bluuebunny/crossref_metadata_2025 huggingface dataset:
The characteristics of negative corona discharge and radio interference at different altitudes based on coaxial wire–cylinder gap
Authors: HE 何 Wangling 旺龄 , WEI 魏 Hongyu 宏宇 , ZHANG 张 Yinlu 胤禄 , LIU 刘 Yongcong 永聪 , LIU 刘 Yunpeng 云鹏 , WAN 万 Baoquan 保权 , ZHOU 周 Yang 阳 , WANG 王 Yanzhao 延召 , GAN 干 Zheyuan 喆渊
Published: November 2023

The corona discharge from transmission lines in high-altitude areas is more severe than at lower altitudes. The radio interference caused thereby is a key factor to be considered when designing transmission lines. To study the influence of altitude on negative corona characteristics, an experimental platform comprising a movable small corona cage was established: experiments were conducted at four altitudes in the range of 1120‒4320 m, and data on the corona current pulse and radio interference level of 0.8-mm diameter fine copper wire under different negative voltages were collected. The experimental results show that the average amplitude, repetition frequency and average current of the corona current pulse increase with increasing altitude. The dispersion of pulse amplitude increases with increase in altitude, while the randomness of the pulse interval decreases continuously. Taking the average current as an intermediate variable, the relationship between radio interference level and altitude is obtained. The result of this research has some significance for understanding the corona discharge characteristics of ultra-high-voltage lines.
Merging Philosophical Traditions for a New Way to Research Music: On the Ekphrastic Description of Musical Experience
Authors: Krawiec Andrzej
Published: November 2023

This article addresses the subject of the ekphrastic description of experiencing music. It shows the main differences between ekphrasis and commonly used analysis in music theory and musicology. In approaching the problem of ekphrasis with what is called pure music, I emphasize its ancient understanding, thus differing from Lydia Goehr (2010) and Siglind Bruhn (2000, 2001, 2019). The ekphrastic analysis of the first movement of Arnold Schoenberg’s Six Little Piano Pieces Op. 19 conducted in this article uses the methodology developed by Gottfried Boehm (2014) and Georges Didi-Huberman (2005, 2015, 2017, 2018) in the discipline of art history. This article aims to delineate a new way of researching the art of music, an essential feature of which is the combination of the traditions of analytic philosophy and phenomenology.
Wollheim on art’s historicity: an intersection of theoretical art history and the philosophy of art
Authors: Berryman Jim
Published: November 2023

Art and its Objects by Richard Wollheim had a major impact on aesthetics and the philosophy of art when it was first published in 1968. Of the arguments offered in response to Wollheim’s essay, Jerrold Levinson’s intentional-historical theory of art has been one of the most enduring. Levinson was influenced by three key sections of Wollheim’s enquiry: Section 40, which considers the claim that works of art fall under a concept of art, or that we are disposed to regard certain things as works of art; and Sections 60 and 61, which deal with art as a historical phenomenon, and problems arising from its identification and interpretation. To date, these claims have been raised as points of contention in the philosophy of art. This paper takes a different perspective. Wollheim’s understanding of art’s historicity draws explicitly on the literature of theoretical art history. Via Wollheim, old art-historical problems will reappear as new philosophical questions.
Non-coding RNA regulates the immune microenvironment in recurrent spontaneous abortion (RSA): new insights into immune mechanisms
Authors: Tang Cen , Hu Wanqin
Published: November 2023

Recurrent spontaneous abortion (RSA) has various causes, including chromosomal abnormalities, prethrombotic state, and abnormal uterine anatomical factors. However, the pathogenesis of RSA is still unclear. Surprisingly, non-coding RNA can stably express at the maternal-fetal interface and regulate immune cells’ proliferation, apoptosis, invasion, metastasis, and angiogenesis. Accumulating evidence suggests that the competing endogenous RNA (ceRNA) regulatory network between non-coding RNAs complicates RSA’s pathological process and maybe a new starting point for exploring RSA. In this review, we mainly discuss the regulatory network and potential significance of non-coding RNA in the immune microenvironment of RSA patients. In addition, the cellular interactions of non-coding RNA transported through vesicles were introduced from aspects of trophoblast function and immune regulation. Finally, we analyze previous studies and further discuss that the stable expression of non-coding RNA may be used as a biomarker of some disease states and a prediction target of RSA.
Microglia sense astrocyte dysfunction and prevent disease progression in an Alexander disease model
Authors: Saito Kozo , Shigetomi Eiji , Shinozaki Youichi , Kobayashi Kenji , Parajuli Bijay , Kubota Yuto , Sakai Kent , Miyakawa Miho , Horiuchi Hiroshi , Nabekura Junichi , Koizumi Schuichi
Published: November 2023

Alexander disease (AxD) is an intractable neurodegenerative disorder caused by GFAP mutations. It is a primary astrocyte disease with a pathological hallmark of Rosenthal fibres within astrocytes. AxD astrocytes show several abnormal phenotypes. Our previous study showed that AxD astrocytes in model mice exhibit aberrant Ca2+ signals that induce AxD aetiology. Here, we show that microglia have unique phenotypes with morphological and functional alterations, which are related to the pathogenesis of AxD. Immunohistochemical studies of 60TM mice (AxD model) showed that AxD microglia exhibited highly ramified morphology. Functional changes in microglia were assessed by Ca2+ imaging using hippocampal brain slices from Iba1-GCaMP6-60TM mice and two-photon microscopy. We found that AxD microglia showed aberrant Ca2+ signals, with high frequency Ca2+ signals in both the processes and cell bodies. These microglial Ca2+ signals were inhibited by pharmacological blockade or genetic knockdown of P2Y12 receptors but not by tetrodotoxin, indicating that these signals are independent of neuronal activity but dependent on extracellular ATP from non-neuronal cells. Our single-cell RNA sequencing data showed that the expression level of Entpd2, an astrocyte-specific gene encoding the ATP-degrading enzyme NTPDase2, was lower in AxD astrocytes than in wild-type astrocytes. In situ ATP imaging using the adeno-associated virus vector GfaABC1D ATP1.0 showed that exogenously applied ATP was present longer in 60TM mice than in wild-type mice. Thus, the increased ATP level caused by the decrease in its metabolizing enzyme in astrocytes could be responsible for the enhancement of microglial Ca2+ signals. To determine whether these P2Y12 receptor-mediated Ca2+ signals in AxD microglia play a significant role in the pathological mechanism, a P2Y12 receptor antagonist, clopidogrel, was administered. Clopidogrel significantly exacerbated pathological markers in AxD model mice and attenuated the morphological features of microglia, suggesting that microglia play a protective role against AxD pathology via P2Y12 receptors. Taken together, we demonstrated that microglia sense AxD astrocyte dysfunction via P2Y12 receptors as an increase in extracellular ATP and alter their morphology and Ca2+ signalling, thereby protecting against AxD pathology. Although AxD is a primary astrocyte disease, our study may facilitate understanding of the role of microglia as a disease modifier, which may contribute to the clinical diversity of AxD.
Association between atopic dermatitis and inflammatory bowel disease among US adults in the All of Us Research Program
Authors: Joel Marina Z , Damsky William , Cohen Jeffrey M , Wride Mitchel
Published: November 2023

Our study investigated the association between atopic dermatitis (AD) and inflammatory bowel disease using the All of Us Research Program, a US National Institutes of Health database providing health information on over 300 000 Americans. This cross-sectional study demonstrated that individuals with AD have an approximately twofold increase in odds of having inflammatory bowel disease, Crohn disease and ulcerative colitis, compared with individuals without AD.
The emergence of the EEG dominant rhythm across the first year of life
Authors: Elhamiasl Mina , Sanches Braga Figueira Jessica , Barry-Anwar Ryan , Pestana Zoe , Keil Andreas , Scott Lisa S
Published: November 2023

The spectral composition of EEG provides important information on the function of the developing brain. For example, the frequency of the dominant rhythm, a salient features of EEG data, increases from infancy to adulthood. Changes of the dominant rhythm during infancy are yet to be fully characterized, in terms of their developmental trajectory and spectral characteristics. In this study, the development of dominant rhythm frequency was examined during a novel sustained attention task across 6-month-old (n = 39), 9-month-old (n = 30), and 12-month-old (n = 28) infants. During this task, computer-generated objects and faces floated down a computer screen for 10 s after a 5-second fixation cross. The peak frequency in the range between 5 and 9 Hz was calculated using center of gravity (CoG) and examined in response to faces and objects. Results indicated that peak frequency increased from 6 to 9 to 12 months of age in face and object conditions. We replicated the same result for the baseline. There was high reliability between the CoGs in the face, object, and baseline conditions across all channels. The developmental increase in CoG was more reliable than measures of mode frequency across different conditions. These findings suggest that CoG is a robust index of brain development across infancy.
Single-cell transcriptomes of kidneys in a 6-month-old boy with Denys-Drash syndrome reveal stromal cell heterogeneity in the tumor microenvironment
Authors: Li Tao , Zhou Jiangfeng , Wu Haiyan , Gao Xiucheng , Shen Qiyang , Cheng Rui , Zhang Mingshun
Published: November 2023

Background

Denys-Drash syndrome (DDS) is a rare disease characterized with pseudohermaphroditism, nephroblastoma (also known as Wilms tumor), and diffuse mesangial sclerosis. The therapy for DDS is largely supportive, i.e. surgery and chemotherapy for Wilms tumor and renal replacement therapy. Due to the limited understanding of the pathogenesis, precision therapy for DDS is yet to be explored. We sought to explore the cellular components and interactions in kidney tissues from an infant with DDS.

Methods

Whole-exome sequencing was performed to examine the mutations associated with DDS. Single-cell RNA sequencing (scRNA-seq) was performed to explore the heterogenicity of kidney tissue samples.

Results

A 6-month-old infant with bilateral Wilms tumors and genital ambiguity was diagnosed as having DDS. Whole exome sequencing revealed a novel de novo mutation (p.F185fs*118) in exon 1 of WT1. scRNA-seq was performed in tissue samples from bilateral Wilms tumors and the normal kidney from this infant. Fibroblasts, myocytes, epithelial cells, endothelial cells, and mononuclear phagocytes (MPs) ranked at the top of the 31 135 total cells. Fibroblasts and myocytes were dominant in the Wilms tumor samples. In contrast, most epithelial cells and endothelial cells were found in normal kidney tissues. CD44 and TUBA1A were significantly changed in myocyte subclusters, which may contribute to chemotherapy drug resistance. Macrophages intensively interacted with cancerous cells, including fibroblasts, epithelial cells, and myocytes.

Conclusions

A novel mutation (p.F185fs*118) in exon 1 of WT1 was identified in an infant with DDS. scRNA-Seq revealed the heterogenicity of cellular components in Wilms tumors and kidney tissues, shedding light on the pathogenesis of DDS.
Simultaneous determination of steroid hormones and pharmaceuticals in killer whale (Orcinus orca) faecal samples by liquid chromatography tandem mass spectrometry
Authors: Ross Andrew R S , Liao Xiangjun , Brown Tanya M
Published: November 2023

We describe a non-invasive method for profiling selected hormones, pharmaceuticals and personal care products (PPCPs) in killer whales (Orcinus orca) based on analysis of faecal samples by liquid chromatography tandem mass spectrometry (LC–MS/MS). The method targets 21 compounds of interest including glucocorticoids, mineralocorticoids, androgens, estrogens, progestogens, selective serotonin uptake inhibitors and an antibacterial/antifungal agent. This method is suitable for routine simultaneous determination of target compounds in killer whale faecal samples as well as validation of immunoassays for the detection and measurement of steroid hormones in faeces. The optimized method involves extraction of freeze-dried faecal material with reagent alcohol and water followed by isolation of the analytes using solid phase extraction with hydrophilic–lipophilic balance cartridges and liquid–liquid extraction with methyl tertiary-butyl ether. Reconstituted extracts were analysed by LC–MS/MS using an electrospray ionization interface. Method limit of quantification ranged from 0.06 to 45.2 ng/g in freeze-dried faecal samples. Except for sertraline, triclosan and estradiol (which was not recovered at the lowest spiked concentration), average intra- and inter-day precisions were within 10%, and average recoveries were between 89.3% and 129.3%, for faecal samples spiked with 5.3, 26.7 or 133 ng/g of each analyte. The method was applied successfully to the analysis of hormones and PPCPs in whale faeces during which 17α-hydroxyprogesterone, a common intermediate in steroid biosynthesis that cross-reacts with precursors and sulphated conjugates in immunoassays, was identified and quantified in all samples.
Targeting the apelin system for the treatment of cardiovascular diseases
Authors: Chapman Fiona A , Maguire Janet J , Newby David E , Davenport Anthony P , Dhaun Neeraj
Published: November 2023

Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity, and diabetes that are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare systems, and newer treatments are needed. The apelin system, comprising the apelin receptor and its two endogenous ligands apelin and elabela, is a broad regulator of physiology that opposes the actions of the renin-angiotensin and vasopressin systems. Activation of the apelin receptor promotes endothelium-dependent vasodilatation and inotropy, lowers blood pressure, and promotes angiogenesis. The apelin system appears to protect against arrhythmias, inhibits thrombosis, and has broad anti-inflammatory and anti-fibrotic actions. It also promotes aqueous diuresis through direct and indirect (central) effects in the kidney. Thus, the apelin system offers therapeutic promise for a range of cardiovascular, kidney, and metabolic diseases. This review will discuss current cardiovascular disease targets of the apelin system and future clinical utility of apelin receptor agonism.
Long-term radiographic and periodontal evaluations of the bone-grafted alveolar cleft region in young adults born with a UCLP
Authors: Lemberger Mathias , Peterson Petra , Andlin Sobocki Anna , Setayesh Hedieh , Karsten Agneta
Published: November 2023

Background

Studies addressing the periodontal health of the teeth surrounding the bone-grafted cleft in patients born with unilateral cleft lip and palate disagree on whether periodontal health is compromised.

Objectives

To determine periodontal health differences between the cleft and the non-cleft sides nearly a decade after secondary alveolar bone grafting.

Methods

This prospective, controlled (split-mouth design) study comprised an intraoral apical radiographic and a periodontal examination of 40 consecutive patients from one centre (n = 26 males) who had undergone bone grafting at mean age of 10.2 years (±1.6). Probing pocket depth, gingival index, gingival recession, and radiographic bone support were assessed.

Results

No significant difference occurred in probing pocket depth between teeth at cleft and non-cleft sites (OR 1.8, P = .488). Gingival recession was present at 6.6% of all examined sites on the cleft side and at 1.7% on the non-cleft side (OR 17.3, P < .001). Gingival recession occurred most often on the buccal and disto-buccal surfaces of the central incisor on the cleft side. The gingival index was significantly higher on the cleft side (OR 8.0, P < .001). The Bergland index was I or II in most patients (87%).

Limitations

Recruitment of eligible patients was lengthy.

Conclusion

The teeth on the cleft side had high levels of gingival inflammation. Few pathological gingival pockets, however, were found. Shallow gingival recessions frequently occurred around the central incisor on the cleft side. Teeth in the bone-grafted cleft region generally had good bone support.
Local institutions and human capital formation in pre-industrial societies: evidence from Valencia
Authors: Beltrán Tapia Francisco J , Díez-Minguela Alfonso , Gómez-Tello Alicia , Martinez-Galarraga Julio , Tirado-Fabregat Daniel A
Published: November 2023

This article analyses the relationship between institutions and human capital formation. We use literacy rates in 1860 at the municipal level in Valencia where the expulsion of the Moriscos in 1609 was followed by the Christian resettlement. Our findings show that male literacy was consistently lower in Morisco areas by mid-19th century. Yet, the analysis also shows the disappearance of this effect at the beginning of the 20th century. We argue that the deployment of the liberal state would have entailed the gradual decoupling of educational outcomes from the institutional heterogeneity characteristic of the Old Regime.
Validation of the European SCORE2 models in a Canadian primary care cohort
Authors: Sud Maneesh , Sivaswamy Atul , Austin Peter C , Abdel-Qadir Husam , Anderson Todd J , Khera Rohan , Naimark David M J , Lee Douglas S , Roifman Idan , Thanassoulis George , Tu Karen , Wijeysundera Harindra C , Ko Dennis T
Published: November 2023

Aims

Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort.

Methods and results

A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40–69 while the models for older persons (OPs) were applied to 9885 individuals 70–89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men.

Conclusion

The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions.
A nematode model to evaluate microdeletion phenotype expression
Authors: Antkowiak Katianna R , Coskun Peren , Noronha Sharon T , Tavella Davide , Massi Francesca , Ryder Sean P
Published: November 2023

Microdeletion syndromes are genetic diseases caused by multilocus chromosomal deletions too small to be detected by karyotyping. They are typified by complex pleiotropic developmental phenotypes that depend both on the extent of the deletion and variations in genetic background. Microdeletion alleles cause a wide array of consequences involving multiple pathways. How simultaneous haploinsufficiency of numerous adjacent genes leads to complex and variable pleiotropic phenotypes is not well understood. CRISPR/Cas9 genome editing has been shown to induce microdeletion-like alleles at a meaningful rate. Here, we describe a microdeletion allele in Caenorhabditis elegans recovered during a CRISPR/Cas9 genome editing experiment. We mapped the allele to chromosome V, balanced it with a reciprocal translocation crossover suppressor, and precisely defined the breakpoint junction. The allele simultaneously removes 32 protein-coding genes, yet animals homozygous for this mutation are viable as adults. Homozygous animals display a complex phenotype including maternal effect lethality, producing polynucleated embryos that grow into uterine tumors, vulva morphogenesis defects, body wall distensions, uncoordinated movement, and a shortened life span typified by death by bursting. Our work provides an opportunity to explore the complexity and penetrance of microdeletion phenotypes in a simple genetic model system.
Blood donation practices, processing and utilisation of blood components in government tertiary hospitals in Nigeria: a multicentre cooperative study
Authors: Umar Garba , Abdulqadir Ibrahim , Ugwu Ngozi , Adeyemo Titilope , Yau Nabila , Hassan Abdulazziz , Olaniyi John , Musa Abubakar , Abubakar Sharafa , Ndakotsu Muhammad , James Jasini , Uche Chika , Musa Awwal , Ukoma Chikadibia , Nwogoh Benedict , David Ekaete , Ugwu Angela , Nwankwo Chizoba , Omokanye Olaitan , Abba Aisha , Owojuyigbe Temilola , Isyaku Mujtabba , Obi Esther , Jatau Ezra , Ekwere Timothy , Oladosu-Olayiwola Rashidat , Isah Hezekiah , Diggi Sirajo , Nwannadi Alexander , Yuguda Saleh , Iheanacho Obinna , Tikau Hadiza , Adeleke Ibijola , Ekanem Mabel , Madu Anazoeze , Ikusemoro Augustina , Chukwu Celestine , Galadanci Amal , Bassey Okon , Otu Theresa , Agwu Obineche , Osho Patrick , Gwarzo Aisha , Hassan Sadiya , Majeed Adepoju , Umar Anas , Abubakar Habib , Gimba Mohamed , Ugbor Michael , Ali Abdulmalik , Ajuba Clara
Published: November 2023

Background

Timely access to safe blood and blood components is still a challenge in Nigeria. This study aimed to determine blood donation practices, processing and utilization of blood components across government tertiary hospitals (THs) in Nigeria.

Methods

This was a descriptive cross-sectional study done in Nigeria in June–July 2020. Data were analysed with SPSS version 21.0.

Results

Data were collected from 50 THs. The majority (68%) of the THs lack facilities for blood component preparation and only 18% and 32% provide cryoprecipitate and platelet concentrate, respectively. Whole blood was most commonly requested (57.04%). All facilities tested blood for HIV, HBV and HCV, but the majority (23 [46%]) employed rapid screening tests alone and nucleic acid testing was not available in any hospitals. The manual method was the most common method of compatibility testing in 90% (45/50) and none of the THs routinely perform extended red cell typing. The average time to process routine, emergency and uncross-matched requests were a mean of 109.58±79.76 min (range 45.00–360.00), 41.62±25.23 (10.00–240.00) and 11.09±4.92 (2.00–20.00), respectively.

Conclusion

Facilities for blood component preparation were not widely available. Concerned government authorities should provide facilities for blood component preparation.
Energy justice in times of crisis: protection of consumers and market-based renewable energy investments
Authors: Boute Anatole
Published: November 2023

In response to the 2022 energy crisis, caused by the disruption of Russian gas supplies to Europe, the European Union (EU) emphasized the importance of accelerating the deployment of renewable energy to ensure supply security and lower energy prices. Paradoxically, renewable energy investments were also one of the main targets of the EU efforts to contain the hardship of the crisis. Based on the reasoning that investors in wind and solar energy received profits that by far exceeded pre-crisis levels, the EU capped their ‘surplus revenues’ and initially proposed to decouple electricity from gas prices. These initiatives were justified based on considerations of distributive energy justice. Yet, by interfering with revenues and the electricity market structure, the EU signalled to renewable energy investors the risk of regulatory intervention with the market basis governing their investments. Building on the arbitral practice on renewable energy and electricity regulation, this article examines the international protection of market-based renewable energy investments and critically reflects on how investment protection affects states’ right to ensure energy justice in times of crisis.
Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair
Authors: Oka Naoyuki , Masai Kyohei , Okubo Yu , Kaseda Kaoru , Hishida Tomoyuki , Asakura Keisuke
Published: November 2023

Pectus excavatum (PE) is often associated with scoliosis and can elicit cardiovascular disturbances under rare conditions. Here we report a patient who was treated with a combined Ravitch and Nuss procedure for PE with dyspnea following scoliosis repair to improve her symptoms. The patient was a 49-year-old woman with a history of PE and scoliosis. Right inferior pulmonary vein stenosis was caused by posterior spinal fusion for scoliosis prior to the PE repair. We could safely correct the chest wall deformity and treat dyspnea by performing a modified Ravitch repair in combination with the Nuss procedure.
The Question of Logic
Authors: Kripke Saul A
Published: November 2023

Under the influence of Quine’s famous manifesto, many philosophers have thought that logical theories are scientific theories that can be ‘adopted’ and tested as scientific theories. Here we argue that this idea is untenable. We discuss it with special reference to Putnam’s proposal to ‘adopt’ a particular non-classical logic to solve the foundational problems of quantum mechanics in his famous paper ‘Is Logic Empirical?’ (1968), which we argue was not really coherent.
The characteristic shape of damping wings during reionization
Authors: Chen Huanqing
Published: November 2023

Spectroscopic analysis of Ly α damping wings of bright sources at z > 6 is a promising way to measure the reionization history of the universe. However, the theoretical interpretation of the damping wings is challenging due to the inhomogeneous nature of the reionization process and the proximity effect of bright sources. In this Letter, we analyse the damping wings arising from the neutral patches in the radiative transfer cosmological simulation suite cosmic reionization on computers. We find that the damping wing profile remains a tight function of volume-weighted neutral fraction v, especially when v > 0.5, despite the patchy nature of reionization and the proximity effect. This small scatter indicates that with a well-measured damping wing profile, we could constrain the volume-weighted neutral fraction as precise as Δ v ≲ 0.1 in the first half of reionization. Due to resonant Ly α absorption from the residual neutral hydrogen inside the ionized bubble, it may be challenging to find the starting point of the damping wing for faint sources like normal galaxies or gamma-ray bursts. However, for bright sources like quasars, it is hopeful to measure the entire damping wing and use them to measure the neutral fraction accurately.
Single molecule MATAC-seq reveals key determinants of DNA replication origin efficiency
Authors: Chanou Anna , Weiβ Matthias , Holler Karoline , Sajid Atiqa , Straub Tobias , Krietsch Jana , Sanchi Andrea , Ummethum Henning , Lee Clare S K , Kruse Elisabeth , Trauner Manuel , Werner Marcel , Lalonde Maxime , Lopes Massimo , Scialdone Antonio , Hamperl Stephan
Published: November 2023

Stochastic origin activation gives rise to significant cell-to-cell variability in the pattern of genome replication. The molecular basis for heterogeneity in efficiency and timing of individual origins is a long-standing question. Here, we developed Methylation Accessibility of TArgeted Chromatin domain Sequencing (MATAC-Seq) to determine single-molecule chromatin accessibility of four specific genomic loci. MATAC-Seq relies on preferential modification of accessible DNA by methyltransferases combined with Nanopore-Sequencing for direct readout of methylated DNA-bases. Applying MATAC-Seq to selected early-efficient and late-inefficient yeast replication origins revealed large heterogeneity of chromatin states. Disruption of INO80 or ISW2 chromatin remodeling complexes leads to changes at individual nucleosomal positions that correlate with changes in their replication efficiency. We found a chromatin state with an accessible nucleosome-free region in combination with well-positioned +1 and +2 nucleosomes as a strong predictor for efficient origin activation. Thus, MATAC-Seq identifies the large spectrum of alternative chromatin states that co-exist on a given locus previously masked in population-based experiments and provides a mechanistic basis for origin activation heterogeneity during eukaryotic DNA replication. Consequently, our single-molecule chromatin accessibility assay will be ideal to define single-molecule heterogeneity across many fundamental biological processes such as transcription, replication, or DNA repair in vitro and ex vivo.
The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered
Authors: Abarenkov Kessy , Nilsson R Henrik , Larsson Karl-Henrik , Taylor Andy F S , May Tom W , Frøslev Tobias Guldberg , Pawlowska Julia , Lindahl Björn , Põldmaa Kadri , Truong Camille , Vu Duong , Hosoya Tsuyoshi , Niskanen Tuula , Piirmann Timo , Ivanov Filipp , Zirk Allan , Peterson Marko , Cheeke Tanya E , Ishigami Yui , Jansson Arnold Tobias , Jeppesen Thomas Stjernegaard , Kristiansson Erik , Mikryukov Vladimir , Miller Joseph T , Oono Ryoko , Ossandon Francisco J , Paupério Joana , Saar Irja , Schigel Dmitry , Suija Ave , Tedersoo Leho , Kõljalg Urmas
Published: November 2023

UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into ∼2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms.
DGIdb 5.0: rebuilding the drug–gene interaction database for precision medicine and drug discovery platforms
Authors: Cannon Matthew , Stevenson James , Stahl Kathryn , Basu Rohit , Coffman Adam , Kiwala Susanna , McMichael Joshua F , Kuzma Kori , Morrissey Dorian , Cotto Kelsy , Mardis Elaine R , Griffith Obi L , Griffith Malachi , Wagner Alex H
Published: November 2023

The Drug–Gene Interaction Database (DGIdb, https://dgidb.org) is a publicly accessible resource that aggregates genes or gene products, drugs and drug–gene interaction records to drive hypothesis generation and discovery for clinicians and researchers. DGIdb 5.0 is the latest release and includes substantial architectural and functional updates to support integration into clinical and drug discovery pipelines. The DGIdb service architecture has been split into separate client and server applications, enabling consistent data access for users of both the application programming interface (API) and web interface. The new interface was developed in ReactJS, and includes dynamic visualizations and consistency in the display of user interface elements. A GraphQL API has been added to support customizable queries for all drugs, genes, annotations and associated data. Updated documentation provides users with example queries and detailed usage instructions for these new features. In addition, six sources have been added and many existing sources have been updated. Newly added sources include ChemIDplus, HemOnc, NCIt (National Cancer Institute Thesaurus), Drugs@FDA, HGNC (HUGO Gene Nomenclature Committee) and RxNorm. These new sources have been incorporated into DGIdb to provide additional records and enhance annotations of regulatory approval status for therapeutics. Methods for grouping drugs and genes have been expanded upon and developed as independent modular normalizers during import. The updates to these sources and grouping methods have resulted in an improvement in FAIR (findability, accessibility, interoperability and reusability) data representation in DGIdb.
ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs
Authors: Cao Xinyu , Zhou Xu , Hou Fei , Huang Yu-e , Yuan Mengqin , Long Min , Chen Sina , Lei Wanyue , Zhu Jicun , Chen Jiahao , Zhang Tao , Guo An-Yuan , Jiang Wei
Published: November 2023

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.
VarCards2: an integrated genetic and clinical database for ACMG-AMP variant-interpretation guidelines in the human whole genome
Authors: Wang Zheng , Zhao Guihu , Zhu Zhaopo , Wang Yijing , Xiang Xudong , Zhang Shiyu , Luo Tengfei , Zhou Qiao , Qiu Jian , Tang Beisha , Xia Kun , Li Bin , Li Jinchen
Published: November 2023

VarCards, an online database, combines comprehensive variant- and gene-level annotation data to streamline genetic counselling for coding variants. Recognising the increasing clinical relevance of non-coding variations, there has been an accelerated development of bioinformatics tools dedicated to interpreting non-coding variations, including single-nucleotide variants and copy number variations. Regrettably, most tools remain as either locally installed databases or command-line tools dispersed across diverse online platforms. Such a landscape poses inconveniences and challenges for genetic counsellors seeking to utilise these resources without advanced bioinformatics expertise. Consequently, we developed VarCards2, which incorporates nearly nine billion artificially generated single-nucleotide variants (including those from mitochondrial DNA) and compiles vital annotation information for genetic counselling based on ACMG-AMP variant-interpretation guidelines. These annotations include (I) functional effects; (II) minor allele frequencies; (III) comprehensive function and pathogenicity predictions covering all potential variants, such as non-synonymous substitutions, non-canonical splicing variants, and non-coding variations and (IV) gene-level information. Furthermore, VarCards2 incorporates 368 820 266 documented short insertions and deletions and 2 773 555 documented copy number variations, complemented by their corresponding annotation and prediction tools. In conclusion, VarCards2, by integrating over 150 variant- and gene-level annotation sources, significantly enhances the efficiency of genetic counselling and can be freely accessed at http://www.genemed.tech/varcards2/.
Topoisomerase 1 facilitates nucleosome reassembly at stress genes during recovery
Authors: Vega Montserrat , Barrios Rubén , Fraile Rodrigo , de Castro Cogle Kevin , Castillo David , Anglada Roger , Casals Ferran , Ayté José , Lowy-Gallego Ernesto , Hidalgo Elena
Published: November 2023

Chromatin remodeling is essential to allow full development of alternative gene expression programs in response to environmental changes. In fission yeast, oxidative stress triggers massive transcriptional changes including the activation of hundreds of genes, with the participation of histone modifying complexes and chromatin remodelers. DNA transcription is associated to alterations in DNA topology, and DNA topoisomerases facilitate elongation along gene bodies. Here, we test whether the DNA topoisomerase Top1 participates in the RNA polymerase II-dependent activation of the cellular response to oxidative stress. Cells lacking Top1 are resistant to H2O2 stress. The transcriptome of Δtop1 strain was not greatly affected in the absence of stress, but activation of the anti-stress gene expression program was more sustained than in wild-type cells. Top1 associated to stress open reading frames. While the nucleosomes of stress genes are partially and transiently evicted during stress, the chromatin configuration remains open for longer times in cells lacking Top1, facilitating RNA polymerase II progression. We propose that, by removing DNA tension arising from transcription, Top1 facilitates nucleosome reassembly and works in synergy with the chromatin remodeler Hrp1 as opposing forces to transcription and to Snf22 / Hrp3 opening remodelers.
The UCSC Genome Browser database: 2024 update
Authors: Raney Brian J , Barber Galt P , Benet-Pagès Anna , Casper Jonathan , Clawson Hiram , Cline Melissa S , Diekhans Mark , Fischer Clayton , Navarro Gonzalez Jairo , Hickey Glenn , Hinrichs Angie S , Kuhn Robert M , Lee Brian T , Lee Christopher M , Le Mercier Phillipe , Miga Karen H , Nassar Luis R , Nejad Parisa , Paten Benedict , Perez Gerardo , Schmelter Daniel , Speir Matthew L , Wick Brittney D , Zweig Ann S , Haussler David , Kent W James , Haeussler Maximilian
Published: November 2023

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides annotation data on thousands of genome assemblies, ranging from human to SARS-CoV2. This year, we have introduced new data from the Human Pangenome Reference Consortium and on viral genomes including SARS-CoV2. We have added 1,200 new genomes to our GenArk genome system, increasing the overall diversity of our genomic representation. We have added support for nine new user-contributed track hubs to our public hub system. Additionally, we have released 29 new tracks on the human genome and 11 new tracks on the mouse genome. Collectively, these new features expand both the breadth and depth of the genomic knowledge that we share publicly with users worldwide.
Surufatinib combined camrelizumab as a valuable third-line rescue therapy for a patient with extensive-stage for small-cell lung cancer: a case report and literature review
Authors: Pan Chi , Yu Tao , Han Li , Hao Daxuan , Yang Ming , Li Lin , Chu Laili , Ni Qingtao
Published: November 2023

Lung cancer is one of the most common malignant tumors with the highest incidence. Gene mutations are rare in small-cell lung carcinoma (SCLC), resulting in targeted therapy being only a third-line recommendation. Surufatinib (Sulanda) is an oral angio-immune kinase inhibitor used to treat solid tumors. We report a case of SCLC treated with surufatinib combined with camrelizumab, with good therapeutic results in our department. The patient experienced over 18 months of progression-free survival and over 28 months of overall survival. This suggests that surufatinib combined with camrelizumab is an effective third-line treatment for SCLC patients. However, the response rate to surufatinib treatment in all patients with SCLC remains unknown and needs to be determined in a large population.
Enablers and Hindrances of Lifestyle Changes Among Patients With Atrial Fibrillation
Authors: Liu Mengdi , Zhang Qianghuizi , Liu Leyang , Liu Weiwei
Published: November 2023

Background

Atrial fibrillation (AF) seriously affects the health status and quality of life of affected patients. However, the lifestyle changes recommended by the guidelines for patients are not ideal. Hence, understanding the factors that promote and hinder healthy behavior changes in patients with AF is crucial for self-management.

Objective

The aims of this study were to understand the factors enabling and hindering health behaviors in patients with AF and to provide a reference for promoting health management among these patients.

Methods

Using the purposive sampling method, 22 patients with AF admitted to the Cardiac Center of Beijing Chaoyang Hospital, Capital Medical University, from March 2021 to June 2021 were selected for in-depth face-to-face interviews. The thematic analysis method was used to summarize and refine the themes.

Results

The following 2 themes and 15 subthemes were eventually extracted by analyzing and summarizing the interview data. The 7 factors facilitating health behaviors in patients with AF were risk perception, outcome expectancy, behavioral intention, action plan, response plan, self-efficacy, and social support. There were 8 hindering factors: personal preferences and habits, specific customary culture, weak self-control, accessibility of exercise conditions, symptom-related distress, cognitive weakness, multiple medication use, and insufficient awareness of condition monitoring.

Conclusions

The factors affecting health behaviors in patients with AF are complex, and healthcare providers should reinforce the facilitators of health behaviors in these patients and provide them with targeted interventions against hindering factors. Results can be used to develop health behavior intervention programs for patients with AF.
Effect of Daily Activity Record-Based Self-monitoring Intervention on the Perception of Physical Sensations in Patients With Chronic Heart Failure
Authors: Matsuda Misako , Saito Nao , Izawa Kazuhiro P. , Taniguchi Ryoji , Shogaki Junko , Miyawaki Ikuko
Published: November 2023

Background

To prevent rehospitalization for heart failure (HF), patients need to be able to perceive physical changes that occur at the onset of HF exacerbation and seek early help.

Objective

The aim of this study was to evaluate the effect of a self-monitoring intervention on patients' perceptions of physical sensations during daily activities in the context of HF via a randomized controlled trial.

Methods

Participants (N = 70) were randomly assigned to the intervention (received daily activity record-based self-monitoring intervention support; group A) or control (only explained the measured results from the records; group B) group. Group A reflected on and described the physical sensations in their daily activities within 1 month after discharge. Outcome measures were assessed at 1 month after the intervention using the European Heart Failure Self-care Behavior Scale, Evaluation Scale for Self-Monitoring by patients with Heart Failure, clinical events, physical activity, and sleep.

Results

There was no significant difference in the change in the “asking for help” subscale score of the European Heart Failure Self-care Behavior Scale between the groups (+0.7 vs +0.4 points, P = .716). Group A had improved score on the self-monitoring subscale related to “concern about how movements affect body” from baseline (from 12.7 to 14.0 points, P = .026). There was no significant effect of self-monitoring intervention support on the first rehospitalization related to HF and all-cause death (log-rank χ2 = 0.432, P = .511). A significant difference in moderate-intensity physical activity between the groups was observed (+4.6 vs −0.5 minutes, P = .029).

Conclusions

A focused strategy that enables patients to perceive their physical sensations and promotes early help-seeking behavior is needed.
Exploring the Relationship Between Techno-Unreliability at Work and Burnout
Authors: Meyer Sophie-Charlotte , Tisch Anita
Published: November 2023

Objective

With the growing dissemination of digital technologies in the workplace, technologies itself and related factors are increasingly discussed as an additional source of work stress, often referred to as technostress. This article explores whether techno-unreliability as a dimension of technostress is associated with burnout.

Methods

We perform linear regression analyses based on a large representative sample of German employees collected in 2019. We distinguish between information and communication technology users (n= 4702) and tool users (n= 1953). Interaction models explore whether individual and workplace-related factors might moderate the relationship.

Results

The results indicate that the more frequently employees experience techno-induced interruptions (as an indicator for techno-unreliability), the stronger their burnout symptoms. Interaction models reveal that social support and job autonomy might buffer this association.

Conclusions

Ensuring reliable technology and technical support can reduce employee stress.