bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyaluronic acid fuels pancreatic cancer cell growth
Authors: Kim Peter K , Halbrook Christopher J , Kerk Samuel A , Radyk Megan , Wisner Stephanie , Kremer Daniel M , Sajjakulnukit Peter , Andren Anthony , Hou Sean W , Trivedi Ayush , Thurston Galloway , Anand Abhinav , Yan Liang , Salamanca-Cardona Lucia , Welling Samuel D , Zhang Li , Pratt Matthew R , Keshari Kayvan R , Ying Haoqiang , Lyssiotis Costas A
Published: December 2021

Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in human PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not preclude the growth of human tumor xenografts in mice, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. We found that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles.
Nano-scale architecture of blood-brain barrier tight-junctions
Authors: Sasson Esther , Anzi Shira , Bell Batia , Yakovian Oren , Zorsky Meshi , Deutsch Urban , Engelhardt Britta , Sherman Eilon , Vatine Gad , Dzikowski Ron , Ben-Zvi Ayal
Published: December 2021

Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-resolution microscopy (dSTORM) to uncover new structural and functional properties of BBB TJs. Focusing on three major components, Nano-scale resolution revealed sparse (occludin) vs. clustered (ZO1/claudin-5) molecular architecture. In mouse development, permeable TJs become first restrictive to large molecules, and only later to small molecules, with claudin-5 proteins arrangement compacting during this maturation process. Mechanistically, we reveal that ZO1 clustering is independent of claudin-5 in vivo. In contrast to accepted knowledge, we found that in the developmental context, total levels of claudin-5 inversely correlate with TJ functionality. Our super-resolution studies provide a unique perspective of BBB TJs and open new directions for understanding TJ functionality in biological barriers, ultimately enabling restoration in disease or modulation for drug delivery.
A modular platform for automated cryo-FIB workflows
Authors: Klumpe Sven , Fung Herman KH , Goetz Sara K , Zagoriy Ievgeniia , Hampoelz Bernhard , Zhang Xiaojie , Erdmann Philipp S , Baumbach Janina , Müller Christoph W , Beck Martin , Plitzko Jürgen M , Mahamid Julia
Published: December 2021

Lamella micromachining by focused ion beam milling at cryogenic temperature (cryo-FIB) has matured into a preparation method widely used for cellular cryo-electron tomography. Due to the limited ablation rates of low Ga+ ion beam currents required to maintain the structural integrity of vitreous specimens, common preparation protocols are time-consuming and labor intensive. The improved stability of new-generation cryo-FIB instruments now enables automated operations. Here, we present an open-source software tool, SerialFIB, for creating automated and customizable cryo-FIB preparation protocols. The software encompasses a graphical user interface for easy execution of routine lamellae preparations, a scripting module compatible with available Python packages, and interfaces with three-dimensional correlative light and electron microscopy (CLEM) tools. SerialFIB enables the streamlining of advanced cryo-FIB protocols such as multi-modal imaging, CLEM-guided lamella preparation and in situ lamella lift-out procedures. Our software therefore provides a foundation for further development of advanced cryogenic imaging and sample preparation protocols.
De novo synthesized polyunsaturated fatty acids operate as both host immunomodulators and nutrients for Mycobacterium tuberculosis
Authors: Laval Thomas , Pedró-Cos Laura , Malaga Wladimir , Guenin-Macé Laure , Pawlik Alexandre , Mayau Véronique , Yahia-Cherbal Hanane , Delos Océane , Frigui Wafa , Bertrand-Michel Justine , Guilhot Christophe , Demangel Caroline
Published: December 2021

Successful control of Mycobacterium tuberculosis (Mtb) infection by macrophages relies on immunometabolic reprogramming, where the role of fatty acids (FAs) remains poorly understood. Recent studies unraveled Mtb’s capacity to acquire saturated and monounsaturated FAs via the Mce1 importer. However, upon activation, macrophages produce polyunsaturated fatty acids (PUFAs), mammal-specific FAs mediating the generation of immunomodulatory eicosanoids. Here, we asked how Mtb modulates de novo synthesis of PUFAs in primary mouse macrophages and whether this benefits host or pathogen. Quantitative lipidomics revealed that Mtb infection selectively activates the biosynthesis of ω6 PUFAs upstream of the eicosanoid precursor arachidonic acid (AA) via transcriptional activation of Fads2. Inhibiting FADS2 in infected macrophages impaired their inflammatory and antimicrobial responses but had no effect on Mtb growth in host cells nor mice. Using a click-chemistry approach, we found that Mtb efficiently imports ω6 PUFAs via Mce1 in axenic culture, including AA. Further, Mtb preferentially internalized AA over all other FAs within infected macrophages by mechanisms partially depending on Mce1 and supporting intracellular persistence. Notably, IFNγ repressed de novo synthesis of AA by infected mouse macrophages and restricted AA import by intracellular Mtb. Together, these findings identify AA as a major FA substrate for intracellular Mtb, whose mobilization by innate immune responses is opportunistically hijacked by the pathogen and downregulated by IFNγ.
Generation and diversification of recombinant monoclonal antibodies
Authors: DeLuca Keith F , Mick Jeanne E , Ide Amy H , Lima Wanessa C , Sherman Lori , Schaller Kristin L , Anderson Steven M , Zhao Ning , Stasevich Timothy J , Varma Dileep , Nilsson Jakob , DeLuca Jennifer G
Published: December 2021

Antibodies are indispensable tools used for a large number of applications in both foundational and translational bioscience research; however, there are drawbacks to using traditional antibodies generated in animals. These include a lack of standardization leading to problems with reproducibility, high costs of antibodies purchased from commercial sources, and ethical concerns regarding the large number of animals used to generate antibodies. To address these issues, we have developed practical methodologies and tools for generating low-cost, high-yield preparations of recombinant monoclonal antibodies and antibody fragments directed to protein epitopes from primary sequences. We describe these methods here, as well as approaches to diversify monoclonal antibodies, including customization of antibody species specificity, generation of genetically encoded small antibody fragments, and conversion of single chain antibody fragments (e.g. scFv) into full-length, bivalent antibodies. This study focuses on antibodies directed to epitopes important for mitosis and kinetochore function; however, the methods and reagents described here are applicable to antibodies and antibody fragments for use in any field.
Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation
Authors: Rousová Dorota , Nivsarkar Vaishnavi , Altmannova Veronika , Raina Vivek B , Funk Saskia K , Liedtke David , Janning Petra , Müller Franziska , Reichle Heidi , Vader Gerben , Weir John R
Published: December 2021

In meiosis, DNA double-strand break (DSB) formation by Spo11 initiates recombination and enables chromosome segregation. Numerous factors are required for Spo11 activity, and couple the DSB machinery to the development of a meiosis-specific ‘axis-tethered loop’ chromosome organisation. Through in vitro reconstitution and budding yeast genetics, we here provide architectural insight into the DSB machinery by focussing on a foundational DSB factor, Mer2. We characterise the interaction of Mer2 with the histone reader Spp1, and show that Mer2 directly associates with nucleosomes, likely highlighting a contribution of Mer2 to tethering DSB factors to chromatin. We reveal the biochemical basis of Mer2 association with Hop1, a HORMA domain-containing chromosomal axis factor. Finally, we identify a conserved region within Mer2 crucial for DSB activity, and show that this region of Mer2 interacts with the DSB factor Mre11. In combination with previous work, we establish Mer2 as a keystone of the DSB machinery by bridging key protein complexes involved in the initiation of meiotic recombination.
Structure and ion-release mechanism of PIB-4-type ATPases
Authors: Grønberg Christina , Hu Qiaoxia , Mahato Dhani Ram , Longhin Elena , Salustros Nina , Duelli Annette , Lyu Pin , Bågenholm Viktoria , Eriksson Jonas , Rao Komal Umashankar , Henderson Domhnall Iain , Meloni Gabriele , Andersson Magnus , Croll Tristan , Godaly Gabriela , Wang Kaituo , Gourdon Pontus
Published: December 2021

Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here, we present structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism and diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
Cost-sensitive learning strategies for high-dimensional and imbalanced data: a comparative study
Authors: Pes Barbara , Lai Giuseppina
Published: December 2021

High dimensionality and class imbalance have been largely recognized as important issues in machine learning. A vast amount of literature has indeed investigated suitable approaches to address the multiple challenges that arise when dealing with high-dimensional feature spaces (where each problem instance is described by a large number of features). As well, several learning strategies have been devised to cope with the adverse effects of imbalanced class distributions, which may severely impact on the generalization ability of the induced models. Nevertheless, although both the issues have been largely studied for several years, they have mostly been addressed separately, and their combined effects are yet to be fully understood. Indeed, little research has been so far conducted to investigate which approaches might be best suited to deal with datasets that are, at the same time, high-dimensional and class-imbalanced. To make a contribution in this direction, our work presents a comparative study among different learning strategies that leverage both feature selection, to cope with high dimensionality, as well as cost-sensitive learning methods, to cope with class imbalance. Specifically, different ways of incorporating misclassification costs into the learning process have been explored. Also different feature selection heuristics have been considered, both univariate and multivariate, to comparatively evaluate their effectiveness on imbalanced data. The experiments have been conducted on three challenging benchmarks from the genomic domain, gaining interesting insight into the beneficial impact of combining feature selection and cost-sensitive learning, especially in the presence of highly skewed data distributions.
The debate about the effects of habitat fragmentation: causes and consequences
Authors: Arasa-Gisbert Ricard , Arroyo-Rodríguez Víctor , Andresen Ellen
Published: December 2021

Con la creciente pérdida y fragmentación de los ecosistemas naturales, entender cómo responden las especies a estos cambios nunca ha sido más urgente. Hoy existe consenso acerca del fuerte impacto negativo de la pérdida de hábitat sobre la biodiversidad. Sin embargo, el efecto de la fragmentación del hábitat ha sido muy debatido. En esta revisión, proponemos un esquema que evalúa las causas y consecuencias del debate. Sugerimos que es causado por el uso de diferentes definiciones y conceptualizaciones de la fragmentación (causas distales), las cuales promueven el uso de distintas metodologías de estudio (causas proximales). Algunos estudios consideran la fragmentación como un proceso inseparable de la pérdida de hábitat y de otras amenazas locales (p.ej. efectos de borde y aislamiento), por lo que miden sus efectos a escala de sitio, de parche o de paisaje, sin controlar necesariamente el efecto de la pérdida de hábitat. Otros consideran la fragmentación como un patrón que describe la configuración del hábitat en el paisaje, y cuyo efecto puede y debe ser evaluado independientemente del efecto de la cantidad de hábitat (i.e. fragmentación per se) usando el paisaje como unidad de análisis. Como consecuencia, los primeros usualmente concluyen que la fragmentación tiene efectos fuertes y negativos sobre la biodiversidad, mientras que los segundos concluyen que dichos efectos son generalmente débiles, y positivos cuando son significativos. Entender las causas y consecuencias de este debate es crítico para aplicar medidas de conservación más adecuadas.
System Dynamics for understanding desertification processes
Authors: Martinez-Valderrama Jaime , Ibáñez Javier , Gartzia Rolando , https://orcid.org/0000-0002-8165-8669 Francisco J.
Published: December 2021

La desertificación es un proceso complejo y contraintuitivo cuyo estudio demanda un enfoque multidisciplinar. Ello la convierte en un campo de investigación ideal sobre el que aplicar la Dinámica de Sistemas (DS). Se trata de una metodología de construcción de modelos dinámicos de simulación por ordenador que se concibe como herramienta de apoyo para el estudio y la gestión de problemas que, especialmente, muestren las características aludidas. Este artículo repasa los fundamentos de la metodología, muestra sus ventajas y desventajas, e ilustra su funcionamiento con un caso de estudio de desertificación. A través de este modelo, que describe un sistema de pastoreo en el que tanto la erosión como la invasión de matorrales son dos amenazas contrapuestas y latentes, se explican dos de las principales señas de identidad de la DS: la detección de bucles de realimentación y la implementación de multiplicadores. Mediante los primeros se trata de explicitar los mecanismos subyacentes al comportamiento del sistema y con los “multis” se demuestra la necesidad de considerar el comportamiento de un sistema en situaciones extremas, propias de problemas como la desertificación. El trabajo presenta, además, diversas maneras de utilizar un modelo DS. Más allá de la evolución temporal de las variables que forman parte del modelo, es posible acoplar distintos tipos de análisis que resultan muy útiles en el estudio y prevención de la desertificación, como es la estimación de riesgos de desertificación y los análisis de sensibilidad que permiten detectar los factores más determinantes de este problema.
Drought tolerance of Paspalum notatum subjected to defoliation
Authors: Ruiz Verónica , Rocha Lester , Savé Robert
Published: December 2021

La sequía asociada al cambio climático y a la variabilidad climática es el principal factor que afecta la productividad y diversidad de los ecosistemas terrestres. El objetivo de este estudio evaluar la tolerancia a la sequía y el crecimiento compensatorio de dos procedencias de Paspalum notatum sometidas a defoliación y déficit hídrico. El experimento se llevó a cabo en condiciones de invernadero, ubicado en la Estación Experimental para el Estudio del Trópico Seco “El Limón”, adscrita a la UNAN Managua. Se realizó un experimento con arreglo factorial de tratamientos con tres repeticiones. Los individuos de dos procedencias de P. notatum fueron sometidos a dos niveles de defoliación y dos niveles de régimen hídrico. Las variables evaluadas fueron producción de materia seca, tasa de crecimiento relativo y potencial hídrico. Los principales resultados muestran las plantas de P. notatum en condiciones sin estrés hídrico presentaron un aumento en su biomasa aérea en un 15 %, la acumulación de biomasa de rizoma de plantas defoliadas fue menor en relación a las plantas no defoliadas, la biomasa de raíces estuvo en dependencia del régimen hídrico, la biomasa acumulada total aumentó en un 20 % en condiciones no defoliadas y las plantas defoliadas de Muy Muy mostraron una sobrecompensación y las plantas defoliadas de Rivas presentaron una compensación parcial. El potencial hídrico en plantas defoliadas no mostró diferenciación, indistintamente del régimen hídrico al que fueron sometidos. La sequía es un factor determinante que modifica la capacidad compensatoria de gramíneas sometidas a defoliación en biomasa aérea y rizomas.
Can desertification be mapped? Lights and shadows of a challenging task
Authors: Martinez-Valderrama Jaime , Guirado Emilio , Maestre Fernando T.
Published: December 2021

La desertificación es un fenómeno complejo con múltiples caras. Han existido numerosos intentos por cartografiarla. Sin embargo, ninguna de las aproximaciones se ha consolidado y los criterios y metodologías han cambiado con los años. La falta de robustez hace que la interpretación de estos mapas sea confusa y poco operativa. En este trabajo repasamos sucintamente las tentativas por plasmar en un mapa este complejo problema medioambiental, analizamos sus dificultades y mostramos las últimas tendencias. El último Atlas Mundial de Desertificación, publicado en 2018 por la Comisión Europea, renuncia a ello y propone un enfoque alternativo. Su propuesta es identificar aquellos lugares que pueden ser más proclives a la degradación al coincidir en ellos una serie de factores que amenazan el equilibro entre el uso de recursos y su regeneración. La creciente disponibilidad de recursos cartográficos abre las puertas a nuevos enfoques. Sin embargo, este enorme potencial de datos debe conjugarse con una clara concepción del problema, distinguiendo entre mapear el estado de desertificación o su riesgo y determinando, con la mayor objetividad posible, los umbrales de degradación que dan lugar a una degradación persistente.
The socioeconomic determinants of timber use in the buffer zone of the Sumaco Napo Galeras National Park, Ecuadorian Amazon
Authors: Zambrano Erika , Torres Bolier , Ochoa-Moreno Santiago , Reyes Héctor , Torres Alexandra , Velasco Christian , Heredia-R Marco
Published: December 2021

Este trabajo evalúa las determinantes socioeconómicas del uso forestal maderable, tipos de ingresos económicos y la dependencia del aprovechamiento de madera a nivel de hogares en poblaciones indígenas kichwas y colonas/mestizas asentadas en la Región Amazónica Ecuatoriana (RAE). Los datos se obtuvieron a través de una encuesta socioeconómica en 180 hogares, realizada en siete comunidades de la parroquia Hatun Sumaku. Los resultados indicaron que, en promedio, los ingresos económicos son un 12% mayor para los hogares colonos/mestizos (USD 2787.68) que para los hogares kichwa (USD 2445.45), para quienes en esta zona su principal ingreso económico es el aprovechamiento de madera (33%), mientras que para los colonos/mestizos el 3% dado que sus ingresos principales provienen de actividades fuera de la finca (43%) a diferencia de los Kichwa (17%). El modelo de regresión Probit mostró que el área en bosques secundarios y el acceso a comunicación celular influyen positivamente en el aprovechamiento maderero, mientras que las áreas en cultivos influyen negativamente en la probabilidad de que un hogar decida aprovechar madera del bosque.
Potential of artificial intelligence to advance the study of desertification
Authors: Guirado Emilio , Martínez-Valderrama Jaime
Published: December 2021

La desertificación es un problema global que afecta a más de 1.500 millones de personas que viven en los lugares más pobres y vulnerables del planeta. En los últimos años numerosos estudios han contribuido a aportar información para evaluar el problema. Algunos de ellos se basan en analizar variables biofísicas y socio-económicas mediante técnicas de inteligencia artificial. Por ejemplo, se han usado para completar datos de anomalías en la estimación de almacenamiento de agua, la identificación precisa de cobertura del suelo, estimación de la radiación solar diaria a nivel global y mejora en predicciones climáticas, entre otras. Si bien su uso todavía no está muy extendido, el futuro en los estudios sobre desertificación parece prometedor. En este trabajo revisamos el potencial de las técnicas de inteligencia artificial (aprendizaje automático y aprendizaje profundo) en el estudio de la desertificación y su reciente crecimiento en los últimos años. Durante el periodo 2015-2020 el número de publicaciones que implementan el aprendizaje profundo se incrementó un 63%, mientras que para el aprendizaje automático su crecimiento fue más modesto, del 3%. En particular, cuando buscamos estudios relacionados con la desertificación, las cifras de crecimiento son más llamativas: un incremento medio del 103% en estudios con aprendizaje profundo, y del 43% en aprendizaje automático. Sin embargo, se requieren más estudios y esfuerzos que agrupen todas las disciplinas implicadas en el estudio de la desertificación para obtener una visión global y transversal de este fenómeno y así diseñar acciones efectivas para mitigar sus efectos adversos o anticiparse a ellos.
Participatory planning for ecological restoration of a highly anthropised semi-arid landscape
Authors: Silva Elysa , Derak Mchich , Climent-Gil Emilio , Aledo Antonio , Bonet Andreu , López Germán , Cortina-Segarra Jordi
Published: December 2021

La restauración ecológica tiene un enorme potencial para proteger la biodiversidad, aumentar el suministro de servicios ecosistémicos y mejorar el bienestar humano. Para desarrollar plenamente este potencial y hacerlo de una manera eficiente, es necesario diseñar procedimientos operativos que permitan identificar acciones y zonas prioritarias para la restauración. Estos procedimientos, además, deben armonizar los múltiples criterios de priorización y las múltiples expectativas sobre sus resultados. En este estudio hemos diseñado y aplicado un sistema de identificación de zonas de alta prioridad para la restauración de un paisaje semiárido muy antropizado en el sureste de la península ibérica. Nuestra aproximación conjuga los criterios de prioridad identificados y ponderados por una plataforma de partes interesadas, y la efectividad de la restauración, medida como incremento potencial en el suministro de servicios. Las partes interesadas identificaron y ponderaron 33 criterios de priorización y 24 servicios ecosistémicos. Las zonas de alta prioridad para la restauración, según criterio de la plataforma, coincidieron sustancialmente con zonas de alto suministro de servicios. Por el contrario, estas zonas apenas se solapaban con zonas de alta efectividad. Nuestro estudio muestra que ambas aproximaciones pueden contribuir, de forma complementaria, a mejorar la calidad de las decisiones y facilitar el consenso entre las partes. Nuestra metodología es flexible y puede ser replicada en otros paisajes, incluso fuera del ámbito del estudio.
Desertification is a prisoner of history: An essay on why young scientists should care
Authors: Reynolds James F.
Published: December 2021

Since its origins, the concept of desertification has been shrouded in controversy and ambiguity. As a result, no single definition of the term has been acceptable; there is no agreement on its extent or seriousness; and the solutions proposed are often disparate and counterproductive. This essay suggests all of this is due to the concept of desertification being a permanent ‘prisoner of history’, a historical process led by the United Nations Convention on Desertification (UNCCD). In this essay, I describe why the prisoner of history narrative applies to the concept of desertification. To do this, I review the historical events that built a metaphorical prison for desertification; show why definitions of the term ‘desertification’ are products of this prison; describe how so much misunderstanding and confusion in this field has led to real, negative consequences; and lastly, provide recommendations to young scientists as to how to avoid becoming incarcerated in this prison.
Haematological and Histopathological Examinations of African Catfish (Clarias gariepinus) Exposed to Sub-Lethal Concentrations of Paraquat
Authors: Okey I. B. , Ekpenyong J. J. , Inya F. U.
Published: December 2021

The study was designed to investigate the sub-lethal effects of paraquat on haematological parameters and histopathology of the gills, skin and liver of Clarias gariepinus juveniles of mean weight (38.26±1.20g) and length (17.50±1.55cm). The fish were exposed to 10, 20, 30, 40 and 50% of the 96hrsLC50 value of 107mg/l estimated from the 96 hours acute toxicity test. Blood samples were collected into heparinized tubes for the analyses of some haematological parameters, while the gills, skin and liver were also removed for histological examinations following standard procedures. The result revealed a significant reduction (P < 0.05) in the values of red blood cells (RBCs), haemoglobin (Hgb), packed cell volume (PCV) and erythrocytes indices from the control. The white blood cells (WBCs) and platelets (Plt) were however increasing significantly (P < 0.05) from those of the control as the test concentrations increased. The histology of the gills revealed some alterations such as epithelial proliferation, vacuolation of the mucus, hyperplasia of epithelial tissue of the gill filament, lifting and necrosis of the secondary lamellae. The exposed skin showed mucous cell proliferation, erosion of the epithelial lining, hypertrophy, necrosis of epithelial cells and widening of the epidermal and dermal layers. The liver exhibited cellular proliferation, sinusoid enlargement, congestion of the central vein, paranchymatous degeneration, vacuolar degeneration, pyknotic nucleic degeneration, legions and necrosis with severity as concentration of paraquat increases. The gills and skin were observed to be the most affected tissues in this study. The study also revealed that paraquat was toxic to C. gariepinus and causes some haematological and histopathological alterations in the fish blood and tissues at concentrations higher than 30mg/l. Therefore, the use of paraquat by farmers should be regulated particularly in area close to the aquatic environment.
Overview on Neurological Manifestations of Thyroid Disease
Authors: Hussein Mohammed Salah , Alyahya Faisal Mohammed , Barradah Husam Fouad K. , Almuhanaa Adeeb Abdullah , Mohammed B. Alzhrani, Olayan , Alanazi Abeer Dhaifallah , Almutairi Norah Talal , Alkhamis Riam Saleh , Aljaber Taif Nasser , Saaed Albishi, Haya , Alghamdi Ahmed Dhaifallah , Baqir Hussain Ali Al
Published: December 2021

Hypothyroidism and hyperthyroidism are both prevalent medical conditions that are frequently accompanied with neurologic and neuromuscular dysfunction. Triiodothyronine (T3) and thyroxine (T4) hormones are produced by the thyroid gland and play a crucial role in tissue formation and metabolism. Both of these hormones have a variety of impacts on the brain and neuromuscular system. Specially in children, because brain development can be effected by any disturbances in Thyroidal hormones level. And thus, conditions like Allan-Herndon-Dudley Syndrome & Benign Hereditary Chorea is considered genetic thyroidal diseases both will be discussed in this review. hypothyroidism can have serious consequences for neuropsychiatric function. The pathophysiological processes underlying the neurological symptoms of hypothyroidism and hyperthyroidism are likely to be multifactorial, in this review we will be looking at multiple neurological as well as psychiatric manifestations related to thyroidal hormones disorders.

Methods: We used the phrases "hypothyroidism," "hyperthyroidism," "neurological problems," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy" in a PubMed search, google scholar and google search engines. Case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials were among the papers examined. Classification of thyroidal dysfunction has been made depending on the thyroidal hormones level. The neurological consequences of congenital hypothyroidism were examined, as well as the clinical aspects of hypothyroidism and hyperthyroidism-related neuromuscular disorders, as well as other autoimmune illnesses. Hashimoto encephalopathy's evidence and pathophysiological issues were also examined.

Conclusion: Thyroid is critical organ due to role of its thyroidal hormones, both hypothyroidism and hyperthyroidism induce some serious neurological and phycological disorders, some of which is genetic, hypothyroidism can impact the development of child and thus regular thyroidal hormones testing is recommended in children who demonstrates any signs of neurological psychiatric  or cognitive disease.
Determination of Coagulation Profile among Children with Sickle Cell: Anemia in Steady-State and Crisis
Authors: Ali Maysaa Ali Hassan , Abdallah Elharam Ibrahim , Omer Alaa Eltayeb , Eltayeb Lienda Bashier
Published: December 2021

Background: Patients with Sickle Cell Disease (SCD) have been found to have an aberrant coagulation profile. One of the primary elements hypothesized to contribute to the vaso-occlusive crisis that characterizes sickle cell disease is coagulopathy (SCD)

Material and Methods: A total of 150 children were enrolled as follows, 50 children with Sickle Cell Anemia (SCA) in steady-state, 50 in crisis, and 50 with Hb AA genotype as control. 5 ml of Venous blood was collected. The platelets count was performed using Sysmex KX21N, the electrical impedance principle. The Mean Platelet Volume (MPV) is derived from the impedance platelet size distribution curve. STAGO PT31039352) semi-automated machine was used for estimation of PT, and APTT.

Result: children with SCA have significantly a prolonged PT, and APTT compared with children with normal hemoglobin genotype (P. value < 0.001) the mean of PT was (16.64, and 12.6) respectively, and APTT (41.45 and 37.94) consequently. A significant increase in platelet count between patients with SCA when compared with control (p. value 0.02), however a significant prolonged in APTT when compared to steady-state (P. value 0.005). MPV among children with crises when compared with steady-state revealed a significant result (p. value 0.006) the mean of MPV in steady-state = 6.79 while the mean of MPV in crisis = 7.09.

Conclusion: children with sickle cell anemia had a longer coagulation profile and marked variation in platelet count, which may increase the risk of thrombosis or bleeding.
Cytotoxic Effect of Ethanol Extract of Abrus precatorius Leaves on Raw 264.7 and SK-N-SH Cell lines
Authors: Naduchamy Krishnaprabha , Parthasarathy Varadarajan
Published: December 2021

Aim: This study was aimed to investigate the cytotoxic effect of ethanol extract of Abrus precatorius. leaves on Raw 264.7 and SK-N-SH cell lines.

Methodology: Soxhlet extraction was carried out using absolute alcohol and subsequently, the profiling of phytoconstituents of ethanol extract was performed by LC-MS analysis.

Results: The results showed that the presence of anthocyanin, phenolic acid, carboxylic acid, amino acid and monoester in ethanol extract of Abrus precatorius. The phytoconstituents such as picolinic acid, N-Acetyl-DL-tryptophan, 3-Hydroxybenzoic acid, kuromanin, aflatoxin G2, monobutyl Phthalate, laurolactam, 4-Dodecylbenzenesulfonic acid, 4-Methoxycinnamic acid, caffeic acid and octyl decyl phthalate were found  in ethanol extract. In addition to this, the cytotoxic effect of the ethanol extract was tested on Raw 264.7 and SK-N-SH cell lines using MTT assay. The cytotoxic study revealed that the ethanol extract of Abrus precatorius was non-toxic to Raw 264.7 cell, but it showed a toxic effect on human neuroblastoma cell line, SK-N-SH.

Conclusion: In this study, it was observed that the ethanol extract of Abrus precatorius was non-toxic to Raw 264.7 cell line, but it exhibited strong inhibition on the viability of SK-N-SH cell line.
Transfiguring Healthcare: Three-Dimensional Printing in Pharmaceutical Sciences; Trends during COVID-19: A Review
Authors: Siree K. G. , Amulya T. M. , Kumar T. M. Pramod , Sowmya S. , Divith K. , Ramu B. G. , Gowrav M. P.
Published: December 2021

Three-dimensional (3D) printing is a unique technique that allows for a high degree of customisation in pharmacy, dentistry and in designing of medical devices. 3D printing satiates the increasing exigency for consumer personalisation in these fields as custom-made medicines catering to the patients’ requirements are novel advancements in drug therapy. Current research in 3D printing indicates towards reproducing an organ in the form of a chip; paving the way for more studies and opportunities to perfecting the existing technique. In addition, we will also attempt to shed light on the impact of 3D printing in the COVID-19 pandemic.
Effects of Kinesio-Taping in Lateral Epicondylitis: A Narrative Review
Authors: Rodrigues Aloysius , Srivastava Saumya
Published: December 2021

Aim: The objective of this narrative review was to assess the effects of Kinesio-Taping in Lateral Epicondylitis.

Methods: A comprehensive search of already published relevant articles only from medical databases like Google Scholar, PubMed and ScienceDirect was carried out for obtaining the same from the year 2014-2019.

Background: Lateral epicondylitis is a familiar musculoskeletal disorder that primarily affects the extensors of the wrist. Kinesio-taping (KT) is a newer generation taping technique that aid's the body’s healing process whilst supporting and giving stability to the muscles and joints without hindering the range of motion of the body.

Conclusion: The current review recognises the need for Kinesio-Taping in individuals with Lateral Epicondylitis as it has shown to enhance the functionality of the wrists and reduce pain.

Limitations:  More in-depth studies are to be conducted to find out the mechanism behind Kinesio-Taping.
Applications and Biological Functions of Exosomes: A Comprehensive Review
Authors: Kowsalya N. , Meenakshi S. , Gowrav M. P. , Gowda D. V. , Divith K.
Published: December 2021

Exosomes are also known as extracellular vesicles (EVs) which is bounded by a membrane mostly seen in eukaryotic cells secreted within the endosomal compartment along with some of the selected composition of RNA, proteins, lipids and DNA. They are capable of transferring signals among cells therefore it is used as a mediator for cell-to-cell communication. Exosomes helps in the excretion of cellular waste from the body. Exosomes possess various widespread activity in many of the biological functions such as transferring the biomolecules like enzymes, proteins, ribonucleic acid, lipids and also in the regulation of various pathological and physiological process in various diseases. Exosomes are released in to the in vitro growth medium with the help of cultured cells. They are said to be identified in coined matrix and tissue matrix. They are also identified in some of the biological fluids such as cerebrospinal fluid, urine, blood. Exosomes are considered as promising biomarkers in identification and treatment of many diseases as they contribute a lot in the diagnosis of various therapies. The efficacy and stability of imaging probes and therapeutics are enhanced by its biocompatible nature. Exosomes play a major role because of their use in the field of clinical application. It is important to understand the molecular mechanism behind their function and transport in order to explore more about exosomes. Here we discuss about the review and advancement done in the field of exosomes along with their biomedical applications, isolation techniques and biological functions.
Frequency of Musculoskeletal Disorders and their Counter Measures Adopted by Final Year Students and Young Dentists: A Questionnaire Based Multicenter Study
Authors: Mahmood Hina , Zaidi Murtaza , Saleem Tayyaba , Khan Muhammad Farhan
Published: December 2021

Aim: Musculoskeletal disorders have significantly been related to poor ergonomics practice during clinics. There is limited data regarding the prevalence and reasons for work-related musculoskeletal disorders in young dentists. This study was conducted to find out the prevalence of musculoskeletal disorders in young dentists, identification of the perceived reasons for musculoskeletal disorders, and measures taken to manage them.

Study Design: Cross-sectional observational study.

Methods: A cross-sectional study was conducted on 408 house officers from ten dental institutes of twin cities and Karachi, Pakistan. The subjects were inquired through a validated questionnaire about the presence of muscular pain, affected body regions, frequency, intensity, nature of onset, aggravating factors, and average duration of the pain episodes. They were also asked about measures taken to counter musculoskeletal pain and their effectiveness.

Results: The overall prevalence of musculoskeletal disorders was n=231(56.6%) with n=172(39.2%) of participants reporting it to be work-related with a higher percentage of females n=138/172 (80.2%) The most affected body regions were the back n=101/172 (58.7%), shoulders n=91/172 (52.9%) and neck n=80/172(46.5%). Improper posture n=108(62.8%) followed by prolonged sitting n=88(51.2%) were the most common reasons perceived by the young dentists for their pain. Bed rest was adopted 93(54.1%) to alleviate pain followed by posture rectification 76(44.2%). Most n=134(77.9%) of them thought that these measures are helpful for the alleviation of pain.

Conclusion: The prevalence of work-related musculoskeletal disorders among young dentists is high. The back, shoulder, and neck areas were more frequently affected. A higher percentage of females suffered from MSD as compared to males. Bed rest was the most common measure adopted to alleviate the pain. Very few of them sought professional help for their musculoskeletal disorders.
Self‐Healing of Crystal Voids in Double Perovskite Nanocrystals Is Related to Surface Passivation
Authors: Khalfin Sasha , Veber Noam , Dror Shaked , Shechter Reut , Shaek Saar , Levy Shai , Kauffmann Yaron , Klinger Leonid , Rabkin Eugen , Bekenstein Yehonadav
Published: December 2021

Double perovskites are considered for future photovoltaic and electro‐optic applications as a toxic‐free alternative to lead halide perovskites. Alas, due to the lower efficiency of lead‐free devices, material properties need to improve to compete. In this work, the self‐healing and annealing of crystal voids is reported. Experiments are conducted on nanocrystals and in situ a transmission electron microscopy (TEM) microscope. The setup enables creation of crystal voids and to monitor their dynamics in real time. Void trajectories and velocities are calculated for TEM videos. An inaccessible, protected volume for migration near the nanocrystal outer surface is discovered, confining the migration of voids to inner crystal parts. Once surface passivation in the form of organic ligands is removed, void dynamics changes, to enable annealing of the voids and self‐healing of the crystal. It is determined that surface ligand protection against void migration is extending several atomic layers below the crystal surface. Modeling based on these results predict equilibrium positions for the voids, which are discovered in the data. The study suggests that tuning of organic ligand density influences structural stability and crystal defect tolerance in double perovskites. Engineering surfaces with inherent self‐healing properties may increase efficiencies in future devices based on these materials.
A Portable Optical Fiber Sensing Platform Based on Fluorescent Carbon Dots for Real‐Time pH Detection
Authors: Cai Yi , Wang Minghao , Liu Mengxian , Zhang Jing , Zhao Yong
Published: December 2021

An optical fiber sensing platform based on the nitrogen‐doped carbon dots (N‐CDs) for online detection of pH value in real time has been developed. The pH‐sensitive N‐CDs are synthesized by a one‐pot hydrothermal method. To compose the sensing probe, the N‐CDs are immobilized on the surface of the fiber tip by the biocompatible hydrogel. According to the results of optical simulation, the fiber tip is designed to be tapered for efficient excitation and fluorescence collection. The assembling process of the sensing probe can be accomplished by the method of in‐situ polymerization without any mold in seconds. The fluorescence of the sensing probe can be enhanced or quenched by pH value variation in a certain range and transmits to the spectrometer. The maximum diameter of the proposed sensing probe is only 450 µm. Therefore, the sensing platform with rapid response has great potential application for remote monitoring in the narrow space. Besides, the proposed platform is portable and provides a new photonic‐sensing method for emergency analysis.
Porous PdWM (M = Nb, Mo and Ta) Trimetallene for High C1 Selectivity in Alkaline Ethanol Oxidation Reaction
Authors: Qin Yingnan , Huang Hao , Yu Wenhao , Zhang Haonan , Li Zhenjiang , Wang Zuochao , Lai Jianping , Wang Lei , Feng Shouhua
Published: December 2021

Direct ethanol fuel cells are among the most efficient and environmentally friendly energy‐conversion devices and have been widely focused. The ethanol oxidation reaction (EOR) is a multielectron process with slow kinetics. The large amount of by‐product generated by incomplete oxidation greatly reduces the efficiency of energy conversion through the EOR. In this study, a novel type of trimetallene called porous PdWM (M = Nb, Mo and Ta) is synthesized by a facile method. The mass activity (15.6 A mgPd−1) and C1 selectivity (55.5%) of Pd50W27Nb23/C trimetallene, obtained after optimizing the compositions and proportions of porous PdWM, outperform those of commercial Pt/C (1.3 A mgPt−1, 5.9%), Pd/C (5.0 A mgPd−1, 7.2%), and Pd97W3/C bimetallene (9.5 A mgPd−1, 14.1%). The mechanism by which Pd50W27Nb23/C enhances the EOR performance is evaluated by in situ Fourier transform infrared spectroscopy and density functional theory calculations. It is found that W and Nb enhance the adsorption of CH3CH2OH and oxophilic high‐valence Nb accelerates the subsequent oxidation of CO and CHx species. Moreover, Nb promotes the cleavage of CC bonds and increases the C1 selectivity. Pd60W28Mo12/C and Pd64W27Ta9/C trimetallene synthesized by the same method also exhibit excellent EOR performance.
Atomically Dispersed Cu Nanozyme with Intensive Ascorbate Peroxidase Mimic Activity Capable of Alleviating ROS‐Mediated Oxidation Damage
Authors: Chen Yuan , Zou Hang , Yan Bo , Wu Xiaoju , Cao Weiwei , Qian Yihang , Zheng Lei , Yang Guowei
Published: December 2021

Ascorbate peroxidase (APX) as a crucial antioxidant enzyme has drawn attentions for its utilization in preventing cells from oxidative stress responses by efficiently scavenging H2O2 in plants. For eliminating the specific inactivation of natural APXs and regulating the catalytic activity, single‐atom nanozymes are considered as promising classes of alternatives with similar active sites and maximal atomic utilization efficiency to natural APXs. Herein, graphitic carbon nitride (g‐C3N4) anchored with isolated single copper atoms (Cu SAs/CN) is designed as an efficient nanozyme with intrinsic APX mimetic behavior. The engineered Cu SAs/CN exhibits comparable specific activity and kinetics to the natural APXs. Based on the density functional theory (DFT), Cu‐N4 moieties in the active center of Cu SAs/CN are determined to exert such favorable APX catalytic performance, in which the electron transfer between Cu and coordinated N atoms facilitates the activation and cleavage of the adsorbed H2O2 molecules and results in fast kinetics. The constructed Cu SAs/CN nanozyme with superior APX‐like performance and high biocompatibility can be applied for effectively protecting the H2O2‐treated cells against oxidative injury in vitro. These findings report the single‐atom nanozymes as a successful paradigm for guiding nanozymes to implement APX mimetic performance for reactive oxygen species‐related biotherapeutic.
Super Electrical Insulating Materials Based on Honeycomb‐Inspired Nanostructure: High Electrical Strength and Low Permittivity and Dielectric Loss
Authors: Sun Potao , Li Chuang , Sima Wenxia , Yuan Tao , Yang Ming , Chen Yongqing
Published: December 2021

The high breakdown field strength is the most important index to evaluate the performance of insulating materials. It is theoretically found that the breakdown field strength of dielectric samples can be significantly improved by up to 1–2 orders of magnitude by constructing nanopore structures. Thus, bridged silsesquioxane super electrical insulating materials (BSSEIM) are developed with nanosized pore structures and their extremely high electrical insulation performance is realized. The results indicate that the breakdown field strength of the BSSEIM is dramatically higher than aluminosilicate fiber insulating materials (ASFIM) by 570.5% for dry samples and 118.1% for oil‐impregnated samples. Specifically, the prepared BSSEIM samples have excellent dielectric performances with permittivity and dielectric losses that are only 51.3% and 1.1% of ASFIM, which are significantly lower than most existing insulating materials. Finally, the theoretical analysis indicates that the nanopore structures can effectively limit the scale of the head size for an electron avalanche and significantly reduce the number of effective gas molecules by dividing the gas into nanounits. This significantly inhibits the ionization of gas molecules and improves the breakdown field strength of samples. This discovery overturns previous understandings of traditional insulating materials and opens an avenue toward super electrical insulating materials.