bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tandem Repeat Generation and Novel Isothermal Amplification Based on Nonspecific Tailing and Replication Slippage
Authors: Luo Guangcheng , He Hongfei , Wang Dongsheng , Liu Shanshan , Tian Shisu , Chen Miaomiao , Wang Qiang , Zhao Changsong , Leng Zhengwei , Hou Lingmi , Guo Xiaolan 
Published: April 2023

AbstractBackgroundIsothermal amplification is considered to be one of the most promising tools for point-of-care testing molecular diagnosis. However, its clinical application is severely hindered by nonspecific amplification. Thus, it is important to investigate the exact mechanism of nonspecific amplification and develop a high-specific isothermal amplification assay.MethodsFour sets of primer pairs were incubated with Bst DNA polymerase to produce nonspecific amplification. Gel electrophoresis, DNA sequencing, and sequence function analysis were used to investigate the mechanism of nonspecific product generation, which was discovered to be nonspecific tailing and replication slippage mediated tandem repeats generation (NT&RS). Using this knowledge, a novel isothermal amplification technology, bridging primer assisted slippage isothermal amplification (BASIS), was developed.ResultsDuring NT&RS, the Bst DNA polymerase triggers nonspecific tailing on the 3′-ends of DNAs, thereby producing sticky-end DNAs over time. The hybridization and extension between these sticky DNAs generate repetitive DNAs, which can trigger self-extension via replication slippage, thereby leading to nonspecific tandem repeats (TRs) generation and nonspecific amplification. Based on the NT&RS, we developed the BASIS assay. The BASIS is carried out by using a well-designed bridging primer, which can form hybrids with primer-based amplicons, thereby generating specific repetitive DNA and triggering specific amplification. The BASIS can detect 10 copies of target DNA, resist interfering DNA disruption, and provide genotyping ability, thereby offering 100% accuracy for type 16 human papillomavirus detection.ConclusionWe discovered the mechanism for Bst-mediated nonspecific TRs generation and developed a novel isothermal amplification assay (BASIS), which can detect nucleic acids with high sensitivity and specificity.
Dicentric chromosome breakage in Drosophila melanogaster is influenced by pericentric heterochromatin and occurs in nonconserved hotspots
Authors: Hill Hunter J , Bonser Danielle , Golic Kent G 
Published: April 2023

Abstract
Chromosome breakage plays an important role in the evolution of karyotypes and can produce deleterious effects within a single individual, such as aneuploidy or cancer. Forces that influence how and where chromosomes break are not fully understood. In humans, breakage tends to occur in conserved hotspots called common fragile sites (CFS), especially during replication stress. By following the fate of dicentric chromosomes in Drosophila melanogaster, we find that breakage under tension also tends to occur in specific hotspots. Our experimental approach was to induce sister chromatid exchange in a ring chromosome to generate a dicentric chromosome with a double chromatid bridge. In the following cell division, the dicentric bridges may break. We analyzed the breakage patterns of 3 different ring-X chromosomes. These chromosomes differ by the amount and quality of heterochromatin they carry as well as their genealogical history. For all 3 chromosomes, breakage occurs preferentially in several hotspots. Surprisingly, we found that the hotspot locations are not conserved between the 3 chromosomes: each displays a unique array of breakage hotspots. The lack of hotspot conservation, along with a lack of response to aphidicolin, suggests that these breakage sites are not entirely analogous to CFS and may reveal new mechanisms of chromosome fragility. Additionally, the frequency of dicentric breakage and the durability of each chromosome's spindle attachment vary significantly between the 3 chromosomes and are correlated with the origin of the centromere and the amount of pericentric heterochromatin. We suggest that different centromere strengths could account for this.
Haplotype resolved chromosome level genome assembly of Citrus australis reveals disease resistance and other citrus specific genes
Authors: Nakandala Upuli , Masouleh Ardashir Kharabian , Smith Malcolm W , Furtado Agnelo , Mason Patrick , Constantin Lena , Henry Robert J 
Published: April 2023

ABSTRACT
Recent advances in genome sequencing and assembly techniques have made it possible to achieve chromosome level reference genomes for citrus. Relatively few genomes have been anchored at the chromosome level and/or are haplotype phased, with the available genomes of varying accuracy and completeness. We now report a phased high-quality chromosome level genome assembly for an Australian native citrus species; Citrus australis (round lime) using highly accurate PacBio HiFi long reads, complemented with Hi-C scaffolding. Hifiasm with Hi-C integrated assembly resulted in a 331 Mb genome of C. australis with two haplotypes of nine pseudochromosomes with an N50 of 36.3 Mb and 98.8% genome assembly completeness (BUSCO). Repeat analysis showed that more than 50% of the genome contained interspersed repeats. Among them, LTR elements were the predominant type (21.0%), of which LTR Gypsy (9.8%) and LTR copia (7.7%) elements were the most abundant repeats. A total of 29 464 genes and 32 009 transcripts were identified in the genome. Of these, 28 222 CDS (25 753 genes) had BLAST hits and 21 401 CDS (75.8%) were annotated with at least one GO term. Citrus specific genes for antimicrobial peptides, defense, volatile compounds and acidity regulation were identified. The synteny analysis showed conserved regions between the two haplotypes with some structural variations in Chromosomes 2, 4, 7 and 8. This chromosome scale, and haplotype resolved C. australis genome will facilitate the study of important genes for citrus breeding and will also allow the enhanced definition of the evolutionary relationships between wild and domesticated citrus species.
Motzkin Combinatorics in Linear Degenerations of the Flag Variety
Authors: Cerulli Irelli Giovanni , Esposito Francesco , Marietti Mario 
Published: April 2023

Abstract
We establish an explicit combinatorial/homological characterization of supports for linear degenerations of flag varieties. For such purpose, we introduce the concept of an excessive multisegment. It provides a new class of combinatorial objects counted by Motzkin numbers.
The legal personhood of human brain organoids
Authors: Kataoka Masanori , Lee Tsung-Ling , Sawai Tsutomu 
Published: April 2023

Abstract
Research using three-dimensional neural tissues derived from human pluripotent stem cells—known as ‘human brain organoids’—has progressed rapidly in recent years. Although related ethical issues have been intensively discussed, legal issues have only been sparsely examined compared with the related ethical issues. In this paper, we explore a fundamental issue concerning the legal status of human brain organoids: whether they can be considered legal persons. We clearly distinguish between two types of legal personhood: ‘natural person’ as a human legal person and ‘juridical person’ as a nonhuman legal person. By examining natural and juridical personhood separately, we point out the bias and confusion in the remarks on the legal personhood of human brain organoids and provide a more comprehensive picture of the problem.
Statistical inference for high-dimensional panel functional time series
Authors: Zhou Zhou , Dette Holger 
Published: April 2023

AbstractIn this paper, we develop statistical inference tools for high-dimensional functional time series. We introduce a new concept of physical dependent processes in the space of square integrable functions, which adopts the idea of basis decomposition of functional data in these spaces, and derive Gaussian and multiplier bootstrap approximations for sums of high-dimensional functional time series. These results have numerous important statistical consequences. Exemplarily, we consider the development of joint simultaneous confidence bands for the mean functions and the construction of tests for the hypotheses that the mean functions in the panel dimension are parallel. The results are illustrated by means of a small simulation study and in the analysis of Canadian temperature data.
Permutation-based true discovery guarantee by sum tests
Authors: Vesely Anna , Finos Livio , Goeman Jelle J 
Published: April 2023

Abstract
Sum-based global tests are highly popular in multiple hypothesis testing. In this paper, we propose a general closed testing procedure for sum tests, which provides lower confidence bounds for the proportion of true discoveries (TDPs), simultaneously over all subsets of hypotheses. These simultaneous inferences come for free, i.e., without any adjustment of the α-level, whenever a global test is used. Our method allows for an exploratory approach, as simultaneity ensures control of the TDP even when the subset of interest is selected post hoc. It adapts to the unknown joint distribution of the data through permutation testing. Any sum test may be employed, depending on the desired power properties. We present an iterative shortcut for the closed testing procedure, based on the branch and bound algorithm, which converges to the full closed testing results, often after few iterations; even if it is stopped early, it controls the TDP. We compare the properties of different choices for the sum test through simulations, then we illustrate the feasibility of the method for high-dimensional data on brain imaging and genomics data.
Ordering Gospel Textuality in the Second Century
Authors: Coogan Jeremiah , Rodriguez Jacob A 
Published: April 2023

Abstract
This article interrogates how several second-century figures ordered a pluriform Gospel corpus. Focusing on approaches to Gospel plurality visible in the Epistula apostolorum, Tatian the Syrian, Irenaeus of Lyons, and Ammonius of Alexandria, we argue that a number of Christian readers—across the Roman Mediterranean, from Alexandria to Gaul and from Syria to Rome—employed similar approaches. Drawing on evidence for second-century reading practices, we demonstrate continuities in both textual practices and conceptual frameworks that illuminate Gospel reading and writing. These figures engaged Gospels in multiple dimensions—horizontal juxtaposition of parallel material and vertical coordination of narrative sequence—in order to map relationships between imperfectly parallel texts. These spatial textual practices enabled synthetic reading of an emergent pluriform Gospel corpus.
Neutral Models of De Novo Gene Emergence Suggest that Gene Evolution has a Preferred Trajectory
Authors: Iyengar Bharat Ravi , Bornberg-Bauer Erich 
Published: April 2023

Abstract
New protein coding genes can emerge from genomic regions that previously did not contain any genes, via a process called de novo gene emergence. To synthesize a protein, DNA must be transcribed as well as translated. Both processes need certain DNA sequence features. Stable transcription requires promoters and a polyadenylation signal, while translation requires at least an open reading frame. We develop mathematical models based on mutation probabilities, and the assumption of neutral evolution, to find out how quickly genes emerge and are lost. We also investigate the effect of the order by which DNA features evolve, and if sequence composition is biased by mutation rate. We rationalize how genes are lost much more rapidly than they emerge, and how they preferentially arise in regions that are already transcribed. Our study not only answers some fundamental questions on the topic of de novo emergence but also provides a modeling framework for future studies.
Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular schwannoma
Authors: Plotkin Scott R , Allen Jeffrey , Dhall Girish , Campian Jian L , Clapp D Wade , Fisher Michael J , Jain Rakesh K , Tonsgard James , Ullrich Nicole J , Thomas Coretta , Edwards Lloyd J , Korf Bruce , Packer Roger , Karajannis Matthias A , Blakeley Jaishri O 
Published: April 2023

Abstract

Background
Prospective data on maintenance therapy with bevacizumab for persons with NF2-related schwannomatosis (NF2-SWN) is lacking. In this prospective multicenter phase II study, we evaluated the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in children and adults with NF2-SWN and hearing loss due to vestibular schwannomas (VS).

Methods
Following induction therapy, participants received bevacizumab 5 mg/kg every 3 weeks for 18 months. Participants were monitored for changes in hearing, tumor size, and quality of life (QOL), and for adverse events. Hearing loss was defined as a statistically significant decline in word recognition score (WRS) or pure-tone average compared to the study baseline; tumor growth was defined as &gt;20% increase in volume compared to baseline.

Results
Twenty participants with NF2-SWN (median age 23.5 years; range, 12.5–62.5 years) with hearing loss in the target ear (median WRS 70%, range 2%–94%) received maintenance bevacizumab. Freedom from hearing loss in the target ear was 95% after 48 weeks, 89% after 72 weeks, and 70% after 98 weeks. Freedom from tumor growth in the target VS was 94% after 48 weeks, 89% after 72 weeks, and 89% after 98 weeks. NF2-related QOL remained stable for 98 weeks whereas tinnitus-related distress decreased. Maintenance bevacizumab was well tolerated, with 3 participants (15%) discontinuing treatment due to adverse events.

Conclusions
Maintenance bevacizumab (5 mg/kg every 3 weeks) is associated with high rates of hearing and tumor stability during 18 months of follow-up. No new unexpected adverse events related to bevacizumab were identified in this population.
Efficacy and Dose-Response Relationship of Stereotactic Body Radiotherapy for Abdominal Lymph Node Metastases from Hepatocellular Carcinoma
Authors: Wang Yuting , Li Qiaoqiao , Zhang Li , Liu Shiliang , Zhu Jinhan , Yang Yadi , Liu Mengzhong , Zhang Yaojun , Xi Mian 
Published: April 2023

Abstract

Background
The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC).

Patients and methods
Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed.

Results
With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED &lt;60 Gy (80.1% vs. 63.4%, P = .004; 68.3% vs. 33.0%, P &lt; .001). On multivariate analysis, BED was an independent prognostic factor for both FFLP and OS.

Conclusions
SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED.
Financial Disruptions and the Organization of Innovation: Evidence from the Great Depression
Authors: Babina Tania , Bernstein Asaf , Mezzanotti Filippo 
Published: April 2023

AbstractWe examine innovation following the Great Depression using data on a century’s worth of U.S. patents and a difference-in-differences design that exploits regional variation in the crisis severity. Harder-hit areas experienced large and persistent declines in independent patenting, mostly reflecting the disruption in access to finance during the crisis. This decline was larger for young and inexperienced inventors and lower-quality patents. In contrast, innovation by large firms increased, especially among young and inexperienced inventors. Overall, the Great Depression contributed to the decline in technological entrepreneurship and accelerated the shift of innovation into larger firms.
The Political Work of Migration Governance Binaries: Responses to Zimbabwean “Survival Migration” at the Zimbabwe–South Africa Border
Authors: Vanyoro Kudakwashe 
Published: April 2023

Abstract
This article’s purpose is to analyse the political work of binaries used in both domestic and global migration governance responses with a particular focus on Zimbabwean “survival migration” at the Zimbabwe–South Africa border. This article finds that there is peculiar complementarity between South Africa’s domestic migration governance framework and global migration governance frameworks aimed at a migration management approach. This article argues that this nice fit normalises the ostensibly clear distinction between migrants and refugees to deny protection to deserving asylum-seekers, which is productive in serving the political interests of the South African government. Without access to the appropriate papers and encountering a border refugee reception office that has developed de facto gatekeeping measures to prevent them from seeking asylum, as well as a United Nations High Commissioner for Refugees field office that perceives them as economic migrants, many Zimbabweans living in South Africa occupy a liminal area of categorisation and protection. Hence, the possibilities of the global migration governance providing legitimacy to exclusionary practices at the national level in South Africa are immense. This points to the need for serious engagement with “survival migration” as a category of mobility in analysis, policy, law as well as practice.
Association between circadian sleep regulation and cortical gyrification in young and older adults
Authors: Deantoni Michele , Reyt Mathilde , Berthomier Christian , Muto Vincenzo , Hammad Gregory , De Haan Stella , Dourte Marine , Taillard Jacques , Lambot Eric , Cajochen Christian , Reichert Carolin F , Maire Micheline , Baillet Marion , Schmidt Christina 
Published: April 2023

Abstract
The circadian system orchestrates sleep timing and structure and is altered with increasing age. Sleep propensity, and particularly REM sleep is under strong circadian control and has been suggested to play an important role in brain plasticity. In this exploratory study, we assessed whether surface-based brain morphometry indices are associated with circadian sleep regulation and whether this link changes with age. Twenty-nine healthy older (55–82 years; 16 men) and 28 young participants (20–32 years; 13 men) underwent both structural magnetic resonance imaging and a 40-h multiple nap protocol to extract sleep parameters over day and night time. Cortical thickness and gyrification indices were estimated from T1-weighted images acquired during a classical waking day. We observed that REM sleep was significantly modulated over the 24-h cycle in both age groups, with older adults exhibiting an overall reduction in REM sleep modulation compared to young individuals. Interestingly, when taking into account the observed overall age-related reduction in REM sleep throughout the circadian cycle, higher day–night differences in REM sleep were associated with increased cortical gyrification in the right inferior frontal and paracentral regions in older adults. Our results suggest that a more distinctive allocation of REM sleep over the 24-h cycle is associated with regional cortical gyrification in aging, and thereby point towards a protective role of circadian REM sleep regulation for age-related changes in brain organization.
Di(2-ethylhexyl) phthalate mediates oxidative stress and activates p38MAPK/NF-kB to exacerbate diabetes-induced kidney injury in vitro and in vivo models
Authors: Ding Wen-Jie , Huang Shou-Lin , Huang Song , Xu Wei-Ping , Wei Wei 
Published: April 2023

Abstract
Plasticizer di(2-ethylhexyl) phthalate (DEHP) is employed to make polyethylene polymers. Some studies in epidemiology and toxicology have shown that DEHP exposure over an extended period may be hazardous to the body, including nephrotoxicity, and aggravate kidney damage in the context of underlying disease. However, studies on the toxicity of DEHP in diabetes-induced kidney injury have been rarely reported. Using a high-fat diet (HFD) and streptozotocin (STZ, 35 mg/kg)-induced kidney injury in mice exposed to various daily DEHP dosages, we explored the impacts of DEHP on diabetes-induced kidney injury. We discovered that DEHP exposure significantly promoted the renal inflammatory response and oxidative stress in mice, with increased P-p38 and P-p65 protein levels and exacerbated the loss of podocin. The same findings were observed in vitro after stimulation of podocytes with high glucose (30 mmol/L) and exposure to DEHP. Our results suggest that DEHP exacerbates diabetes-induced kidney injury by mediating oxidative stress and activating p38MAPK/NF-κB.
Clinical Interpretation of Word-Recognition Scores for Listeners with Sensorineural Hearing Loss: Confidence Intervals, Limits, and Levels
Authors: Margolis Robert H. , Wilson Richard H. , Saly George L. 
Published: April 2023

Objectives:
Confidence levels were established to determine if a word-recognition score is within the expected range for a hearing loss group (based on 3-frequency pure-tone average) or significantly below or above the expected range.

Design:
Two large clinical databases were mined to produce data-sets composed of word-recognition scores obtained with Q/MASS NU-6 materials and VA NU-6 materials for patients with average hearing losses ranging from 0 to 70 dB HL. Percentiles representing scores that are below (2.5%, 5%, and 10%) and above (90%, 95%, and 97.5%) the expected range (defined as the 80% confidence interval) were established. To estimate the distribution of scores and percentiles for the Auditec NU-6 materials (for which a large database is not available) Q/MASS scores were transformed to Auditec scores based on published psychometric functions.

Results:
The resulting confidence levels and expected ranges of word-recognition scores should be useful for interpreting the relationship between a score and the distribution of scores for the patient’s hearing loss severity. Confidence levels are described as low, moderate, and high corresponding to the statistical level of assurance that a score is lower or higher than the expected score.

Conclusions:
The confidence levels and expected ranges may be helpful for interpreting word-recognition scores obtained with three widely used sets of NU-6 test materials.