carcinomas and 11 uncommon diagnoses including Solitary fibrous tumour, Synovial sarcoma, Pulmonary blastoma, Askin’s tumour, Schwannoma and Metastasis were found. Subtle rib erosion in Askin’s tumour (p-value=0.004), intra-tumoural vessels in Synovial sarcomas (p-value=0.0006) and intense enhancement in some non-bronchogenic tumours (p-value=0.0137) were found to be significantly associated features. Conclusion: When encountering an opaque hemithorax on chest radiograph and a large mass on CT, one should look for certain peculiar features of these unusual lung masses to suggest them as a differential diagnosis, as “Our eyes see only what our mind knows”.
Endocrinopathy Causing Skeletal Decalcification and Ectopic Calcification Highlighted by Imaging Tour
Authors: Bhargav PRK , Kota Sunil Kumar , Sabaretnam M
Published: March 2021

Primary Hyperparathyroidism (PHPT) is an endocrine disorder which is caused by increased production of Parathyroid Hormone (PTH). Hypercalcemia leads to a number of symptoms and may cause patient's morbidity and even mortality if left untreated. In the present case, a 21-year-old female presenting with frequent attacks of urinary tract infection, diffuse bone pain and episodic pain abdomen since 15 months. On clinical, biochemical and radiological evaluation, the case was diagnosed as PHPT due to left superior parathyroid adenoma. Patient underwent uneventful surgical parathyroidectomy following preoperative optimisation. She achieved normocalcaemia without any surgical complications. This case is presented to highlight the impact of hyperparathyroidism on calcium metabolism leading to extensive skeletal decalcification and ectopic deposition of calcium leading to end organ damage. Various images are used to highlight this phenomenon of decalcification and calcification.
Role of MRI in Evaluation of Focal Liver Lesions: A Cross-sectional Study
Authors: Kotnis Sanket Manoj , Nagaraj Roopa Hosahalli , Brahma Prakash Jain Rajanna
Published: March 2021

Introduction: The non-invasive diagnosis of liver lesions is usually achieved with contrast material-enhanced computed tomography and Magnetic Resonance (MR) imaging. Dynamic three dimensional gradient-recalled-echo MR imaging provides dynamic contrast-enhanced thin-section images with fat saturation and a high signal-to-noise ratio and is excellent for the evaluation of various focal hepatic lesions. Aim: To explore the effectiveness and hence the clinical utility of plain and contrast MR characterisation of focal hepatic lesions in patients and their correlation with the histopathological findings. Materials and Methods: The present study was a multicenteric study done on both Inpatients and Outpatients of Department of Radiology of Tertiary care hospitals in Bengaluru, from January 2020 to August 2020. A total of 42 patients diagnosed with focal liver lesions by Ultrasonography were included in this study. Plain MRI study was done by using spin echo technique and contrast MRI study was done after rapid bolus injection (0.1 mmol/kg body weight) of gadolinium dimeglumine. Pathological and post-operative histopathological findings were noted. Microsoft excel software was used for data analysis and tables were prepared for comparison of collected data. Specificity and sensitivity were calculated for diagnostic accuracy of MRI. Results: This study included forty-two patients in total, twenty-five male and seventeen female patients, in age group of 15 to 84 years with a mean age of 48 years. Metastasis and Hepatocellular Carcinoma (HCC) were most common malignant lesions in liver while Hemangiomas were most common benign lesions followed by simple and complex cysts and hepatic adenoma. The present study calculated the specificity and sensitivity of MRI of focal hepatic lesions and correlated the findings clinically, pathologically and histopathologically. The specificity of MRI for characterisation of focal liver disease was high (90.4%). Specificity of MRI for HCC was found to be 96.7 % and that for metastasis was 97% while sensitivity for Haemangiomas is found to be 100%.MRI is superior compared to other modalities like ultrasound and CT in having high spatial resolution. Multiple sequences like T1, T2 and fat suppression techniques like IN PHASE, OUT OF PHASE helps in demonstrating lesion characters like architecture, margin, haemorrhage, fat component and vascular invasion of the lesions. Conclusion: MRI is valuable for the characterization of focal liver lesions detected on Ultrasonography. Basic MRI sequences along with chemical shift imaging sequences and dynamic contrast imaging has significant role in characterising the focal liver lesions. Despite that, It should be the modality choice for the lesions which are undetected or doubtful on ultrasound and CT examinations.