bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc sequestration by human calprotectin facilitates manganese binding to the bacterial solute-binding proteins PsaA and MntC
Authors: Rosen Tomer , Hadley Rose C , Bozzi Aaron T , Ocampo Daniel , Shearer Jason , Nolan Elizabeth M 
Published: January 2022

Abstract
Zinc is an essential transition metal nutrient for bacterial survival and growth but may become toxic when present at elevated levels. The Gram-positive bacterial pathogen Streptococcus pneumoniae is sensitive to zinc poisoning, which results in growth inhibition and lower resistance to oxidative stress. Streptococcus pneumoniae has a relatively high manganese requirement, and zinc toxicity in this pathogen has been attributed to the coordination of Zn(II) at the Mn(II) site of the solute-binding protein (SBP) PsaA, which prevents Mn(II) uptake by the PsaABC transport system. In this work, we investigate the Zn(II)-binding properties of pneumococcal PsaA and staphylococcal MntC, a related SBP expressed by another Gram-positive bacterial pathogen, Staphylococcus aureus, which contributes to Mn(II) uptake. X-ray absorption spectroscopic studies demonstrate that both SBPs harbor Zn(II) sites best described as five-coordinate, and metal-binding studies in solution show that both SBPs bind Zn(II) reversibly with sub-nanomolar affinities. Moreover, both SBPs exhibit a strong thermodynamic preference for Zn(II) ions, which readily displace bound Mn(II) ions from these proteins. We also evaluate the Zn(II) competition between these SBPs and the human S100 protein calprotectin (CP, S100A8/S100A9 oligomer), an abundant host-defense protein that is involved in the metal-withholding innate immune response. CP can sequester Zn(II) from PsaA and MntC, which facilitates Mn(II) binding to the SBPs. These results demonstrate that CP can inhibit Zn(II) poisoning of the SBPs and provide molecular insight into how S100 proteins may inadvertently benefit bacterial pathogens rather than the host.
Transcription-replication coordination revealed in single live cells
Authors: Tsirkas Ioannis , Dovrat Daniel , Thangaraj Manikandan , Brouwer Ineke , Cohen Amit , Paleiov Zohar , Meijler Michael M , Lenstra Tineke , Aharoni Amir 
Published: January 2022

Abstract
The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter. We found a wave of partial transcriptional repression ahead of the moving replication fork, which may contribute to efficient fork progression through the transcribed gene. Real-time detection of conflicts revealed their negative impact on both processes, leading to fork stalling or slowdown as well as lower transcription levels during gene replication, with different trade-offs observed in defined subpopulations of cells. Our real-time measurements of transcription-replication encounters demonstrate how these processes can proceed simultaneously while maintaining genomic stability, and how conflicts can arise when coordination is impaired.
SLX4 dampens MutSα-dependent mismatch repair
Authors: Guervilly Jean-Hugues , Blin Marion , Laureti Luisa , Baudelet Emilie , Audebert Stéphane , Gaillard Pierre-Henri 
Published: January 2022

Abstract
The tumour suppressor SLX4 plays multiple roles in the maintenance of genome stability, acting as a scaffold for structure-specific endonucleases and other DNA repair proteins. It directly interacts with the mismatch repair (MMR) protein MSH2 but the significance of this interaction remained unknown until recent findings showing that MutSβ (MSH2-MSH3) stimulates in vitro the SLX4-dependent Holliday junction resolvase activity. Here, we characterize the mode of interaction between SLX4 and MSH2, which relies on an MSH2-interacting peptide (SHIP box) that drives interaction of SLX4 with both MutSβ and MutSα (MSH2-MSH6). While we show that this MSH2 binding domain is dispensable for the well-established role of SLX4 in interstrand crosslink repair, we find that it mediates inhibition of MutSα-dependent MMR by SLX4, unravelling an unanticipated function of SLX4.
Liquid Biopsy-based Precision Therapy in Patients with Advanced Solid Tumors: A Real-world Experience from a Community-based Oncology Practice
Authors: Choucair Khalil , Mattar Bassam Ibrahim , Van Truong Quoc , Koeneke Travis , Van Truong Phu , Dakhil Christopher , Cannon Michael W , Page Seth Joel , Deutsch Jeremy Michael , Carlson Eric , Moore Dennis Frederic , Nabbout Nassim H , Kallail K James , Dakhil Shaker R , Reddy Pavan S 
Published: January 2022

Abstract

Background
Liquid biopsy testing offers a significant potential in selecting signal-matched therapies for advanced solid malignancies. The feasibility of liquid biopsy testing in a community-based oncology practice, and its actual impact on selecting signal-matched therapies, and subsequent survival effects have not previously been reported.

Patients and Methods
A retrospective chart review was conducted on adult patients with advanced solid cancer tested with a liquid-biopsy assay between December 2018 and 2019, in a community oncology practice. The impact of testing on treatment assignment and survival was assessed at 1-year follow-up.

Results
A total of 178 patients underwent testing. A positive test was reported in 140/178 patients (78.7%), of whom 75% had an actionable mutation. The actual overall signal-based matching rate was 17.8%. While 85.7% of patients with no actionable mutation had a signal-based clinical trial opportunity, only 10% were referred to a trial. Survival analysis of lung, breast, and colorectal cancer patients with actionable mutations who received any therapy (n = 66) revealed a survival advantage for target-matched (n = 22) compared to unmatched therapy (n = 44): patients who received matched therapy had significantly longer progression-free survival (PFS) (mPFS: 12 months; 95%CI, 10.6-13.4 vs. 5.0 months; 95%CI, 3.4-6.6; P = .029), with a tendency towards longer overall survival (OS) (mOS: 15 months; 95%CI, 13.5-16.5 vs. 13 months; 95%CI: 11.3-14.7; P = .087).

Conclusions
Implementation of liquid biopsy testing is feasible in a US community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched therapies conferred added survival benefits.
Comparing Barriers and Facilitators to Adolescent and Young Adult Clinical Trial Enrollment Across High- and Low-Enrolling Community-Based Clinics
Authors: Siembida Elizabeth J , Loomans-Kropp Holli A , Tami-Maury Irene , Freyer David R , Sung Lillian , Crosswell Howland E , Pollock Brad H , Roth Michael E 
Published: January 2022

Abstract

Background
Adolescent and young adult (AYA) patients with cancer are underrepresented on cancer clinical trials (CCTs), and most AYAs are treated in the community setting. Past research has focused on individual academic institutions, but factors impacting enrollment vary across institutions. Therefore, we examined the patterns of barriers and facilitators between high- and low-AYA enrolling community-based clinics to identify targets for intervention.

Materials and Methods
We conducted 34 semi-structured interviews with stakeholders employed used at National Cancer Institute Community Oncology Research Program (NCORP) affiliate sites (“clinics”). Stakeholders (eg, clinical research associates, patient advocates) were recruited from high- and low-AYA enrolling clinics. We conducted a content analysis and calculated the percentage of stakeholders from each clinic type that reported the barrier or facilitator. A 10% gap between high- and low-enrollers was considered the threshold for differences.

Results
Both high- and low-enrollers highlighted insufficient resources as a barrier and the presence of a patient eligibility screening process as a facilitator to AYA enrollment. High-enrolling clinics reported physician gatekeeping as a barrier and the improvement of departmental collaboration as a facilitator. Low-enrollers reported AYAs’ uncertainty regarding the CCT process as a barrier and the need for increased physician endorsement of CCTs as a facilitator.

Conclusions
High-enrolling clinics reported more barriers downstream in the enrollment process, such as physician gatekeeping. In contrast, low-enrolling clinics struggled with the earlier steps in the CCT enrollment process, such as identifying eligible trials. These findings highlight the need for multi-level, tailored interventions rather than a “one-size-fits-all” approach to improve AYA enrollment in the community setting.
Digital Platforms and Antitrust
Authors: Parker Geoffrey , Petropoulos Georgios , Van Alstyne Marshall W. 
Published: January 2022

Abstract
At the heart of economic activity, digital platforms connect multi-sided markets of producers and consumers of various goods and services. Their market power and privileged ecosystem position raise concerns that they may engage in anti-competitive practices that reduce innovation and consumer welfare. This chapter deals with the role of market competition and regulation in addressing these concerns. Traditional (ex post) antitrust intervention will be less effective in markets driven by network effects unless it is combined with a proper (ex ante) regulatory framework. Antitrust tools should focus on value creation and its distribution before focusing on competition. The scope of regulatory intervention should satisfy three criteria: (1) value creation from operation of the platforms does not decrease due to the policy intervention; (2) allocative efficiency is based on distributing the value created in a fair way among market participants; (3) dynamic efficiency and competition ensure that incentives for market misconduct and anti-competitive strategies such as artificial entry barriers are eliminated. Market interventions that target a firm’s market power should ideally retain value creation while also encouraging small firm entry and innovation. Data has a central role in online markets. Value creation is reinforced through a recursive data capture and data deployment feedback loop enabled by machine learning technologies. A regulatory intervention that facilitates data sharing mechanisms, such that data will not only confer value to market leaders but also to their competitors to the benefit of consumers, is crucial for creating more competitive and innovative digital markets.
Charles W. Mills,The Racial Contract
Authors: Marwah Inder S. 
Published: January 2022

AbstractCharles Mills’ The Racial Contract (TRC) was a landmark intervention that set itself no less a task than raising the topic of race up to mainstream philosophical investigation. As remarkable in its scope as in its perspicacity, the book re-envisions modern political theory by centering its racialized constitution and imbrications in Euro-American practices of racial exploitation. Taking a half-millennium of global white supremacy as its point of departure, it both exposes racial divides encoded within social contractarianism and lays the groundwork for a non-ideal theory of justice, conjoining a penetrating critique of white domination with a methodologically innovative liberalism. This chapter (a) situates TRC’s main arguments within their contexts of emergence, (b) considers certain lines of criticism to which it has been subjected, along with Mills’ adaptations to them, and (c) reflects on its downstream impacts, in terms of Mills’ own trajectory and of the discipline’s grappling with race.
The TGN/EE SNARE protein SYP61 and the ubiquitin ligase ATL31 cooperatively regulate plant responses to carbon/nitrogen conditions in Arabidopsis
Authors: Hasegawa Yoko , Huarancca Reyes Thais , Uemura Tomohiro , Baral Anirban , Fujimaki Akari , Luo Yongming , Morita Yoshie , Saeki Yasushi , Maekawa Shugo , Yasuda Shigetaka , Mukuta Koki , Fukao Yoichiro , Tanaka Keiji , Nakano Akihiko , Takagi Junpei , Bhalerao Rishikesh P , Yamaguchi Junji , Sato Takeo 
Published: January 2022

Abstract
Ubiquitination is a post-translational modification involving the reversible attachment of the small protein ubiquitin to a target protein. Ubiquitination is involved in numerous cellular processes, including the membrane trafficking of cargo proteins. However, the ubiquitination of the trafficking machinery components and their involvement in environmental responses are not well understood. Here, we report that the Arabidopsis thaliana trans-Golgi network/early endosome localized SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein SYP61 interacts with the transmembrane ubiquitin ligase ATL31, a key regulator of resistance to disrupted carbon (C)/nitrogen/(N)-nutrient conditions. SYP61 is a key component of membrane trafficking in Arabidopsis. The subcellular localization of ATL31 was disrupted in knockdown mutants of SYP61, and the insensitivity of ATL31-overexpressing plants to high C/low N-stress was repressed in these mutants, suggesting that SYP61 and ATL31 cooperatively function in plant responses to nutrient stress. SYP61 is ubiquitinated in plants, and its ubiquitination level is upregulated under low C/high N-nutrient conditions. These findings provide important insights into the ubiquitin signaling and membrane trafficking machinery in plants.
Recombinase-mediated gene stacking in cotton
Authors: Li Yamei , Li Ruyu , Han Zhiguo , Wang Haitang , Zhou Sixian , Li Yongqing , Wang Yumei , Qi Junsheng , Ow David W 
Published: January 2022

Abstract
Site-specific gene stacking could reduce the number of segregating loci and expedite the introgression of transgenes from experimental lines to field lines. Recombinase-mediated site-specific gene stacking provides a flexible and efficient solution, but this approach requires a recombinase recognition site in the genome. Here, we describe several cotton (Gossypium hirsutum cv. Coker 312) target lines suitable for Mycobacteriophage Bxb1 recombinase-mediated gene stacking. Obtained through the empirical screening of random insertion events, each of these target lines contains a single intact copy of the target construct with precise sequences of RS2, lox, and attP sites that is not inserted within or close to a known gene or near a centromere and shows good expression of the reporter gene gfp. Gene stacking was tested with insertion of different combinations of three candidate genes for resistance to verticillium wilt into three cotton target lines: CTS1, CTS3, and CTS4. Nine site-specific integration events were recovered from 95 independently transformed embryogenic calluses. Southern and DNA sequence analyses of regenerated plants confirmed precise site-specific integration, and resistance to verticillium wilt was observed for plant CTS1i3, which has a single precise copy of site-specifically integrated DNA. These cotton target lines can serve as foundation lines for recombinase-mediated gene stacking to facilitate precise DNA integration and introgression to field cultivars.
Ethylene response factor MdERF4 and histone deacetylase MdHDA19 suppress apple fruit ripening through histone deacetylation of ripening-related genes
Authors: Hu Yanan , Han Zhenyun , Wang Ting , Li Hua , Li Qiqi , Wang Shuai , Tian Ji , Wang Yi , Zhang Xinzhong , Xu Xuefeng , Han Zhenhai , Lü Peitao , Wu Ting 
Published: January 2022

Abstract
Histone deacetylase enzymes participate in the regulation of many aspects of plant development. However, the genome-level targets of histone deacetylation during apple (Malus domestica) fruit development have not been resolved in detail, and the mechanisms of regulation of such a process are unknown. We previously showed that the complex of ethylene response factor 4 (MdERF4) and the TOPLESS co-repressor (MdTPL4; MdERF4–MdTPL4) is constitutively active during apple fruit development (Hu et al., 2020), but whether this transcriptional repression complex is coupled to chromatin modification is unknown. Here, we show that a histone deacetylase (MdHDA19) is recruited to the MdERF4–MdTPL4 complex, thereby impacting fruit ethylene biosynthesis. Transient suppression of MdHDA19 expression promoted fruit ripening and ethylene production. To identify potential downstream target genes regulated by MdHDA19, we conducted chromatin immunoprecipitation (ChIP) sequencing of H3K9 and ChIP-quantitative polymerase chain reaction assays. We found that MdHDA19 affects ethylene production by facilitating H3K9 deacetylation and forms a complex with MdERF4–MdTPL4 to directly repress MdACS3a expression by decreasing the degree of acetylation. We demonstrate that an early-maturing-specific acetylation H3K9ac peak in MdACS3a and expression of MdACS3a were specifically up-regulated in fruit of an early-maturing, but not a late-maturing, cultivar. We provide evidence that a C-to-G mutation in the ethylene-responsive element binding factor-associated amphiphilic repression motif of MdERF4 reduces the repression of MdACS3a by the MdERF4–MdTPL4–MdHDA19 complex. Taken together, our results reveal that the MdERF4–MdTPL–MdHDA19 repressor complex participates in the epigenetic regulation of apple fruit ripening.
Fixed point structure of the gradient flow exact renormalization group for scalar field theories
Authors: Abe Yoshihiko , Hamada Yu , Haruna Junichi 
Published: January 2022

Abstract
The gradient flow exact renormalization group (GFERG) is a framework for defining the Wilson action via a gradient flow equation. We study the fixed point structure of the GFERG equation associated with a general gradient flow equation for scalar field theories, and show that it is the same as that of the conventional Wilson–Polchinski (WP) equation in general. Furthermore, we see that the GFERG equation has a similar RG flow structure around a fixed point to the WP equation. We illustrate these results with the O(N) non-linear sigma model in 4 − ϵ dimensions and the Wilson–Fisher fixed point.
Short- and long-term prognosis of glycemic control in COVID-19 patients with type 2 diabetes
Authors: Zhan K , Zhang X , Wang B , Jiang Z , Fang X , Yang S , Jia H , Li L , Cao G , Zhang K , Ma X 
Published: January 2022

AbstractBackground and aimTo systematically evaluate the associations between glycemic control and short- to long-term outcomes in coronavirus disease 2019 (COVID-19) patients with type 2 diabetes (T2D).Design and methodsA multi-center prospective cohort study including 574 COVID-19 patients with T2D was conducted in Wuhan, China. All patients were followed-up 1 year after hospital discharge using a uniformed questionnaire including self-reported symptoms, and the chronic obstructive pulmonary disease assessment test items.ResultsOf the 574 patients, 443 (77.2%) had well-controlled blood glucose. Glycemic control was significantly associated with decreased risk of death [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.10–0.57], intensive care unit admission (OR 0.22, 95% CI 0.10–0.49), invasive mechanical ventilation (OR 0.25, 95% CI 0.08–0.72), disease progression (OR 0.25, 95% CI 0.11–0.55), and composite outcome (OR 0.26, 95% CI 0.14–0.49). The top five long-term sequelae include fatigue (31.5%), sweating (21.2%), chest tightness (15.1%), anxiety (12.2%), myalgia (10.6%) and short breath (6.4%). Glycemic control was associated with decreased risk of respiratory sequelae (OR 0.42, 95% CI 0.18–0.99; P = 0.048).ConclusionsGlycemic control was significantly associated with short-term outcomes in COVID-19 patients with T2D and showed a significant association with long-term respiratory sequelae. The management and control of blood glucose has a positive impact on prognosis of COVID-19.
Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: an international collaborative scoping review
Authors: Lescoat Alain , Sandler Robert D , Zimmermann François , Roofeh David , Hughes Michael , Pauling John D , Murphy Susan L , Chen Yen T , Townsend Whitney  , Buch Maya H , Khanna Dinesh 
Published: January 2022

Abstract

Objectives
The aim of this study was to comprehensively identify instruments within relevant domains employed to assess lcSSc since the endorsement of its consensus definition in 1988. The overall objective is to inform the creation of a Combined Response Index for Scleroderma Trials Assessing lcSSc (CRISTAL).

Methods
MEDLINE and Embase were searched using terms selected to comprehensively retrieve titles and abstracts mentioning both lcSSc and dcSSc, along with those only mentioning lcSSc, SSc sine scleroderma, limited SSc and/or CREST/CRST. Because our initial assessment of the literature revealed that very few studies included only lcSSc subjects, we also assessed literature that included both cutaneous subsets. A total of 3964 titles and abstracts were screened by two reviewers, and 270 articles were selected for data extraction.

Results
We identified 27 domains encompassing 459 instruments. Instruments from ‘Skin involvement’, ‘Pulmonary involvement’ and ‘Health-related quality of life and general functioning’ were the most frequently retrieved. Among the 15 most represented instruments announced as primary end points in efficacy or effectiveness studies, 7 were clinician-reported outcomes (ROs), 7 were patient ROs, and one was a performance outcome (6 min-walk test). The mean proportion of lcSSc patients in studies of lcSSc, including studies that mention both lcSSc and dcSSc, was 56.4%, demonstrating that this subset is underrepresented in the literature, given that the prevalence of lcSSc ranges from 60% to 80% in national registries and international cohorts.

Conclusion
This scoping literature review provides a comprehensive identification of domains and outcomes used to assess lcSSc. Our results also highlight that lcSSc is underrepresented in the literature.
Activity interference in patients with Sjögren’s syndrome: a cross-sectional study of 149 patients in the UK
Authors: Schoon Hannah , Slack Emma , Pearce Mark , Ng Wan-Fai , Hackett Katie L 
Published: January 2022

Abstract

Objectives
To investigate which five activity interference categories out of pain, fatigue, mood, dryness and brain fog/mental fatigue scored highest in patients with primary Sjögren’s syndrome (pSS) and to investigate the association between activity interference and mood and physical functioning in these patients.

Methods
The Comprehensive Pain Evaluation Questionnaire (CPEQ) assessed activity interference (actions performed in daily life that are hindered) in 149 UK pSS patients. This was modified to include four additional symptoms (fatigue, mood, dryness and brainfog/mental fatigue). Functional impairment was measured using the Hospital Anxiety and Depression Scale (HADS) and the Improved Health Assessment Questionnaire (Improved HAQ). Univariable linear regression models were estimated to investigate the association between CPEQ results and the outcome scores obtained from the HADS and Improved HAQ. Multivariable linear regression models were estimated adjusting for patient age and length of disease.

Results
Fatigue had the biggest impact on seven activity domains: physical exercise (mean score of 3.49 out of 5 [s.d. 1.26]), performing household chores (mean 3.14 [s.d. 1.18]), gardening or shopping (mean 3.18 [s.d. 1.20]), socializing with others (mean 2.62 [s.d. 1.24]), recreation/hobbies (mean 2.88 [s.d. 1.20]), sexual relations (mean 3.00 [s.d. 1.52]), and mental efficacy (mean 2.69 [s.d. 1.17]). Regression analysis showed a positive correlation in which every point increase in an activity interference category saw the overall mood and physical functioning scores increase.

Conclusion
Fatigue has the largest impact on pSS patients’ daily activities in this cohort. Length of disease reduced the impact of activity interference on patients’ overall health score.