bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of risk prediction model using m6A RNA methylation regulators in prostate cancer: comprehensive bioinformatic analysis and histological validation
Authors: Quan Yongjun , Zhang Xiaodong , Ping Hao 
Published: October 2021

Abstract
Background

Epigenetic reprogramming reportedly has a crucial role in prostate cancer (PCa) progression. RNA modification is a hot topic in epigenetics, and N6-methyladenosine (m6A) accounts for approximately 60% of RNA chemical modifications. The aim of this study was to construct risk prediction model using m6A RNA regulators in PCa.

Materials and methods

Analyses were based on levels of 25 m6A regulators in The Cancer Genome Atlas (TCGA). Differential expression gene (DEG) and survival analyses were performed according to TCGA-PRAD clinicopathologic and follow-up information. To detect the influence of m6A regulators and their DEGs, consensus clustering analysis was performed, and tumor mutational burden (TMB) estimation and tumor microenvironment (TME) cell infiltration were assessed. mRNA levels of representative genes were verified using clinical PCa data.

Results

Diverse expression patterns of m6A regulators between tumor and normal (TN) were detected regarding Gleason score (GS), pathological T stage (pT), TP53 mutation, and survival comparisons, with HNRNPA2B1 and IGFBP3 being intersecting genes. HNRNPA2B1 was upregulated in advanced stages (GS > 7, pT3, HR >1, and TP53 mutation), as verified using clinical PCa tissue. Three distinct m6A modification patterns were identified through consensus clustering analysis but no significant difference was found among these groups in recurrence -free survival (RFS) analysis. Six DEGs of m6A clusters were screened through univariate Cox regression analysis. MMAB and PAIAP2 were intersecting genes for the five clinical factors. MMAB, which was upregulated in PCa compared with TN, was verified using clinical PCa samples. Three distinct subgroups were established according to the 6 DEGs. Cluster A involved the most advanced stages and had the poorest RFS. The m6A score (m6Ascore) was calculated based on the 6 genes, and the low m6Ascore group showed poor RFS with a negative association with infiltration of 16 of 23 immune-related cells.

Conclusion

We screened DEGs of m6A clusters and identified 6 genes (BAIAP2, TEX264, MMAB, JAGN1, TIMM8AP1, and IMP3), with which constructed a high predictive model with prognostic value by dividing TCGA-PRAD into three distinct subgroups and performing m6A core analysis. This study helps in elucidating the integral effects of m6A signaling on PCa progression.
Cellular coverage probability is independent of base station density under stochastic geometric model
Authors: Nassar Hamed , Taher Gehad , El-Hady El-Sayed 
Published: October 2021

Abstract
Stochastic geometry (SG) has been extensively used to model cellular communications, under the assumption that the base stations (BS) are deployed as a Poisson point process in the Euclidean plane. This use has spawned a huge number of articles over the past years for different scenarios, culminating in an equally huge number of expressions for the coverage probability in both the uplink (UL) and downink (DL) cellular directions. The problem is that those expressions include the BS density, l, which we prove irrelevant in this article. We start by developing a SG model for a baseline cellular scenario, then prove that its coverage probability is independent of l, contrary to popular belief.
Augmented Perpetual Manifolds and Perpetual Mechanical Systems-Part II: Theorem for Dissipative Mechanical Systems Behaving as Perpetual Machines
Authors: GEORGIADES FOTIOS 
Published: October 2021

Abstract
Perpetual points in mathematics defined recently, and their significance in nonlinear dynamics and their application in mechanical systems is currently ongoing research. The perpetual points significance relevant to mechanics so far is that they form the perpetual manifolds of rigid body motions of mechanical systems. The concept of perpetual manifolds extended to the definition of augmented perpetual manifolds that an externally excited multi-degree of freedom mechanical system is moving as a rigid body. As a continuation of this work, herein the internal force’s and their associated energies, for a motion of multi-degree of freedom dissipative flexible mechanical system with solutions in the exact augmented perpetual manifolds, leads to the proof of a theorem that based on a specific decomposition with respect to their state variables dependence, all the internal forcing vectors are equal to zero. Therefore there is no energy storage as potential energy, and the process is internally isentropic. This theorem provides the conditions that a mechanical system behaves as a perpetual machine of a 2nd and a 3rd kind. The developed theory leads to a discussion for the conditions of the violation of the 2nd law of thermodynamics for mechanical systems that their motion is described in the exact augmented perpetual manifolds. Moreover, the necessity of a reversible process to violate the 2nd thermodynamics law, which is not valid, is shown. The findings of the theorem analytically and numerically are verified. The energies of a perpetual mechanical system in the exact augmented perpetual manifolds for two types of external forces have been determined. Then, in two examples of mechanical systems, all the analytical findings with numerical simulations, certified with excellent agreement. This work is essential in physics since the 2nd law of thermodynamics is not admitting internally isentropic processes in the dynamics of dissipative mechanical systems. Also, the operation of a machine in the exact augmented perpetual manifolds is of extremely high significance to avoid internal damage, and degradation of any internal part of the machine, without energy loss. This article is dedicated to my educators, in all levels of my studies from school to post-doctoral researcher, including summer schools in Greece about Nonlinear dynamics and Chaos, naming few of them that cannot be easily found: Mr. Dimitris Aliapoulios, Prof. Michael Fridakis, Prof. Ajay Kapoor. (in chronological order)
Extended Characterisation of Five Archival Tick-borne Viruses Provides Insights for Virus Discovery in Australian Ticks
Authors: O’Brien Caitlin A. , Huang Bixing , Warrilow David , Hazlewood Jessamine E. , Bielefeldt-Ohmann Helle , Hall-Mendelin Sonja , Pegg Cassandra L. , Harrison Jessica J. , Paramitha Devina , Newton Natalee D. , Schulz Benjamin L. , Suhrbier Andreas , Hobson-Peters Jody , Hall Roy Alexander 
Published: October 2021

Abstract
BackgroundA subset of Australians who have been bitten by ticks experience a complex of chronic and debilitating symptoms which cannot be attributed to the known pathogenic species of bacteria present in Australia. As a result, there has been a renewed effort to identify and characterise viruses in Australian terrestrial ticks. Recent transcriptome sequencing of Ixodes and Amblyomma ticks have revealed the presence of multiple virus sequences. However, without virus isolates our ability to understand the host-range and pathogenesis of newly identified viruses is limited. We have established a successful method for high-throughput virus discovery and isolation in mosquitoes using antibodies to double-stranded RNA. In this study we sought to characterise five archival tick-borne viruses in order to adapt our virus discovery protocol for Australian ticks.MethodsWe performed virus characterisation using a combination of bioinformatic sequence analysis and in vitro techniques including replication kinetics, antigenic profiling, virus purification and mass spectrometry. ResultsOur sequence analysis of three archival viruses revealed marked genetic stability in isolates collected from the same location approximately 30 years apart. We demonstrate that the Ixodes scapularis-derived ISE6 cell line supports replication of Australian members of the Flaviviridae, Nairoviridae, Phenuiviridae and Reoviridae families, including a virus isolated from the soft tick Ornithodoros capensis. While antibodies against double-stranded RNA could be used to detect replication of a tick-borne reovirus and mosquito-borne flavivirus, the tick-borne flaviviruses Gadgets Gully virus and Saumarez Reef virus could not be detected using this method. Finally, four novel virus-like sequences were identified in transcriptome sequencing of the Australian native tick Ixodes holocyclus.Conclusions﻿Genetic and antigenic characterisation of archival viruses in this study confirm that three viruses described in 2002 represent contemporary isolates of virus species first identified 30 years prior. Our findings with antibodies to double-stranded RNA highlight an unusual characteristic shared by two Australian tick-borne flaviviruses. Overall, this work provides a valuable resource for isolation of Australian tick-borne viruses using existing cell lines.
Monitoring the Distribution of Banana Bunchy Top Virus in South Africa: A Country-Wide Survey
Authors: Ximba Sinethemba Patience Fanelwe , Gubba Augustine , Tshabalala Jeffrey , Jooste Anna Elizabeth Catharina 
Published: October 2021

Abstract
Banana bunchy top disease (BBTD) is the most devastating viral disease of bananas worldwide and is caused by the banana bunchy top virus (BBTV). The disease is spread by the banana aphid Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae) and through infected propagation material. In 2015, the virus was detected in an isolated area in the South Coast region of the KwaZulu-Natal Province (KZN), South Africa. The aim of this study was to conduct surveys across three banana-producing regions in South Africa, viz. KwaZulu-Natal, Mpumalanga and Limpopo provinces. Over 1700 plant and aphid samples were collected from commercial farms and rural households in the three provinces and more intense sampling was done in the affected KZN region. A BBTV-specific polymerase chain reaction (PCR), targeting the putative replicase gene, was performed to detect virus-infected samples. The amplicons that yielded an expected band size of 349 bp, were sequenced. Comparative phylogenetic analyses showed that the South African BBTV isolates clustered within the Pacific Indian Ocean genomic group that included isolates from India and other regions in Africa with a bootstrap value of 94% . To date, the virus has been identified only in the South Coast region of the KwaZulu-Natal province. Intense management strategies, including scouting, removal of infected plants and control of aphids, have been implemented in areas where positive samples were identified to minimize the spread of the virus. Findings from this study emphasize the need to continue monitoring and containing the spread in the KZN South Coast region.
Pediatric Traumatic Cataract in Southwest China: Epidemiological Profile
Authors: Wang Pingping , Yin Hongbo , Wang Lin , Liu Longqian 
Published: October 2021

Abstract
Background: Pediatric traumatic cataract is an important but preventable cause of acquired monocular blindness. Knowing the epidemiology of pediatric traumatic cataract is the prerequisite for prevention. This study aimed to characterize the epidemiology in the southwest of China. Methods: The medical record of children with lens damage following open-globe injury managed in the West China Hospital (aged 1–14 years) from January 2011 to December 2020 were reviewed, and the demographic data, cause of injury, and post-traumatic complications were recorded and analyzed.Results: A total of 716 eyes of 716 patients were enrolled in this study, including 488 (68.2%) male and 228 female patients in a ratio of 2.14:1; 117 patients were from a minority nationality region. The pediatric traumatic cataract was more likely to occur in winter (40.2%). Sharp metal object–related (scissors/knife/needle/sheet metal/dart) eye injuries accounted for the highest proportion, followed by botanic sticks (wooden /bamboo /bamboo skewers), and stationery (pencil/pen/ruler/paper). A majority (68.7%) of patients were 2–8 years old, with a higher frequency in the age group of 4–6 years. Penetrating trauma accounted for 64.9% of patients, and the remaining were accounted for blunt trauma (35.1%). 131 cases (18.3%) developed into post-traumatic endophthalmitis. The eye injuries caused by needles(P=0.007), wooden sticks(P=0.016), and bamboo skewers(P=0.002) have greater risk for developing into endophthalmitis. The most common organism identified was Streptococcus, which accounted for 42% (21/50) of all culture-positive specimens and was sensitive to vancomycin. Conclusion: The epidemiology of pediatric traumatic cataract in the southwest of China, especially the causative agent, was different from that in other regions, therefore the emphasized educative measures such as informing guardian and children about the causative factors should also be different.
Long-term Outcomes of Stereotactic Radiosurgery for Skull Base Tumors Involving the Cavernous Sinus
Authors: Umekawa Motoyuki , SHINYA YUKI , Hasegawa Hirotaka , Shin Masahiro , Kawashima Mariko , Katano Atsuto , Saito Nobuhito 
Published: October 2021

Abstract
PurposeStereotactic radiosurgery (SRS) is an effective and less invasive therapeutic option for cavernous sinus (CS) tumors. However, its long-term effectiveness and neurological outcomes have yet to be fully elucidated. We aimed to examine the long-term outcomes of SRS for CS tumors.MethodsOverall, 127 patients with benign CS tumors, including 91 with meningioma, 14 with trigeminal schwannoma (TS), 14 with non-functioning pituitary adenoma (PA), and eight with cavernous hemangioma (CH), treated with SRS at our institution from 1990 to 2018, were included. Tumor control and functional preservation/recovery were evaluated in detail.ResultsThe mean post-SRS follow-up period was 102 months. The progression-free survivals (PFSs) were 97% at 5 years, 90% at 10 years, and 88% at 15 years for the entire cohort; 96% at 5 years and 87% at 10 years for meningiomas; and 100% at 10 years for the other tumors. No significant difference was observed among the tumor types (log-rank test; meningioma vs. TS, p = 0.232, meningioma vs. PA, p = 0.297, meningioma vs. CH, p = 0.277). Improvement in cranial nerve (CN) function was observed in 35 (27%) patients. TSs tended to show CN improvements more often than meningiomas did (total improvements, 62% vs. 23%; p = 0.004, eye movement function, 100% vs. 20%; p = 0.002). Deterioration, or development of new CN deficits, was observed in 11 (9%) patients.ConclusionSRS provides durable tumor control and contributes to sufficient preservation of CN function.
Engineered PAM-flexible FnCas9 variants for robust and specific genome editing and diagnostics
Authors: Acharya Sundaram , Ansari Asgar , Hirano Seiichi , Paul Deepanjan , Rauthan Riya , Kumar Manoj , Phutela Rhythm , Sarkar Sajal , Gulati Sneha , Mahato Sudipta , Maddileti Savitri , Pulimamidi Vinay , Mariappan Indumathi , Nishimasu Hiroshi , Nureki Osamu , Maiti Souvik , Chakraborty Debojyoti 
Published: October 2021

Abstract
The clinical success of CRISPR therapies is dependent on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) has negligible affinity for mismatched substrates enabling it to discriminate off-targets in DNA with very high precision even at the level of binding. However, its cellular targeting efficiency is low, limiting its use in therapeutic applications. Here, we rationally engineer the protein to develop enhanced (enFnCas9) variants and expand its cellular editing activity to genomic loci previously inaccessible. Notably, some of the variants release the protospacer adjacent motif (PAM) constraint from NGG to NGR/NRG making them rank just below SpCas9-RY and SpCas9-NG in their accessibility across human genomic sites. The enFnCas9 proteins, similar to Cas12a and Cas12f, harbor high intrinsic specificity and can diagnose single nucleotide variants accurately. Importantly, they provide superior outcomes in terms of editing efficiency, knock-in rates, and off-target specificity over other engineered high-fidelity versions of SpCas9 (SpCas9-HF1 and eSpCas9). Broad targeting range coupled with remarkable specificity of DNA interrogation underscores the utility of these variants for safe and efficient therapeutic gene correction across multiple cell lines and target loci.
The Representation of Dry-Season Low-Level Clouds Over Western Equatorial Africa in Reanalyses and Historical CMIP6 Simulations
Authors: Camberlin Pierre , Togbedji Christian F , Pergaud Julien , Berger Alexandre , Aellig Raffael , Fink Andreas H , Knippertz Peter , Moron Vincent , Philippon Nathalie 
Published: October 2021

Abstract
Western Equatorial Africa (WEA) has a record low sunshine duration during the June–September dry season due to the persistence of low clouds. This study examines the ability of two reanalysis products (ERA5 and MERRA-2) and 8 CMIP6 models (both coupled and atmosphere-only historical simulations) to reproduce the climatology of these low clouds, by comparing it with ground observations and a satellite product. All datasets show a reasonable representation of the regional distribution of low clouds over the Tropical Atlantic and the neighbouring African continent. However, CMIP6 models tend to underestimate the low cloud fraction, especially over WEA in the coupled simulations. This underestimation is partly due to an insufficient seasonal sea-surface temperature (SST) cooling over the Eastern Equatorial Atlantic from April to July in most models, which contributes to reducing the lower-tropospheric stability (LTS). ERA5 data, whose dry season WEA low-cloud fraction is close to observations, indicate that LTS strongly controls the interannual variability of WEA low clouds. Interestingly, the ability to reproduce the mean low cloud fraction does not necessarily scale with the SST biases of the CMIP6 models. The strong dependence of low clouds on interannual SST variations in ERA5 is captured by less than half of the CMIP6 models. Additional key drivers of interannual variations identified in this study, such as Bight of Bonny surface winds and mid-tropospheric temperatures, actually show up inconsistently in CMIP6. Further analyses are needed to disentangle the roles played by SST and independent atmospheric forcings on WEA low cloud formation.
Genomics stratification and differential natural selection signatures among the human Norovirus genogroup-II isolates
Authors: Kakakhel Sehrish , Khan Hizbullah , Nigar Kiran , Khan Asifullah 
Published: October 2021

Abstract
The Norovirus (NoV) from the family Caliciviridae is the most common cause of gastroenteritis diseases in human. There are ten NoV genogroups are reported so far. Among these, the genogroup II (GII) is commonly prevalent and causes serious infection worldwide. The complete genome sequences of NoV GII isolates from different continental origin were retrieved from the public database. The model-based clustering approach implemented in the STRUCTURE resource was employed for assessment of genetic composition. The Mega-X and IQ tree were tools used for phylogenetic analyses. Genome-wide natural selection analyses were pursued via the maximum likelihood based methods. The demography features of NoV GII genome sequences were assessed using the BEAST package. All the NoV GII sequences initially clustered into two main subpopulations at significant K=2. The genotype GII.4 samples clearly split from the rest of all the genotypes. This indicate marked genetic distinction between norovirus GII.4 and non-GII.4 samples. The phylogenetic analyses depicted five distinct sub-clades for genotype GII.2 and seven sub-clades for GII.4 samples, speculate about the emergence of new lineages from these genotypes. Several isolates with admixed ancestry were identified, that constituted distinct sub-clusters. No continental-specific genetic distinction was observed among the NoV GII isolates. Significant genomic signatures of both positive and negative natural selection were identified across the NoV GII genes. Differential pattern of positive selection signal inferred between the GII.4 and non-GII.4 genotypes. The demographic analyses unveiled a rise in effective population size of NoV GII during 2009-2010, followed by a rapid fall in 2015.
Electrocardiographic Changes and Serum Troponin Levels in Patients with Acute Stroke, A prospective cohort study from Sudan
Authors: Ibrahim Etedal Ahmed A , Taha Salma Mohmed , Ahmed Khabab Abbasher Hussien Mohamed , Omer Mohammed Eltahier Abdalla 
Published: October 2021

Abstract
Background:Electrocardiographic changes and elevated serum troponin are frequent findings in acute stroke . They may reflect what is known as the neuro-genic myocardial injury . However, as stroke and cardiac disease share the same risk factors. Coexistence of the two is highly susceptible.Objectives:To determine the electrocardiographic changes and serum troponin level in acute stroke patients and to correlate these changes to the anatomical location and pathological type of the stroke.Methods:A Prospective cohort study conducted at the national center of neurological Science, from January to December 2019 Study was done at the neurological center in Sudan , The National Center of Neurological sciences. All cases presented with acute stroke during the study period were included. Non probability sample, with total coverage during study period. 50 patients were included in the study. Data were analyzed by using (SPSS) version 2512 standard ECG were performed in the first hours of admission. 2 samples from each patient were obtained for serum troponin with at least 8 hours apart.Results:All patients had wide variants of ECG changes.But tachycardia was the most frequent one identified in 54% of patients(27/50). Half of them were found to have an anterior circulation stroke. 14% of patients (7/50) have positive troponin, ECGchanges identified in all of patients who represent positive troponin100 %( 7patients).Moreover, anterior circulation stroke was recognized in all patients with positive troponin I marker.Conclusion:This study suggest that ECG abnormalities in patients with acute stroke are very common, especially tachycardia.The site of lesion appear to play major factor as a cause of genesis of arrhythmia.Concomitant cardiac diseases may present. Serum troponin elevation may play a role in diagnosing neuro-cardiogenic injury but, ECG appears to be more sensitive and familial.