bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic testing of leukodystrophies unraveling extensive heterogeneity in a large cohort and report of five common diseases and 38 novel variants
Authors: Mahdieh Nejat , Soveizi Mahdieh , Tavasoli Ali Reza , Rabbani Ali , Ashrafi Mahmoud Reza , Kohlschütter Alfried , Rabbani Bahareh 
Published: February 2021

AbstractThis study evaluates the genetic spectrum of leukodystrophies and leukoencephalopathies in Iran. 152 children, aged from 1 day to 15 years, were genetically tested for leukodystrophies and leukoencephalopathies based on clinical and neuroradiological findings from 2016 to 2019. Patients with a suggestive specific leukodystrophy, e. g. metachromatic leukodystrophy, Canavan disease, Tay-Sachs disease were tested for mutations in single genes (108; 71%) while patients with less suggestive findings were evaluated by NGS. 108 of 152(71%) had MRI patterns and clinical findings suggestive of a known leukodystrophy. In total, 114(75%) affected individuals had (likely) pathogenic variants which included 38 novel variants. 35 different types of leukodystrophies and genetic leukoencephalopathies were identified. The more common identified disorders included metachromatic leukodystrophy (19 of 152; 13%), Canavan disease (12; 8%), Tay-Sachs disease (11; 7%), megalencephalic leukodystrophy with subcortical cysts (7; 5%), X-linked adrenoleukodystrophy (8; 5%), Pelizaeus–Merzbacher-like disease type 1 (8; 5%), Sandhoff disease (6; 4%), Krabbe disease (5; 3%), and vanishing white matter disease (4; 3%). Whole exome sequencing (WES) revealed 90% leukodystrophies and genetic leukoencephalopathies. The total diagnosis rate was 75%. This unique study presents a national genetic data of leukodystrophies; it may provide clues to the genetic pool of neighboring countries. Patients with clinical and neuroradiological evidence of a genetic leukoencephalopathy should undergo a genetic analysis to reach a definitive diagnosis. This will allow a diagnosis at earlier stages of the disease, reduce the burden of uncertainty and costs, and will provide the basis for genetic counseling and family planning.
Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia
Authors: Kulthong Kornphimol , Hooiveld Guido J. E. J. , Duivenvoorde Loes , Miro Estruch Ignacio , Marin Victor , van der Zande Meike , Bouwmeester Hans 
Published: February 2021

AbstractGut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.
Domeless receptor loss in fat body tissue reverts insulin resistance induced by a high-sugar diet in Drosophila melanogaster
Authors: Lourido Fernanda , Quenti Daniela , Salgado-Canales Daniela , Tobar Nicolás 
Published: February 2021

AbstractInsulin resistance is a hallmark of type 2 diabetes resulting from the confluence of several factors, including genetic susceptibility, inflammation, and diet. Under this pathophysiological condition, the dysfunction of the adipose tissue triggered by the excess caloric supply promotes the loss of sensitivity to insulin at the local and peripheral level, a process in which different signaling pathways are involved that are part of the metabolic response to the diet. Besides, the dysregulation of insulin signaling is strongly associated with inflammatory processes in which the JAK/STAT pathway plays a central role. To better understand the role of JAK/STAT signaling in the development of insulin resistance, we used a simple organism, Drosophila melanogaster, as a type 2 diabetes model generated by the consumption of a high-sugar diet. In this model, we studied the effects of inhibiting the expression of the JAK/STAT pathway receptor Domeless, in fat body, on adipose metabolism and glycemic control. Our results show that the Domeless receptor loss in fat body cells reverses both hyperglycemia and the increase in the expression of the insulin resistance marker Nlaz, observed in larvae fed a high sugar diet. This effect is consistent with a significant reduction in Dilp2 mRNA expression and an increase in body weight compared to wild-type flies fed high sugar diets. Additionally, the loss of Domeless reduced the accumulation of triglycerides in the fat body cells of larvae fed HSD and also significantly increased the lifespan of adult flies. Taken together, our results show that the loss of Domeless in the fat body reverses at least in part the dysmetabolism induced by a high sugar diet in a Drosophila type 2 diabetes model.
Adaptive evolution in a conifer hybrid zone is driven by a mosaic of recently introgressed and background genetic variants
Authors: Menon Mitra , Bagley Justin C. , Page Gerald F. M. , Whipple Amy V. , Schoettle Anna W. , Still Christopher J. , Wehenkel Christian , Waring Kristen M. , Flores-Renteria Lluvia , Cushman Samuel A. , Eckert Andrew J. 
Published: February 2021

AbstractExtant conifer species may be susceptible to rapid environmental change owing to their long generation times, but could also be resilient due to high levels of standing genetic diversity. Hybridisation between closely related species can increase genetic diversity and generate novel allelic combinations capable of fuelling adaptive evolution. Our study unravelled the genetic architecture of adaptive evolution in a conifer hybrid zone formed betweenPinus strobiformisandP. flexilis. Using a multifaceted approach emphasising the spatial and environmental patterns of linkage disequilibrium and ancestry enrichment, we identified recently introgressed and background genetic variants to be driving adaptive evolution along different environmental gradients. Specifically, recently introgressed variants fromP. flexiliswere favoured along freeze-related environmental gradients, while background variants were favoured along water availability-related gradients. We posit that such mosaics of allelic variants within conifer hybrid zones will confer upon them greater resilience to ongoing and future environmental change and can be a key resource for conservation efforts.
Crystal structure of the human PRPK–TPRKB complex
Authors: Li Jian , Ma Xinli , Banerjee Surajit , Chen Hanyong , Ma Weiya , Bode Ann M. , Dong Zigang 
Published: February 2021

AbstractMutations of the p53-related protein kinase (PRPK) and TP53RK-binding protein (TPRKB) cause Galloway-Mowat syndrome (GAMOS) and are found in various human cancers. We have previously shown that small compounds targeting PRPK showed anti-cancer activity against colon and skin cancer. Here we present the 2.53 Å crystal structure of the human PRPK-TPRKB-AMPPNP (adenylyl-imidodiphosphate) complex. The structure reveals details in PRPK-AMPPNP coordination and PRPK-TPRKB interaction. PRPK appears in an active conformation, albeit lacking the conventional kinase activation loop. We constructed a structural model of the human EKC/KEOPS complex, composed of PRPK, TPRKB, OSGEP, LAGE3, and GON7. Disease mutations in PRPK and TPRKB are mapped into the structure, and we show that one mutation, PRPK K238Nfs*2, lost the binding to OSGEP. Our structure also makes the virtual screening possible and paves the way for more rational drug design.
Lipid Traffic Analysis reveals the impact of high paternal carbohydrate intake on offsprings’ lipid metabolism
Authors: Furse Samuel , Watkins Adam J. , Hojat Nima , Smith James , Williams Huw E. L. , Chiarugi Davide , Koulman Albert 
Published: February 2021

AbstractIn this paper we present an investigation of parental-diet-driven metabolic programming in offspring using a novel computational network analysis tool. The impact of high paternal carbohydrate intake on offsprings’ phospholipid and triglyceride metabolism in F1 and F2 generations is described. Detailed lipid profiles were acquired from F1 neonate (3 weeks), F1 adult (16 weeks) and F2 neonate offspring in serum, liver, brain, heart and abdominal adipose tissues by MS and NMR. Using a purpose-built computational tool for analysing both phospholipid and fat metabolism as a network, we characterised the number, type and abundance of lipid variables in and between tissues (Lipid Traffic Analysis), finding a variety of reprogrammings associated with paternal diet. These results are important because they describe the long-term metabolic result of dietary intake by fathers. This analytical approach is important because it offers unparalleled insight into possible mechanisms for alterations in lipid metabolism throughout organisms.
Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane
Authors: Zamprogno Pauline , Wüthrich Simon , Achenbach Sven , Thoma Giuditta , Stucki Janick D. , Hobi Nina , Schneider-Daum Nicole , Lehr Claus-Michael , Huwer Hanno , Geiser Thomas , Schmid Ralph A. , Guenat Olivier T. 
Published: February 2021

AbstractThe air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Here, we present a lung-on-a-chip, based on a biological, stretchable and biodegradable membrane made of collagen and elastin, that emulates an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms PDMS in many ways: it does not absorb rhodamine-B, is biodegradable, is created by a simple method, and can easily be tuned to modify its thickness, composition and stiffness. The air-blood barrier is reconstituted using primary lung alveolar epithelial cells from patients and primary lung endothelial cells. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks.
Surprisingly long lifetime of methacrolein oxide, an isoprene derived Criegee intermediate, under humid conditions
Authors: Lin Yen-Hsiu , Yin Cangtao , Takahashi Kaito , Lin Jim Jr-Min 
Published: February 2021

AbstractOzonolysis of isoprene, the most abundant alkene, produces three distinct Criegee intermediates (CIs): CH2OO, methyl vinyl ketone oxide (MVKO) and methacrolein oxide (MACRO). The oxidation of SO2 by CIs is a potential source of H2SO4, an important precursor of aerosols. Here we investigated the UV-visible spectroscopy and reaction kinetics of thermalized MACRO. An extremely fast reaction of anti-MACRO with SO2 has been found, kSO2 = (1.5 ± 0.4) × 10−10 cm3 s−1 (±1σ, σ is the standard deviation of the data) at 298 K (150 − 500 Torr), which is ca. 4 times the value for syn-MVKO. However, the reaction of anti-MACRO with water vapor has been observed to be quite slow with an effective rate coefficient of (9 ± 5) × 10−17 cm3 s−1 (±1σ) at 298 K (300 to 500 Torr), which is smaller than current literature values by 1 or 2 orders of magnitude. Our results indicate that anti-MACRO has an atmospheric lifetime (best estimate ca. 18 ms at 298 K and RH = 70%) much longer than previously thought (ca. 0.3 or 3 ms), resulting in a much higher steady-state concentration. Owing to larger reaction rate coefficient, the impact of anti-MACRO on the oxidation of atmospheric SO2 would be substantial, even more than that of syn-MVKO.
Metachronal waves in magnetic micro-robotic paddles for artificial cilia
Authors: Bryan Matthew T. , Martin Elizabeth L. , Pac Aleksandra , Gilbert Andrew D. , Ogrin Feodor Y. 
Published: February 2021

AbstractBiological cilia generate fluid movement within viscosity-dominated environments using beating motions that break time-reversal symmetry. This creates a metachronal wave, which enhances flow efficiency. Artificially mimicking this behaviour could improve microfluidic point-of-care devices, since viscosity-dominated fluid dynamics impede fluid flow and mixing of reagents, limiting potential for multiplexing diagnostic tests. However, current biomimicry schemes require either variation in the hydrodynamic response across a cilia array or a complex magnetic anisotropy configuration to synchronise the actuation sequence with the driving field. Here, we show that simple modifications to the structural design introduce phase differences between individual actuators, leading to the spontaneous formation of metachronal waves. This generates flow speeds of up to 16 μm/s as far as 675 μm above the actuator plane. By introducing metachronal waves through lithographic structuring, large scale manufacture becomes feasible. Additionally, by demonstrating that metachronal waves emerge from non-uniformity in internal structural mechanics, we offer fresh insight into the mechanics of cilia coordination.
Light-induced carboxylation of aryl derivatives with cooperative COF as an active photocatalyst and Ni(ii) co-catalyst
Authors: Chakrabortty Pekham , Das Anjan , Chowdhury Arpita Hazra , Ghosh Swarbhanu , Khan Aslam , Islam Sk. Manirul 
Published: February 2021

The photocatalytic carboxylation of aryl derivatives was demonstrated under CO2 at atmospheric pressure using a mesoporous COF as the active photocatalyst with triethylamine (TEA) as a sacrificial electron source under visible light.
Diastereoselective trans Cyclopropanation of 3-Alkylidene Oxindoles with In Situ Generated α-Diazo Carbonyls or α,β-Unsaturated Diazo Compounds
Authors: Mukhopadhyay Chhanda , Pramanik Sayan , Ray Suman , Maity Suvendu , Ghosh Prasanta 
Published: February 2021

AbstractAn efficient diastereoselective trans cyclopropanation of 3-alkylidene oxindoles with in situ generated α-diazo carbonyl compounds or α,β-unsaturated diazo compounds under metal-free conditions has been developed to synthesize 3-spirocyclopropyl-2-oxindole derivatives. The procedure is based on the 1,3-dipolar character of the corresponding diazo compounds under base-catalyzed conditions. The method has a wide substrate scope and uses easily available starting materials.
Giant hand osteolipoma: Case Report
Authors: Torres Echavarría María Eugenia , Fraga García Liber Joaquín , Machado Silveira María Victoria 
Published: February 2021

AbstractHand lipomas are rare in the hand, and they account for less than 1% of tumors. Osteolipoma is a rare variant of lipoma that is associated with bone metaplasia. It presents as a painless tumor that can cause symptoms when compressing adjacent structures. Magnetic resonance imaging (MRI) is the imaging study of choice. The treatment is surgical resection, with no recurrences being reported. We present the case of a patient with a giant subfascial hand osteolipoma, which, to the best of our knowledge has not yet been reported in the literature.
Infección de vías urinarias no complicada en mujeres
Authors: Becerra Ana María , Parra Daniel , Trujillo Carlos Gustavo , Azuero Julián , García Sandra , Daza Fabián , Plata Mauricio 
Published: February 2021

ResumenLa infección de vías urinarias (IVU) es una patología común, que afecta a gran parte de la población y que generalmente se resuelve con manejo antibiótico. Se compone de una amplia variedad de entidades clínicas que pueden variar desde una cistitis no complicada hasta un shock séptico de origen urinario. Los patógenos etiológicos de la IVU no complicada están ampliamente establecidos y se han mantenido de forma consistente a lo largo del tiempo, siendo la Escherichia coli el microorganismo más predominante. En la actualidad, la resistencia bacteriana a los antibióticos es de gran preocupación y por esa razón, se busca optimizar la terapia antimicrobiana con el fin de disminuir la estancia hospitalaria, la severidad clínica de la infección y los costos a los sistemas de salud. La presente revisión, tiene como objetivo servir como guía para la correcta definición, clasificación, diagnóstico, tratamiento y prevención de la IVU no complicada.
Flujo vaginal y semen: La microbiota de las relaciones sexuales
Authors: Restrepo Arenas Valentina , Velásquez Rivera Valentina , Puerta Suárez Jenniffer , Cardona Maya Walter D. 
Published: February 2021

ResumenDurante las relaciones sexuales, se da el intercambio de especies bacterianas entre las parejas, siendo las relaciones sexuales un factor crucial en la modificación de la microbiota genital. En el presente artículo de reflexión, se analizó el efecto de las relaciones sexuales sobre el intercambio de la microbiota vaginal y seminal. Las parejas que sostienen relaciones sexuales sin protección comparten especies bacterianas que podrían influir negativamente o positivamente sobre los parámetros seminales, como los Lactobacillus con potencial probiótico para el mantenimiento de la calidad del semen.
Estadificación clínica como factor pronóstico en cáncer de vejiga músculo-invasor
Authors: Orozco-López Ana Paola , Moreno-Mesa David , Saldarriaga-Botero Juan Pablo , García-Valencia Jenny 
Published: February 2021

ResumenEl cáncer de vejiga músculo invasor (CV-MI), requiere de una adecuada estadificación clínica y patológica, ya que eso determina las estrategias terapéuticas y el pronóstico de la enfermedad, caracterizada por una alta morbimortalidad. Este articulo tiene como objetivo realizar una revisión de la literatura sobre la exactitud diagnóstica de las técnicas de imagen disponibles para la estadificación clínica de los pacientes con CV-MI y cómo se debería realizar el seguimiento radiológico en los pacientes llevados a cirugía. Para eso se realizó una búsqueda en la base de datos Pubmed de artículos en inglés y en español, se incluyeron artículos de revisión, metanálisis, guías clínicas, estudios retrospectivos y prospectivos de pronóstico y diagnóstico desde el año 1988 hasta el año 2020.
Skull Base Anatomy in Patients with Bilateral Choanal Atresia: A Radiographic Study
Authors: Pool Christopher , Slonimsky Einat , Nayak Roshan , Engle Lisa , Zhu Junjia , Wilson Meghan 
Published: February 2021

Abstract
Introduction The risk of skull base injury during choanal atresia repair can be mitigated via thorough understanding of skull base anatomy. There is a paucity of data describing differences in skull base anatomy between patients with coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities (CHARGE) syndrome and those without.
Objectives The aim of this study was to measure nasal and skull base anatomy in patients with isolated bilateral choanal atresia (BCA), CHARGE syndrome, and other syndromic congenital anomalies.
Methods Retrospective chart review of patients with bilateral choanal atresia and computed tomography of the face between 2001 and 2019 were evaluated. Choanal width, height, mid-nasal height, and skull base slope were measured radiographically. Differences in anatomy between healthy patients, those with CHARGE syndrome, and those with other congenital anomalies were compared.
Results Twenty-one patients with BCA and relevant imaging were identified: 7 with isolated BCA, 6 with CHARGE syndrome, and 8 with other congenital anomalies. A t-test indicated insignificant difference in skull base slope, choanal height, choanal width, or mid-nasal skull base height between isolate BCA cases and patients with any congenital anomaly. When comparing CHARGE to isolated BCA cases, mid-nasal height was shorter in CHARGE patients (p = 0.03). There were no differences in measurements between patients with congenital anomalies excluding CHARGE (p > 0.05). Two patients in the congenital anomaly group were found to have bony skull base defects preoperatively.
Conclusion This study represents the largest description of skull base and nasal anatomy in patients with CHARGE syndrome and BCA. Surgeons should be aware of the lower skull base in CHARGE patients to avoid inadvertent skull base injury.
Correlation between Children Respiratory Virus Infections and Climate Factors
Authors: Saadi Souhir , Kallala Ouafa , Fodha Imene , Jerbi Amira , BenHamida-Rebai Meriem , Ben Hadj Fredj Mouna , Ben Hamouda Hichem , Mathlouthi Jihen , Khlifa Monia , Boussofara Raoudha , Boussetta Khadija , Abroug Saoussen , Trabelsi Abdelhalim 
Published: February 2021

AbstractObjective Respiratory viruses are the most important cause of lower respiratory tract infections (LRTI) in children. Meteorological factors can influence viral outbreaks. The objective of this study was to determine the association between climate variables and respiratory virus detection.Methods Multicenter prospective 1-year surveillance was conducted among children hospitalized for LRTI in Tunisia. Nasopharyngeal aspirates were tested by direct immunofluorescence assay (DIFA) for the detection of respiratory syncytial virus (RSV); adenovirus (AdV); influenza virus (IFV) A and B; and parainfluenza virus 1, 2, and 3 (PIV1/2/3). Samples were further analyzed by reverse-transcription polymerase chain reaction for the detection of human metapneumovirus (hMPV). Monthly meteorological data were determined by consulting the National Institute of Meteorology and the World Weather Online Meteorological Company websites. Pearson's correlation tests were used to determine the statistical association between the detection of respiratory viruses and climatic characteristics.Results Among 572 patients, 243 (42.5%) were positive for at least one virus. The most frequently detected viruses by DIFA were RSV (30.0%), followed by IFVA (3.8%), IFVB (3.5%), PIV (0.9%), and AdV (0.9%). HMPV was detected in 13 RSV-negative samples (3.3%). Dual infections were detected in seven cases (1.2%). Monthly global respiratory viruses and RSV detections correlated significantly with temperature, rainfall, cloud cover, wind speed, wind temperature, and duration of sunshine. Monthly IFV detection significantly correlated with rainfall, wind speed, wind temperature, and duration of sunshine. HMPV detection significantly correlated with temperature and wind temperature.Conclusion Respiratory viral outbreaks are clearly related to meteorological factors in Tunisia.