bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein stability governed by α1–2 helices in Pvr4 is essential for localization and cell death
Authors: Lee Hye‐Young , Choi Jeen , Kang Minji , Lee Joo Hyun , Kim Myung‐Shin , Choi Doil 
Published: July 2023

SUMMARYPlant nucleotide‐binding domain leucine‐rich‐repeat receptor (NLR) confers disease resistance to various pathogens by recognizing effectors derived from the pathogen. Previous studies have shown that overexpression of the CC domain in several NLRs triggers cell death, implying that the CC domain plays an important role as a signaling module. However, how CC domain transduces immune signals remains largely unknown. A Potyvirus‐resistant NLR protein, Pvr4, possesses a CC domain (CCPvr4) that induces cell death upon transient overexpression in Nicotiana benthamiana. In this study, loss‐of‐function mutants were generated by error‐prone PCR‐based random mutagenesis to understand the molecular mechanisms underlying CCPvr4‐mediated cell death. Cell biology and biochemical studies revealed that M16 and Q52 in the α1 and α2 helices, respectively, are crucial for protein stability, and mutation of these residues disrupts localization to the plasma membrane and oligomerization activity. The increase of the protein stability of these mutants by tagging a green fluorescent protein (GFP) variant led to restoration of cell death‐inducing activity and plasma membrane localization. Another mutant, I7E in the very N‐terminal region, lost cell death‐inducing activity by weakening the interaction with plasma membrane H+‐ATPase compared to CCPvr4, although the protein remained in the plasma membrane. Moreover, most of the mutated residues are on the outer surface of the funnel shape in the predicted pentameric CCPvr4, implying that the disordered N‐terminal region plays a crucial role in association with PMA as well as targeting to the plasma membrane. This work could provide insights into the molecular mechanisms of cell death induced by NLR immune receptors.
Evaluation of residual antibacterial effects on canine skin surface and hair following treatment with five commercial mousse products againstStaphylococcus pseudintermedius
Authors: Wu Chi‐Yen , Parsiola Rebecca , Mitchell Mark , Mitchell Maria , Ramos Sara , Ravera Ivan , Pucheu‐Haston Cherie 
Published: July 2023

AbstractBackgroundAntibacterial effect studies of commercial antiseptics typically have evaluated hair and not the skin.ObjectivesTo evaluate the antibacterial effects of mousse products on both canine skin and hair.AnimalsFifteen short‐haired and eight long‐haired dogs without skin disease.Materials and MethodsFive mousses were applied once: (1) 2% chlorhexidine and 2% miconazole; (2) 0.05% phytosphingosine; (3) 2% salicylic acid and 10% ethyl lactate; (4) 3% chlorhexidine and 0.5% climbazole; and (5) 2% chlorhexidine and 1% ketoconazole. Skin swabs and hair were collected from application sites before treatment, and at 1 h and at Day (D)2, D4, D8, D10 and D14 post‐treatment. Skin swabs and hair were placed on Mueller–Hinton plates inoculated withStaphylococcus pseudintermediusinoculum suspension. Inhibition zones were measured after incubation.ResultsInhibition was not noted with mousses 2 and 3. In mousse 5, inhibition zone sizes produced by swabs from long‐ and short‐haired dogs were not significantly different (p = 0.105), and all swabs and hair produced inhibition until D14, regardless of hair length. By contrast, in mousse 1, inhibition zones produced by swabs from long‐haired dogs were smaller than those from short‐haired dogs (p < 0.001), and swabs from long‐haired dogs produced a shorter duration of bacterial inhibition than hair.Conclusions and Clinical RelevanceThe antibacterial effects of mousse 5 were not affected by hair length. Hair may be acceptable for evaluating effects on the skin in short‐haired dogs. However, long hair may interfere with product distribution and duration of bacterial inhibition. Therefore, the evaluation of hair alone may overestimate clinically relevant antibacterial effects.
Wildly ramified rigid G2$G_2$‐local systems
Authors: Jakob Konstantin 
Published: July 2023

AbstractIn earlier work of the author, rigid irregular connections with differential Galois group and whose slopes have numerator 1 were classified and new rigid connections were constructed. The same construction can be carried out for ‐adic local systems in the setting of positive characteristic. In this article, we provide the results that are needed to obtain the classification of wildly ramified rigid ‐local systems whose slopes have numerator 1. The overall strategy of the classification is very similar but the methods needed to obtain some invariants differ.
Characterization of critical health promotion: a scoping review protocol
Authors: Fincham Susanne , O’Hara Lily , Cole Rachel , Taylor Jane 
Published: July 2023

Objective:
This scoping review will explore how critical health promotion is characterized in the health promotion literature.

Introduction:
Critical health promotion has emerged as a social justice approach to health promotion to address the persistent global issue of health inequity. Whilst critical health promotion is not conceptually new and the term has been used in the literature, albeit sparingly, this approach has not been adopted as standard health promotion practice, compromising the advancement of health equity. Given that language shapes the understanding and practice of health promotion, it is imperative to explore how critical health promotion is characterized in the literature to increase uptake of the approach.

Inclusion criteria:
This review will consider sources that explore critical health promotion and are explicitly positioned as health promotion sources.

Methods:
Scopus, CINAHL (EBSCOhost), PubMed, Global Health (CABI), and the Public Health Database (ProQuest) will be searched to identify relevant full-text papers, including original research, reviews, editorials, and opinion papers. Searches of Google Scholar, Google, and ProQuest Dissertations & Theses Global (ProQuest) will be undertaken to identify gray literature. No language or date restrictions will be applied. Two reviewers will screen sources and extract data using a tool that will be pilot tested, modified, and revised, as necessary. Analysis will involve basic frequency counts and descriptive qualitative content analysis through basic coding. The results will be presented in tables, charts, and word clouds, accompanied by a narrative summary.
Entorno laboral de enfermería en un hospital de Bogotá, 2022
Authors: Arango Bayer Gloria Lucía , PEÑA ALFARO BAIRON , Alvarez Hernández Sindy Lorena 
Published: July 2023

Introducción: La preocupación por el entorno laboral en enfermería se ha hecho aun mayor desde la pandemia Covid-19, que afectó la cantidad y calidad del personal de enfermería alrededor del mundo. Objetivo. Describir el entorno laboral de los enfermeros que desempeñan funciones asistenciales en un hospital de Bogotá, Colombia. Método: Estudio descriptivo exploratorio, con un componente correlacional. Se remitió el cuestionario ENLASA a todos los enfermeros asistenciales del hospital objeto de estudio a través de RedCapÒ. Resultados. El cuestionario completo fue respondido por el 50% de los enfermeros asistenciales (49 enfermeros) de la institución e invitados a participar en el estudio. El 57,1% de los respondientes consideró el entorno laboral no saludable. La dimensión de elementos estructurales se consideró no saludable (64,49/100), y la de procesos organizacionales como saludable (71,18/100). Las subdimensiones no saludables fueron, en estructura, la planeación del recurso de enfermería, (54,66/100) y políticas de recursos humanos (58,91/100) y en procesos, la interacción enfermero-organización (63,10/100) y autonomía (66,07/100). No se encontró asociación entre las variables sociodemográficas y el entorno laboral de enfermería. La única asociación estadísticamente significativa entre entorno laboral y resultados fue la relativa a la motivación para trabajar. (Phi 0,362, p=0,040). Conclusiones. Se sugiere intervenir las dimensiones y subdimensiones identificadas como no saludables, y continuar monitoreando este fenómeno.
Entre omisiones y silencios. Reflexiones en relación a la construcción discursiva del “yo trabajadora” del ama de casa en políticas sociales argentinas
Authors: Pizarro Tatiana Marisel 
Published: July 2023

Este artículo explora aquellas políticas sociales que tienen y tuvieron al ama de casa como merecedora de haberes previsionales en Argentina, durante el periodo 2004-2016. Se pretende observar hasta qué punto estas medidas cumplen con los objetivos propuestos a partir de un análisis del discurso institucional legislativo y sus planteamientos originales.
La propuesta metodológica de esta investigación es cualitativa y su abordaje es desde el Análisis Crítico del Discurso –ACD- bajo los lineamientos de Fairclough y Wodak (2000) y Burman y Parker (1993). Los textos y los diarios de sesiones analizados corresponden a las leyes 25.994 –Plan de Inclusión Previsional-, 26.970 -2da etapa del Plan de Inclusión Previsional- y 27.260 –Pensión Universal para el Adulto Mayor-, tales han sido seleccionados para observar cómo se construye discursivamente la mujer trabajadora derivada de su papel como ama de casa. De éstas se extrajeron las construcciones discursivas más relevantes de la muestra mencionada.
Hepatitis delta virus RNA decline post-inoculation in human NTCP transgenic mice is biphasic
Authors: Maya Stephanie , Hershkovich Leeor , Cardozo-Ojeda E. Fabian , Shirvani-Dastgerdi Elham , Srinivas Jay , Shekhtman Louis , Uprichard Susan L. , Berneshawi Andrew R. , Cafiero Thomas R. , Dahari Harel , Ploss Alexander 
Published: July 2023

ABSTRACT
Chronic infection with hepatitis B and delta viruses (HDV) is the most serious form of viral hepatitis due to more severe manifestations of an accelerated progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma. We characterized early HDV kinetics post-inoculation and incorporated mathematical modeling to provide insights into host-HDV dynamics. We analyzed HDV RNA serum viremia in 192 immunocompetent (C57BL/6) and immunodeficient (NRG) mice that did or did not transgenically express the HDV receptor—human sodium taurocholate co-transporting polypeptide (hNTCP). Kinetic analysis indicates an unanticipated biphasic decline consisting of a sharp first-phase and slower second-phase decline regardless of immunocompetence. HDV decline after re-inoculation again followed a biphasic decline; however, a steeper second-phase HDV decline was observed in NRG-hNTCP mice compared to NRG mice. HDV-entry inhibitor bulevirtide administration and HDV re-inoculation indicated that viral entry and receptor saturation are not major contributors to clearance, respectively. The biphasic kinetics can be mathematically modeled by assuming the existence of a non-specific-binding compartment with a constant on/off-rate and the steeper second-phase decline by a loss of bound virus that cannot be returned as free virus to circulation. The model predicts that free HDV is cleared with a half-life of 35 minutes (standard error, SE: 6.3), binds to non-specific cells with a rate of 0.05 per hour (SE: 0.01), and returns as free virus with a rate of 0.11 per hour (SE: 0.02). Characterizing early HDV-host kinetics elucidates how quickly HDV is either cleared or bound depending on the immunological background and hNTCP presence.

IMPORTANCE

The persistence phase of HDV infection has been studied in some animal models; however, the early kinetics of HDV
in vivo
is incompletely understood. In this study, we characterize an unexpectedly HDV biphasic decline post-inoculation in immunocompetent and immunodeficient mouse models and use mathematical modeling to provide insights into HDV-host dynamics.
Hemin availability induces coordinated DNA methylation and gene expression changes in
Porphyromonas gingivalis
Authors: Costeira Ricardo , Aduse-Opoku Joseph , Vernon Jon J. , Rodriguez-Algarra Francisco , Joseph Susan , Devine Deirdre A. , Marsh Philip D. , Rakyan Vardhman , Curtis Michael A. , Bell Jordana T. 
Published: July 2023

ABSTRACT

Periodontal disease is a chronic inflammatory disease in which the oral pathogen
Porphyromonas gingivalis
plays an important role.
Porphyromonas gingivalis
expresses virulence determinants in response to higher hemin concentrations, but the underlying regulatory processes remain unclear. Bacterial DNA methylation has the potential to fulfil this mechanistic role. We characterized the methylome of
P. gingivalis
, and compared its variation to transcriptome changes in response to hemin availability.
Porphyromonas gingivalis
W50 was grown in chemostat continuous culture with excess or limited hemin, prior to whole-methylome and transcriptome profiling using Nanopore and Illumina RNA-Seq. DNA methylation was quantified for Dam/Dcm motifs and all-context N6-methyladenine (6mA) and 5-methylcytosine (5mC). Of all 1,992 genes analyzed, 161 and 268 were respectively over- and under-expressed with excess hemin. Notably, we detected differential DNA methylation signatures for the Dam “GATC” motif and both all-context 6mA and 5mC in response to hemin availability. Joint analyses identified a subset of coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify altered methylation and expression responses to hemin availability in
P. gingivalis
, with insights into mechanisms regulating its virulence in periodontal disease.

IMPORTANCE

DNA methylation has important roles in bacteria, including in the regulation of transcription.
Porphyromonas gingivalis
, an oral pathogen in periodontitis, exhibits well-established gene expression changes in response to hemin availability. However, the regulatory processes underlying these effects remain unknown. We profiled the novel
P. gingivalis
epigenome, and assessed epigenetic and transcriptome variation under limited and excess hemin conditions. As expected, multiple gene expression changes were detected in response to limited and excess hemin that reflect health and disease, respectively. Notably, we also detected differential DNA methylation signatures for the Dam “GATC” motif and both all-context 6mA and 5mC in response to hemin. Joint analyses identified coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify novel regulatory processes underlying the mechanism of hemin regulated gene expression in
P. gingivalis,
with phenotypic impacts on its virulence in periodontal disease.
Disruption to routine diabetes care processes during the pandemic: evidence from a large integrated health system in the Southeast United States
Authors: Harding Jessica L , Wang Yanan , McDonald Bennett , Gander Jennifer C , Oviedo Sofia A , Ali Mohammed K 
Published: July 2023

IntroductionWe investigated the impact of the COVID-19 pandemic on annual adherence to seven diabetes care guidelines and risk factor management among people with diabetes.Research design and methodsWe included all adults (aged ≥18 years) with prevalent diabetes as of 1 January 2018, who were continuously enrolled at Kaiser Permanente Georgia (KPGA) through 31 December 2021 (n=22 854). Prevalent diabetes was defined as a history of at least one of a diagnosis code for diabetes, use of antihyperglycemic medication, or at least one laboratory value of HbA1c, fasting plasma glucose or random glucose in the diabetic range. We defined pre-COVID (2018–2019) and during COVID (2020–2021) cohorts. Cohort-specific laboratory measurements (ie, blood pressure (BP), HbA1c, cholesterol, creatinine, urine-albumin-creatinine ratio (UACR)) and procedures (ie, eye and foot examinations) were determined from KPGA’s electronic medical record data. We used logistic generalized estimating equations (GEE), adjusted for baseline age, to assess the within-subject change in guideline adherence (ie, at least one measurement per year per period) from pre-COVID to during COVID era overall, and by age, sex, and race. Linear GEE compared mean laboratory measurements pre and during COVID.ResultsThe proportion of adults meeting each of the seven diabetes care guidelines decreased significantly during (vs pre) COVID (range in absolute reductions: −0.8% to −11.2%) with greatest reductions seen for BP (−11.2%) and cholesterol (−8.8%). Declines were similar across age, sex, and race subgroups. Average HbA1c and systolic BP increased 0.11% and 1.6 mmHg, respectively, while low-density lipoprotein cholesterol declined 8.9 mg/dL. The proportion of adults at high risk of kidney disease (ie, UACR ≥300 mg/g) increased from 6.5% to 9.4%.ConclusionsIn an integrated healthcare system, the proportion of people with diabetes meeting guideline-recommended screenings decreased during the pandemic, coinciding with worsening glucose, kidney, and (some) cardiovascular risk profiles. Follow-up is needed to assess the long-term implications of these care gaps.
Did children’s symptoms and infections decline during the COVID-19 pandemic? A comparison of parental reports before and during the pandemic from a birth cohort study in New Hampshire, USA
Authors: Peacock Janet L , Diaz-Coto Susana , Sayarath Vicki , Madan Juliette , Karagas Margaret 
Published: July 2023

BackgroundRestrictive measures were widely introduced at the start of the COVID-19 pandemic to reduce the spread of the virus. These restrictions have been linked to reductions in laboratory-diagnosed infections and hospitalisations. It is unclear if the observed decreases reflect a reduction in health-seeking behaviour or results from fewer infections per se.MethodsWe have explored trends in caregiver reports of respiratory infections and symptoms needing a doctor visit in children aged 0–11 years using data from the New Hampshire Birth Cohort Study in 2011–2021, comparing the prepandemic and pandemic periods. Generalized Estimating Equations were used to model pandemic/prepandemic risk ratios (RRs) with adjustment for maternal and child characteristics.ResultsThe overall probability of a report of an upper respiratory tract infection (RTI) needing a doctor visit in children aged 0–11 years was 16.7%. There was strong evidence of a decline during the pandemic: 17.9% pre pandemic versus 8.19% in the pandemic period, adjusted RR 0.51 (95% CI: 0.42 to 0.64). Similar trends were seen for any lower RTI, any respiratory symptom and any other acute symptom with overall probabilities of 4.33%, 24.8% and 13.8%, respectively, and adjusted rate ratios 0.61 (0.41 to 0.91), 0.59 (0.51 to 0.68) and 0.72 (0.59 to 0.87), respectively. In contrast, respiratory syncytial virus and bronchiolitis remained steady.ConclusionsThe steep decline in caregiver-reported infections and symptoms mirrored trends reported in laboratory-diagnosed infections and hospitalisations and suggests a real decrease in prevalence. Longer follow-up is needed to determine later consequences of the reduction in childhood infections.
Combination oncolytic virus, radiation therapy, and immune checkpoint inhibitor treatment in anti-PD-1-refractory cancer
Authors: Jhawar Sachin R , Wang Shang-Jui , Thandoni Aditya , Bommareddy Praveen K , Newman Jenna H , Giurini Eileena F , Marzo Amanda L , Kuzel Timothy M , Gupta Vineet , Reiser Jochen , Daniels Preston , Schiff Devora , Mitchell Darrion , LeBoeuf Nicole R , Simmons Christopher , Goyal Sharad , Lasfar Ahmed , Guevara-Patino Jose A , Haffty Bruce G , Kaufman Howard L , Silk Ann W , Zloza Andrew 
Published: July 2023

BackgroundImmunotherapies are becoming front-line treatments for many advanced cancers, and combinations of two or more therapies are beginning to be investigated. Based on their individual antitumor capabilities, we sought to determine whether combination oncolytic virus (OV) and radiation therapy (RT) may improve cancer outcomes.MethodsTo investigate the activity of this combination therapy, we used in vitro mouse and human cancer cell lines as well as a mouse model of skin cancer. After initial results, we further included immune checkpoint blockade, whose addition constituted a triple combination immunotherapy.ResultsOur findings demonstrate that OV and RT reduce tumor growth via conversion of immunologically ‘cold’ tumors to ‘hot’, via a CD8+ T cell-dependent and IL-1α-dependent mechanism that is associated with increased PD-1/PD-L1 expression, and the triple combination of OV, RT, and PD-1 checkpoint inhibition impedes tumor growth and prolongs survival. Further, we describe the response of a PD-1-refractory patient with cutaneous squamous cell carcinoma who received the triple combination of OV, RT, and immune checkpoint inhibitor (ICI), and went on to experience unexpected, prolonged control and survival. He remains off-treatment and is without evidence of progression for >44 months since study entry.ConclusionsEffective systemic antitumor immune response is rarely elicited by a single therapy. In a skin cancer mouse model, we demonstrate improved outcomes with combination OV, RT, and ICI treatment, which is associated with mechanisms involving augmented CD8+ T cell infiltration and IL-1α expression. We report tumor reduction and prolonged survival of a patient with skin cancer treated with combination OV, RT, and ICI. Overall, our data provide strong rationale for combining OV, RT, and ICI for treatment of patients with ICI-refractory skin and potentially other cancers.
Cosmological perturbations engendered by discrete relativistic species
Authors: Brilenkov Maksym , Canay Ezgi , Eingorn Maxim 
Published: July 2023

AbstractWithin the extension of the $$\varLambda $$
Λ
CDM model, allowing for the presence of neutrinos or warm dark matter, we develop the analytical cosmological perturbation theory. It covers all spatial scales where the weak gravitational field regime represents a valid approximation. Discrete particles – the sources of the inhomogeneous gravitational field – may be relativistic. Similarly to the previously investigated case of nonrelativistic matter, the Yukawa interaction range is naturally incorporated into the first-order scalar metric corrections.