bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a novel variant allele, HLA‐C*03:587, identified in a Chinese Han individual
Authors: He Liu‐Mei , Yang Xiao‐Ke , Zou Hong‐Yan
Published: March 2022

The novel HLA‐C*03:587 allele differs from the closest allele C*03:03:01:01 in exon 5.
Nurses' sources of information to inform clinical practice: An integrative review to guide evidence‐based practice
Authors: Fossum Mariann , Opsal Anne , Ehrenberg Anna
Published: March 2022

Background

Evidence‐based practice in nursing is challenging and relies on the sources of information used by nurses to inform clinical practice. An integrative review from 2008 revealed that nurses more frequently relied on information from colleagues than information from high‐level sources such as systematic reviews and evidence‐based clinical practice guidelines.

Aims

To describe the information sources used by registered nurses to inform their clinical practice.

Methods

An integrative review was conducted according to the PRISMA guidelines, based on empirical research studies published from January 2007 until June 2021. The included studies were appraised, following which the identified sources of information from quantitative studies were compiled and ranked. Finally, the qualitative text data were summarized into categories.

Results

Fifty‐two studies from various countries were included. The majority of studies employed a quantitative design and used original instruments. Peers were ranked as the number one source of information to inform nurses' clinical practice. However, computers and reference materials are now ranked among the top four most used information sources.

Linking Evidence to Action

Improvement in computer and information searching skills, as well as the availability of computerized decision support tools, may contribute to nurses' frequent use of digital sources and reference material to inform clinical practice. This review shows that nurses' most frequently reported peer nurses as their source of information in clinical practice. Information sources such as computers and reference materials were ranked higher, and information from patients was ranked lower than in the 2008 review. Developing and standardizing instruments and ensuring high‐quality study design is critical for further research on nurses’ sources of information for clinical practice.
The HVCN1 voltage‐gated proton channel contributes to pH regulation in canine ventricular myocytes
Authors: Ma Jianyong , Gao Xiaoqian , Li Yutian , DeCoursey Thomas E. , Shull Gary E. , Wang Hong‐Sheng
Published: March 2022

Regulation of intracellular pH (pHi) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage‐sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+, while avoiding Na+ loading, as occurs during direct acid extrusion via Na+/H+ exchange or indirect acid extrusion via Na+–HCO3− cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage‐gated H+ current that was highly H+‐selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5‐chloro‐2‐guanidinobenzimidazole. Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1‐mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+/H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+ extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+‐independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport‐mediated CO2 disposal.

Key points

Intracellular pH (pHi) regulation is crucial for cardiac function, as acidification depresses contractility and causes arrhythmias. H+ ions are generated in cardiomyocytes from metabolic processes and particularly from CO2 hydration, which has been shown to facilitate CO2 venting from mitochondria.

Currently, the NHE1 Na+/H+ exchanger is viewed as the dominant H+ extrusion mechanism in cardiac muscle.

We show that the HVCN1 voltage‐gated proton channel is present and functional in canine ventricular myocytes, and that HVCN1 and NHE1 both contribute to pHi regulation.

HVCN1 provides an energetically efficient mechanism of H+ extrusion that would not cause Na+ loading, which can cause pathology, and that could contribute to transport‐mediated CO2 disposal.

These results provide a major advance in our understanding of pHi regulation in cardiac muscle.
Factores asociados con el cumplimiento de las precauciones de contacto en un hospital de alto nivel de complejidad
Authors: Arango Castrillón Laura
Published: March 2022

Introducción: La prevención de infecciones intrahospitalarias es uno de los aspectos más inquietantes en enfermería en los últimos años. Para esto, se han establecido diversas estrategias, entre ellas, los aislamientos hospitalarios. Sin embargo, se encuentra gran dificultad para el cumplimiento de las medidas de aislamiento. Objetivo: Determinar los factores sociodemográficos y de la atención en salud relacionados con el cumplimiento de las precauciones de contacto por parte de los visitantes en un hospital de alta complejidad de la ciudad de Medellín. Método: Se realizó un estudio descriptivo de corte trasversal a un total de 126 visitantes de pacientes aislados por contacto. Se identificaron factores asociados al cumplimiento del aislamiento mediante una encuesta, se analizó la información en el programa SPSS mediante una regresión logística y se asumió significancia estadística si valor P menor a 0,05. Resultados: La adherencia total al aislamiento fue de un 40,5 % y está asociada principalmente con dos factores: disponibilidad de los elementos de protección y estar de acuerdo con el uso de estos. Conclusiones: Los factores mejor asociados con el cumplimiento del aislamiento hacen necesario que las instituciones garanticen suficientes insumos para los visitantes y que tanto el personal de salud como los visitantes reciban una mayor sensibilización en este tema.
Percepción sobre actividades de enfermería para satisfacción de necesidades familiares en cuidado intensivo adulto
Authors: Ardila Suárez Edinson Fabian , Salazar Blandon Diego Alejandro
Published: March 2022

Introducción: la satisfacción de las necesidades de la familia en una unidad de cuidado intensivo (UCI) hace parte integral del cuidado del paciente críticamente enfermo y trae beneficios al paciente, la familia y la institución. Objetivo: describir la percepción sobre la frecuencia, pertinencia y viabilidad de actividades de cuidado de enfermería para la satisfacción de las necesidades familiares en UCI. Método: estudio cuantitativo, descriptivo, transversal, realizado a 75 profesionales de enfermería en UCI en un departamento colombiano, mediante muestreo no probabilístico en 11 instituciones hospitalarias de nivel III y IV; la información se recolectó en un periodo de 3 meses, y se aplicó un cuestionario ad hoc diseñado a partir de una revisión integrativa, el cual pasó pruebas por expertos y una prueba piloto; el análisis estadístico se realizó mediante el software SPSS 25.0 y los gráficos mediante el software R, adoptándose como punto de referencia en el análisis una percepción igual o superior al 75 %. Resultados: 75 profesionales de enfermería en UCI perciben que, de las 63 actividades propuestas por el cuestionario, 16 se realizan con mayor frecuencia, 27 son muy pertinentes y 24 muy viables. Conclusiones: según los enfermeros de UCI encuestados, basados en la frecuencia, pertinencia y viabilidad, las actividades de mayor importancia son las de satisfacción de las necesidades de seguridad, seguidas de las de información y proximidad, y finalizando por el apoyo y el confort.
Prevención de la amputación en pacientes con pie diabético Prevention of amputation in patients with diabetic foot - Prevenção de amputação em pacientes com pé diabético
Authors: Mateus Laura , Díaz Angarita María Paula , Neira López Caren Lorena , Pimienta de la Hoz María Camila , Salamanca Zamora Geraldine Stefany , Castiblanco Montañez Ruth Alexandra
Published: March 2022

Introducción: las intervenciones estratégicas para reducir las tasas de amputación y mejorar la sobrevida de los pacientes con Diabetes Mellitus parte de la prevención, es decir, de la educación del paciente sobre los factores de riesgo y el tratamiento multidisciplinario de las heridas. Objetivo: describir cuáles son las intervenciones efectivas para prevenir la amputación en pacientes con pie diabético. Metodología: revisión integrativa de la literatura. Se incluyeron artículos en español, inglés y portugués de cualquier nacionalidad y diseño metodológico, publicados entre los años 2015 a 2020, en bases de datos como: Clinicalkey, BVS biblioteca virtual en salud, Scopus, EBSCOHost, Pubmed y Cuiden. Se filtraron por título, resumen y texto completo; se clasificaron según nivel de evidencia y grado de recomendación. Finalmente, se efectuó la lectura crítica mediante las escalas de Amstar, Consort, Strobe, CASPe y Trend. Resultados: se seleccionaron 29 artículos y se organizaron las estrategias en tres temáticas, por niveles de prevención: 1) promoción, prevención y mitigación del daño; 2) identificación, diagnóstico y tratamiento, y 3) rehabilitación. Conclusiones: la evaluación periódica del pie diabético es de vital importancia y debe ser realizada por el equipo interdisciplinario.
Relación entre nivel de adherencia al tratamiento y apoyo social en pacientes con falla cardiaca
Authors: Jaraba Suarez Silvia Juliana , Muñoz Acuña Doraly , Pomar Hoyos Margarita María
Published: March 2022

Introducción: La falla cardiaca (FC) es una de las enfermedades cardiovasculares con mayor índice de hospitalizaciones en la unidad de cuidado intensivo. En esta enfermedad es imperativo determinar aquellos factores asociados con el reingreso, como la adherencia al tratamiento y el apoyo social. Objetivo: determinar la relación entre la adherencia al tratamiento y el apoyo social de pacientes con falla cardiaca. Método: se realizó un estudio correlacional, con muestreo no probabilístico; el tamaño de la muestra fue de 64 pacientes con diagnóstico de FC. Para la medición del nivel de adherencia, se utilizó la escala para evaluación de comportamientos de adherencia con un alfa Cronbach de 0,72, para medir la percepción del apoyo social; se empleó la escala Medical Outcomes Study Social Supportsurvey (MOS) con una alfa de Cronbach de 0,94. Se realizó un análisis descriptivo y, para establecer la relación del nivel de adherencia con el apoyo social, se aplicó la prueba de independencia de distribuciones categóricas de Fisher. Resultados: Los participantes, en su mayoría, se encontraron adheridos al tratamiento (56,2 %); el índice global de apoyo social (media: 76,18) y sus dimensiones se encontraron en un rango medio. En cuanto a la asociación entre la adherencia al tratamiento, el apoyo social emocional (p: 0,006336) y el apoyo afectivo (p: 0,03025), esta fue moderada. Conclusiones: Existe asociación entre la adherencia y el apoyo social, por lo que es fundamental que el profesional de enfermería incluya la evaluación e intervención del apoyo social previo al alta del paciente, para optimizar los niveles de adherencia.
How Leadership Should Be Exercised in Early Childhood Education?
Authors: Cabrera-Murcia Elsa Piedad
Published: March 2022

This research article gathers the perceptions about how directors and pedagogical teams understand and experience leadership within five Junji preschools in Chile. Data were collected for from five semi-structured interviews and a participant observation. Findings suggest three forms of exercising leadership: pedagogical,supervisory, and administrative. In all cases, there are the same threats to leadership. The study uncovers some personal skills and characteristics common to the ways of leading. The article also highlights the context as a key element to the exercise of leadership, and the importance of modeling collaborative cultures, which consider the centrality of children's learning in preschool education.
¿Por qué directores y tesistas deciden discontinuar la relación pedagógica?
Authors: Fernandez-Fastuca Lorena
Published: March 2022

La dirección de tesis es un pilar de la formación de posgrado. Por ello, se propone analizar la relación director-tesista indagando las razones que pueden llevar a su discontinuidad desde la perspectiva de ambos. Se realizó un estudio cuantitativo descriptivo, con base en una encuesta diseñada ad hoc, que se aplicó a una muestra no representativa de 1607 directores y tesistas de universidades argentinas. El 58 % de los directores ha discontinuado este vínculo. Algunas razones son: insuficiente dedicación del tesista e insuficiente seguimiento de las indicaciones. Para los tesistas el motivo central es la falta de dedicación del director.
How to Use the Levers of Modularity Properly—Linking Modularization to Economic Targets
Authors: Schwede Lea-Nadine , Greve Erik , Krause Dieter , Otto Kevin , Moon Seung Ki , Albers Albert , Kirchner Eckhard , Lachmayer Roland , Bursac Nikola , Inkermann David , Rapp Simon , Hausmann Maximilian , Schneider Jannik
Published: March 2022

Product developers are faced with the challenge of covering an ever-increasing external variety with as little internal variety as possible. Modular product architectures offer one way of resolving the challenge. They have an impact on all life phases and on economic targets. These effects are represented in the Impact Model of Modular Product Families. A large number of modularization methods can be found in the literature. The modularization methods consist of different activities: decomposition of product, analysis and revision of components, and reintegration to modules. Module drivers play a major role in reintegration, as they determine which components together form a module. It is not yet clear what effects different modularization methods involving different module drivers have on economic targets. For this reason, the module drivers are examined in their role as levers of modularity and integrated into the Impact Model via access points. By documenting the results in a specially developed uniform method step description and the Impact Model, we enable the selection of modularization methods with regard to their economic impact. The introduction is followed by the state of research. In Sec.3, the research problem and the research approach are presented. In Sec.4, the generic method step description is applied to seven modularization methods. Based thereon, the modularization methods are compared with each other with regard to their addressed economic objectives. In an explanatory example, the method selection made possible by this is presented. Finally, the results are discussed and an outlook is given.
Ultrasound characterization of bioinspired functionally graded soft-to-hard composites: Experiment and modeling
Authors: Aghaei Ali , Bochud Nicolas , Rosi Giuseppe , Grossman Quentin , Ruffoni Davide , Naili Salah
Published: March 2022

Functional grading is a distinctive feature adopted by nature to improve the transition between tissues that present a strong mismatch in mechanical properties, a relevant example being the tendon-to-bone attachment. Recent progress in multi-material additive manufacturing now allows for the design and fabrication of bioinspired functionally graded soft-to-hard composites. Nevertheless, this emerging technology depends on several design variables, including both material and mechanistic ingredients, that are likely to affect the mechanical performance of such composites. In this paper, a model-based approach is developed to describe the interaction of ultrasound waves with homogeneous and heterogeneous additively manufactured samples, which respectively display a variation either of the material ingredients (e.g., ratio of the elementary constituents) or of their spatial arrangement (e.g., functional gradients, damage). Measurements are performed using longitudinal bulk waves, which are launched and detected using a linear transducer array. First, model is calibrated by exploiting the signals measured on the homogeneous samples, which allow identifying relationships between the model parameters and the material composition. Second, the model is validated by comparing the signals measured on the heterogeneous samples with those predicted numerically. Overall, the reported results pave the way for characterizing and optimizing multi-material systems that display complex bioinspired features.
Conservation opportunities and challenges in Brazil’s roadless and railroad-less areas
Authors: Tisler Trevor R. , Teixeira Fernanda Z. , Nóbrega Rodrigo A.A.
Published: March 2022

Policy and legislation rarely acknowledge the importance of keeping intact ecosystems road- and railroad-free. By modeling Brazil’s remaining roadless and railroad-less (RLRL) areas, we found that, although they hold the vast majority of the country’s remaining native vegetation (81.5%), because of their limited protection status, only 38% of Brazil’s remaining native vegetation is both protected and in RLRL areas. Current federal policy aims to develop transportation infrastructure designed with antiquated planning methods that threaten remaining intact ecosystems, while concurrently weakening the country’s hallmark environmental protections and commitments. Where Brazil builds its new roads and railroads matters for conservation planning. The occurrence of native vegetation and anthropic land use is associated, at varying degrees, to transportation infrastructure throughout most of Brazil. We highlight that by pursuing conservation opportunities in RLRL areas, Brazil could instead make impactful steps for conservation, restoration planning, and tangible progress toward achieving national and international environmental and conservation commitments.
Rational inattention in mice
Authors: Grujic Nikola , Brus Jeroen , Burdakov Denis , Polania Rafael
Published: March 2022

Behavior exhibited by humans and other organisms is generally inconsistent and biased and, thus, is often labeled irrational. However, the origins of this seemingly suboptimal behavior remain elusive. We developed a behavioral task and normative framework to reveal how organisms should allocate their limited processing resources such that sensory precision and its related metabolic investment are balanced to guarantee maximal utility. We found that mice act as rational inattentive agents by adaptively allocating their sensory resources in a way that maximizes reward consumption in previously unexperienced stimulus-reward association environments. Unexpectedly, perception of commonly occurring stimuli was relatively imprecise; however, this apparent statistical fallacy implies “awareness” and efficient adaptation to their neurocognitive limitations. Arousal systems carry reward distribution information of sensory signals, and distributional reinforcement learning mechanisms regulate sensory precision via top-down normalization. These findings reveal how organisms efficiently perceive and adapt to previously unexperienced environmental contexts within the constraints imposed by neurobiology.
Structure of the Wilson disease copper transporter ATP7B
Authors: Bitter Ryan M. , Oh SeCheol , Deng Zengqin , Rahman Suhaila , Hite Richard K. , Yuan Peng
Published: March 2022

ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains a P-type ATPase core consisting of a membrane transport domain and three cytoplasmic domains, the A, P, and N domains, and a unique amino terminus comprising six consecutive metal-binding domains. Here, we present a cryo–electron microscopy structure of frog ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues lines the cytoplasmic copper entrance that is presumably gated by a conserved basic residue sitting at the center. Within the membrane, a network of copper-coordinating ligands delineates a stepwise copper transport pathway. This work provides the first glimpse into the structure and function of ATP7 proteins and facilitates understanding of disease mechanisms and development of rational therapies.
BRN2
as a key gene drives the early primate telencephalon development
Authors: Zhu Xiaoqing , Guo Yicheng , Chu Chu , Liu Dahai , Duan Kui , Yin Yu , Si Chenyang , Kang Yu , Yao Junjun , Du Xuewei , Li Junliang , Zhao Shumei , Ai Zongyong , Zhu Qingyuan , Ji Weizhi , Niu Yuyu , Li Tianqing
Published: March 2022

Evolutionary mutations in primate-specific genes drove primate cortex expansion. However, whether conserved genes with previously unidentified functions also play a key role in primate brain expansion remains unknown. Here, we focus on
BRN2
(
POU3F2
), a gene encoding a neural transcription factor commonly expressed in both primates and mice. Compared to the limited effects on mouse brain development,
BRN2
biallelic knockout in cynomolgus monkeys (
Macaca fascicularis
) is lethal before midgestation. Histology analysis and single-cell transcriptome show that
BRN2
deficiency decreases RGC expansion, induces precocious differentiation, and alters the trajectory of neurogenesis in the telencephalon.
BRN2
, serving as an upstream factor, controls specification and differentiation of ganglionic eminences. In addition, we identified the conserved function of
BRN2
in cynomolgus monkeys to human RGCs.
BRN2
may function by directly regulating
SOX2
and
STAT3
and maintaining
HOPX
. Our findings reveal a previously unknown mechanism that
BRN2
, a conserved gene, drives early primate telencephalon development by gaining novel mechanistic functions.
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing
Authors: Stevanovski Igor , Chintalaphani Sanjog R. , Gamaarachchi Hasindu , Ferguson James M. , Pineda Sandy S. , Scriba Carolin K. , Tchan Michel , Fung Victor , Ng Karl , Cortese Andrea , Houlden Henry , Dobson-Stone Carol , Fitzpatrick Lauren , Halliday Glenda , Ravenscroft Gianina , Davis Mark R. , Laing Nigel G. , Fellner Avi , Kennerson Marina , Kumar Kishore R. , Deveson Ira W.
Published: March 2022

More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing with Oxford Nanopore’s ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of STR sites, from a list of predetermined candidates. This correctly diagnoses all individuals in a small cohort (
n
= 37) including patients with various neurogenetic diseases (
n
= 25). Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing and identifies noncanonical STR motif conformations and internal sequence interruptions. We observe a diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of repeat disorders. Last, we show how the inclusion of pharmacogenomic genes as secondary ReadUntil targets can further inform patient care.
MTHFD2, metabolic mastermind of CD4
+
T cell destiny
Authors: Gouirand Victoire , Rosenblum Michael D.
Published: March 2022

MTHFD2 is a metabolic checkpoint of T cell fate and function.
Too much and not enough: tuning human primary T cell cytokine signaling networks
Authors: Henrickson Sarah E.
Published: March 2022

Combining CRISPR activation and interference screens to perturb cytokine secretion in primary human T cells clarifies regulation of cytokine production.
Supplemental Material: How old are the Jack Hills metasediments really?: The case for contamination of bedrock by zircon grains in transported regolith
Authors: Kinny Peter , al. et
Published: March 2022

Analytical details, concordant zircon U-Pb data table, comparative age plots, and statistics.
Supplemental Material: Magmatism at oceanic core complexes on the ultraslow Southwest Indian Ridge: Insights from near-seafloor magnetics
Authors: Zhou Fei , Dyment Jerome , al. et
Published: March 2022

Supplemental figures, explanations on methodology and specific points, and tables of dredge and hydrothermal vent locations
Effect of the Addition of Copper Particles on the Thermoelectric Properties of the Ca3Co4O9 + δ Ceramics Produced by Two-Step Sintering
Authors: Klyndyuk A. I. , Chizhova E. A. , Latypov R. S. , Shevchenko S. V. , Kononovich V. M.
Published: March 2022

Composite thermoelectric materials based on layered calcium cobaltite Ca3Co4O9 + δ doped with copper particles were synthesized by two-step sintering, and their microstructure, and electrotransport and thermoelectric properties were studied. It was determined that the introduction of copper particles into the ceramics improves their sinterability at moderate sintering temperatures (Tsint ≤ 1273 K), leading to a decrease in the porosity of the samples and an increase in their electrical conductivity and power factor, whereas the oxidation of copper to less conductive copper(II) oxide significantly decreases the electrical conductivity and power factor of the ceramics sintered at elevated temperatures (Tsint ≥ 1373 K). The power factor is maximum for the Ca3Co4O9 + δ + 3 wt % Cu ceramic sintered at 1273 K (335 μW/(m K2) at a temperature of 1100 K), which is by a factor of 2.3 higher than the power factor of the base material Ca3Co4O9 + δ with the same thermal history (145 μW/(m K2) at 1100 K) and more than 3 times higher than the power factor of the Ca3Co4O9+δ ceramic synthesized by the conventional solid-phase method.
Giant high-pressure pulmonary artery aneurysm (PAA) in a patient with COPD and chronic pulmonary embolism (PE)
Authors: Fong Hee Kong , Pinson Amber , Bhardwaj Bhaskar , Samad Fatima
Published: March 2022

A woman in her 60s with a history of known severe chronic obstructive pulmonary disease (COPD), former smoker of 50 pack-years and small patent foramen ovale (PFO) without significant shunt was admitted for acute on chronic hypoxic respiratory failure. Diagnostic workup showed severe dilatation of main pulmonary artery (MPA) (75.5 mm axial view and 86.6 mm sagittal view) and left and right PAs measuring 40 mm and 34 mm, respectively, on CT angiography of the chest. Right heart catheterisation showed severe pulmonary hypertension (PH). A diagnosis of giant high-pressure pulmonary arterial aneurysm (PAA) secondary to PH, induced by COPD, and chronic pulmonary embolism was made. Despite aggressive medical management, she passed away on comfort care. Giant high-pressure PAAs are rarely reported. This is a unique case that demonstrates this very rare condition in a living patient. The management of giant PAA is controversial. Experts recommend medical management or aneurysmectomy for sizes of >55–60 mm. Death could have been prevented if our patient was screened earlier and received appropriate medical care.
Combined central retinal artery and vein occlusion associated with antiphospholipid syndrome
Authors: Choudhary Roha Ahmad , Siddiqui M A Rehman , Moiz Bushra , Ishaq Saliha
Published: March 2022

A female patient in early 50s presented to us several months after developing severe visual loss in her right eye. The patient was diagnosed with resolved central retinal vein occlusion (CRVO) based on the clinical picture at the time of presentation, however, retroactive evaluation of fundus imaging and further multi-disciplinary workup led to the rare diagnosis of combined central retinal artery and vein occlusion associated with antiphospholipid syndrome (APS). Only a few cases reporting retinal arterial and venous occlusions in patients with APS are found in the literature. To the best of our knowledge, no case of simultaneous CRAO and CRVO has been reported with APS. The patient was started on lifelong warfarin therapy to prevent a similar episode in the left eye. It is important to properly evaluate patients presenting with retinal vascular occlusions, as a missed diagnosis of APS can lead to recurrent and more devastating vascular events.
Insidious ocular surface lesion in an 81-year-old woman
Authors: Lee Jay J , Stephenson Kirk A J , Forristal Mark T , McElnea Elizabeth M
Published: March 2022

Ocular surface melanoma (OSM) is rare. An 81-year-old Caucasian woman presented with a 4-month history of right eye pain and reduced vision. Histopathological examination of the excisional biopsy identified invasive amelanotic melanoma of the conjunctiva expressing Melan A and SOX10. X-ray of chest, CT of liver and MRI of the brain and orbit did not identify macroscopic metastases. She was given adjuvant topical mitomycin-C 0.04% for four cycles of 2 weeks. Her vision improved and the cornea was clear at 6 months.
Longitudinal study of the effects of price and promotion incentives on purchases of unhealthy foods: evidence for restricting food promotions
Authors: Kopasker Daniel , Ejebu Ourega-Zoé , Norwood Patricia , Ludbrook Anne
Published: March 2022

Objectives

Taxes and restrictions on promotions have recently been proposed as policy instruments to reduce consumption of unhealthy foods. The objective of this study is to add to the limited evidence on the comparative effectiveness of price changes, price promotions and volume promotions in changing household purchasing of unhealthy foods, using biscuits, crisps and savoury snacks as examples.

Design

Longitudinal regression analysis of consumer microdata.

Setting

Secondary data on itemised household purchases of biscuits, crisps and savoury snacks from 2006 to 2012.

Participants

Sample of 3024 households in Scotland.

Main outcome measures

Changes in the number of calories (kcal) purchased in the product category by a household caused by changes in the price for the product category, any temporary in-store price promotions and any temporary in-store volume promotions. Changes are measured at the mean, median, 25th percentile and 75th percentile of the household purchasing distribution for the full sample. Subgroup analyses were conducted by household income band and for households with and without children.

Results

Between product categories, the scale of purchasing response to incentives varies significantly. Within product categories, the mean calories (kcal) purchased by a household are more responsive to any volume promotion than to price or any price promotion for all product categories. As the volume of items purchased increases, households are less responsive to price, less responsive to any volume promotion and more responsive to any price promotion. Statistically significant differences are observed between household income groups in their response to price and promotion incentives within the biscuits category only. In cases where statistically significant differences are observed, households with children are more responsive to promotion and price incentives than households without children.

Conclusions

For all product categories analysed (biscuits, crisps and savoury snacks), household purchasing is most responsive to any volume promotion. Therefore, assuming the response of consumers to incentives remains constant following legislation, the most effective policy instrument to reduce the calorie intake from these products may be a ban on volume promotions.
Effectiveness and cost-effectiveness of a combined lifestyle intervention compared with usual care for patients with early-stage knee osteoarthritis who are overweight (LITE): protocol for a randomised controlled trial
Authors: Jansen Nuria E J , Schiphof Dieuwke , Oei Edwin , Bosmans Judith , van Teeffelen Jolande , Feleus Anita , Runhaar Jos , van Meurs Joyce , Bierma-Zeinstra Sita M A , van Middelkoop Marienke
Published: March 2022

Introduction

Obesity is the most important modifiable risk factor for knee osteoarthritis (KOA). Especially in an early stage of the disease, weight loss is important to prevent further clinical and structural progression. Since 2019, general practitioners (GPs) in the Netherlands can refer eligible patients to a combined lifestyle intervention (GLI) to promote physical activity, healthy nutrition and behavioural change. However, GPs scarcely refer patients with KOA to the GLI potentially due to a lack of evidence about the (cost-)effectiveness. The aim of this study is to determine the (cost-)effectiveness of the GLI for patients with early-stage KOA in primary care.

Methods and analysis

For this pragmatic, multi-centre randomised controlled trial, 234 participants (aged 45–70 years) with National Institute for Health and Care Excellence (NICE) guideline diagnosis of clinical KOA and a body mass index above 25 kg/m2will be recruited using a range of online and offline strategies and from general practices in the Netherlands. Participants will receive nine 3-monthly questionnaires. In addition, participants will be invited for a physical examination, MRI assessment and blood collection at baseline and at 24-month follow-up. After the baseline assessment, participants are randomised to receive either the 24-month GLI programme in addition to usual care or usual care only. Primary outcomes are self-reported knee pain over 24 months, structural progression on MRI at 24 months, weight loss at 24 months, as well as societal costs and Quality-Adjusted Life-Years over 24-month follow-up. Analyses will be performed following the intention-to-treat principle using linear mixed-effects regression models.

Ethics and dissemination

Ethical approval was obtained through the Medical Ethical Committee of the Erasmus MC University Medical Center Rotterdam, The Netherlands (MEC-2020-0943). All participants will provide written informed consent. The results will be disseminated through publications in peer-reviewed journals, presentations at international conferences and among study participants and healthcare professionals.

Trial registration number

Netherlands Trial Registry (NL9355).
Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial
Authors: Menne Tobias , Slade Daniel , Savage Joshua , Johnson Sarah , Irving Julie , Kearns Pamela , Plummer Ruth , Shenton Geoff , Veal Gareth J , Vormoor Britta , Vormoor Josef , Billingham Lucinda
Published: March 2022

Introduction

Event-free survival rates at 15 years for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia (ALL) are 30%–50%, with 5-year survival for adult patients only 20%. Many patients with newly diagnosed and relapsed ALL harbour somatic RAS-signalling activation mutations. Induction therapy for ALL involves steroids, with preclinical data suggesting the combination of dexamethasone with the MEK1/2 inhibitor, selumetinib (ARRY-142886) has a synergistic anticancer effect.

Methods and analysis

The SeluDex trial is an international, parallel-group, dose-finding with expansion, phase I/II trial to assess the selumetinib/dexamethasone combination in adult and paediatric patients with relapsed/refractory, RAS pathway mutant ALL. The Cancer Research UK Clinical Trials Unit at University of Birmingham is the UK Coordinating Centre, with national hubs in Copenhagen, Denmark; Monza, Italy; Münster, Germany; Paris, France; and Utrecht, Netherlands. Patients with morphologically proven relapsed/refractory or progressive B-cell precursor or T-cell ALL, with demonstrated RAS pathway activating mutations are eligible. Adult patients are>18 years old, ECOG<2 and paediatric <18 years old, Lansky play scale ≥60% or Karnofsky score ≥60%. Phase I primary objective is the recommended phase II dose of selumetinib as defined by occurrence/non-occurrence of dose limiting toxicities using the continual reassessment method; phase II will evaluate preliminary antileukaemic activity of the combination, as defined by morphological response 28 days post-treatment using a Bayesian approach. Target recruitment is between 26 and 42 patients (minimum 13 and maximum 21 per group), depending the number of phase I patients included in phase II.

Ethics and dissemination

Medical ethical committees of all the participating countries have approved the study protocol; initial (UK) ethics approval (17/YH/0123) was granted by Yorkshire & The Humber—Leeds West Research Ethics Committee. Participants are required to provide written informed consent/assent. Results will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ISRCTN92323261.
Development stage of novel digital health interventions for postoperative monitoring: protocol of a systematic review
Authors: McLean Kenneth A , Knight Stephen R , Diehl Thomas M , Zafar Syed Nabeel , Bouamrane Matt , Harrison Ewen M
Published: March 2022

Introduction

The postoperative period represents a time where patients are at a high-risk of morbidity, which warrants effective surveillance. While digital health interventions (DHIs) for postoperative monitoring are promising, a coordinated, standardized and evidence-based approach regarding their implementation and evaluation is currently lacking. This study aimed to identify DHIs implemented and evaluated in postoperative care to highlight research gaps and assess the readiness for routine implementation.

Methods

A systematic review will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies describing the implementation and evaluation of DHIs for postoperative monitoring published since 2000 (PROSPERO ID: CRD42021264289). This will encompass the Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and ClinicalTrials.gov databases, and manual search of bibliographies for relevant studies and gray literature. Methodological reporting quality will be evaluated using the Idea, Development, Exploration, Assessment and Long-term Follow-up (IDEAL) reporting guideline relevant to the IDEAL stage of the study, and risk of bias will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Data will be extracted according to the WHO framework for monitoring and evaluating DHIs, and a narrative synthesis will be performed.

Discussion

This review will assess the readiness for implementation of DHIs for routine postoperative monitoring and will include studies describing best practice from service changes already being piloted out of necessity during the COVID-19 pandemic. This will identify interventions with sufficient evidence to progress to the next IDEAL stage, and promote standardized and comprehensive evaluation of future implementational studies.
Educational and ecological assessment for unintentional injuries among children under 7 years: directed qualitative research based on PRECEDE–PROCEED model
Authors: Lael-Monfared Elaheh , Rakhshanderou Sakineh , Ramezankhani Ali , Ghaffari Mohtasham
Published: March 2022

Background

Child injury is not seen as a new issue in medical science and public health; however, for years it has been either generally brushed aside or been conspicuously absent from the world health agenda. This study aims at investigating the factors leading to house injuries and attempts to highlight mothers’ pivotal role to provide a safe place for children at home.

Methods

A qualitative research method was used. There were 29 interviews in total: 12 interviews with mothers, 9 with cure and prevention specialists and 8 with researchers. The data were gathered through semistructured interviews conducted in participants’ workplaces namely universities, research centres, health centres and in some cases through telephone in 3 months from February 2021 to May 2021 in Tehran, Iran. The participants were selected through non-probability and purposive sampling. All of the recorded interviews and notes were accurately evaluated and data analysis was performed based on the content analysis.

Results

In this study, 29 participants’ views were examined: 12 mothers (41.37%), 8 researchers (27.5%) and 9 treatment and prevention experts (31%). After the analysis of the interviews, 96 codes, 14 subcategories and 3 main categories were extracted. The main categories included the predisposing factors, reinforcing factors and enabling factors. The subcategories included perceived sensitivity, perceived susceptibility, health control centre, perceived benefits, observational or peripheral learning, social support, family support, abstract norms, valuing children’s health, background factors, skills, rules and regulations, child’s character traits and self-efficacy to overcome barriers.

Conclusion

House injuries among children are a complicated and multifaceted issue that requires a comprehensive investigation to determine the contributing factors.
Natural killer T cell immunotherapy combined with IL-15-expressing oncolytic virotherapy and PD-1 blockade mediates pancreatic tumor regression
Authors: Nelson Adam , Gebremeskel Simon , Lichty Brian D , Johnston Brent
Published: March 2022

Background

Pancreatic cancer is one of the leading causes of cancer death, with a 5-year -year survival rate of less than 10%. This results from late detection, high rates of metastasis, and resistance to standard chemotherapies. Furthermore, chemotherapy and radiation are associated with significant morbidity, underscoring the need for novel therapies. Recent clinical studies have shown that immunotherapies can provide durable outcomes in cancer patients, but successes in pancreatic cancer have been limited. It is likely that novel and combined therapies will be needed to achieve clinical benefits.

Methods

Using experimental mouse models of pancreatic ductal adenocarcinoma, we examined natural killer T (NKT) cell activation therapy in combination with a recombinant oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express the cytokine IL-15 (VSV-IL-15). Panc02 pancreatic ductal carcinoma cells were implanted subcutaneously or orthotopically into syngeneic C57BL/6 mice. Mice were then treated with VSV expressing green fluorescent protein (VSV-GFP) or VSV-IL-15 and/or NKT cell activation therapy via delivery of α-GalCer-loaded DCs. We further assessed whether the addition of PD-1 blockade could increase the therapeutic benefit of our combination treatment. Three days after NKT cell activation, some groups of mice were treated with anti-PD-1 antibodies weekly for 3 weeks.

Results

VSV-GFP and VSV-IL-15 mediated equal killing of human and mouse pancreatic cancer lines in vitro. In vivo, VSV-IL-15 combined with NKT cell activation therapy to enhance tumor regression and increase survival time over individual treatments, and was also superior to NKT cell therapy combined with VSV-GFP. Enhanced tumor control was associated with increased immune cell infiltration and anti-tumor effector functions (cytotoxicity and cytokine production). While ineffective as a monotherapy, the addition of blocking PD-1 antibodies to the combined protocol sustained immune cell activation and effector functions, resulting in prolonged tumor regression and complete tumor clearance in 20% of mice. Mice who cleared the initial tumor challenge exhibited reduced tumor growth uponon rechallenge, consistent with the formation of immune memory.

Conclusion

TThese results demonstrate that NKT cell immunotherapy combined with oncolytic VSV-IL-15 virotherapy and PD-1 blockade enhances tumor control and presents a promising treatment strategy for targeting pancreatic cancer.
In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies
Authors: Ieranò Caterina , Righelli Dario , D'Alterio Crescenzo , Napolitano Maria , Portella Luigi , Rea Giuseppina , Auletta Federica , Santagata Sara , Trotta Anna Maria , Guardascione Giuseppe , Liotti Federica , Prevete Nella , Maiolino Piera , Luciano Antonio , Barbieri Antonio , Di Mauro Annabella , Roma Cristin , Esposito Abate Riziero , Tatangelo Fabiana , Pacelli Roberto , Normanno Nicola , Melillo Rosa Marina , Scala Stefania
Published: March 2022

Background

Colorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with high-microsatellite instability, high tumor mutation burden, and intratumoral lymphocytic infiltration. Programmed death-ligand 1 (PD-L1)/PD-1 signaling was described in solid tumor cells. In melanoma, liver, and thyroid cancer cells, intrinsic PD-1 signaling activates oncogenic functions, while in lung cancer cells, it has a tumor suppressor effect. Our work aimed to evaluate the effects of the anti-PD-1 nivolumab (NIVO) on CRC cells.

Methods

In vitro NIVO-treated human colon cancer cells (HT29, HCT116, and LoVo) were evaluated for cell growth, chemo/radiotherapeutic sensitivity, apoptosis, and spheroid growth. Total RNA-seq was assessed in 6–24 hours NIVO-treated human colon cancer cells HT29 and HCT116 as compared with NIVO-treated PES43 human melanoma cells. In vivo mice carrying HT29 xenograft were intraperitoneally treated with NIVO, OXA (oxaliplatin), and NIVO+OXA, and the tumors were characterized for growth, apoptosis, and pERK1/2/pP38. Forty-eight human primary colon cancers were evaluated for PD-1 expression through immunohistochemistry.

Results

In PD-1+ human colon cancer cells, intrinsic PD-1 signaling significantly decreased proliferation and promoted apoptosis. On the contrary, NIVO promoted proliferation, reduced apoptosis, and protected PD-1+ cells from chemo/radiotherapy. Transcriptional profile of NIVO-treated HT29 and HCT116 human colon cancer cells revealed downregulation of BATF2, DRAM1, FXYD3, IFIT3, MT-TN, and TNFRSF11A, and upregulation of CLK1, DCAF13, DNAJC2, MTHFD1L, PRPF3, PSMD7, and SCFD1; the opposite regulation was described in NIVO-treated human melanoma PES43 cells. Differentially expressed genes (DEGs) were significantly enriched for interferon pathway, innate immune, cytokine-mediated signaling pathways. In vivo, NIVO promoted HT29 tumor growth, thus reducing OXA efficacy as revealed through significant Ki-67 increase, pERK1/2 and pP38 increase, and apoptotic cell reduction. Eleven out of 48 primary human colon cancer biopsies expressed PD-1 (22.9%). PD-1 expression is significantly associated with lower pT stage.

Conclusions

In PD-1+ human colon cancer cells, NIVO activates tumor survival pathways and could protect tumor cells from conventional therapies.