bluuebunny/crossref_metadata_2025_split huggingface dataset:
A perspective on human cell models for POLG-spectrum disorders: advantages and disadvantages of CRISPR-Cas-based vs. patient-derived iPSC models
Authors: Cakmak Cagla , Zempel Hans 
Published: December 2021

Abstract
Neurogenetic diseases represent a broad group of diseases with variable genetic causes and clinical manifestations. Among these, polymerase-gamma (POLG)-spectrum disorders are relatively frequent with an estimated disease frequency of ∼1:10.000. Also, mutations in the POLG gene are by far the most important cause for mitochondriopathy. POLG-spectrum disorders usually result in progressive loss of brain function and may involve severe and deadly encephalopathy, seizures, and neuromuscular disease, as well as cardiac and hepatic failure in some cases. Onset of disease may range from birth to late adulthood, and disease duration ranges from weeks in severe cases to decades. There is no curative treatment; current animal models do not faithfully recapitulate human disease, complicating preclinical therapeutic studies. Human-based preclinical model systems must be developed to understand the human disease mechanisms and develop therapeutic approaches. In this review, we provide an overview of the current approaches to model neurogenetic disorders in a human cellular and neuronal environment with a focus on POLG-spectrum disorders. We discuss the necessity of using neuronal cells and the advantages and pitfalls of currently available cell model approaches, namely (i) CRISPR-based (i. e., genetically engineered) and induced pluripotent stem cell (iPSC) (i. e., stem cell like)-derived neuronal models and (ii) the reprogramming of patient-derived cells into iPSCs and derived neurons. Despite the fact that cell models are by definition in vitro systems incapable of recapitulating all aspects of human disease, they are still the reasonable point of start to discover disease mechanisms and develop therapeutic approaches to treat neurogenetic diseases.
Robo2 Drives Target-Selective Peripheral Nerve Regeneration in Response to Glia-Derived Signals
Authors: Murphy Patricia L. , Isaacman-Beck Jesse , Granato Michael 
Published: December 2021

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized.Danio Rerio(zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identifyrobo2as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate thatrobo2function in regenerating axons is required and sufficient to drive target-selective regeneration, and thatrobo2acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined, our results reveal a glia-derived mechanism that acts locally via axonalrobo2to promote target-selective regeneration.SIGNIFICANCE STATEMENTDespite its relevance for functional recovery, the molecular mechanisms that direct regenerating peripheral nerve axons toward their original targets are not well defined. Zebrafish spinal motor nerves are composed of a dorsal and a ventral branch that diverge at a stereotyped nerve branch-point, providing a unique opportunity to decipher the molecular mechanisms critical for target-selective regeneration. Using a combination of live cell imaging and molecular-genetic manipulations, we demonstrate that therobo2guidance receptor is necessary and sufficient to promote target-selective regeneration. Moreover, we demonstrate thatrobo2is part of a genetic pathway that generates transient, spatially restricted, and tightly coordinated signaling events that direct axons of the dorsal nerve branch toward their original, pre-injury targets.
Identification of glucocorticoid-related molecular signature by whole blood methylome analysis
Authors: Armignacco Roberta , Jouinot Anne , Bouys Lucas , Septier Amandine , Lartigue Thomas , Neou Mario , Gaspar Cassandra , Perlemoine Karine , Braun Leah , Riester Anna , Bonnet-Serrano Fidéline , Blanchard Anne , Amar Laurence , Scaroni Carla , Ceccato Filippo , Rossi Gian Paolo , Williams Tracy Ann , Larsen Casper K , Allassonnière Stéphanie , Zennaro Maria-Christina , Beuschlein Felix , Reincke Martin , Bertherat Jérôme , Assié Guillaume 
Published: December 2021

Objective
Cushing’s syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing’s syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing’s syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers.

Design
We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing’s syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation.

Methods
Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features.

Results
Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing’s syndrome correction. In Cushing’s syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts.

Conclusions
Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays.
The progress on the estimation of DNA methylation level and the detection of abnormal methylation
Authors: Fan Shicai , Wang Likun , Liang Liang , Cao Xiaohong , Tang Jianxiong , Tian Qi 
Published: December 2021

BackgroundDNA methylation is a key heritable epigenetic modification that plays a crucial role in transcriptional regulation and therefore a broad range of biological processes. The complex patterns of DNA methylation highlight the significance of the profiling the DNA methylation landscape.ResultsIn this review, the main high‐throughput detection technologies are summarized, and then the three trends of computational estimation of DNA methylation levels were analyzed, especially the expanding of the methylation data with lower coverage. Furthermore, the detection methods of differential methylation patterns for sequencing and array data were presented.ConclusionsMore and more research indicated the great importance of DNA methylation changes across different diseases, such as cancers. Although a lot of enormous progress has been made in understanding the role of DNA methylation, only few methylated genes or functional elements serve as clinically relevant cancer biomarkers. The bottleneck in DNA methylation advances has shifted from data generation to data analysis. Therefore, it is meaningful to develop machine learning models for computational estimation of methylation profiling and identify the potential biomarkers.
Vision Payment Claims Analyses with Health Insurance
Authors: Houston MPH Aaron , Ruskiwewicz Joseph , Gaal MHA John , Baviskar MHSA Chaitali , Latimer Atiya 
Published: December 2021

The purpose of this study was to identify associations between insurance type and costs and to investigate specified variables’ influence on individuals’ access to adequate coverage. This was a cross sectional study, using secondary data analyses. The study was completed at The Eye Institute (TEI) East Oak Lane Campus in Philadelphia, PA. The study population was all patients seen at TEI East Oak Lane Campus, specifically patients seen at TEI clinic from January 1st, 2019, - to December 31st, 2019, whose encounter generated an insurance claim (n=68,484). The exposure was insurance type and outcomes were patient total amount, billed amount, and pay amount by patient. Data analyses were performed using SAS, version 9.4. In all statistical analyses, p-values were one-sided and considered statistically significant if 0.05 or lower. The study protocol was approved by the Institutional Review Boards of Salus University. The sample represented an older population with an average age of about 55. There was a significant association found between financial class with patient total amount (p<0.0001), billed amount(p<0.0001), and pay amount (p<0.0001). People with managed PPO pay the least, while those on Medicaid and workers compensation pay the most out of pocket. The two Philadelphia zip codes which pay the most out of pocket have two of the lowest average household incomes in the Greater Philadelphia area. Insurance type and out of pocket expenses potentially have a negative effect on patient vision health and affordability of care as well as access to care. These findings contribute to the identification of variables that influence individual’s healthcare accessibility and evidence for opportunities to improve insurance coverage.
Caracterización de suspensiones de nanopartículas de oro en presencia del copolímero poli (N-isopropilacrilamida)-co-poli (3-acrilamidopropil trimetilamonio): Influencia de la fuerza iónica y la temperatura.
Authors: Herrera Robalino David 
Published: December 2021

El recubrimiento de nanopartículas metálicas con un polímero es de interés para dotar de estabilidad a las suspensiones de dichas nanopartículas. Por otro lado, existen polímeros termosensibles que responden de acuerdo a las temperaturas a las que sean expuestos. Este estudio tuvo como objetivo evaluar y caracterizar el sistema conformado por nanopartículas de oro y una versión del copolímero termosensible PNIPAAM-PAMPTMA (+) 48/6. Para esto se utilizó técnicas de dispersión dinámica de la luz, potencial zeta y espectroscopía visible ultravioleta. El PNIPAAM-PAMPTMA (+) 48/6 fue sometido a ensayos a distintas temperaturas en las cuales se confirmó que la temperatura crítica inferior de disolución del copolímero es de aproximadamente 35 oC y que en presencia de un medio salino tiende a agregar independientemente de la temperatura. Por otra parte, el copolímero se mezcló con nanoparticulas de oro para estudiar su comportamiento a fuerzas iónicas entre 0 M y 0,75 M.
Se encontró que, al variar la fuerza iónica en el rango mencionado, el recubrimiento de las nanopartículas de oro por parte del polímero es efectivo puesto que no se observó agregación de las mismas. Esto fue corroborado por el espectro UV-visible en donde, los espectros del sistema (o nanocomposite) copolímero-nanopartícula a fuerzas iónicas de 0 M y 0,75 M son prácticamente iguales al espectro cuando las nanopartículas de oro no han agregado, es decir, el pico del plasmón aparece en todos los casos a la misma longitud de onda aproximada de 530 nm. Finalmente, se estudió la evolución del sistema copolímero-nanopartícula a distintas temperaturas y a fuerzas iónicas de 0 M y 0,75 M. Se detectó que tanto la influencia de la temperatura como de la fuerza iónica provocan que el sistema copolímero-nanopartícula aumente su tamaño. Sin embargo, las nanopartículas de oro en su interior permanecen sin agregarse.
Phylogenetic Relationships of ChineseCoptotermes(Blattodea: Isoptera: Rhinotermitidae) Termites and a New Synonym Inferred from Morphological Data
Authors: Ke Yunling , Zhang Shijun , Li Zhiqiang 
Published: December 2021

AbstractCoptotermes (Blattodea: Isoptera: Rhinotermitidae) is an economically important genus. There are many problematic taxa within the genus because of small differences between different species and large variations within the same species with respect to morphology. Coptotermes species, especially those in China, are in need of careful monographic revisions. In this paper, type specimens of 14 Coptotermes species were reexamined. Their relationship was preliminarily studied with statistical methods. The phylogenetic relationships among the 21 species that are recorded in China were investigated based on soldier morphological characters. The cladistic analysis inferred that Chinese Coptotermes species are divided into two main clades and there were some species closely related to C. formosanus Shiraki and C. gestroi (Wasmann), respectively. Based on a comparison of measurement data of the closely related species C. cochlearus Xia and He and C. gestroi in the cladogram, we propose that C. cochlearus is a new synonym of C. gestroi. In the situation where it is difficult to obtain more molecular data of Chinese Coptotermes species, the present work serves as a basis for further revisionary work on Coptotermes.
Interpretación de la curación periapical en imágenes radiológicas. Una revisión
Authors: Archila-Montañez Eloísa , Medina-Ocampo Paola Elena 
Published: December 2021

La interpretación mediante imágenes radiológicas del estado de curación de una periodontitis apical crónica o de un curetaje apical con apicectomía, se basa en el análisis de los cambios en el aspecto del área periapical, en la estructura del hueso adyacente al sitio de la inflamación o de la intervención quirúrgica, que se observan proyectados sobre estructuras óseas normales como las corticales. Por esto, al interpretar radiografías, se deben considerar limitaciones propias como la distorsión de estructuras o la superposición de imágenes anatómicas. En los estudios tradicionales de evaluación del área periapical después de un tratamiento, apoyados en imágenes 2D, los casos considerados exitosos o los fallidos se han comparado con un estándar de referencia, como el índice periapical o los criterios de evaluación del resultado del tratamiento quirúrgico endodóntico. Actualmente, algunos autores han referido otras condiciones que podrían intervenir en la evaluación, por ejemplo, que la apariencia radiográfica de la corona y la raíz del diente a evaluar pueden influir en la interpretación del área periapical. Adicionalmente, la tomografía computarizada de haz cónico (TCHC) permite relacionar el tejido lesionado o en proceso de reparación con las tablas vestibular y lingual para medir su periferia en una reconstrucción transversal. En efecto, durante el proceso de curación de los tejidos periapicales y radiculares, se presentan eventos biológicos complejos y mecanismos que pueden ocurrir a un mismo o en diferente tiempo. El conocimiento de la diversidad de tejidos es fundamental para identificar la dinámica de los signos de regeneración o si se produjo la curación por reparación. Por tales razones, el propósito de este artículo fue identificar en la literatura actual los criterios utilizados para interpretar la curación periapical en imágenes bidimensionales o tridimensionales, y su relación con el diagnóstico y tratamiento.
Beliefs and Perceptions About Parenteral Nutrition and Hydration By Advanced Cancer Patients
Authors: Abe Akiko , Amano Koji , Morita Tatsuya , Miura Tomofumi , Mori Naoharu , Tatara Ryohei , Kessoku Takaomi , Matsuda Yoshinobu , Tagami Keita , Otani Hiroyuki , Mori Masanori , Taniyama Tomohiko , Nakajima Nobuhisa , Nakanishi Erika , Kako Jun , Kiuchi Daisuke , Ishiki Hiroto , Matsuoka Hiromichi , Satomi Eriko , Miyashita Mitsunori 
Published: December 2021

Abstract
PurposeObjectives of this study are to clarify the beliefs and perceptions of parenteral nutrition and hydration (PNH) by patients with advanced cancer and to examine the relationships between their beliefs and perceptions and cachexia stages.MethodsWe conducted a questionnaire survey. We asked about patient characteristics and anthropometric measurements. We subsequently asked patients to answer 15 items regarding their beliefs and perceptions. The proportions of patients were calculated. Comparisons were performed using the Mann-Whitney U test. We conducted an explanatory factor analysis and calculated Cronbach’s alpha coefficients to assess the internal consistency. A multiple logistic regression analysis was performed to identify the independent factors affecting cancer cachexia stages.ResultsAmong 495 patients, 378 responded. Due to missing data, 357 remained in the frequency distribution analysis and explanatory factor analysis, and 344 were classified into the non-cachexia group (n = 174) and cachexia group (n = 170). Approximately 60% of patients thought that PNH were beneficial. Approximately 70% considered PNH as a standard medical practice. Approximately 70% did not feel that they received a sufficient explanation. There were no significant differences in any items between the two groups. We extracted four conceptual groups and Cronbach’s alpha coefficients were 0.87, 0.73, 0.71, and 0.48, respectively. The concept of ‘Belief that PNH are harmful’ was identified as an independent factor [odds ratio 2.57 (95% confidence interval 1.10-6.01), P = 0.030].ConclusionsThis study revealed that patients had a strong preference for receiving PNH with or without cancer cachexia.
The Feasibility of Edoxaban for Asymptomatic Cancer-associated Thrombosis in Japanese Gastrointestinal Cancer Patients (ExCAVE study)
Authors: Nakamura Michio , Ishiguro Atsushi , Dazai Masayoshi , Kawamoto Yasuyuki , Yuki Satoshi , Sogabe Susumu , Hosokawa Ayumu , Sawada Kentaro , Muto Osamu , Izawa Naoki , Nakashima Koji , Horie Yoshiki , Yagisawa Masataka , Kajiura Shinya , Ando Takayuki , Mitsuhashi Yosuke , Sunakawa Yu , Kikuchi Yasuka , Komatsu Yoshito 
Published: December 2021

Abstract
BackgroundAlthough an initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at a high risk of bleeding.MethodsIn this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. ResultsOf the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who had experienced MB and CRNMB recovered.ConclusionsThe risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.
Estimation of the Present Status of the Species Based on the Theoretical Bounds of Environmental Noise Intensity: An Illustration Through a Big Abundance Data and Simulation
Authors: Paul Ayan , Ghosh Nabakumar , Bhattacharya Sabyasachi 
Published: December 2021

Abstract
Sibly et al. (2005) described that most species have a fundamental characteristic to follow the theta-logistic growth trait with the convex downward trend. The fundamental yardstick of this research work builds under the deterministic setup, whereas the involvement of the external noise in any growth system is inevitable. But, the involvement of external affairs in any species growth can't be well judged only through its density dependence; it requires a further assessment. So, we frame the theta-logistic model with the stochastic analog in two directions, i.e., the discrete and continuous setup. The analysis of the discrete stochastic model is manifested by the bifurcation analysis, which shows that the attainment of the chaotic regime enhances with the increase in noise intensity level. Although the role of chaos in species extinction is debatable, a literature survey suggests that chaos with stochasticity accelerates the extinction of species. Similarly, in the case of the continuous version, we performed a theoretical study on the stochastic theta-logistic model to provide a critical value of the noise intensity parameter. This threshold magnitude act as the sustainability criteria of any species environmental tolerability. In this connection, we use the data of four major taxonomic groups, i.e., Bird, Insect, Mammal, and Fish, from the GPDD database and classify the species based on environmental sensitivity. The high sensitive species have a low tolerance level, associated with the small magnitude of environmental noise intensity parameter. Moreover, the simulation prediction model on these four taxonomic classes also shows that the overall extinction probability of the Bird is almost negligible for the current time window.
The Critical Role of Polyketide Synthase Gene On The Swainsonine Biosynthesis in The Fungus Metarhizium Anisopliae
Authors: Sun Lu , Huang Enxia , Zhang Yu , Guo Ziyu , Wu Kexin , Zhang Yunhao , Mo Chonghui , Wang Jinglong , Zhao Baoyu , Lu Hao 
Published: December 2021

Abstract
Swainsonine (SW) is the principal toxic ingredient of locoweeds, and is produced by fungi including Metarhizium anisopliae, Slafractonia leguminicola, and Alternaria oxytropis. While the SW biosynthesis pathway of fungi and the catalytic enzyme genes that regulate synthesis are not cleanly. In this study, we used homologous recombination (HR) to knock out and interfere with the polyketide synthase gene (pks) of M. anisopliae to determine its effect on the SW biosynthesis pathway. The concentration of SW was measured in the fermentation broth of M. anisopliae at 1 d, 2 d, 3 d, 4 d, 5 d, 6 d or 7 d using LC-MS. The gene for the pks gene was detected by RT-qPCR. Day 5 of M. anisopliae gave the highest content of SW and the highest expression of the pks gene. To determine the role of the pks gene in the SW biosynthesis pathway of M. anisopliae, we used PEG-mediated homologous recombination (HR) to transform a wild-type strain (WT) with a Benomyl (ben)-resistant fragment to knock out the pks gene producing a mutant-type strain (MT) and used PEG-mediated RNAi to transform a wild-type strain (WT) with a Benomyl (ben)-resistant plasmid to interfere with the pks gene. A complemented-type (CT) strain was produced by adding a complementation vector that contains the geneticin (G418) resistance gene as a marker. The content of SW didn’t detected in MT strain, and returned to the original level in the CT strain, while the content of SW was significantly decreased in RNAi strain. We suggest that mutation and RNAi in the pks gene affect the cell wall formation of M. anisopliae, while the colony diameters, phenotypes, and growth rates did not change significantly, and no obvious changes in other cellular organelles were noted. These results indicate that the pks gene plays a crucial role in the SW biosynthesis of M. anisopliae, which provides an important theoretical basis for illuminating the SW biosynthesis and solving locoism in livestock.