bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Prevalence of Antimalarial Resistance Mutations in India During 2014–2015: Impact of Combining First-line Therapy With Primaquine
Authors: Ali Nazia A , Nema Shrikant , Schneider Kristan A , Krishna Sri , Verma Anil Kumar , Das Aparup , Bharti Praveen Kumar 
Published: November 2023

Abstract

Background
Antimalarial drug resistance surveillance and containment are crucial for countries aiming to eliminate malaria. Monitoring resistance evolution through studies before and after treatment policy changes is essential.

Methods
A total of 939 Plasmodium falciparum-positive blood samples were collected between 2014 and 2015 across 10 sites in India, categorized into 4 geographic clusters. Polymerase chain reaction-amplified products were sequenced to identify point mutations at drug resistance-conferring genes (Pfdhfr, Pfdhps, Pfmdr1, and Pfk13).

Results
Triple Pfdhfr mutants were found only in northeast India bordering Myanmar, while the wild type (WT) was dominant in central India. Pfdhps WTs were prevalent in all areas, and no double mutants were found. Except in northwest India, Pfmdr1 WT was dominant in all clusters. Nonsynonymous double mutations were only found in northwest India. Only synonymous mutations occurred in Pfk13. These were found in central India at a low frequency. The pattern of linkage disequilibrium and principal component analysis reflects low pressure for drug resistance and heterogeneity between the geographic clusters.

Conclusions
Resistance levels were highest in northeast India, close to the Myanmar border, where resistance is common. Primaquine has been widely used as a gametocidal and schizonticidal drug, likely contributing to maintaining low drug resistance levels and preventing strong selection for resistance.
Dephosphorylation of NFAT by Calcineurin inhibits Skp2-mediated degradation
Authors: Hanaki Shunsuke , Habara Makoto , Sato Yuki , Tomiyasu Haruki , Miki Yosei , Shibutani Shusaku , Shimada Midori 
Published: November 2023

Abstract
The transcription factor NFAT plays key roles in multiple biological activities, such as immune responses, tissue development and malignant transformation. NFAT is dephosphorylated by calcineurin, which is activated by intracellular calcium levels, and translocated into the nucleus, resulting in transcriptional activation. Calcineurin dephosphorylates various target proteins and regulates their functions. However, the regulation of NFAT degradation is largely unknown, and it is unclear whether calcineurin contributes to the stability of NFAT. We investigated the effect of calcineurin inhibition on NFAT protein stability and found that the dephosphorylation of NFAT by calcineurin promotes the NFAT stabilization, whereas calcineurin mutant that is defective in phosphatase activity was unable to stabilize NFAT. Increased intracellular calcium ion concentration, which is essential for calcineurin activation, also induced NFAT stability. In addition, we identified S-phase kinase associated protein 2 (Skp2), an F-box protein of the SCF ubiquitin ligase complex, as a factor mediating degradation of NFAT when calcineurin was depleted. In summary, these findings revealed that the dephosphorylation of NFAT by calcineurin protects NFAT from degradation by Skp2 and promotes its protein stability.
Exploring the photometric variability of ultra-cool dwarfs with TESS
Authors: Petrucci Romina P , Gómez Maqueo Chew Yilen , Jofré Emiliano , Segura Antígona , Ferrero Leticia V 
Published: November 2023

ABSTRACT
We present a photometric characterization of 208 ultra-cool dwarfs (UCDs) with spectral types between M4 and L4, from 20-s and 2-min cadence TESS light curves. We determine rotation periods for 87 objects ($\sim 42~{{\ \rm per\ cent}}$) and identify 778 flare events in 103 UCDs ($\sim 49.5~{{\ \rm per\ cent}}$). For 777 flaring events (corresponding to 102 objects), we derive bolometric energies between 2.1 × 1030 and $1.1 \times 10^{34}\ \mathrm{erg}$, with 56 superflare events. No transiting planets or eclipsing binaries were identified. We find that the fraction of UCDs with rotation and flaring activity is, at least, 20 per cent higher in M4–M6 spectral types than in later UCDs (M7–L4). For spectral types between M4 and L0, we measure the slope of the flare bolometric energy–duration correlation to be γ = 0.497 ± 0.058, which agrees with that found in previous studies for solar-type and M dwarfs. Moreover, we determine the slope of the flare frequency distribution to be α = −1.75 ± 0.04 for M4–M5 dwarfs, α = −1.69 ± 0.04 and α = −1.72 ± 0.1 for M6–M7 and M8–L0 dwarfs, respectively, which are consistent with previous works that exclusively analysed UCDs. These results support the idea that independently of the physical mechanisms that produce magnetic activity, the characteristics of the rotational modulation and flares are similar for both fully convective UCDs and partially convective solar-type and early-M stars. Based on the measured UCD flare distributions, we find that ultraviolet radiation emitted from flares does not have the potential to start prebiotic chemistry.
Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a
Authors: Sinha Souvik , Molina Vargas Adrian M , Arantes Pablo R , Patel Amun , O’Connell Mitchell R , Palermo Giulia 
Published: November 2023

AbstractCas13a is a recent addition to the CRISPR-Cas toolkit that exclusively targets RNA, which makes it a promising tool for RNA detection. It utilizes a CRISPR RNA (crRNA) to target RNA sequences and trigger a composite active site formed by two ‘Higher Eukaryotes and Prokaryotes Nucleotide’ (HEPN) domains, cleaving any solvent-exposed RNA. In this system, an intriguing form of allosteric communication controls the RNA cleavage activity, yet its molecular details are unknown. Here, multiple-microsecond molecular dynamics simulations are combined with graph theory to decipher this intricate activation mechanism. We show that the binding of a target RNA acts as an allosteric effector, by amplifying the communication signals over the dynamical noise through interactions of the crRNA at the buried HEPN1-2 interface. By introducing a novel Signal-to-Noise Ratio (SNR) of communication efficiency, we reveal critical allosteric residues—R377, N378, and R973—that rearrange their interactions upon target RNA binding. Alanine mutation of these residues is shown to select target RNA over an extended complementary sequence beyond guide-target duplex for RNA cleavage, establishing the functional significance of these hotspots. Collectively our findings offer a fundamental understanding of the Cas13a mechanism of action and pave new avenues for the development of highly selective RNA-based cleavage and detection tools.
The 2024Nucleic Acids Researchdatabase issue and the online molecular biology database collection
Authors: Rigden Daniel J , Fernández Xosé M 
Published: November 2023

AbstractThe 2024 Nucleic Acids Research database issue contains 180 papers from across biology and neighbouring disciplines. There are 90 papers reporting on new databases and 83 updates from resources previously published in the Issue. Updates from databases most recently published elsewhere account for a further seven. Nucleic acid databases include the new NAKB for structural information and updates from Genbank, ENA, GEO, Tarbase and JASPAR. The Issue's Breakthrough Article concerns NMPFamsDB for novel prokaryotic protein families and the AlphaFold Protein Structure Database has an important update. Metabolism is covered by updates from Reactome, Wikipathways and Metabolights. Microbes are covered by RefSeq, UNITE, SPIRE and P10K; viruses by ViralZone and PhageScope. Medically-oriented databases include the familiar COSMIC, Drugbank and TTD. Genomics-related resources include Ensembl, UCSC Genome Browser and Monarch. New arrivals cover plant imaging (OPIA and PlantPAD) and crop plants (SoyMD, TCOD and CropGS-Hub). The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Over the last year the NAR online Molecular Biology Database Collection has been updated, reviewing 1060 entries, adding 97 new resources and eliminating 388 discontinued URLs bringing the current total to 1959 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.
‘To get freedom, one went abroad a lot’: British Homosexual Men and Continental Europe as a Site of Emancipation, 1950–75
Authors: Maclachlan Julia Andrea Erika 
Published: November 2023

Abstract
This article traces the leisure travel of British homosexual men in continental Europe between 1950 and 1975. The aim of this article is to challenge narratives of British post-war sexual rights discourses as isolated from continental Europe. Taking a transnational approach, which examines the ways in which Britain was embedded in processes of social and cultural change across Europe, it charts informal encounters and networks of cultural communication forged by homosexual men themselves during the post-war tourist boom. Using Oral Histories deposited at the British Library Sound Archive, I emphasize the role of homosocial spaces in the production and performance of the sexual self and establish how affluence provided access to spaces for sexual self-development during a period when homosexuality remained criminalized in Britain. It explores two distinct types of holidays taken by homosexual travellers, examined via a life writing approach—the Amsterdam city break and the southern European beach holiday—and shows how these experiences shaped their self-conception and hopes for a more tolerant society at home. In revealing how foreign forms of homosexual sociability influenced domestic politics, I argue for a stronger emphasis on British entanglements with continental Europe when tracing political and social transformations during the post-war period.
Parent Guidance on Alcohol Use for Youth With Chronic Medical Conditions
Authors: Calihan Jessica B. , Minegishi Machiko , Levy Sharon , Weitzman Elissa R. 
Published: November 2023

Purpose
Youth with chronic medical conditions are vulnerable to unique alcohol-related health consequences, yet there are few prevention strategies targeting this group. Youth with chronic medical conditions parents’ beliefs and provision of alcohol-related guidance have not yet been explored, which limits the development of effective family-based interventions.

Methods
We evaluated baseline surveys of youth with chronic medical conditions and their parents (n = 268 dyads) enrolled in a randomized controlled trial of a psychoeducational intervention to reduce alcohol use by youth with chronic medical conditions. Surveys evaluated youth alcohol use, parent beliefs about their child’s alcohol use, and parental provision of alcohol guidance, including disease-related and disease-independent (ie, “drinking and driving”) topics. Paired bivariate tests (χ2, Fisher exact) were used to measure associations between youth with chronic medical conditions alcohol use and parent alcohol-related beliefs and provision of alcohol-related guidance.

Results
In this study of 268 parent-youth dyads, many parents did not provide guidance on disease-specific topics, such as mixing alcohol with medications (47.8%) or risk of flares (37.6%). Furthermore, youth with chronic medical conditions whose parents had expectant beliefs about alcohol use (ie, alcohol use is “inevitable” or “OK with supervision”) were more likely to report alcohol use (all P values <0.05).

Discussion
These findings suggest parent beliefs may influence youth with chronic medical conditions alcohol use. Proactive, disease-specific education from medical providers to parents of youth with chronic medical conditions may help to reduce adverse consequences of alcohol use in these vulnerable youth.
Universal Difference-in-Differences for Causal Inference in Epidemiology
Authors: Tchetgen Tchetgen Eric J. , Park Chan , Richardson David B. 
Published: November 2023

Difference-in-differences is undoubtedly one of the most widely used methods for evaluating the causal effect of an intervention in observational (i.e., nonrandomized) settings. The approach is typically used when pre- and postexposure outcome measurements are available, and one can reasonably assume that the association of the unobserved confounder with the outcome has the same absolute magnitude in the two exposure arms and is constant over time; a so-called parallel trends assumption. The parallel trends assumption may not be credible in many practical settings, for example, if the outcome is binary, a count, or polytomous, as well as when an uncontrolled confounder exhibits nonadditive effects on the distribution of the outcome, even if such effects are constant over time. We introduce an alternative approach that replaces the parallel trends assumption with an odds ratio equi-confounding assumption under which an association between treatment and the potential outcome under no treatment is identified with a well-specified generalized linear model relating the pre-exposure outcome and the exposure. Because the proposed method identifies any causal effect that is conceivably identified in the absence of confounding bias, including nonlinear effects such as quantile treatment effects, the approach is aptly called universal difference-in-differences. We describe and illustrate both fully parametric and more robust semiparametric universal difference-in-differences estimators in a real-world application concerning the causal effects of a Zika virus outbreak on birth rate in Brazil.
A supplementary digital video is available at: http://links.lww.com/EDE/C90
Mass Probation: Effects of Sentencing Severity on Mental Health for Black and White Individuals
Authors: LeMasters Katherine , Ross Rachael K. , Edwards Jessie K. , Lee Hedwig , Robinson Whitney R. , Brinkley-Rubinstein Lauren , Delamater Paul , Pence Brian W. 
Published: November 2023

Background:
Incarceration is associated with negative impacts on mental health. Probation, a form of community supervision, has been lauded as an alternative. However, the effect of probation versus incarceration on mental health is unclear. Our objective was to estimate the impact on mental health of reducing sentencing severity at individuals’ first adult criminal–legal encounter.

Methods:
We used the US National Longitudinal Survey on Youth 1997, a nationally representative dataset of youth followed into their mid-thirties. Restricting to those with an adult encounter (arrest, charge alone or no sentence, probation, incarceration), we used parametric g-computation to estimate the difference in mental health at age 30 (Mental Health Inventory-5) if (1) everyone who received incarceration for their first encounter had received probation and (2) everyone who received probation had received no sentence.

Results:
Among 1835 individuals with adult encounters, 19% were non-Hispanic Black and 65% were non-Hispanic White. Median age at first encounter was 20. Under hypothetical interventions to reduce sentencing, we did not see better mental health overall (Intervention 1, incarceration to probation: RD = −0.01; CI = −0.02, 0.01; Intervention 2, probation to no sentence: RD = 0.00; CI = −0.01, 0.01) or when stratified by race.

Conclusion:
Among those with criminal–legal encounters, hypothetical interventions to reduce sentencing, including incremental sentencing reductions, were not associated with improved mental health. Future work should consider the effects of preventing individuals’ first criminal–legal encounter.
Characterizing Extreme Phenotypes for Perceived Improvement From Treatment in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project
Authors: Hoffman Jeanne M. , Ketchum Jessica M. , Agtarap Stephanie , Dams-O'Connor Kristen , Hammond Flora M. , Martin Aaron M. , Sevigny Mitch , Walker William C. , Harrison-Felix Cynthia , Zafonte Ross , Nakase-Richardson Risa 
Published: November 2023

Objective:
To define and characterize extreme phenotypes based on perceived improvement in pain for persons with chronic pain following traumatic brain injury (TBI).

Setting:
Eighteen Traumatic Brain Injury Model System (TBIMS) Centers.

Participants:
A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview.

Primary Measures:
The Patient's Global Impression of Change (PGIC) related to pain treatment. Sociodemographic, injury, functional outcome, pain, and pain treatment characteristics.

Results:
Participants were mostly male (73%), White (75%), middle-aged (mean 46 years), injured in motor vehicle accidents (53%), or falls (20%). Extreme phenotypes were created for an extreme improvement phenotype (n = 512, 29.8%) defined as “moderately better” or above on the PGIC and an extreme no-change group (n = 290, 16.9%) defined as no change or worse. Least absolute shrinkage and selection operator (LASSO) regression combined with logistic regression identified multivariable predictors of improvement versus no-change extreme phenotypes. Higher odds of extreme improvement phenotype were significantly associated with being female (odds ratio [OR] = 1.85), married versus single (OR = 2.02), better motor function (OR = 1.03), lower pain intensity (OR = 0.78), and less frequent pain, especially chest pain (OR = 0.36). Several pain treatments were associated with higher odds of being in the extreme improvement versus no-change phenotypes including pain medication (OR = 1.85), physical therapy (OR = 1.51), yoga (OR = 1.61), home exercise program (OR = 1.07), and massage (OR = 1.69).

Conclusion:
Investigation of extreme phenotypes based on perceived improvement with pain treatment highlights the ability to identify characteristics of individuals based on pain treatment responsiveness. A better understanding of the biopsychosocial characteristics of those who respond and do not respond to pain treatments received may help inform better surveillance, monitoring, and treatment. With further research, the identification of risk factors (such as pain intensity and frequency) for treatment response/nonresponse may provide indicators to prompt changes in care for individuals with chronic pain after TBI.
Advancing home-like environments for memory care residents within nursing homes
Authors: Strickfaden Megan , Welch Orsolya 
Published: November 2023

Abstract

Objective:
This article reports on 5 specialized memory care environments within nursing homes in Canada through the theory of affordances with the aim of understanding the layered implications of affordances on memory care residents by curating objects within and configuring or designing spatial environments.

Methods:
A spatial/object-centric approach was taken by using a detailed analysis framework based on a robust interpretation of the theory of affordances and well-known elements, principles, and physical/construction properties of interior and spatial design. A web content analysis method, using hundreds of photographs, drawings, and textual information belonging to 5 nursing homes posted on websites and on social media, was used.

Results:
The results include a detailed analysis framework informed by affordance theory and 3 themes that reveal details about the designed environments. The 3 themes are: (1) how contextual factors of affordances of place and care played out, (2) how physical, cultural, and semantic affordances aided or detracted from memory care, and (3) how home-like environments with public, semiprivate, and private spaces involved multiple affordances and constraints that provided multisensory clues towards supporting and/or limiting memory care residents’ possible actions.

Conclusions:
We conclude that although affordances can open a range of possible actions, they are not ideal for configuring or designing home-like environments, and it is necessary for memory care residents to be presented with constraints that limit alternatives and misaffordances. This article provides evidence about how affordances and constraints are (and could be) intentionally embedded in home-like memory care environments in nursing homes.
Agreement Between the Gross Motor Ability Estimator-2 and the Gross Motor Ability Estimator-3 in Young Children With Cerebral Palsy
Authors: Pierce Samuel R. , Skorup Julie , Kolobe Thubi H. A. , Smith Beth A. , Prosser Laura A. 
Published: November 2023

Purpose:
The purpose of this study was to determine the agreement between Gross Motor Ability Estimator-2 (GMAE-2) and Gross Motor Ability Estimator-3 (GMAE-3) calculations of Gross Motor Function Measure-66 (GMFM-66) scores in infants and young children with cerebral palsy.

Methods:
Data from 53 children 5 to 53 months of age were analyzed. Agreement between GMFM-66 scores using the GMAE-2 and the GMAE-3 was calculated using Bland-Altman plots and interclass correlation coefficients (ICCs). Eleven participants who had at least 1 GMFM-66 score of less than 25 using either method were identified for further analysis.

Results:
The average difference between GMFM-66 scores was 0.27 for all participants and 0.63 for the subset of lower-scoring participants. Good agreement was found for GMFM-66 scores for all participants (ICC = 0.998) and for subset of lower-scoring participants (ICC = 0.879).

Conclusions:
High levels of agreement exist between the GMAE-2 and the GMAE-3, which suggests that scores are comparable using either algorithm.
Hot Topic: A Systematic Review and Content Analysis of Heat-Related Messages During the 2021 Heat Dome in Canada
Authors: Tetzlaff Emily J. , Goulet Nicholas , Gorman Melissa , Richardson Gregory R. A. , Enright Paddy M. , Meade Robert D. , Kenny Glen P. 
Published: November 2023

Context:
During the summer of 2021, western Canada experienced a deadly heat event. From the first heat alert to postevent reporting, thousands of media articles were published that reference the heat event. However, a gap remains in understanding how this communication chain—from the release of a public heat alert to information shared through media outlets to the public—currently operates to disseminate heat-related messaging across Canada.

Objective:
To understand the role of digital media in delivering heat-health messaging during an extreme heat event in Canada.

Design:
A qualitative content analysis was conducted using Canadian news articles published on the 2021 Heat Dome between June 2021 and February 2022 (n = 2909). The coding frame was designed to align with the basic framework for information gathering used in journalism (who, what, where, when, and how) and included both concept-driven and data-driven codes.

Results:
Overall, 2909 unique media articles discussing the 2021 Heat Dome were identified, with the majority (74%) published by online news agencies (how). The highest article count was on June 29, 2021 (n = 159), representing 5% of the total data set (n = 2909) spanning 260 days (when); 57% of the identified locations were in British Columbia (where). Although we found that the top voices providing media-based heat-health messages are government officials (who), only 23% of articles included heat-health messaging that aligns with the government health alert bulletins released during extreme heat. In addition, heat-health messaging frequently included contradictory content, inconsistent language, or incorrect advice (what).

Conclusion:
The findings demonstrate clear opportunities to improve health communication related to extreme heat, perhaps most importantly, including updates to mass media messaging educating the public on heat-protective behaviors.