bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule visualization of twin-supercoiled domains generated during transcription
Authors: Janissen Richard , Barth Roman , Polinder Minco , van der Torre Jaco , Dekker Cees 
Published: December 2023

Abstract
Transcription-coupled supercoiling of DNA is a key factor in chromosome compaction and the regulation of genetic processes in all domains of life. It has become common knowledge that, during transcription, the DNA-dependent RNA polymerase (RNAP) induces positive supercoiling ahead of it (downstream) and negative supercoils in its wake (upstream), as rotation of RNAP around the DNA axis upon tracking its helical groove gets constrained due to drag on its RNA transcript. Here, we experimentally validate this so-called twin-supercoiled-domain model with in vitro real-time visualization at the single-molecule scale. Upon binding to the promoter site on a supercoiled DNA molecule, RNAP merges all DNA supercoils into one large pinned plectoneme with RNAP residing at its apex. Transcription by RNAP in real time demonstrates that up- and downstream supercoils are generated simultaneously and in equal portions, in agreement with the twin-supercoiled-domain model. Experiments carried out in the presence of RNases A and H, revealed that an additional viscous drag of the RNA transcript is not necessary for the RNAP to induce supercoils. The latter results contrast the current consensus and simulations on the origin of the twin-supercoiled domains, pointing at an additional mechanistic cause underlying supercoil generation by RNAP in transcription.
cGAS-STING signalling regulates microglial chemotaxis in genome instability
Authors: Talbot Emily J , Joshi Lisha , Thornton Peter , Dezfouli Mahya , Tsafou Kalliopi , Perkinton Michael , Khoronenkova Svetlana V 
Published: December 2023

Abstract
Defective DNA damage signalling and repair is a hallmark of age-related and genetic neurodegenerative disease. One mechanism implicated in disease progression is DNA damage-driven neuroinflammation, which is largely mediated by tissue-resident immune cells, microglia. Here, we utilise human microglia-like cell models of persistent DNA damage and ATM kinase deficiency to investigate how genome instability shapes microglial function. We demonstrate that upon DNA damage the cytosolic DNA sensing cGAS-STING axis drives chronic inflammation and a robust chemokine response, exemplified by production of CCL5 and CXCL10. Transcriptomic analyses revealed that cell migratory pathways were highly enriched upon IFN-β treatment of human iPSC-derived microglia, indicating that the chemokine response to DNA damage mirrors type I interferon signalling. Furthermore, we find that STING deletion leads to a defect in microglial chemotaxis under basal conditions and upon ATM kinase loss. Overall, this work provides mechanistic insights into cGAS-STING-dependent neuroinflammatory mechanisms and consequences of genome instability in the central nervous system.
An exonuclease-resistant chain-terminating nucleotide analogue targeting the SARS-CoV-2 replicase complex
Authors: Shannon Ashleigh , Chazot Aurélie , Feracci Mikael , Falcou Camille , Fattorini Véronique , Selisko Barbara , Good Steven , Moussa Adel , Sommadossi Jean-Pierre , Ferron François , Alvarez Karine , Canard Bruno 
Published: December 2023

Abstract
Nucleotide analogues (NA) are currently employed for treatment of several viral diseases, including COVID-19. NA prodrugs are intracellularly activated to the 5′-triphosphate form. They are incorporated into the viral RNA by the viral polymerase (SARS-CoV-2 nsp12), terminating or corrupting RNA synthesis. For Coronaviruses, natural resistance to NAs is provided by a viral 3′-to-5′ exonuclease heterodimer nsp14/nsp10, which can remove terminal analogues. Here, we show that the replacement of the α-phosphate of Bemnifosbuvir 5′-triphosphate form (AT-9010) by an α-thiophosphate renders it resistant to excision. The resulting α-thiotriphosphate, AT-9052, exists as two epimers (RP/SP). Through co-crystallization and activity assays, we show that the Sp isomer is preferentially used as a substrate by nucleotide diphosphate kinase (NDPK), and by SARS-CoV-2 nsp12, where its incorporation causes immediate chain-termination. The same -Sp isomer, once incorporated by nsp12, is also totally resistant to the excision by nsp10/nsp14 complex. However, unlike AT-9010, AT-9052-RP/SP no longer inhibits the N-terminal nucleotidylation domain of nsp12. We conclude that AT-9052-Sp exhibits a unique mechanism of action against SARS-CoV-2. Moreover, the thio modification provides a general approach to rescue existing NAs whose activity is hampered by coronavirus proofreading capacity.
Behavior Change Intervention for Smokeless Tobacco Cessation Delivered Through Dentists in Dental Settings: A Pragmatic Pilot Trial
Authors: Rasool Shaista , Holliday Richard , Khan Zohaib , Dobbie Fiona , Bauld Linda 
Published: December 2023

Abstract

Introduction
Evidence on smokeless tobacco (ST) cessation interventions is scarce. The South Asian (SA) region that shares more than 90% of the burden of ST use is grossly underrepresented in research on ST cessation. This study aimed to assess the feasibility of delivering and investigating a behavioral support intervention for ST cessation in dental settings in Pakistan.

Methods
A multicenter, pilot, two-armed parallel-group, individually randomized control trial, with a 1:1 allocation ratio, was conducted at two dental hospitals. Eligibility criteria included being an ST user seeking dental treatment and not currently accessing cessation support. All participants were provided written self-help ST cessation material. The intervention group also received a dentist-delivered, bespoke behavioral support intervention for ST cessation developed for users of SA origin. Participants were followed up telephonically at 3 and 6 months. Self-reported 6-month abstinence was verified by salivary cotinine. Analysis was descriptive, with 95% confidence intervals presented where appropriate.

Results
One hundred participants were successfully recruited from the selected hospitals. Of these, 78% continued to engage throughout the study duration and provided primary outcome data, whereas 63% completed all hospital visits. The outcome measures were successfully collected. Biochemically verified 6-month abstinence in the intervention and control groups was 10% and 4%.

Conclusions
It was feasible to deliver and evaluate a dentist-delivered behavioral support intervention for ST cessation in Pakistan. The data suggested that the intervention may improve ST quit rates. The findings of this study will be useful in informing the design of future definitive studies.

Implications
To our knowledge, this is the first pragmatic pilot trial on ST cessation in dental settings in Pakistan and the first trial on dentist-delivered structured behavioral support intervention for ST cessation. It adds to the scarce, trial evidence based on ST cessation interventions. The findings suggest behavioral support intervention for ST cessation may improve quit rates. The trial was conducted in a country with poor ST control measures, where ST products are not taxed, the products are sold openly to and by minors, and the users are offered negligible cessation support. The findings may, therefore, be generalizable to low–middle-income countries, particularly SA countries, with similar policy backgrounds.
Drought as a trigger of the rapid rise of professional skateboarding in 1970s Southern California
Authors: Büntgen Ulf , Oppenheimer Clive , Li Paco , Frachetti Michael , Esper Jan , Torbenson Max C A , Krusic Paul J 
Published: December 2023

Abstract
In 1977 California, authorities responded to an extreme drought with an unprecedented state order to drastically reduce domestic water usage and leave countless newly built swimming pools empty. These curved pools became “playgrounds” for inspired surfers to develop professional vertical skateboarding in the Los Angeles area. Industrial production of polyurethane, and the advent of digital photography, laser printing, and high gloss mass media further contributed to the explosive popularization of skateboarding, creating a global subculture and multibillion-dollar industry that still impacts music, fashion, and lifestyle worldwide. Our interdisciplinary investigation demonstrates that neither the timing nor the location of the origin of professional skateboarding was random. This modern case study highlights how environmental changes can affect human behavior, transform culture, and engender technical innovation in the Anthropocene.
Autocratic Legalism, Partisanship, and Popular Legitimation in Authoritarian Cameroon
Authors: Letsa Natalie Wenzell , Morse Yonatan L 
Published: December 2023

Abstract
Authoritarian regimes regularly turn to the law to justify repression. This article examines whether invoking legal institutions has a persuasive effect on public perceptions of repression, and whether that effect is shaped by partisanship. The article uses the case of Cameroon’s Special Criminal Tribunal, created in 2011 to prosecute high-profile corruption cases. A survey experiment was designed that describes the arrest and trial of a suspected corrupt oppositional minister and reminds a treatment group about the Special Criminal Tribunal. The results show that neither regime nor opposition partisans are swayed by legal justifications for repression. By contrast, nonpartisans respond negatively to autocratic legalism, particularly those with low levels of regime trust. The article clarifies when autocratic legalism might be used for public legitimation, suggests that partisanship is a useful lens for understanding public opinion in an autocracy, and elaborates upon the meaning of nonpartisanship in electoral authoritarian regimes.
The Reverse Backlash: How the Success of Populist Radical Right Parties Relates to More Positive Immigration Attitudes
Authors: Dennison James , Kustov Alexander 
Published: December 2023

Abstract
What is the relationship between the electoral success of populist radical right parties (PRRPs) and public attitudes toward immigration? Previous research suggests that PRRP success can lead to more negative attitudes due to the breaking down of antiprejudice norms and more prominent anti-immigration party cues. However, we argue that greater PRRP success could have a positive relationship with immigration attitudes, reflecting negative partisanship, polarization, and a desire to reemphasize antiprejudice norms, which we call a “reverse backlash effect.” Using the best available electoral and public opinion data across the last thirty years in twenty-four European countries, our TSCS analyses show the predominance of such “reverse backlash effects” across several operationalizations of PRRP success. Our argument has important consequences for the understanding of possible PRRP effects on public opinion, as well as attitudinal formation via party cueing and social norms more generally.
Disjunctivism and the Paradox of Tragedy
Authors: Gaskin Richard 
Published: December 2023

Abstract
The paper offers a disjunctivist solution to the paradox of tragedy. The first part of the paper defends a version of disjunctivism as that doctrine is understood in the epistemology of perception, and contrasts it with its rival, conjunctivism. In the second part of the paper, it is argued that the traditional paradox of tragedy—the question why tragedy gives pleasure—can be solved by adopting a disjunctivist approach to the relevant felt emotions. The tragic audience does not really feel ‘sorrow, terror, anxiety’ (so Hume), but simulacra thereof, emotions which resemble the originals in certain respects but which have quite different connections with action. A conjunctivist approach to the paradox discerns a ‘highest common factor’ in both non-fictional and fictional scenarios: but this is not only phenomenologically implausible; it decouples the agent from the actions that are essentially keyed to particular emotions, and so splits the self.
Cancer risks in patients with ankylosing spondylitis and the effects of biologic agents: a population-based study
Authors: Eom Sang-Yong , Jang Hyun-a , Im Yo Han , Choi Kyung-Hwa , Kim Ji Hyoun 
Published: December 2023

Abstract

Objective
The objective of this study was to conduct a population-based analysis of the malignancy risks of patients with AS.

Methods
A total of 1796 patients with AS and 7184 age- and sex-matched controls (1:4 ratio) were selected from the Korea National Health Insurance Service–National Sample Cohort database. Data of patients diagnosed with AS (code M45) according to the International Classification of Diseases (ICD) 10th edition, between 2002 and 2019, were reviewed. These data were extracted based on the ICD codes assigned to cancer patients.

Results
Cancer developed in 168/1796 patients (9.3%) after the AS diagnosis. After adjusting for confounders, the cancer risk of patients with AS was not significantly increased compared with that of controls [adjusted hazard ratio (HR): 1.1; 95% CI: 0.93–1.31]. However, the risks for upper gastrointestinal (GI) cancer (adjusted HR: 1.51; 95% CI: 1.07–2.12) and haematologic malignancy (adjusted HR: 2.36; 95% CI: 1.2–4.65) were significantly higher in patients with AS than in controls. There were no significant differences in the risks for other major cancers between patients with AS and controls. Regarding medication for AS, the HR of upper GI cancer was higher in patients with AS compared with controls (adjusted HR: 1.51; 95% CI: 1.00–2.29).

Conclusion
The overall cancer risk in patients with AS was not significantly different compared with that in the controls. However, while the effect of NSAIDs on upper GI cancer cannot be ruled out, patients with AS exhibited a significant increase in the risk of both upper GI cancer and haematologic malignancy.
Coevolutionary phage training and Joint application delays the emergence of phage resistance in Pseudomonas aeruginosa
Authors: Wang Mianzhi , Wei Jingyi , Jiang Lei , Jiang Li , Zhang Junxuan , He Xiaolu , Ren Yiwen , Wang Zixuan , Sun Yongxue , Wang Zhiqiang 
Published: December 2023

Abstract
Antibiotic-resistant bacteria are current threats to available antibiotic therapies, and this has renewed interest in the therapeutic use of phage as an alternative. However, development of phage resistance has led to unsuccessful therapeutic outcomes. In the current study, we applied phage training to minimize bacterial phage resistance and to improve treatment outcome by adapting the phage to their target hosts during co-evolution. We isolated and characterized a novel Pseudomonas aeruginosa N4-like lytic phage (PWJ) from wastewater in Yangzhou, China. PWJ is a double-stranded DNA podovirus that can efficiently lyse the model strain ATCC 27,853 and opportunistic pathogen PAO1. Genome sequencing of PWJ revealed features similar to those of the N4-like P. aeruginosa phage YH6. We used PWJ to screen for an evolved trained phage (WJ_Ev14) that restored infectivity to PWJ phage bacterial resisters. BLASTN analysis revealed that WJ_Ev14 is identical to its ancestor PWJ except for the amino acid substitution R1051S in its tail fiber protein. Moreover, phage adsorption tests and transmission electron microscopy of resistant bacteria demonstrated that the R1051S substitution was most likely the reason WJ_Ev14 could re-adsorb and regain infectivity. Furthermore, phage therapy assays in vitro and in a mouse P. aeruginosa lung infection model demonstrated that PWJ treatment resulted in improved clinical results and a reduction in lung bacterial load whereas the joint phage cocktail (PWJ+ WJ_Ev14) was better able to delay the emergence of resister bacteria. The phage cocktail (PWJ +WJ_Ev14) represents a promising candidate for inclusion in phage cocktails developed for clinical applications.
The first record of the genus Prosantorhinus (Perissodactyla: Rhinocerotidae) of East Asia
Authors: Sun Danhui , Deng Tao , Wang Shiqi 
Published: December 2023

Abstract
Prosantorhinus is a genus of small extinct teleoceratine rhinoceroses with shortened limb bones, widely distributed in Europe. However, the Asian evolution of the teleoceratine Prosantorhinus has remained unclear because of a scarcity of fossil records of the genus. Here, we report the first record of Prosantorhinus in East Asia from the Middle Miocene of Tongxin, Ningxia. The new specimen is characterized by a concave dorsal skull profile and elevated nasals; short and stout nasal bones with drooping margins on both sides; the thickened, enlarged, and roughened nasal extremity supporting a small horn; the semi-molarized upper premolars with a lingual bridge between the protocone and hypocone; the metaloph constriction present on P2–4; the protocone equal to the hypocone on P2; the crista present on P3; and the cement on the cheek teeth developed. With all the morphological evidence considered, we establish a new species, Prosantorhinus yei sp. nov.. A phylogenetic analysis based on 282 morphological characters scored for 36 taxa reveals that Prosantorhinus yei sp. nov. is a relatively derived taxon in the genus. We hypothesize that Prosantorhinus yei sp. nov. lived in relatively moist environments.
Gene Expression Clusters Suggest Potential Mechanisms of Resistance to Powdery Mildew in Hop (Humulus lupulus)
Authors: Eriksen Renée L. , Wiseman Michele S. , Magana Armando Alcazar , Dhar Nikhilesh , Reed Ralph L. , Stevens Jan F. , Gent David H. , Henning John A. 
Published: December 2023

Powdery mildew, caused by Podosphaera macularis, is one of the most important diseases of hop in the Pacific Northwest of the United States. Resistant cultivars exist; however, recently, the pathogen has overcome two sources of resistance in popular cultivars. Breeding for new, emerging races of the pathogen is thus a continuing priority. We used RNA-seq to understand gene expression trends in a resistant (cv. USDA Nugget) and a susceptible (cv. Symphony) hop cultivar along a time series following inoculation. We found stronger transcriptional reprogramming in the resistant cultivar than the susceptible cultivar. Transcripts that increased in expression within 12 h post-inoculation in the resistant cultivar included genes in the jasmonic acid biosynthesis pathway, as well as phenylpropanoid biosynthesis. Transcripts that had a positive correlation with time post-inoculation in the resistant cultivar included genes involved in phosphorylation, cell-surface signaling pathways, and response to jasmonic acid. We used untargeted HPLC–HR-MS/MS analysis and confirmed an increase in jasmonic acid and several phenolic compounds. We hypothesize that resistance to powdery mildew in cv. Nugget may be at least partially due to perception of the pathogen outside of the cell, and transcriptional and metabolic reprogramming is mediated by jasmonic acid signaling. At least part of that transcriptional and metabolic reprogramming involves changes to lignin production, which might reinforce the cell wall. The multi-omics approach to describe the contrasting responses of a resistant and a susceptible hop cultivar following inoculation with this important pathogen may indicate new strategies for developing resistant germplasm and control methods. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Impact of Surge Strain and Pandemic Progression on Prognostication by an Established COVID-19–Specific Severity Score
Authors: Yek Christina , Wang Jing , Fintzi Jonathan , Mancera Alex G. , Keller Michael B. , Warner Sarah , Kadri Sameer S. 
Published: December 2023

IMPORTANCE:
Many U.S. State crisis standards of care (CSC) guidelines incorporated Sequential Organ Failure Assessment (SOFA), a sepsis-related severity score, in pandemic triage algorithms. However, SOFA performed poorly in COVID-19. Although disease-specific scores may perform better, their prognostic utility over time and in overcrowded care settings remains unclear.

OBJECTIVES:
We evaluated prognostication by the modified 4C (m4C) score, a COVID-19–specific prognosticator that demonstrated good predictive capacity early in the pandemic, as a potential tool to standardize triage across time and hospital-surge environments.

DESIGN:
Retrospective observational cohort study.

SETTING:
Two hundred eighty-one U.S. hospitals in an administrative healthcare dataset.

PARTICIPANTS:
A total of 298,379 hospitalized adults with COVID-19 were identified from March 1, 2020, to January 31, 2022. m4C scores were calculated from admission diagnosis codes, vital signs, and laboratory values.

MAIN OUTCOMES AND MEASURES:
Hospital-surge index, a severity-weighted measure of COVID-19 caseload, was calculated for each hospital-month. Discrimination of in-hospital mortality by m4C and surge index-adjusted models was measured by area under the receiver operating characteristic curves (AUC). Calibration was assessed by training models on early pandemic waves and measuring fit (deviation from bisector) in subsequent waves.

RESULTS:
From March 2020 to January 2022, 298,379 adults with COVID-19 were admitted across 281 U.S. hospitals. m4C adequately discriminated mortality in wave 1 (AUC 0.779 [95% CI, 0.769–0.789]); discrimination was lower in subsequent waves (wave 2: 0.772 [95% CI, 0.765–0.779]; wave 3: 0.746 [95% CI, 0.743–0.750]; delta: 0.707 [95% CI, 0.702–0.712]; omicron: 0.729 [95% CI, 0.721–0.738]). m4C demonstrated reduced calibration in contemporaneous waves that persisted despite periodic recalibration. Performance characteristics were similar with and without adjustment for surge.

CONCLUSIONS AND RELEVANCE:
Mortality prediction by the m4C score remained robust to surge strain, making it attractive for when triage is most needed. However, score performance has deteriorated in recent waves. CSC guidelines relying on defined prognosticators, especially for dynamic disease processes like COVID-19, warrant frequent reappraisal to ensure appropriate resource allocation.
A Case of Superficial Papular Neuroma: A Rare Neural Neoplasm
Authors: Suzuki Shuji , Fukumoto Takuya , Hiraki Tsubasa , Goldberg Lynne J. 
Published: December 2023

Abstract:
A case of 67-year-old male patient with superficial papular neuroma (SPN) on the occiput is reported. This is the second report of SPN and the first with clinical images. Histologically, in the superficial dermis and periadnexa, the specimen exhibits a nodule of bland spindle cells with an S-shaped and spindle nucleus, surrounded by eosinophilic collagen fibers and scattered mast cells, which forms focally peripheral nerve-like structures. Lichen simplex chronicus-like changes are observed. Immunostaining result revealed that the tumor cells are positive for S-100, neurofilament, collagen IV, and CD34 but negative for Melan A, epithelial membrane antigen, and glial fibrillary acidic protein. Histological differential diagnosis includes prurigo nodularis, neurotized nevus, benign peripheral nerve sheath tumor, such as neurofibroma or schwannoma, a type of neuroma, such as traumatic neuroma, mucosal neuroma, and palisaded encapsulated neuroma, or a type of neural hamartoma. A careful histological investigation will enable dermatopathologists to make a diagnosis of SPN.
Long COVID and Chronic Conditions in the US Workforce
Authors: Bonner Carole , Ghouralal Sera-Leigh 
Published: December 2023

Objective
This study examines how long COVID, chronic conditions, and work outcomes affect the general workforce.

Methods
It examines the prevalence of long COVID and its associations with chronic conditions, and other sociodemographic characteristics using 2022 National Health Interview Survey data.

Results
Long COVID affected work attendance and disability risk, especially in those with mental health issues, angina, stroke, cancer, diabetes, chronic lung conditions, and musculoskeletal conditions.

Conclusion
This study reveals the relationships between long COVID, chronic conditions, and work outcomes.