bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterial helicase Lhr abets resistance to DNA crosslinking agents mitomycin C and cisplatin
Authors: Warren Garrett M , Ejaz Anam , Fay Allison , Glickman Michael S , Shuman Stewart 
Published: January 2023

Abstract
Mycobacterium smegmatis Lhr exemplifies a novel clade of helicases composed of an N-terminal ATPase/helicase domain (Lhr-Core) and a large C-terminal domain (Lhr-CTD) that nucleates a unique homo-tetrameric quaternary structure. Expression of Lhr, and its operonic neighbor Nei2, is induced in mycobacteria exposed to mitomycin C (MMC). Here we report that lhr deletion sensitizes M. smegmatis to killing by DNA crosslinkers MMC and cisplatin but not to killing by monoadduct-forming alkylating agent methyl methanesulfonate or UV irradiation. Testing complementation of MMC and cisplatin sensitivity by expression of Lhr mutants in Δlhr cells established that: (i) Lhr-CTD is essential for DNA repair activity, such that Lhr-Core does not suffice; (ii) ATPase-defective mutant D170A/E171A fails to complement; (iii) ATPase-active, helicase-defective mutant W597A fails to complement and (iv) alanine mutations at the CTD–CTD interface that interdict homo-tetramer formation result in failure to complement. Our results instate Lhr's ATP-driven motor as an agent of inter-strand crosslink repair in vivo, contingent on Lhr's tetrameric quaternary structure. We characterize M. smegmatis Nei2 as a monomeric enzyme with AP β-lyase activity on single-stranded DNA. Counter to previous reports, we find Nei2 is inactive as a lyase at a THF abasic site and has feeble uracil glycosylase activity.
Cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome
Authors: Nakata Yoshihiro , Ode Hirotaka , Kubota Mai , Kasahara Takaaki , Matsuoka Kazuhiro , Sugimoto Atsuko , Imahashi Mayumi , Yokomaku Yoshiyuki , Iwatani Yasumasa 
Published: January 2023

Abstract
The number of genetic variations in the SARS-CoV-2 genome has been increasing primarily due to continuous viral mutations. Here, we report that the human APOBEC3A (A3A) cytidine deaminase plays a critical role in the induction of C-to-U substitutions in the SARS-CoV-2 genome. Bioinformatic analysis of the chronological genetic changes in a sequence database indicated that the largest UC-to-UU mutation signature, consistent with APOBEC-recognized nucleotide motifs, was predominant in single-stranded RNA regions of the viral genome. In SARS-CoV-2-infected cells, exogenous expression of A3A but not expression of other APOBEC proteins induced UC-to-UU mutations in viral RNA (vRNA). Additionally, the mutated C bases were often located at the tips in bulge or loop regions in the vRNA secondary structure. Interestingly, A3A mRNA expression was drastically increased by interferons (IFNs) and tumour necrosis factor-α (TNF-α) in epithelial cells derived from the respiratory system, a site of efficient SARS-CoV-2 replication. Moreover, the UC-to-UU mutation rate was increased in SARS-CoV-2 produced from lung epithelial cells treated with IFN-ß and TNF-α, but not from CRISPR/Cas9-based A3A knockout cells. Collectively, these findings demonstrate that A3A is a primary host factor that drives mutations in the SARS-CoV-2 RNA genome via RNA editing.
The functions of consciousness in visual processing
Authors: Ludwig Dylan 
Published: January 2023

Abstract
Conscious experiences form a relatively diverse class of psychological phenomena, supported by a range of distinct neurobiological mechanisms. This diversity suggests that consciousness occupies a variety of different functional roles across different task domains, individuals, and species; a position I call functional pluralism. In this paper, I begin to tease out some of the functional contributions that consciousness makes to (human) visual processing. Consolidating research from across the cognitive sciences, I discuss semantic and spatiotemporal processing as specific points of comparison between the functional capabilities of the visual system in the presence and absence of conscious awareness. I argue that consciousness contributes a cluster of functions to visual processing; facilitating, among other things, (i) increased capacities for semantically processing informationally complex visual stimuli, (ii) increased spatiotemporal precision, and (iii) increased capacities for representational integration over large spatiotemporal intervals. This sort of analysis should ultimately yield a plurality of functional markers that can be used to guide future research in the philosophy and science of consciousness, some of which are not captured by popular theoretical frameworks like global workspace theory and information integration theory.
Trends in kidney transplantation rate across Europe: study from the ERA Registry
Authors: Boenink Rianne , Kramer Anneke , Tuinhout Rosalie E , Savoye Emilie , Åsberg Anders , Idrizi Alma , Kerschbaum Julia , Ziedina Ieva , Ziginskiene Edita , Farrugia Emanuel , Garneata Liliana , Zakharova Elena V , Bell Samira , Arnol Miha , Segelmark Mårten , Ioannou Kyriakos , Hommel Kristine , Rosenberg-Ots Mai , Vazelov Evgueniy , Helve Jaakko , Mihály Sándor , Pálsson Runólfur , Nordio Maurizio , Gjorgjievski Nikola , de Vries Aiko P J , Seyahi Nurhan , Magadi Winnie A , Resić Halima , Kalachyk Aleh , Rahmel Axel O , Galvão Ana A , Naumovic Radomir , Lundgren Torbjörn , Arici Mustafa , de Meester Johan M , Ortiz Alberto , Jager Kitty J , Stel Vianda S 
Published: January 2023

ABSTRACT

Background
The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries.

Methods
The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated.

Results
The total KT rate in the 40 participating countries increased with 1.9% annually [95% confidence interval (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East–West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.).

Conclusions
The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.
Objective response rate targets for recurrent glioblastoma clinical trials based on the historic association between objective response rate and median overall survival
Authors: Ellingson Benjamin M , Wen Patrick Y , Chang Susan M , van den Bent Martin , Vogelbaum Michael A , Li Gang , Li Shanpeng , Kim Jiyoon , Youssef Gilbert , Wick Wolfgang , Lassman Andrew B , Gilbert Mark R , de Groot John F , Weller Michael , Galanis Evanthia , Cloughesy Timothy F 
Published: January 2023

Abstract
Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P &lt; .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P &lt; .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P &lt; .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR&gt;25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P &lt; .01) and adequate power (&gt;80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR &gt;25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study.
Histological and molecular classifications of pediatric glioma with time-dependent diffusion MRI-based microstructural mapping
Authors: Zhang Hongxi , Liu Kuiyuan , Ba Ruicheng , Zhang Zelin , Zhang Yi , Chen Ye , Gu Weizhong , Shen Zhipeng , Shu Qiang , Fu Junfen , Wu Dan 
Published: January 2023

Abstract

Background
Gliomas are the most common type of central nervous system tumors in children, and the combination of histological and molecular classification is essential for prognosis and treatment. Here, we proposed a newly developed microstructural mapping technique based on diffusion-time-dependent diffusion MRI td-dMRI theory to quantify tumor cell properties and tested these microstructural markers in identifying histological grade and molecular alteration of H3K27.

Methods
This prospective study included 69 pediatric glioma patients aged 6.14 ± 3.25 years old, who underwent td-dMRI with pulsed and oscillating gradient diffusion sequences on a 3T scanner. dMRI data acquired at varying tds were fitted into a 2-compartment microstructural model to obtain intracellular fraction (fin), cell diameter, cellularity, etc. Apparent diffusivity coefficient (ADC) and T1 and T2 relaxation times were also obtained. H&E stained histology was used to validate the estimated microstructural properties.

Results
For histological classification of low- and high-grade pediatric gliomas, the cellularity index achieved the highest area under the receiver-operating-curve (AUC) of 0.911 among all markers, while ADC, T1, and T2 showed AUCs of 0.906, 0.885, and 0.886. For molecular classification of H3K27-altered glioma in 39 midline glioma patients, cell diameter showed the highest discriminant power with an AUC of 0.918, and the combination of cell diameter and extracellular diffusivity further improved AUC to 0.929. The td-dMRI estimated fin correlated well with the histological ground truth with r = 0.7.

Conclusions
The td-dMRI-based microstructural properties outperformed routine MRI measurements in diagnosing pediatric gliomas, and the different microstructural features showed complementary strength in histological and molecular classifications.
Novel genetically engineered H3.3G34R model reveals cooperation with ATRX loss in upregulation ofHoxacluster genes and promotion of neuronal lineage
Authors: Abdallah Aalaa S , Cardona Herminio J , Gadd Samantha L , Brat Daniel J , Powla Plamena P , Alruwalli Waleed S , Shen Chen , Picketts David J , Li Xiao-Nan , Becher Oren J 
Published: January 2023

AbstractBackgroundPediatric high-grade gliomas (pHGGs) are aggressive pediatric CNS tumors and an important subset are characterized by mutations in H3F3A, the gene that encodes Histone H3.3 (H3.3). Substitution of Glycine at position 34 of H3.3 with either Arginine or Valine (H3.3G34R/V), was recently described and characterized in a large cohort of pHGG samples as occurring in 5–20% of pHGGs. Attempts to study the mechanism of H3.3G34R have proven difficult due to the lack of knowledge regarding the cell-of-origin and the requirement for co-occurring mutations for model development. We sought to develop a biologically relevant animal model of pHGG to probe the downstream effects of the H3.3G34R mutation in the context of vital co-occurring mutations.MethodsWe developed a genetically engineered mouse model (GEMM) that incorporates PDGF-A activation, TP53 loss and the H3.3G34R mutation both in the presence and loss of Alpha thalassemia/mental retardation syndrome X-linked (ATRX), which is commonly mutated in H3.3G34 mutant pHGGs.ResultsWe demonstrated that ATRX loss significantly increases tumor latency in the absence of H3.3G34R and inhibits ependymal differentiation in the presence of H3.3G34R. Transcriptomic analysis revealed that ATRX loss in the context of H3.3G34R upregulates Hoxa cluster genes. We also found that the H3.3G34R overexpression leads to enrichment of neuronal markers but only in the context of ATRX loss.ConclusionsThis study proposes a mechanism in which ATRX loss is the major contributor to many key transcriptomic changes in H3.3G34R pHGGs.Accession numberGSE197988.
Review of progress and challenges of key mechanical issues in high-field superconducting magnets
Authors: Zhou You-He , Park Dongkeun , Iwasa Yukikazu 
Published: January 2023

ABSTRACTThe development of modern science and technology requires high magnetic fields exceeding 25T. Second-generation high-temperature superconducting wires, i.e. REBCO (REBa2Cu3O7-x, RE refers to Y, Gd, Dy, Eu and other rare-earth elements) coated conductors (CCs), have become the first choice for high-field magnet construction because of their high irreversible magnetic field. The mechanical stresses caused by manufacturing, thermal mismatch and Lorenz forces closely influence electromagnetic performance during operation for REBCO CCs. In addition, the recently studied screen currents have effects on the mechanical characteristics of high-field REBCO magnets. In this review, the experimental and main theoretical works on critical current degradation, delamination and fatigue, and shear investigations on REBCO CCs, are reviewed at first. Then, research progress on the screening-current effect in the development of high-field superconducting magnets is introduced. Finally, the key mechanical problems facing the future development of high-field magnets based on REBCO CCs are prospected.
The Role of Emotion Differentiation in the Association Between Momentary Affect and Tobacco/Nicotine Craving in Young Adults
Authors: Walters Kyle J , Gray Kevin M , Gex Kathryn S , McClure Erin A 
Published: January 2023

Abstract

Introduction
Tobacco/nicotine use is commonly initiated during adolescence or young adulthood, which increases the likelihood of continued use into adulthood and related adverse health outcomes. Despite interest in cessation, achieving and maintaining abstinence is difficult among this population. Cravings are often a barrier to abstinence, which have been associated with intensity of affect at the moment level. Emotion differentiation involves the ability to distinguish between discrete emotion states, and previous work suggests it may moderate the effect of momentary affect on craving, which has never been explored among young adults who are smoking or vaping nicotine.

Aims and Methods
In a sample of young adults (N = 37, observations = 2020, ages 18–25, 51% female, and 78% white) interested in quitting smoking or vaping, we used real-time, naturalistic data capture via mobile phones to examine the interaction of momentary affect and trait emotion differentiation on nicotine craving. Participants were prompted with four surveys per day for 35 days and asked to make a 48-h quit attempt on day 7.

Results
Multilevel models showed moments of higher-than-average momentary negative affect (NA; b = 0.39, p &lt; .001), and positive affect (PA; b = 0.26, p = .001) were associated with greater levels of craving. NA emotion differentiation significantly moderated the associations between PA and craving (b = −0.63, p = .031) and NA and craving (b = −0.67, p = .003).

Conclusions
Findings from this exploratory analysis suggest that for young adults engaging in a nicotine quit attempt, greater ability to differentiate NA weakens the momentary association between intense affect and craving.

Implications
Results of this study show that the ability to differentiate between discrete emotional experiences may protect young adults against nicotine craving during moments of intense affective experience. These preliminary findings suggest that emotion differentiation, a modifiable construct, could be an important treatment target for individuals engaged in treatment for nicotine dependence.
Fungal Nomenclature: Managing Change is the Name of the Game
Authors: Kidd Sarah E , Abdolrasouli Alireza , Hagen Ferry 
Published: January 2023

Abstract
Fungal species have undergone and continue to undergo significant nomenclatural change, primarily due to the abandonment of dual species nomenclature in 2013 and the widespread application of molecular technologies in taxonomy allowing correction of past classification errors. These have effected numerous name changes concerning medically important species, but by far the group causing most concern are the Candida yeasts. Among common species, Candida krusei, Candida glabrata, Candida guilliermondii, Candida lusitaniae, and Candida rugosa have been changed to Pichia kudriavzevii, Nakaseomyces glabrata, Meyerozyma guilliermondii, Clavispora lusitaniae, and Diutina rugosa, respectively. There are currently no guidelines for microbiology laboratories on implementing changes, and there is ongoing concern that clinicians will dismiss or misinterpret laboratory reports using unfamiliar species names. Here, we have outlined the rationale for name changes across the major groups of clinically important fungi and have provided practical recommendations for managing change.
In Outpatients Receiving Parenteral Vancomycin, Dosing Adjustments Produced by Area Under the Curve-Based and Trough-Based Monitoring Differ Only at the Extremes of the Therapeutic Trough Range
Authors: Shi Yufei , Alexander Bryan T , Avedissian Sean , Bergman Scott J , Cortés-Penfield Nicolás 
Published: January 2023

Abstract
Area under the curve (AUC)-based vancomycin dosing reduces nephrotoxicity but is burdensome. Reviewing 115 adults receiving ≥2 weeks of outpatient vancomycin, we found AUC-based and trough-based dose adjustments discordant only for troughs &lt;12 or &gt;16 mg/L. Selective versus universal outpatient AUC calculation would likely offer similar benefit with reduced workload.
Efficacy of a Primary Care-Based Mobile Application to Increase Hepatitis C Screening Among Asian Americans: A Secondary Analysis of a Randomized Clinical Trial
Authors: Khalili Mandana , Kim Nicole J , Tsoh Janice Y , Walsh Judith M E , Elizabeth Goldman L , Park Helen , Lau Ivy , Wong Ching , Gildengorin Ginny , Nguyen Tung T 
Published: January 2023

Abstract

Background
Hepatitis C virus (HCV) screening remains suboptimal. We assessed the efficacy of a mobile application and provider alert in enhancing HCV screening among Asian Americans.

Methods
A secondary analysis of a cluster-randomized clinical trial was performed during the birth cohort screening era to assess the efficacy of a Hepatitis App (intervention), a multilingual mobile application delivering interactive video education on viral hepatitis and creating a Provider Alert printout, at primary care clinics within 2 healthcare systems in San Francisco from 2015 to 2017. A comparison group received usual care and a similar intervention on nutrition and physical activity. The outcome was electronic health record (EHR) documentation of HCV screening along with patient-provider communication about testing and test ordering.

Results
Four hundred fifty-two participants (mean age 57 years, 36% male, 80% foreign-born) were randomized by provider clusters to the intervention (n = 270) or comparison groups (n = 182). At 3-month follow up, the intervention group was more likely than the comparison group to be aware of HCV (75% vs 59%, P = .006), to discuss HCV testing with their providers (63% vs 13%, P &lt; .001), to have HCV testing ordered (39% vs 10%, P &lt; .001), and to have EHR-verified HCV testing (30% vs 6%, P&lt; .001). Within the intervention group, being born between 1945 and 1965 (odds ratio, 3.15; 95% confidence interval, 1.35–7.32) was associated with increased HCV testing.

Conclusions
The Hepatitis App delivered in primary care settings was effective in increasing HCV screening in a socioeconomically diverse Asian American cohort. This highlights the importance of mobile technology as a patient-centered strategy to address gaps in HCV care.
Treatment Success Following Standard Antibiotic Treatment for Bacterial Vaginosis Is Not Associated With Pretreatment Genital Immune or Microbial Parameters
Authors: Armstrong Eric , Hemmerling Anke , Joag Vineet , Huibner Sanja , Kulikova Maria , Crawford Emily , Castañeda Gloria R , Anzala Omu , Obila Onyango , Shahabi Kamnoosh , Ravel Jacques , Coburn Bryan , Cohen Craig R , Kaul Rupert 
Published: January 2023

Abstract

Background
Bacterial vaginosis (BV) is a proinflammatory genital condition associated with adverse reproductive health outcomes, including increased HIV incidence. However, BV recurrence rates are high after standard antibiotic treatment. While the composition of the vaginal microbiota before BV treatment may be linked to BV recurrence, it is unclear whether the preceding genital immune milieu is predictive of treatment success.

Methods
Here we assessed whether baseline vaginal soluble immune factors or the composition of the vaginal microbiota predicted treatment success 1 month after metronidazole treatment in 2 separate cohorts of women with BV, 1 in the United States and 1 in Kenya; samples within 48 hours of BV treatment were also available for the US cohort.

Results
Neither soluble immune factors nor the composition of the vaginal microbiota before BV treatment was associated with treatment response in either cohort. In the US cohort, although the absolute abundances of key vaginal bacterial taxa pretreatment were not associated with treatment response, participants with sustained BV clearance had a more pronounced reduction in the absolute abundance of Gardnerella vaginalis immediately after treatment.

Conclusions
Pretreatment immune and microbial parameters were not predictive of BV treatment success in these clinical cohorts.
Infrastructure investment and urban health: Why breaking the cycle of crises is so difficult
Authors: Konvitz Josef W 
Published: January 2023

Abstract
Infrastructure and health, the theme of this journal, are responsible for a major share of GDP. However, GDP alone does not define well-being. Disaggregating the components of GDP, changes over time and variations within countries and social groups, the OECD’s 2013 Better Living Initiative focused on jobs, earning, housing and work–life balance as well as educational attainment, health status and subjective well-being. These indicators took on greater importance as evidence of growing disparities accumulated in the 2010s (OECD, 2013). Under Pressure: The Squeezed Middle Class was not the title of a popular work for the general public, but of a 2019 OECD report for policy- makers. Too often we take the positive, mutual reinforcement of policies and programmes that contribute to well-being for granted. Sectoral silos, which favoured the expansion of public services earlier in the 20th century, now interfere with their delivery [26, 28]. Better policy linkages across sectors remains the holy grail of sound, evidence-based decision-making. It remains aspirational, just out of reach.