bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing High-Resolution Metastasis Signatures for Improved Cancer Prognosis and Drug Sensitivity Prediction using Single-Cell RNA Sequencing Data: A Case Study in Lung Adenocarcinoma
Authors: Zhou Yeman , Li Hanlin , Yu De’en , Zhang Cheng , Yang Heng , Wang Chunping , Zhang Youhua , Deng Wensheng , Li Bo , Zhang Shihua
Published: March 2023

Metastasis remains the reason for chemoresistance and high cancer mortality. It is hence a valuable predictive factor in cancer prognosis and drug sensitivity. Single-cell RNA sequencing (scRNA-seq) can reveal cellular heterogeneity in metastasis microenvironment and capture high-resolution signatures for improved cancer prediction. As a case study, an integrated analysis framework was designed for metastatic lung adenocarcinoma (LUAD) scRNA-seq profiles and we identified nine key prognostic genes (KPGs) that were trained and validated in 407 internal and external patient cohorts using machine learning and other methods. Correlation analysis revealed the strong association between KPGs signatures and several clinical characteristics such as gender, [Formula: see text]-stage and [Formula: see text]-stage. We incorporated these risk clinical variables into a KPGs nomogram model with superior accuracy for overall survival (OS) prediction. We also found that high risk group with high nomogram scores had poorer prognosis accompanied by a higher tumor mutation burden (TMB) and was more sensitive to chemotherapy and targeted agents, which was associated with the upregulation of DNA replication, ECM receptor interaction, P53 signaling pathway, spliceosome and proteasome pathway. Collectively, we proposed a simple and feasible strategy to mine single-cell resolution metastasis signatures from scRNA-seq data for improved cancer prognosis and drug sensitivity prediction, which will be a useful tool in risk gene discovery and targeted therapy in metastatic cancers.
Reliable sensing with unreliable sensors: Rethinking the theoretical foundation of field-deployed wearable/implantable/environmental sensors
Authors: Alam Muhammad A. , Saha Ajanta , Fratus Marco
Published: March 2023

There is a widely shared and potentially well-justified enthusiasm for autonomous field-deployed (FD) wearable, implantable, and environmental sensors for the continuous monitoring of a variety of chronic conditions, such as diabetes, depression, irritable bowel syndrome, and soil nitrate depletion. These FD sensors are often viewed as miniaturized versions of laboratory-based or point-of-care (POC) biosensors, with the primary focus being on material development and mechanical form factor challenges (e.g., stretchability, flexibility, and biocompatibility). In this article, we highlight that the FD sensors are fundamentally different compared to lab-based or POC sensors. We borrow concepts from biology (e.g., bacteria) to quantify the fundamental challenges inherent to such sensors and strategies to overcome them.
Mild inflammation impairs acute intermittent hypoxia-induced phrenic long-term facilitation by a spinal adenosine-dependent mechanism
Authors: Marciante Alexandria B. , Mitchell Gordon S.
Published: March 2023

Mild inflammation undermines motor plasticity elicited by mAIH. In a model of mAIH-induced respiratory motor plasticity (phrenic long-term facilitation; pLTF), we report that inflammation induced by low-dose lipopolysaccharide undermines mAIH-induced pLTF by a mechanism requiring increased cervical spinal adenosine and adenosine 2 A receptor activation. This finding advances the understanding of mechanisms impairing neuroplasticity, potentially undermining the ability to compensate for the onset of lung/neural injury or to harness mAIH as a therapeutic modality.
Plan- versus motion-referenced generalization of fast and slow processes in reach adaptation
Authors: Rudolph Judith L. , Selen Luc P. J. , Medendorp W. Pieter
Published: March 2023

Error-based reach adaptation can be modeled by fast and slow adaptive processes. Using a spontaneous recovery paradigm and model-based analyses, we tested how these processes generalize during force-field reach adaptation. Depending on whether the fast and slow adaptive processes operate by crediting the planned or actual motion, the model predicts distinct contributions of them to the overall generalization function. We show that human participants fall within a continuum of evidence for plan-referenced to motion-referenced updating.
The sensorimotor system modulates muscular co-contraction relative to visuomotor feedback responses to regulate movement variability
Authors: Calalo Jan A. , Roth Adam M. , Lokesh Rakshith , Sullivan Seth R. , Wong Jeremy D. , Semrau Jennifer A. , Cashaback Joshua G. A.
Published: March 2023

The sensorimotor system has the constant challenge of dealing with the naturally occurring variability in our movements. Here, we investigated the potential roles of muscular co-contraction and visuomotor feedback responses to regulate movement variability. When we visually amplified movements, we found that the sensorimotor system primarily uses muscular co-contraction to regulate movement variability. Interestingly, we found that muscular co-contraction was modulated relative to inherent visuomotor feedback responses, suggesting an interplay between impedance and feedback control.
Heterosynaptic long-term potentiation of non-nociceptive synapses requires endocannabinoids, NMDARs, CamKII, and PKCζ
Authors: Franzen Avery D. , Paulsen Riley T. , Kabeiseman Emily J. , Burrell Brian D.
Published: March 2023

Pain-related sensitization involves increases in signaling by non-nociceptive sensory neurons. This can allow non-nociceptive afferents to have access to nociceptive circuitry. In this study, we examine a form of synaptic potentiation in which nociceptor activity elicits increases in non-nociceptive synapses. This process involves endocannabinoids, “gating” the activation of NMDA receptors, which in turn activate CamKII and PKCζ. This study provides an important link in how nociceptive stimuli can enhance non-nociceptive signaling related to pain.
Simulation Study of Breakage in Coral Sand Particles under Dynamic Confined Compression
Authors: Wang Jianping , Zhang Haotian , Chen Tao , Ma Linjian
Published: March 2023

This paper reports a simulation-based dynamic confined compression analysis of coral sand under an impact load using the discrete element method (DEM). The evolution of particle breakage on the mesoscale was studied by investigating force chain distributions, crack development, and breakage modes. Crushable sand particles were simulated by replacing rigid particles with flexible basic unit aggregates. The Weibull parameters were incorporated within the mesoscopic parameters of particles, and random numbers were introduced. The obtained results for particle strengths were consistent with the experimental data. The numerical results demonstrated that the force chain was significantly strengthened along the loading axis during loading and weakened during unloading. The cracks were primarily generated along the strong force chain, and particle breakage caused the strong force chain to move towards relatively more complete fragments nearby. The crack was primarily oriented along the loading axis, and its anisotropy was observed to decrease with an increase in the load. Before yielding, particle breakage in the specimen was dominated by attrition at the edges and corners. After yielding, the crack extended into the particle perpendicular to the intergranular contact surface and was deflected by the simultaneous influence of pores. The fracture and shattering of particles occurred successively, and the consequent fall-off and slip filling of the fragments promoted the deformation development.
Effect of Radial Artery Compression with a Novel Automatic Pressure-Controlled Radial Compression Device: A Short-Term Prospective Interventional Pilot Study
Authors: Xu HaiZhen , Cheng Junya , Zhang DanYing , Shen Liang , Jiang Yingjie , Zhai ChangLin
Published: March 2023

This study was conducted to design a novel radial compression device with the function of automatic pressure control and evaluate the feasibility and safety of this new technique. Patients who underwent transradial access (TRA) coronary angiography and percutaneous coronary intervention (PCI) in the First Hospital of Jiaxing between August 2021and October 2021 were prospectively enrolled in this pilot interventional study. The patients were grouped in a 1 : 1 ratio to receive compression with a novel device (the experimental group) or a conventional device without pressure control (the control group). The primary endpoint was the compression time, and the main secondary endpoints were rebleeding, upper-limb swelling, radial artery occlusion (RAO), and device-related pressure injury (DPI). Eighty-four patients were enrolled in this study. No significant differences were found in the baseline clinical characteristics between the two groups. Compared with the control group, the compression time in the experimental group was significantly reduced (207.4 ± 15.5 vs. 378.1 ± 19 min,

p

 < 0.001). Besides, the rate of upper-limb swelling was also significantly lower in the novel device group (2.4% vs. 85.7%,

p

 < 0.001), as well as the rate of DPI (19.05% vs. 100%,

p

 = 0.005). Furthermore, the pain score in the experimental group was significantly lower than in the control group (0.79 ± 0.42 vs. 1.83 ± 0.58,

p

 < 0.001). There were no significant differences in the rate of rebleeding (7.1% vs. 14.3,

p

 = 0.48) between the two groups. In addition, no RAO occurred in any of the groups. The novel automatic pressure-controlled radial compression device could reduce the hemostasis time and decrease the rate of adverse complications. It might be a promising and effective compression device in TRA coronary invasive procedures.
Meningococcemia in an 11 Months Old Infant
Authors: Shrestha Rachana , Karki Saurab , Khadka Manoj , Sapkota Suhail , Timilsina Bibek , Khadka Sulochana
Published: March 2023

Meningococcemia is the infection of the blood caused by Neisseria meningitidis. Herein, we report a case of meningococcemia in an 11 months old infant who had a high-grade fever, nonblanching purpuric rash over the face and limbs, low blood pressure, tachycardia, and prolonged capillary refill time, but without neck rigidity and focal neurologic signs. He recovered after supportive care and treatment with antibiotics (intravenous ceftriaxone, vancomycin, and teicoplanin). Therefore, in a febrile, ill-looking child in shock with a nonblanching rash, meningococcal disease should be suspected. The study shows the importance of vaccination against meningococcal disease.
Alopecia Areata Barbae in a Nutshell
Authors: Nwosu Adaeze , Miteva Mariya
Published: March 2023

Beard alopecia areata, or alopecia areata barbae, (BAA) is a subset of alopecia areata, a T-cell mediated inflammatory disease that disrupts the hair follicle cycle leading to early onset of catagen. The aim of this review is to help strengthen clinicians' skills in the evaluation, diagnosis, and management of BAA. We performed a literature review according to the modified PRISMA guidelines, using a combination of relevant key words in electronic databases. According to the data from the 25 articles on BAA reviewed here, BAA mostly affects middle-aged men (mean age 31 years) who typically experience patchy hair loss in the neck region, which spreads to the scalp within 12 months. Similar to AA, BAA is associated with autoimmune diseases such as H. pylori and thyroiditis; however, BAA has no clear genetic pattern of inheritance which is observed in alopecia areata. Common dermoscopic findings in BAA include vellus white hairs and exclamation mark hairs, which may help distinguish it from other pathologies affecting facial hair. In clinical trials, the ALBAS tool offers clinicians an objective metric to evaluate BAA severity. Until recently, topical steroids have been the mainstay therapy; however, topical and oral janus kinase inhibitors are achieving improved results, with up to 75% beard regrowth in an average of 12 months.
Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans
Authors: Rizk John G. , Hsiung Jui-Ting , Arif Yousif , Hashemi Leila , Sumida Keiichi , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar , Streja Elani
Published: March 2023

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m2), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.
Desafios e implementação do Programa Mais Médicos Campineiro
Authors: Dimarzio Giuliano , Pinto Ilione de Cassia , Guimarães Alóide Ladeia , Rollo Adail de Almeida , Gonçalves Aguinaldo , Zambon Zeliete Linhares Leite , Bedrikow Rubens , Nunes Monica , Silva Camila Ramos da , Costa Douglas , Cugliari Luciana , Abrahão Carlos Eduardo Cantusio , Tófoli Luis Fernando , Zambon Lair , Souza Carmino Antonio de , Souza Clarissa Vasconcellos de
Published: March 2023

O objetivo deste trabalho é descrever a experiência da implementação do Programa Mais Médicos Campineiro (PMMC) na cidade de Campinas, Estado de São Paulo, no período de abril de 2019 a abril de 2020, como resultado de política de saúde que adequou as necessidades do município à formação de médicos especialistas em Medicina da Família e Comunidade. Para tal, foram compilados registros de reuniões realizadas entre integrantes da Secretaria Municipal de Saúde e instituições de ensino superior do município e recuperada a trajetória percorrida pelos diversos atores envolvidos. A situação da atenção básica de saúde no município até 2019 foi analisada com detalhes, o que revelou dificuldades em fixar o médico nas Unidades de Saúde. Como solução optou-se pela instituição de programa de residência médica. Para preservar a manutenção do médico no programa, garantiu-se a sua vinculação à Estratégia de Saúde da Família, foram estabelecidas parcerias com instituições de saúde e foi planejado o financiamento que garantiu remuneração suficiente para atrair e manter profissionais à proposta. O processo seletivo de médicos residentes e preceptores foi amplamente discutido. Foi criado um programa pedagógico e estabelecida a gestão do programa. Foi verificado incremento da ocupação de vagas oferecida, demonstrando-se que por meio de política pública direcionada à formação de Médico da Família e Comunidade é possível alterar o panorama de ociosidade assim como a alta rotatividade de vagas em programas de residência médica em Campinas.
Ducto de Luschka: uma variação anatômica da árvore biliar detectada durante a colecistectomia
Authors: Fonseca Neto Olival Cirilo Lucena da , Martins Beatriz Costa Nava , Pedrosa Maria das Graças Lapenda
Published: March 2023

O ducto de Luschka é uma alteração anatômica que não é facilmente identificada nos exames de imagens pré-operatórios. O conhecimento da anatomia e da possibilidade de encontrar essa estrutura anatômica propicia maior segurança no procedimento cirúrgico. O caso descrito aborda um vazamento biliar intraoperatório pela presença do Ducto de Luschka durante uma colecistectomia aberta e o seu manejo. Objetivo: Descrever o caso de uma paciente com colelitíase, submetida a uma colecistectomia convencional de forma eletiva, na qual foi detectada, no intraoperatório, a presença do ducto de Luschka, bem como foi realizado o manejo cirúrgico e clínico do caso. Resultado: A paciente foi submetida a drenagem cavitaria no intraoperatório, bem como foi realizada a ligadura do ducto. Apresentou boa evolução nos dias seguintes, com melhora clínica, tendo alta hospitalar em boas condições no 4° DPO. Discussão: O ducto de Luschka é uma das variações anatômicas mais comuns da árvore biliar. A identificação desse ducto no pré-operatório é extremamente difícil e rara e seu tratamento cirúrgico usualmente consiste em lavagem de cavidade abdominal, fechamento do ducto de Luschka e colangiografia intraoperatória para confirmar que a árvore biliar está intacta. Conclusão: A importância do conhecimento e da condução cirúrgica e clínica dessa estrutura anatômica é importante para a boa evolução do paciente.
Percepção dos profissionais de saúde acerca da ocorrência e prevenção de acidentes com socorristas do Serviço de Atendimento Móvel de Urgência (SAMU)
Authors: Cernkovic Sueli Afonso Corrêa , Andrade Bruno César de , Fontes Carlos Edmundo Rodrigues , Cavazana William César
Published: March 2023

A Organização Mundial da Saúde (OMS) menciona como uma das principais causas de morte por trauma no mundo as decorrentes de acidentes de trânsito. O aumento de acidentes em vias públicas e rodovias exige o aprimoramento de ações dos socorristas, que expõem suas vidas, ficando constantemente expostos a situações inseguras, seja dentro da ambulância em movimento ou quando estão atendendo no local do incidente. Este estudo objetivou identificar a percepção dos profissionais de saúde acerca da ocorrência e prevenção de acidentes com socorristas do SAMU Maringá. Trata-se de um estudo quali-quantitativo exploratório. A pesquisa ocorreu através de aplicação de questionário realizada com profissionais atuantes no SAMU Maringá. Os resultados demonstraram a necessidade de intervenções prioritárias que garantam: a educação continuada a fim de adequar a conduta dos socorristas, conscientização da população e otimização da sinalização garantida pelo atendimento mínimo com 03 socorristas e com materiais sinalizadores adequados. Esta pesquisa permitiu identificar a percepção da equipe de profissionais atuantes no SAMU M/SNNP sobre os possíveis fatores promotores de acidentes com equipes de socorristas indicando a necessidade de uma sinalização e isolamento adequados das cenas de acidentes e treinamento permanente no sentido de proteção da equipe de socorristas durante o atendimento pré-hospitalar em vias públicas.
Effects of mindfulness and meditation techniques on mental health of Emergency Department healthcare workers: a systematic review
Authors: Correa Eduardo Sorice , Rocha Rafael Martins da , Villari Clarice Arruda , Alencar Júlio César Garcia de , Souza Heraldo Possolo de
Published: March 2023

Background: Working in the Emergency Department (ED) is linked to mental health effects, such as stress and burnout. Meditation and mindfulness are seen as ways of reducing the frequency and intensity of these issues. Objectives: To evaluate if meditation and mindfulness reduce the frequency of negative mental health outcomes among ED Healthcare Workers. Methods: We included studies in English which analyzed interventions using meditation or mindfulness and ED staff’s mental health outcomes. PubMed, SciELO and LILACS were used as databases. Results: 8 studies were included. Meditation techniques and outcomes evaluated were heterogeneous. Interventions were associated with reduced burnout, emotional exhaustion, or increased job satisfaction. Discussion: This study indicates that meditation and mindfulness decrease frequency and intensity of negative mental health outcomes among professionals in the ED. This review has limitations: some studies have methodological problems and limitations such as small sample size; measurements of outcomes were heterogeneous, and results are not always concordant. Studies with higher sample sizes and stricter methodology are needed for us to achieve conclusions about the effectiveness of these interventions.
A teoria da arte e da emoção no trabalho formalista de Boris Eikhenbaum
Authors: Siphone Raquel Abuin , Any Carol
Published: March 2023

Tradução do artigo A teoria da arte e da emoção no trabalho formalista de Boris Eikhenbaum, de Carol Any.
Mulheres, ambulantes e produtoras culturais: as alianças em torno da Garagem das Ambulantes
Authors: Barroso Flávia
Published: March 2023

O artigo investiga as alianças urbanas entre mulheres ambulantes e coletivos culturais constituídas nos últimos anos para a elaboração do espaço festivo Garagem das Ambulantes, no centro do Rio de Janeiro. A constituição do espaço vem sendo acompanhada pela pesquisadora desde 2018, a partir de cartografias de espaços musicais independentes na região. Com base no pensamento de Judith Butler, analisamos o processo de formação de alianças entre grupos na produção de espaços de visibilidade, expressão e renda para mulheres ambulantes.
Análise do perfil de ouvintes e dos módulos mais populares do curso online “feminismos: algumas verdades inconvenientes”
Authors: Brito Carolina , Perry Gabriela Trindade , Santos Marlise Bock , Nodari Carolina , Barbosa Marcia
Published: March 2023

Neste artigo, analisamos o impacto do curso “Feminismos: algumas verdades inconvenientes”, apresentado como videoaulas na plataforma Lúmina e em formato de podcast. O alcance do curso é avaliado através de métricas quantitativas do número de acessos e dos perfis de estudantes do curso. Com base nestes dados, analisamos se o público se interessa mais por temas mais transversais do feminismo ou se assiste igualmente às aulas sobre tópicos que atingem grupos específicos.
Mulheres Muçulmanas, Islamofobia e Mídia: desconstruindo estigmas
Authors: Barbosa Francirosy Campos
Published: March 2023

Este artigo discute dados do primeiro relatório a tratar da islamofobia no Brasil a respeito do preconceito em relação às mulheres revertidas ao Islam. Além disso, traz reflexões sobre a retomada e permanência do Talibã no governo do Afeganistão. Desta forma, busca contribuir para a desconstrução do olhar de jornalistas e pessoas de Comunicação, visando o fim da fala sobre muçulmanas atrelada à perspectiva de “salvá-las”, e a compreensão das diferentes percepções de feminino que nos atravessam e, portanto, que se escrevem e se reproduzem visualmente.
Eu tenho apenas uma literatura e não é minha: reflexões de uma experiência sino-espanhola
Authors: Chen Paloma
Published: March 2023

Reflexões situadas em uma identidade sino-utiel-valenciana-wenzhounesa-espanhola são vistas como experiências particulares e minoritárias pela hegemonia ocidental, que atribui rótulos de hipersexualização, fetichização, exotismo e criminalização às mulheres asiáticas. Diante do cânone reconhecido pelas instituições educativas eurobrancas como literatura universal, autoras e criadoras migrantes e pessoas racializadas reivindicam espaços com obras literárias e artísticas sobre noções críticas como identidade, legado ou memória, em linguagens fronteiriças, mestiças, fraturadas. Assim, desarmam o sujeito dessubjetivado e desencarnado chamado “autor”, que domina um sistema literário que exclui ao invés de incluir.
Quantifying Blood Pressure Visit-to-Visit Variability in the Real-World Setting: A Retrospective Cohort Study
Authors: Lu Yuan , Linderman George C. , Mahajan Shiwani , Liu Yuntian , Huang Chenxi , Khera Rohan , Mortazavi Bobak J. , Spatz Erica S. , Krumholz Harlan M.
Published: March 2023

Background:

Visit-to-visit variability (VVV) in blood pressure values has been reported in clinical studies. However, little is known about VVV in clinical practice and whether it is associated with patient characteristics in real-world setting.

Methods:

We conducted a retrospective cohort study to quantify VVV in systolic blood pressure (SBP) values in a real-world setting. We included adults (age ≥18 years) with at least 2 outpatient visits between January 1, 2014 and October 31, 2018 from Yale New Haven Health System. Patient-level measures of VVV included SD and coefficient of variation of a given patient’s SBP across visits. We calculated patient-level VVV overall and by patient subgroups. We further developed a multilevel regression model to assess the extent to which VVV in SBP was explained by patient characteristics.

Results:

The study population included 537 218 adults, with a total of 7 721 864 SBP measurements. The mean age was 53.4 (SD 19.0) years, 60.4% were women, 69.4% were non-Hispanic White, and 18.1% were on antihypertensive medications. Patients had a mean body mass index of 28.4 (5.9) kg/m
2
and 22.6%, 8.0%, 9.7%, and 5.6% had a history of hypertension, diabetes, hyperlipidemia, and coronary artery disease, respectively. The mean number of visits per patient was 13.3, over an average period of 2.4 years. The mean (SD) intraindividual SD and coefficient of variation of SBP across visits were 10.6 (5.1) mm Hg and 0.08 (0.04). These measures of blood pressure variation were consistent across patient subgroups defined by demographic characteristics and medical history. In the multivariable linear regression model, only 4% of the variance in absolute standardized difference was attributable to patient characteristics.

Conclusions:

The VVV in real-world practice poses challenges for management of patients with hypertension based on blood pressure readings in outpatient settings and suggest the need to go beyond episodic clinic evaluation.
Dyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study
Authors: Hosier Hillary , Lipkind Heather S. , Rasheed Humaira , DeWan Andrew T. , Rogne Tormod
Published: March 2023

Background:

Preeclampsia is a leading cause of maternal morbidity, and dyslipidemia has been associated with preeclampsia in observational studies. We use Mendelian randomization analyses to estimate the association between lipid levels, their pharmacological targets, and the risk of preeclampsia in 4 ancestry groups.

Methods:

We extracted uncorrelated (

R
2

<0.001) single-nucleotide polymorphisms strongly associated (
P
<5×10
-8
) with LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), and triglycerides from genome-wide association studies of European, admixed African, Latino, and East Asian ancestry participants. Genetic associations with risk of preeclampsia were extracted from studies of the same ancestry groups. Inverse-variance weighted analyses were performed separately for each ancestry group before they were meta-analyzed. Sensitivity analyses were conducted to evaluate bias due to genetic pleiotropy, demography, and indirect genetic effects.

Results:

The meta-analysis across 4 ancestry groups included 1.5 million subjects with lipid measurements, 7425 subjects with preeclampsia, and 239 290 without preeclampsia. Increasing HDL-C was associated with reduced risk of preeclampsia (odds ratio, 0.84 [95% CI, 0.74–0.94];
P
=0.004; per SD increase in HDL-C), which was consistent across sensitivity analyses. We also observed cholesteryl ester transfer protein inhibition—a drug target that increases HDL-C—may have a protective effect. We observed no consistent effect of LDL-C or triglycerides on the risk of preeclampsia.

Conclusions:

We observed a protective effect of elevated HDL-C on risk of preeclampsia. Our findings align with the lack of effect in trials of LDL-C modifying drugs but suggest that HDL-C may be a new target for screening and intervention.
Characterisation of Stegelletina salinaria Abolafia & Peña-Santiago, 2003 (Rhabditida, Cephalobidae) from Spain and South Africa including the first molecular study of the species
Authors: Abolafia Joaquín , Robles María-Cristina , Ruiz-Cuenca Alba N. , Shokoohi Ebrahim
Published: March 2023

Stegelletina salinaria is redescribed from Spain and South Africa. Spanish material was collected in sandy soil from the type locality and a nearby area, while one population collected in compost was examined from South Africa. The species is characterised by its small size (0.27-0.41 mm), lateral field with three incisures, lip region with three pairs of dentate lips bearing four tines each, primary axils bearing a large guarding process, secondary axils lacking guarding processes, nerve ring and secretory-excretory pore at isthmus level, spermatheca and post-vulval uterine sac poorly developed, female tail conoid with rounded hyaline terminus and males unknown. The description, light micrographs and scanning electron microscope images, illustrations and molecular analyses are provided. 18S and 28S rDNA sequence analyses show that the isolates of S. salinaria from Spain and South Africa are closely related to each other and to other species of Stegelletina, while also indicating a close relationship with some species of Nothacrobeles, Scottnema and Stegelleta (28S tree) and Zeldia (18S tree).
Detection and identification of Devibursaphelenchus minor sp. n. isolated in the bark from the USA
Authors: Gu Jianfeng , Ma Xinxin
Published: March 2023

Bark in an empty container from the USA was inspected in Ningbo port, China, and a Devibursaphelenchus population was detected. It was processed and identified as Devibursaphelenchus minor sp. n. The new species is characterised by the lateral field with three incisures, female stylet tripartite, 13.9 (12.7-14.6) μm long without basal thickenings, secretory-excretory pore at the same level as nerve ring or slightly posterior, vagina not sclerotised, vulval lips slightly protruding and vulval flap absent. Post-vulval uterine sac (PUS) not well developed, very short and obscure, extending for half vulval body diam. long, anus and rectum indistinct or absent. Posterior body region conical elongated, gradually narrowing, slightly ventrally curved, ending with a bluntly pointed terminus. Male rare, the spicules are arcuate, separate, 8.2 μm along the chord line, with well-developed condylus, triangular rostrum with finely rounded tip, cucullus or apophysis absent. Tail conical, dorsally convex, ventrally slightly concave with bluntly pointed terminus, ventral bursa not confirmed. Two pairs of genital papillae present. It differs from all other species in this genus by extremely short body length of females and males. Molecular phylogenetic analyses based upon rRNA D2-D3 sequences confirmed it as a new species.
Judeo-Spanish Proverbs from Bosnia: Compilers and Their Approaches
Authors: Jovanović Željko
Published: March 2023

This article deals with four unpublished Judeo-Spanish proverb collections from post-Holocaust Bosnia that were gathered there by four different members of the Sephardic community: three men (Binjo Samokovlija, David Baruh, and Jakov Konforti) and one woman (Flora Eškenazi). I specifically examine two working techniques that these authors/collectors applied in order to safeguard and disseminate this important aspect of Sephardic oral tradition—namely, translating proverbs from Ladino to Serbo-Croatian; and the use of glosses. I argue that the choice of both techniques was conditioned by the audience for whom these proverbs were intended: translating proverbs to Serbo-Croatian aimed at accommodating the needs of the general readership in the country, while the introduction of glosses those of the Ladino-speaking Sephardim. I also examine the issue of interpreting proverbs once they appear decontextualized.
Begonia fritschiana (Begoniaceae, Begonia section Baryandra), a new species from Quezon, Bukidnon, Philippines
Authors: AMOROSO VICTOR B. , LAMPARAS RICA JOY V. , LAGUNDAY NOEL E. , DAPAR MARK LLYOD G. , RUBITE ROSARIO R.
Published: March 2023

Begonia fritschiana from Mindanao Island is described as a new species endemic to the Philippines. This is the latest addition to the species-rich Begonia section Baryandra. It resembles Begonia caramoanensis but is distinguished by the consistent obliquely ovate leaves with shorter petioles, lamina glaucous abaxially and with marginal hairs, mostly solitary to singly-branched inflorescences with shorter white-glandular hairs on the pedicels and peduncle, one of the outer tepals pink, and glabrous ovary and ovary wings. Begonia fritschiana is known only from the type locality with one population and less than 100 individuals. The area is not currently protected under the country’s National Integrated Protected Areas System by the Department of Environment and Natural Resources. Because of ongoing threats such as illegal logging, poaching, and over collection of biological resources, the single area of occurrence with estimated extent < 10 km2, and the small number of < 100 individuals, we recommend a classification of B. fritschiana as Critically Endangered.
Brachysira heteropolaris, a new diatom (Brachysiraceae, Bacillariophyta) species observed in an historic Weissflog slide from Scotland (UK)
Authors: VAN DE VIJVER BART
Published: March 2023

During the analysis of an historic slide of Loch Canmor, Aberdeenshire (Scotland, UK) prepared by Eugene Weissflog and conserved in the Van Heurck collection (BR, Belgium), an unknown, heteropolar Brachysira taxon was observed that could not be identified using the currently available literature. The new species, described as Brachysira heteropolaris sp. nov., is characterised in having a strictly heteropolar, broadly lanceolate valve outline with non-protracted, acutely rounded apices. The new species was observed in a dystrophic-oligotrophic, weakly acidic lake, based on the analysis of the composing diatom flora, dominated by several Brachysira species, Gomphonema coronatum and Encyonopsis cesatii var. geitleri.
Tropical Cyclone Tilt and Precession in Moderate Shear: Precession Hiatus in a Critical Shear Regime
Authors: Yu Chau-Lam , Tang Brian , Fovell Robert G.
Published: March 2023

One source of uncertainty associated with vertical wind shear (VWS) on tropical cyclone (TC) intensity evolution arises when the VWS becomes sufficiently strong such that the TC vortex is unable to overcome the inhibiting effects of VWS (the critical shear regime), resulting in a transition from vortex realignment and eventual reintensification to persistent vortex misalignment and failure of reintensification. To uncover the initiation mechanism of the behavioral transition, this study examines the dynamical evolution of the vortex tilt and precession through a set of CM1 ensemble simulations in moderate shear (7.5 m s−1) that includes the behavioral transition by systematically enhancing the TC vorticity amplitude aloft (vortex resiliency) at a restart point. In this critical shear regime, all experiments exhibit a common precession hiatus behavior, during which the tilt magnitude increases and later leads to divergent outcomes in intensity and tilt evolutions. Volume-averaged horizontal vorticity budget reveals an anomalous differential vorticity flux that emerges in the downtilt-left quadrant during the hiatus period. This differential vorticity flux generates horizontal vorticity that points toward the downtilt-right direction, simultaneously increasing the vortex tilt and slowing down the precession rate. This downtilt-left differential vorticity flux is due to midlevel vortex stretching at the rainband terminus region, where there is a transition from convective to stratiform precipitation. Meanwhile, the downdraft associated with stratiform precipitation also causes vorticity compression at the low levels. These results indicate that the stratiform rainband region is important for increasing the vortex tilt and pausing the precession.
Plasma cell derived mtDAMPs activate macrophage STING pathway which promotes myeloma progression.
Authors: Jibril Aisha , Hellmich Charlotte , Wojtowicz Edyta , Hampton Katherine , Maynard Rebecca S , De Silva Ravindu , Fowler-Shorten Dominic J , Mistry Jayna J. , Moore Jamie A , Bowles Kristian M , Rushworth Stuart A
Published: March 2023

Mitochondrial damage-associated molecular patterns (mtDAMPs) include proteins, lipids, metabolites and DNA and have various context specific immunoregulatory functions. Cell-free mitochondrial DNA (mtDNA) is recognised via pattern recognition receptors and is a potent activator of the innate immune system. Cell-free mtDNA is elevated in the circulation of trauma and cancer patients, however the functional consequences of elevated mtDNA are largely undefined. Multiple myeloma (MM) relies upon cellular interactions within the bone marrow (BM) microenvironment for survival and progression. Here, using in-vivo models, we describe the role of MM cell derived mtDAMPs in the pro-tumoral BM microenvironment, and the mechanism and functional consequence of mtDAMPs in myeloma disease progression. Initially, we identified elevated levels of mtDNA in the peripheral blood serum of MM patients compared to healthy controls. Using the MM1S cells engrafted into NSG mice we established that elevated mtDNA was derived from MM cells. We further show that BM macrophages sense and respond to mtDAMPs through the STING pathway and inhibition of this pathway reduces MM tumor-burden in the KaLwRij-5TGM1 mouse model. Moreover, we found that MM derived mtDAMPs induced upregulation of chemokine signatures in BM macrophages and inhibition of this signature resulted in egress of MM cells from the BM. Here, we demonstrate that malignant plasma cells release mtDNA, a form of mtDAMPs, into the myeloma BM microenvironment, which in turn activates macrophages via STING signalling. We establish the functional role of these mtDAMP-activated macrophages in promoting disease progression and retaining MM cells in the pro-tumoral BM microenvironment.
Dabrafenib, alone or in combination with trametinib, in BRAF V600–mutated pediatric Langerhans cell histiocytosis
Authors: Whitlock James A. , Geoerger Birgit , Dunkel Ira J. , Roughton Michael , Choi Jeea , Osterloh Lisa , Russo Mark , Hargrave Darren
Published: March 2023

Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600–mutant solid tumors. Two open-label phase 1/2 studies were conducted in pediatric patients with BRAF V600–mutant, recurrent/refractory malignancies treated with dabrafenib monotherapy (CDRB436A2102; NCT01677741) or dabrafenib plus trametinib (CTMT212X2101; NCT02124772). The primary objectives of both studies were to determine safe and tolerable doses that achieve similar exposure to the approved doses for adults. Secondary objectives included safety, tolerability, and preliminary antitumor activity. Thirteen and 12 patients with BRAF V600–mutant LCH received dabrafenib monotherapy and in combination with trametinib, respectively. Investigator-assessed objective response rates per Histiocyte Society criteria were 76.9% (95% confidence interval [CI], 46.2-95.0) and 58.3% (95% CI, 27.7-84.8) in the monotherapy and combination studies, respectively. More than 90% of responses were ongoing at study completion. The most common treatment-related adverse events (AEs) were vomiting and increased blood creatinine with monotherapy and pyrexia, diarrhea, dry skin, decreased neutrophil count, and vomiting with combination therapy. Two patients each discontinued treatment with monotherapy and combination therapy because of AEs. Overall, dabrafenib monotherapy or in combination with trametinib demonstrated clinical efficacy and manageable toxicity in relapsed/refractory BRAF V600–mutant pediatric LCH, with most responses ongoing. Safety was consistent with that reported in other pediatric and adult conditions treated with dabrafenib plus trametinib.
A single F153Sβ3 mutation causes constitutive integrin αIIbβ3 activation in a variant form of Glanzmann thrombasthenia
Authors: Koukouritaki Sevasti B. , Thinn Aye Myat M. , Ashworth Katrina J. , Fang Juan , Slater Haley S. , Du Lily M. , Nguyen Huong Thi Thu , Pillois Xavier , Nurden Alan T. , Ng Christopher J. , Di Paola Jorge , Zhu Jieqing , Wilcox David A.
Published: March 2023

This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild bleeding in a physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists of activation, although microfluidic analysis with whole blood displays moderate ex vivo platelet adhesion and aggregation consistent with mild bleeding. Immunocytometry shows reduced expression of αIIbβ3 on quiescent platelets that spontaneously bind/store fibrinogen, and activation-dependent antibodies (ligand-induced binding site–319.4 and PAC-1) report β3 extension suggesting an intrinsic activation phenotype. Genetic analysis reveals a single F153Sβ3 substitution within the βI-domain from a heterozygous T556C nucleotide substitution of ITGB3 exon 4 in conjunction with a previously reported IVS5(+1)G>A splice site mutation with undetectable platelet messenger RNA accounting for hemizygous expression of S153β3. F153 is completely conserved among β3 of several species and all human β-integrin subunits suggesting that it may play a vital role in integrin structure/function. Mutagenesis of αIIb-F153Sβ3 also displays reduced levels of a constitutively activated αIIb-S153β3 on HEK293T cells. The overall structural analysis suggests that a bulky aromatic, nonpolar amino acid (F,W)153β3 is critical for maintaining the resting conformation of α2- and α1-helices of the βI-domain because small amino acid substitutions (S,A) facilitate an unhindered inward movement of the α2- and α1-helices of the βI-domain toward the constitutively active αIIbβ3 conformation, while a bulky aromatic, polar amino acid (Y) hinders such movements and restrains αIIbβ3 activation. The data collectively demonstrate that disruption of F153β3 can significantly alter normal integrin/platelet function, although reduced expression of αIIb-S153β3 may be compensated by a hyperactive conformation that promotes viable hemostasis.
Cyclic tensile force modifies calvarial osteoblast function via the interplay between ERK1/2 and STAT3
Authors: Xiao Xiaoyue , Zou Shujuan , Chen Jianwei
Published: March 2023

Background

Mechanical therapies, such as distraction osteogenesis, are widely used in dental clinics. During this process, the mechanisms by which tensile force triggers bone formation remain of interest. Herein, we investigated the influence of cyclic tensile stress on osteoblasts and identified the involvement of ERK1/2 and STAT3.

Materials and methods

Rat clavarial osteoblasts were subjected to tensile loading (10% elongation, 0.5 Hz) for different time periods. RNA and protein levels of osteogenic markers were determined using qPCR and western blot after inhibition of ERK1/2 and STAT3. ALP activity and ARS staining revealed osteoblast mineralization capacity. The interaction between ERK1/2 and STAT3 was investigated by immunofluorescence, western blot, and Co-IP.

Results

The results showed that tensile loading significantly promoted osteogenesis-related genes, proteins and mineralized nodules. In loading-induced osteoblasts, inhibition of ERK1/2 or STAT3 decreased osteogenesis-related biomarkers significantly. Moreover, ERK1/2 inhibition suppressed STAT3 phosphorylation, and STAT3 inhibition disrupted the nuclear translocation of pERK1/2 induced by tensile loading. In the non-loading environment, inhibition of ERK1/2 hindered osteoblast differentiation and mineralization, while STAT3 phosphorylation was elevated after ERK1/2 inhibition. STAT3 inhibition also increased ERK1/2 phosphorylation, but did not significantly affect osteogenesis-related factors.

Conclusion

Taken together, these data suggested that ERK1/2 and STAT3 interacted in osteoblasts. ERK1/2-STAT3 were sequentially activated by tensile force loading, and both affected osteogenesis during the process.
A cross-sectional study of relationships between social risks and prevalence and severity of pediatric chronic conditions
Authors: Brochier Annelise , Messmer Emily , Wexler Mikayla Gordon , Rogers Stephen , Cottrell Erika , Tripodis Yorghos , Garg Arvin
Published: March 2023

Background

To examine the differential relationships between seven social risk factors (individually and cumulatively) with the prevalence and severity of asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and overweight/obesity in children.

Methods

Using the 2017–2018 National Survey of Children's Health, we examined associations between social risk factors (caregiver education, caregiver underemployment, discrimination, food insecurity, insurance coverage, neighborhood support, and neighborhood safety) and the prevalence and severity of asthma, ADHD, ASD, and overweight/obesity. We used multivariable logistic regression to assess the relationship between individual and cumulative risk factors with each pediatric chronic condition, controlling for child sex and age.

Results

Although each social risk factor was significantly associated with increased prevalence and/or severity of at least one of the pediatric chronic conditions we investigated, food insecurity was significantly associated with higher disease prevalence and severity for all four conditions. Caregiver underemployment, low social support, and discrimination were significantly associated with higher disease prevalence across all conditions. For each additional social risk factor a child was exposed to, their odds of having each condition increased: overweight/obesity (aOR: 1.2, 95% CI: [1.2, 1.3]), asthma (aOR: 1.3, 95% CI: [1.2, 1.3], ADHD (aOR: 1.2, 95% CI: [1.2, 1.3]), and ASD (aOR: 1.4, 95% CI: [1.3, 1.5]).

Conclusions

This study elucidates differential relationships between several social risk factors and the prevalence and severity of common pediatric chronic conditions. While more research is needed, our results suggest that social risks, particularly food insecurity, are potential factors in the development of pediatric chronic conditions.