Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of antibiotic-impregnated shunt versus conventional shunts to reduce cerebrospinal fluid infections in children: A systematic review and meta-analysis

Hydrocephalus is among the most common pediatric conditions treated by neurosurgeons. An antibiotic-impregnated shunt (AIS) was designed to reduce the rate of shunt infections. The objective of this systematic review and meta-analysis was to assess the efficiency of AIS in reducing the rate of shunt infection compared with standard shunts (SSs). A systematic search of PubMed, EMBASE, Medline, Cochrane Library, TRIP Database, CINAHL and Google Scholar databases was performed. Eligible studies included observational studies and randomized controlled trials (RCT) that compared the effects of AIS and SS for preventing shunt infections in pediatric patients. Twelve observational studies and one RCT conducted from January 2005 through October 2019 involving 7,952 pediatric patients were included in the analysis. The use of AIS significantly decreased the risk of CRI [risk ratio (RR) 0.42; 95% confidence interval: 0.33 to 0.53; P<0.00001] with no statistical heterogeneity across the included studies (I2=42%). This analysis demonstrates that the use of AIS significantly reduces the risk of shunt infection in pediatric patients.
Gliosis Precedes Amyloid-β Deposition and Pathological Tau Accumulation in the Neuronal Cell Cycle Re-Entry Mouse Model of Alzheimer’s Disease

Background: The presence of cell cycle markers in postmortem Alzheimer’s disease (AD) brains suggest a potential role of cell cycle activation in AD. It was shown that cell cycle activation in postmitotic neurons in mice produces Aβ and tau pathologies from endogenous mouse proteins in the absence of AβPP or tau mutations. Objective: In this study, we examined the microglial and astrocytic responses in these mice since neuroinflammation is another key pathological feature in AD. Methods: Our neuronal cell cycle re-entry (NCCR) mouse model are bitransgenic mice heterozygous for both Camk2a-tTA and TRE-SV40T. Using this tet-off system, we triggered NCCR in our animals via neuronal expression of SV40T starting at 1 month of age. TRE-SV40T Tg mice were used as SV40T transgene controls. The animals were examined at following time points: 2, 3, 4, 6, and 12 months of age. The microglia and astrocyte responses in our mice were determined by image analysis and stereology on brain sections immunofluorescently labeled using the following antibodies: Iba1, CD45, CD68, MHCII, and GFAP. Cellular senescent marker p16 was also used in this study. Results: Our NCCR mice demonstrate early and persistent activation of microglia and astrocytes. Additionally, proinflammatory and senescent microglia phenotype and brain leukocyte infiltration is present at 12 months of age. Conclusion: In the absence of FAD gene mutations, our NCCR mice simultaneously display many of the pathological changes associated with AD, such as ectopic neuronal cell cycle re-entry, Aβ and tau pathologies, neuroinflammation, and neurodegeneration. These animals represent a promising alternative AD mouse model.
Metabolism-based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential

Abstract Background Glioblastoma (GBM) is a highly aggressive brain tumor with rapid subclonal diversification, harboring molecular abnormalities that vary temporospatially, a contributor to therapy resistance. Fluorescence-guided neurosurgical resection utilizes the administration of 5-aminolevulinic acid (5-ALA) generating individually fluorescent tumor cells within a background population of non-neoplastic cells in the invasive tumor region. The aim of the study was to specifically isolate and interrogate the invasive GBM cell population using a novel 5-ALA-based method. Methods We have isolated the critical invasive GBM cell population by developing 5-ALA-based metabolic fluorescence-activated cell sorting. This allows purification and study of invasive cells from GBM without an overwhelming background “normal brain” signal to confound data. The population was studied using RNAseq, real-time PCR, and immunohistochemistry, with gene targets functionally interrogated on proliferation and migration assays using siRNA knockdown and known drug inhibitors. Results RNAseq analysis identifies specific genes such as SERPINE1 which is highly expressed in invasive GBM cells but at low levels in the surrounding normal brain parenchyma. siRNA knockdown and pharmacological inhibition with specific inhibitors of SERPINE1 reduced the capacity of GBM cells to invade in an in vitro assay. Rodent xenografts of 5-ALA-positive cells were established and serially transplanted, confirming tumorigenicity of the fluorescent patient-derived cells but not the 5-ALA-negative cells. Conclusions Identification of unique molecular features in the invasive GBM population offers hope for developing more efficacious targeted therapies compared to targeting the tumor core and for isolating tumor subpopulations based upon intrinsic metabolic properties.
Next-Generation Sequencing at High Sequencing Depth as a Tool to Study the Evolution of Metastasis Driven by Genetic Change Events of Lung Squamous Cell Carcinoma

Background: The aim of this study is to report tumoral genetic mutations observed at high sequencing depth in a lung squamous cell carcinoma (SqCC) sample. We describe the findings and differences in genetic mutations that were studied by deep next-generation sequencing methods on the primary tumor and liver metastasis samples. In this report, we also discuss how these differences may be involved in determining the tumor progression leading to the metastasis stage. Methods: We followed one lung SqCC patient who underwent FDG-PET scan imaging, before and after three months of treatment. We sequenced 26 well-known cancer-related genes, at an average of ~6,000 × sequencing coverage, in two spatially distinct regions, one from a primary lung tumor metastasis and the other from a distal liver metastasis, which was present before the treatment. Results: A total of 3,922,196 read pairs were obtained across all two samples' sequenced locations. Merged mapped reads showed several variants, from which we selected 36 with high confidence call. While we found 83% of genetic concordance between the distal metastasis and primary tumor, six variants presented substantial discordance. In the liver metastasis sample, we observed three de novo genetic changes, two on the FGFR3 gene and one on the CDKN2A gene, and the frequency of one variant found on the FGFR2 gene has been increased. Two genetic variants in the HRAS gene, which were present initially in the primary tumor, have been completely lost in the liver tumor. The discordant variants have coding consequences as follows: FGFR3 (c.746C>G, p. Ser249Cys), CDKN2A (c.47_50delTGGC, p. Leu16Profs*9), and HRAS (c.182A>C, p. Gln61Pro). The pathogenicity prediction scores for the acquired variants, assessed using several databases, reported these variants as pathogenic, with a gain of function for FGFR3 and a loss of function for CDKN2A. The patient follow-up using imaging with 18F-FDG PET/CT before and after four cycles of treatment shows discordant tumor progression in metastatic liver compared to primary lung tumor. Conclusions: Our results report the occurrence of several genetic changes between primary tumor and distant liver metastasis in lung SqCC, among which non-silent mutations may be associated with tumor evolution during metastasis.
Acute kidney injury and kidney replacement therapy in COVID-19: a systematic review and meta-analysis

Abstract Background Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. Methods We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. Results A total of 3042 articles were identified, of which 142 studies were included, with 49 048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.6% [95% confidence interval (CI) 19.8–39.5] among hospitalized COVID-19 patients from the USA and Europe (20 studies) and 5.5% (95% CI 4.1–7.4) among patients from China (62 studies), whereas the pooled incidence of KRT was 7.7% (95% CI 5.1–11.4; 18 studies) and 2.2% (95% CI 1.5–3.3; 52 studies), respectively. Among patients admitted to the intensive care unit, the incidence of KRT was 20.6% (95% CI 15.7–26.7; 38 studies). Meta-regression analyses showed that age, male sex, cardiovascular disease, diabetes mellitus, hypertension and chronic kidney disease were associated with the occurrence of AKI; in itself, AKI was associated with an increased risk of mortality, with a pooled risk ratio of 4.6 (95% CI 3.3–6.5). Conclusions AKI and KRT are common events in hospitalized COVID-19 patients, with estimates varying across geographic locations. Additional studies are needed to better understand the underlying mechanisms and optimal treatment of AKI in these patients.
Discrepancies in Electrolyte Measurements by Direct and Indirect Ion Selective Electrodes due to Interferences by Proteins and Lipids

Abstract Objectives We aim to report the simultaneous effect of different protein and lipid concentrations on sodium (Na+) and potassium (K+) measurement by direct and indirect ion selective electrodes (dISE and iISE) in patient samples. Materials and Methods Na+ and K+ were measured in 195 serum samples received in the laboratory using iISE by Roche Modular P800 autoanalyzer and using dISE by XI-921 ver. 6.0 Caretium electrolyte analyzer. Serum total protein (TP), cholesterol (Chol), and triglycerides (TG) were measured using conventional photometric methods on Roche Modular P800 autoanalyzer. Differences for each pair of results for Na+ (Diff_Na+ = [Na+ dISE–Na+ iISE]) and K+ (Diff_K+ = [K+ dISE–K+ iISE]) were calculated. Patient subgroups with high, normal, or low TP (< 5, 5–7.9, or ≥ 8 g/dL), Chol (< 150, 150–299, or ≥300 mg/dL), or TG (< 150, 150–299, or ≥300 mg/dL) were compared using analysis of variance. Note that 95% confidence interval of Diff_Na+ and Diff_K+ were calculated to see the number of samples showing clinically significant differences. Results Diff_Na+ (p = 0.007) and Diff_K+ (p = 0.002) were found significant between samples with normal and high TP. However, effect of TG was not significant. Chol concentration affected Diff_Na+ significantly between low versus normal (p = 0.002), and high versus normal (p = 0.031) Chol groups. Diff_K+ was significant (p = 0.009) between low versus normal Chol. Clinically relevant disagreement of ≥|5| mmol/L for Na+ was observed in high percentage of samples including all subcategories; however, for K+ only 3.6% of the total samples showed disagreement of ≥ |0.5| mmol/L. A multivariate regression equation based on fit regression model was also derived. Conclusion Summarily, interchangeable use of electrolyte results from dISE and iISE is not advisable, especially in a setting of hyperproteinemia (≥8 g/dL) or hypercholesterolemia (≥300 mg/dL); more so for Na+.
Expression of neuropeptide Y and its receptors in estrogen-induced pituitary adenoma in rats

Objective To explore the expression of neuropeptide Y (NPY) as well as its receptors in estrogen-induced pituitary tumors in Wistar rats, and to investigate their roles in pituitary tumorigenesis. Methods 40 female Wistar rats were divided randomly into experimental and control groups. The rats were induced with estradiol benzoate by peritoneal injection in experimental group. The expression of NPY as well as its receptors in pituitary glands was also detected by immunohistochemical analysis and semi-quantitative reverse transcription polymerase chain reaction ( RT-PCR). Some pituitary tissues were also examined using immuno-electron microscopy in order to study the distribution of NPY at the subcellar level. Results In experimental group, significant increases in pituitary weight were noted three months after peritoneal injection of estrogen. The serum prolactin concentration also increased sharply. NPY concentration in experimental group was significantly lower than that in control group. The expression level of NPY as well as Y1 and Y2 receptors in pituitary of experimental groups were significantly lower compared with that of control group (P0.001). Immuno-electron microscopy examination demonstrated that positive NPY staining with a high density of gold particles located mainly on the secretory granulas. Conclusion These data suggest that expression of NPY as well as its receptors (Y1 R and Y2R) are decreased by estrogen in the pituitary glands, with possible involvement in estrogen induced pituitary tumorigenesis in rats.
JAK/STAT pathway in pathology of rheumatoid arthritis (Review)

Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.
Estudo cinético da produção de ácido lactobiônico e sorbitol por enzimas periplasmáticas de Zymomonas mobilis

Na presenca de lactose e frutose, acido lactobionico e sorbitol sao formados equimolarmente em reacoes catalisadas por glicose-frutose oxidorredutase (GFOR) e glicono--lactonase (GL), enzimas periplasmaticas de Zymomonas mobilis. O acido lactobionico tem alto valor comercial e, como o sorbitol, importantes aplicacoes industriais. Este trabalho objetivou estudar a cinetica de producao de acido lactobionico e sorbitol por celulas de Z. mobilis permeabilizadas com brometo de cetil trimetil amonio, livres ou imobilizadas em alginato de calcio. As constantes de saturacao de Michaelis-Menten de GFOR/GL para lactose e frutose foram estimadas em 0,39 e 0,050mol/L, respectivamente, e Vmax em 7,69 unidades de GFOR/GL por grama de celulas secas (U/g), em que U corresponde a mmol de produto formado por hora. A imobilizacao de Z. mobilis foi avaliada com suspensoes celulares de 30, 50 e 70g/L, observando-se reducao do fluxo de massa dos solutos atraves das esferas de alginato de calcio com maiores massas de celulas. Como na bioconversao de lactose/frutose em acido lactobionico/sorbitol, um consideravel volume do reator e ocupado pelas esferas, o uso da suspensao celular de 70g/L para a imobilizacao se mostrou favoravel devido a menor quantidade do suporte para ter-se a concentracao de celulas/enzimas desejada para o processo. Assim, os problemas operacionais associados a mistura e ao controle de pH foram minimizados. No processo de bioconversao, concentracoes de biocatalisador, livre ou imobilizado, entre 5 a 20g/L resultaram em teores de acido lactobionico semelhantes, em torno de 170g/L, com rendimento de cerca de 70% e produtividades proporcionalmente crescentes. A velocidade especifica de formacao de produto calculada nas primeiras horas de processo com celulas imobilizadas ( 0,76g/g/h) foi menor que a medida com celulas livres (  2,0g/g/h) em razao de o suporte de imobilizacao atuar como uma barreira fisica para o transporte de massa. Na sequencia, porem, constatou-se uma maior estabilidade do sistema imobilizado e, em consequencia, produtividades semelhantes ( 7,1g/L/h) foram alcancadas em ambas as condicoes. Para avaliar-se possibilidade de reutilizacao das celulas imobilizadas, foram realizadas oito bioconversoes seguidas – 193h de operacao –, constatando-se a preservacao de 85% da atividade inicial. Na bioconversao, o pH foi controlado em 6,4 com NaOH, sendo formado lactobionato de sodio. Este sal foi precipitado com etanol e, em seguida, convertido a forma acida – acido lactobionico por cromatografia de troca ionica. O produto purificado apresentou caracteristicas fisico-quimicas semelhantes as da substância padrao comercial.
Transradial approach and its variations for neurointerventional procedures: Literature review

Background: The transfemoral approach (TFA) has been the standard in neuroradiology over the years. However, the transradial approach (TRA) and its variants offer several benefits over the TFA. Methods: Review of the literature about TRA and its variations. We present our results for different neurointerventional procedures at our institution between January 2018 and December 2019. Results: We wrote an educational review describing anatomical and technical aspects, advantages, and complications of this approach. In the past year we increased the percentage of neurointerventional procedures performed through radial or ulnar arteries. Conclusion: There are clearly proven benefits of employing a wrist approach in patients for neurointerventional procedures and its utilization should especially be considered on a daily basis.
Artificial intelligence and deep learning in ophthalmology - present and future (Review)

Since its introduction in 1959, artificial intelligence technology has evolved rapidly and helped benefit research, industries and medicine. Deep learning, as a process of artificial intelligence (AI) is used in ophthalmology for data analysis, segmentation, automated diagnosis and possible outcome predictions. The association of deep learning and optical coherence tomography (OCT) technologies has proven reliable for the detection of retinal diseases and improving the diagnostic performance of the eye's posterior segment diseases. This review explored the possibility of implementing and using AI in establishing the diagnosis of retinal disorders. The benefits and limitations of AI in the field of retinal disease medical management were investigated by analyzing the most recent literature data. Furthermore, the future trends of AI involvement in ophthalmology were analyzed, as AI will be part of the decision-making regarding the scientific investigation, diagnosis and therapeutic management.
High-Throughput Sequencing Reveals the Loss-of-Function Mutations in GALT Cause Recessive Classical Galactosemia

Background: Classical Galactosemia (CG) is a rare autosomal recessive metabolic disease caused by mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. This study aim to identify pathogenic mutations underlying classic galactosemia in two Chinese families. Methods: We collected blood samples from two Chinese families and extracted genomic DNA. High-throughput sequencing, sanger sequencing, and bioinformatics analysis were used to investigate the molecular cause of manifestations in the two Chinese families. Results: We found compound heterozygous mutations (c.396C>G; p.His132Gln and c.974C>T; p.Pro325Leu) in family 1 and a homozygous missense variant (c.974C>T; p.Pro325Leu) in family 2. Bioinformatics and Sanger sequencing were performed to verify the identified variants. Conclusion: The present study identified the GALT mutations as a genetic etiology in the two Chinese families with classic galactosemia and expanded the phenotypic and mutational spectrum of GALT. Our findings could be useful in providing evidence for prenatal interventions and more precise pharmacological treatments to patients. High-throughput sequencing conducted in our study is a convenient and useful tool for clinical diagnosis of galactosemia and other associated genetic disorders.
Combining ability in sesame

Combining ability studies on seed yield, yield components and oil content were conducted from an 8 x 8 half-diallel cross of sesame over two years. Additive genetic variance was of greater importance for number of primary branches/plant, number of secondary branches/plant, number of capsules/plant and seed yield/plant while, additive and non-additive genetic variances were equally important for days to flowering, 1000-seed weight and oil content gca and sca manifested significant interaction with year for all characters. The relative magnitude of non-additive x year interaction was greater than additive x year interaction. The variety B 9 was best general combiner for seed yield and its major components. B14 x B 9 emerged best specific combiner for seed yield and its components. For augmenting seed yield and oil content simultaneously the cross combination MT 67–52 x TC 25 was found promising.
Influence of integrated application of nitrogen sources on growth attributes of rice under system of rice intensification

Growth characteristic of crop plants ultimately decides the crop productivity. In low land rice production growth attributes can be enhanced through integrated nutrient management (INM) and effective cultivation practices. In this view to enhance the crop productivity by influencing better growth of rice plants in low lands, an experiment was conducted at experimental farm, Faculty of Agriculture, Annamalai University, Tamil Nadu, India. Experiment was laid out in split plot design with two main plot treatments (SRI and conventional system of cultivation) and seven sub plots treatments (integrated nutrient management practices) and replicated thrice. Growth attributes viz., plant height, number of tillers, DMP, root length, root volume and root dry weight hill values were recorded at tillering, flowering stages and at harvest. Enhanced growth attributes were noticed under system of rice intensification method of rice cultivation i.e. more than 35 percent increases over conventional system of rice cultivation. Among the integrated nutrient management practices, the application of STCR based IPNS (combined application of NPK fertilizer along with 12.5 t ha FYM and bio-fertilizers viz., Azospirillum and PSB as soil treatment) proved its superiority over other treatments significantly. It was closely followed by application of 75% fertilizer N + 25% organic N through EFYM. Lower values of growth attributes were registered by 100% RDF applied treatment at all the crop growth stages. From the experimental results, it may be concluded that STCR based IPNS or 75 percent N through inorganic and 25 percent N through EFYM or FYM could be the better options for enhancing growth attributes of low land rice crop for improving its sustainable productivity.