bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess Body Weight and Gastroesophageal Reflux Disease
Authors: Thalheimer Andreas , Bueter Marco
Published: May 2021

Background: Gastroesophageal reflux disease (GERD) is strongly associated with excess body weight. Summary: GERD is characterized by typical symptoms with or without mucosal damage because of retrograde flow of gastric content into the esophagus. An ineffective esophagogastric junction (EGJ) combined with anatomical abnormalities is considered to be causative. The incidence of GERD is strongly associated with excess body weight, reflecting the pathophysiological relevance of the abdominothoracic pressure gradient. Key Message: Weight loss has been demonstrated to be an effective therapy for GERD combined with obesity. In cases in which surgical therapy is indicated, traditional antireflux surgery has led to equivocal results, advocating a proximal Roux-en-Y gastric bypass in these patients to correct both GERD and excess body weight.
Senkung des intrakraniellen Drucks durch Senkung des zentralvenösen Drucks: Bewertung möglicher Gegenmaßnahmen zum Raumfahrt-assoziierten neuro-okulären Syndrom
Authors: Siebelmann Sebastian
Published: May 2021

Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Owing to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Owing to the coupling of central venous pressure (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32 ± 13 yr) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an impedance threshold device (ITD, −7 cmH2O) to generate negative intrathoracic pressure for 5 min, and subsequently, wore bilateral thigh cuffs inflated to 30 mmHg for 2 min. Breathing through an ITD reduced both CVP (6 ± 2 vs. 3 ± 1 mmHg; P = 0.02) and ICP (16 ± 3 vs. 12 ± 1 mmHg; P = 0.04) compared to baseline, a result that was not observed during the free breathing condition (CVP, 6 ± 2 vs. 6 ± 2 mmHg, P = 0.87; ICP, 15 ± 3 vs. 15 ± 4 mmHg, P = 0.68). Inflation of the thigh cuffs to 30 mmHg caused no meaningful reduction in CVP in all four individuals (5 ± 4 vs. 5 ± 4 mmHg; P = 0.1), coincident with minimal reduction in ICP (15 ± 3 vs. 14 ± 4 mmHg; P =0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading.
Molecular Identification and Cellular Localization of a Corticotropin-Releasing Hormone-Type Neuropeptide in an Echinoderm
Authors: Cai Weigang , Egertová Michaela , Zampronio Cleidiane G. , Jones Alexandra M. , Elphick Maurice R.
Published: May 2021

Background: Corticotropin-releasing hormone (CRH) mediates physiological responses to stressors in mammals by triggering pituitary secretion of adrenocorticotropic hormone, which stimulates adrenal release of cortisol. CRH belongs to a family of related neuropeptides that include sauvagine, urotensin-I, and urocortins in vertebrates and the diuretic hormone DH44 in insects, indicating that the evolutionary origin of this neuropeptide family can be traced to the common ancestor of the Bilateria. However, little is known about CRH-type neuropeptides in deuterostome invertebrates. Methods: Here, we used mass spectrometry, mRNA in situ hybridization, and immunohistochemistry to investigate the structure and expression of a CRH-type neuropeptide (ArCRH) in the starfish Asterias rubens (phylum Echinodermata). Results: ArCRH is a 40-residue peptide with N-terminal pyroglutamylation and C-terminal amidation, and it has a widespread pattern of expression in A. rubens. In the central nervous system comprising the circumoral nerve ring and 5 radial nerve cords, ArCRH-expressing cells and fibres were revealed in both the ectoneural region and the hyponeural region, which contains the cell bodies of motoneurons. Accordingly, ArCRH immunoreactivity was detected in innervation of the ampulla and podium of locomotory organs (tube feet), and ArCRH is the first neuropeptide to be identified as a marker for nerve fibres located in the muscle layer of these organs. ArCRH immunoreactivity was also revealed in protractile organs that mediate gas exchange (papulae), the apical muscle, and the digestive system. Conclusions: Our findings provide the first insights into CRH-type neuropeptide expression and function in the unique context of the pentaradially symmetrical body plan of an echinoderm.
Autolesão não suicida em adolescentes: Terapia Comunitária Integrativa como estratégia de partilha e de enfrentamento
Authors: Felipe Adriana Olimpia Barbosa , Resck Zélia Marilda Rodrigues , Bressan Vânia Regina , Vilela Sueli de Carvalho , Fava Silvana Maria Coelho Leite , Moreira Denis da Silva
Published: May 2021

Objetivo: apreender por meio da Terapia Comunitária Integrativa (TCI) os fatores relacionados à autolesão não suicida em adolescentes e à contribuição da mesma para as estratégias de enfrentamento. Método: estudo qualitativo, conduzido com adolescentes que participaram das rodas de Terapia Comunitária Integrativa, as quais foram gravadas eregistradas em diário de campo. Utilizou-se análise temática e fundamentou-se no Modelo de Habilidades de Vida. Resultados: a autolesão emergiu em seis rodas, como tema ou envolto a outro sofrimento vivenciado pelas adolescentes mulheres. Foram evidenciadas as categorias “Adolescência e autolesão não suicida: alívio da angustia”, “Roda de Terapia Comunitária Integrativa: espaço terapêutico” e suas subcategorias. Conclusões: as adolescentes encontram na autolesão não suicida uma forma para materializar e aliviar o sofrimento decorrente de múltiplos fatores. A Terapia Comunitária revelou um espaço vivo de partilha e de ressignificação do sofrimento.
Perfil epidemiológico das notificações de violência autoprovocada de 2010 a 2019 em um estado do sul do Brasil
Authors: Fattah Nathalia , Lima Milenne Souza de
Published: May 2021

Objetivo: descrever o perfil das notificações de violência autoprovocada no estado do Rio Grande do Sul no período de 2010 a 2019. Método: estudo epidemiológico observacional descritivo transversal a partir de dados secundários. Foram realizadas análises estatísticas descritivas para estudar a distribuição dos casos segundo as variáveis sociodemográficase aquelas relacionadas ao evento. Resultados: foram notificados 43.390 casos de lesão autoprovocada, dos quais 67,9% foram do sexo feminino. Verificou-se maior proporção de notificações de indivíduos na faixa etária de 20 a 29 anos, ao passo que as maiores taxas de notificação corresponderam à faixa etária de 15 a 19 anos de idade, com aumento expressivo de 2017 a 2019. A residência foi o local predominante de ocorrência das lesões autoprovocadas, e 41% das notificações eram de pessoas que já haviam se autoagredido ou tentado suicídio previamente. Conclusão: verificou-se predomínio de notificações de indivíduos do sexo feminino, na faixa etária de 20 a 29 anos, e aumento expressivo das taxas de notificação na faixa etária de 15 a 19 anos. Aponta-se a necessidade de aprofundamento sobre a violência autoprovocada, especialmente sobre fatores associados à intencionalidade suicida no comportamento autoagressivo entre adolescentes e adultos jovens, a fim de subsidiar estratégias de prevenção.
Autolesão não suicida e contexto escolar: perspectivas de adolescentes e profissionais da educação
Authors: Costa Luiza Cesar Riani , Gabriel Isabela Martins , Lopes Daniela Gonsalves , De Oliveira Wanderlei Abadio , Silva Jorge Luiz da , Carlos Diene Monique
Published: May 2021

Objetivo: compreender as relações entre o contexto escolar e a Autolesão Não Suicida (ALNS) na perspectiva de adolescentes que se autolesionaram e profissionais da educação. Métodos:Pesquisa qualitativa, cujos participantes foram 8 adolescentes e 15 profissionais de educação de uma escola de um municipio do interior de São Paulo. A coleta de dados com as adolescentes foi com entrevistas individuais utilizando o Desenho-Estória com Tema; com os profissionais foi o grupo focal, com uso de Diário de Campo. Os dados foram analisados pela Análise Temática; o referencial teórico foi a teoria psicanalítica winnicottiana. Resultados: Emergiram os temas “O (não) lugar do sofrimento na escola” e “Ações para enfrentamento da ALNS na escola”. Os dados demonstraram a existência de um ambiente pouco saudável ao desenvolvimento adolescente, sendo pouco acolhedor frente ao bullying e a ALNS. Asações realizadas pela escola, apesar de pouco legitimadas pelos profissionais, foram reportadas como suporte para enfrentamento da ALNS pelas adolescentes. Conclusão: Oestudo traz importantes contribuições para o cuidado integral em saúde mental adolescente, visto que a intersetorialidade é inerente a tal aspecto. A interface saúde-escola ainda precisade esforços para que se efetive na prática; tal estudo traz subsídios para este aprimoramento.
A experiência da tentativa de suicídio na perspectiva de adultos
Authors: Alves Andréa Cristina , Silva Aline Conceição , Vedana Kelly Graziani Giacchero
Published: May 2021

Objetivo: analisar a experiência da tentativa de suicídio na perspectiva de adultos que tentaram suicídio. Método: estudo qualitativo com oito adultos brasileiros assistidos em serviço de saúde mental. Os dados foram coletados em 2018 por entrevistas semidirigidas sobre a experiência da tentativa de suicídio e encontros grupais. O Interacionismo Simbólico foi o referencial teórico utilizado. Os dados foram submetidos à análise temática. Resultados: identificamos três temas: Ambiente intrapsíquico: representação e comunicação com o self (generalização de fracassos e expectativas negativas na construção de significados atribuídos ao self, à vida e às relações); Relações interpessoais (necessidade de vínculo, pertença, reconhecimento, acolhimento e sentirem necessários para outras pessoas); e Representações da tentativa de suicídio: a fuga e o encontro com a dor (a tentativa de suicídio é motivada pelo desejo de aliviar a dor, mas resulta no encontro com a dor, e instiga a busca por novos métodos, a evitação do suicídio por medo ou a reconstrução de significados). Conclusão: o estudo fornece importantes achados a serem explorados na prática clínica, no delineamento de protocolos, políticas institucionais, bem como na formação de profissionais.
Comorbidity Burden and Adverse Outcomes After Transcatheter Aortic Valve Replacement
Authors: Feldman Daniel R. , Romashko Mikhail D. , Koethe Benjamin , Patel Sonika , Rastegar Hassan , Zhan Yong , Resor Charles D. , Connors Annie C. , Kimmelstiel Carey , Allen David , Weintraub Andrew R. , Wessler Benjamin S.
Published: May 2021

Background

Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for symptomatic patients with aortic stenosis and elevated procedural risk. Many deaths following TAVR are because of noncardiac causes and comorbid disease burden may be a major determinant of postprocedure outcomes. The prevalence of comorbid conditions and associations with outcomes after TAVR has not been studied.

Methods and Results

This was a retrospective single‐center study of patients treated with TAVR from January 2015 to October 2018. The association between 21 chronic conditions and short‐ and medium‐term outcomes was assessed. A total of 341 patients underwent TAVR and had 1‐year follow‐up. The mean age was 81.4 (SD 8.0) years with a mean Society of Thoracic Surgeons predicted risk of mortality score of 6.7% (SD 4.8). Two hundred twenty (65%) patients had ≥4 chronic conditions present at the time of TAVR. There was modest correlation between Society of Thoracic Surgeons predicted risk of mortality and comorbid disease burden (
r
=0.32,
P
<0.001). After adjusting for Society of Thoracic Surgeons predicted risk of mortality, age, and vascular access, each additional comorbid condition was associated with increased rates of 30‐day rehospitalizations (odds ratio, 1.21; 95% CI, 1.02–1.44), a composite of 30‐day rehospitalization and 30‐day mortality (odds ratio, 1.20; 95% CI, 1.02–1.42), and 1‐year mortality (odds ratio, 1.29; 95% CI, 1.05–1.59).

Conclusions

Comorbid disease burden is associated with worse clinical outcomes in high‐risk patients treated with TAVR. The risks associated with comorbid disease burden are not adequately captured by standard risk assessment. A systematic assessment of comorbid conditions may improve risk stratification efforts.
Predicting Infarct Core From Computed Tomography Perfusion in Acute Ischemia With Machine Learning: Lessons From the ISLES Challenge
Authors: Hakim Arsany , Christensen Søren , Winzeck Stefan , Lansberg Maarten G. , Parsons Mark W. , Lucas Christian , Robben David , Wiest Roland , Reyes Mauricio , Zaharchuk Greg
Published: May 2021

Background and Purpose:

The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally diverse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard.

Methods:

The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance.

Results:

Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180–238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25–79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7–45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team’s algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3; volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance.

Conclusions:

Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.
Multiscale dynamic mean field (MDMF) model relates resting-state brain dynamics with local cortical excitatory–inhibitory neurotransmitter homeostasis
Authors: Naskar Amit , Vattikonda Anirudh , Deco Gustavo , Roy Dipanjan , Banerjee Arpan
Published: May 2021

Previous computational models have related spontaneous resting-state brain activity with local excitatory–inhibitory balance in neuronal populations. However, how underlying neurotransmitter kinetics associated with E–I balance govern resting-state spontaneous brain dynamics remains unknown. Understanding the mechanisms by virtue of which fluctuations in neurotransmitter concentrations, a hallmark of a variety of clinical conditions, relate to functional brain activity is of critical importance. We propose a multiscale dynamic mean field (MDMF) model—a system of coupled differential equations for capturing the synaptic gating dynamics in excitatory and inhibitory neural populations as a function of neurotransmitter kinetics. Individual brain regions are modeled as population of MDMF and are connected by realistic connection topologies estimated from diffusion tensor imaging data. First, MDMF successfully predicts resting-state functional connectivity. Second, our results show that optimal range of glutamate and GABA neurotransmitter concentrations subserve as the dynamic working point of the brain, that is, the state of heightened metastability observed in empirical blood-oxygen-level-dependent signals. Third, for predictive validity the network measures of segregation (modularity and clustering coefficient) and integration (global efficiency and characteristic path length) from existing healthy and pathological brain network studies could be captured by simulated functional connectivity from an MDMF model.
Cortinarius khinganensis (Agaricales), a new species of section Illumini from Northeast China
Authors: XIE MENG-LE , WEI TIE-ZHENG , DIMA BÁLINT , FU YONG-PING , JI RUI-QING , LI YU
Published: May 2021

This study presents one telamonioid species new to science based on morphological characteristics and molecular phylogenetic analyses. Cortinarius khinganensis was collected from the Greater Khingan Mountains, Northeast China and it is characterized by hygrophanous, vivid brownish red and striate pileus, white universal veil, and subglobose spores. According to phylogenetic analyses results, C. khinganensis belongs to the section Illumini, which is a lineage distantly related from subgenus Telamonia sensu stricto. Detailed descriptions of the new species and the comparisons with morphologically similar species are provided. The phylogenetic relationships within the section Illumini are also discussed.
Aristolochia macginitieana (Aristolochiaceae), a replacement name for Aristolochia triangularis MacGinitie non Aristolochia triangularis Chamisso
Authors: FREITAS JOELCIO , DOWELD ALEXANDER B.
Published: May 2021

Aristolochiaceae (order Piperales) traditionally comprises about 600 species and four genera: Aristolochia Linnaeus (1753: 960), Asarum Linnaeus (1753: 442), Saruma Oliver (1889: Pl. 1895) and Thotthea Rottbøll (1783: 529) (González 1990: 2012). Aristolochia is the most diversified genus of the family with about 550 species (González 2012).
Alternanthera kanhae (Amaranthaceae), a new species from Sabarmati Estuary of India

Authors: VANZARA AKASH G. , KATARA ILESH , NAGAR PADAMNABHI S.
Published: May 2021

A new species of Amaranthaceae, Alternanthera kanhae, is described and illustrated from the bank of Sabarmati estuary in the state of Gujarat of Peninsular India. The new species is closely allied with A. caracasana and A. pungens but differs in many attributes. The identity of the newly proposed species is confirmed by molecular analysis of three chloroplast DNA (cpDNA) regions viz., rbcL, psbA–trnH and trnL–trnF. The sequences showed that A. kanhae has an independent lineage to that of its sister clade.
Cymbidium weishanense (Orchidaceae; Epidendroideae), a new species from China: evidence from morphological and molecular data
Authors: YU XIA , ZENG MENG-YAO , CHEN GUI-ZHEN , XU XIN-YU , BI YUAN-YANG , CHEN JIA-TING , WANG QIAN-QIAN , HU WEN-QI , ZHANG DI-YANG , LIU ZHONG-JIAN
Published: May 2021

A new species of Cymbidium (Orchidaceae), C. weishanense, from Yunnan Province, China, is illustrated and described based on morphological and molecular evidence. Morphological comparison indicates that C. weishanense is similar to C. concinnum but differs in several floral characteristics. Molecular analyses based on nuclear ribosomal (ITS) and plastid DNA (matK and rbcL) support the status of C. weishanense as a new species. Due to the low support for nrITS, it is possible that this is a natural hybrid of C. concinnum with C. insigne or another related species.
Impatiens ramasubbuana, a new name for Impatiens palniensis Ramasubbu (Balsaminaceae)
Authors: KOTTAIMUTHU RAMALINGAM , MURUGAN PERUMAL , KUMAR JOHN KENNEDY JOHN PRAVEEN , BASU MUTHURAMALINGAM JOTHI
Published: May 2021

The genus Impatiens Linnaeus (1753: 937) contains a wealth of untapped treasures for gardeners and it is one of the mega diverse genera of angiosperms comprise about 1059 species (POWO 2020). According to the recent estimate, India is known to have 250 species and majority of them occur in Eastern Himalayas (Gogoi et al. 2018) and the Western Ghats (Bhaskar 2012). Tamil Nadu is one of the plant-rich states in the country and with 5674 angiosperm taxa, it ranks first among all the states in the country (Lakshminarasimhan et al. 2014).
On the Literature and Thought of the German Classical Era
Authors: Nisbet Hugh Barr
Published: May 2021

This elegant collection of essays ranges across eighteenth and nineteenth-century thought, covering philosophy, science, literature and religion in the ‘Age of Goethe.’ A recognised authority in the field, Nisbet grapples with the major voices of the Enlightenment and gives pride of place to the figures of Lessing, Herder, Goethe and Schiller.

These eleven essays range widely in their compass of thought and intellectual discourse, dealing incisively with themes including the philosophical implications of literature and the relationship between religion, science and politics. The result is an accomplished reflection on German thought, but also on its rebirth, as Nisbet argues for the relevance of these Enlightenment thinkers for the readers of today.

The first half of this collection focuses predominantly on eighteenth-century thought, where names like Lessing, Goethe and Herder, but also Locke and Voltaire, feature. The second has a wider chronological scope, discussing authors such as Winckelmann and Schiller, while branching out from discussions of religion, philosophy and literature to explore the sciences. Issues of biology, early environmentalism, and natural history also form part of this volume. The collection concludes with an examination of changing attitudes towards art in the aftermath of the ‘Age of Goethe.’

The essays in this volume have been previously published separately, but are brought together in this collection to present Nisbet’s widely-acclaimed perspectives on this fascinating period of German thought. It will be of interest to scholars and students of the intellectual life of Europe during the Enlightenment, while its engaging and lucid style will also appeal to the general reader.
Writing and Publishing Scientific Papers
Authors: Lövei Gábor L.
Published: May 2021

Gábor Lövei’s scientific communication course for students and scientists explores the intricacies involved in publishing primary scientific papers, and has been taught in more than twenty countries. Writing and Publishing Scientific Papers is the distillation of Lövei’s lecture notes and experience gathered over two decades; it is the coursebook many have been waiting for.

The book’s three main sections correspond with the three main stages of a paper’s journey from idea to print: planning, writing, and publishing. Within the book’s chapters, complex questions such as ‘How to write the introduction?’ or ‘How to submit a manuscript?’ are broken down into smaller, more manageable problems that are then discussed in a straightforward, conversational manner, providing an easy and enjoyable reading experience.

Writing and Publishing Scientific Papers stands out from its field by targeting scientists whose first language is not English. While also touching on matters of style and grammar, the book’s main goal is to advise on first principles of communication.

This book is an excellent resource for any student or scientist wishing to learn more about the scientific publishing process and scientific communication. It will be especially useful to those coming from outside the English-speaking world and looking for a comprehensive guide for publishing their work in English.
The Study of Conditions for Bioleaching Heavy Metals from Polluted Soil and Metabonomics in Penicillium chrysogenum
Authors: Deng Xinhui , Tan Ping , Ma Mengqi , Ma Liang , Yu Yunjun , Wang Zhenxing
Published: May 2021

The effects of the temperature, pH value and leaching time on the bioleaching ratio of heavy metals were studied using an orthogonal method in the paper. The metabonomics of Penicillium chrysogenum F1 were detected to deeply illustrate the bioleaching mechanism of Penicillium
chrysogenumF1. The results showed that the bioleaching ratios of lead and zinc are the best at 30 °C on the 7th day, while those of cadmium and copper are the best at 20 °C on the 5th day. A pH value of 7.0 is best for heavy metal bioleaching ratios. The combination of 30 °C,
pH 7.0 and 7 days is best for the total bioleaching ratios. The intensities of metabolites vary with the addition of heavy metal-polluted soil. The main catabolic pathways of glucose are not influenced by the heavy metal-polluted soil, though some metabolic enzymes are influenced, resulting
in some metabolites undergoing upregulation or downregulation. Both organic acids and other metabolites containing functional groups (-NH2, -OH, -CHO, -CO) can extract heavy metals from soil.
Modelling Particle Size Distribution of Residual Fly Ash from Pulverized Biomass Combustion
Authors: Xu Mingzi , Sheng Changdong
Published: May 2021

The present work aims to develop a simple model for describing the particle size distribution (PSD) of residual fly ash from pulverized biomass combustion. The residual ash formation was modelled considering the mechanism of fragmentation and coalescence. The influences of particle
shape and stochastic fragmentation on model description of the PSD of the fly ash were investigated. The results showed that biomass particle shape has a great influence on the model prediction, and a larger fragmentation number is required for cylindrical particles than that for spherical
particles to get the same PSD of fly ash, and the fragment number of the particles increases with the shape factor increasing. For pulverized biomass with a wide size distribution, the model predicted ash PSD considering the stochastic fragmentation is very similar to that assuming uniform
fragmentation. It implies that the simple model assuming uniform fragmentation is applicable for predicting fly ash size distribution in practical processes where biomass particles have a wide range of sizes. For the fuel with a narrower initial PSD, the stochastic fragmentation model generally
predicts a coarser PSD of the residual ash than assuming uniform fragmentation. It means the stochastic fragmentation is of great influence to be considered for accurate description of ash formation from the fuel with a narrow PSD.
Phosphorylation of islet-1 serine 269 by CDK1 increases its transcriptional activity and promotes cell proliferation in gastric cancer
Authors: Shi Qiong , Ni Xiaomei , Lei Ming , Xia Quansong , Dong Yan , Zhang Qiao , Wang Weiping
Published: May 2021

Background

Despite recent advances in diagnostic and therapeutic approaches for gastric cancer (GC), the survival of patients with advanced GC remains very low. Islet-1 (ISL1) is a LIM-homeodomain transcription factor, which is upregulated and promotes cell proliferation in GC. The exact mechanism by which ISL1 influences GC development is unclear.

Methods

Co-immunoprecipitation (co-IP) and glutathione S-transferase (GST)-pulldown assays were employed to evaluate the interaction of ISL1 with CDK1. Western blot and immunohistochemistry analyses were performed to evaluate the ability of CDK1 to phosphorylate ISL1 at Ser 269 in GC cell and tissue specimens. Chromatin immunoprecipitation (ChIP), ChIP re-IP, luciferase reporter, and CCK-8 assays were combined with flow cytometry cell cycle analysis to detect the transactivation potency of ISL1-S269-p and its ability to promote cell proliferation. The self-stability and interaction with CDK1 of ISL1-S269-p were also determined.

Results

ISL1 is phosphorylated by CDK1 at serine 269 (S269) in vivo. Phosphorylation of ISL1 by CDK1 on serine 269 strengthened its binding on the cyclin B1 and cyclin B2 promoters and increased its transcriptional activity in GC. Furthermore, CDK1-dependent phosphorylation of ISL1 correlated positively with ISL1 protein self-stability in NIH3T3 cells.

Conclusions

ISL1-S269-p increased ISL1 transcriptional activity and self-stability while binding to the cyclinB1 and cyclinB2 promoters promotes cell proliferation. ISL1-S269-p is therefore crucial for tumorigenesis and potentially a direct therapeutic target for GC.
Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy
Authors: Zhao Jianan , Hu Yiyang , Peng Jinghua
Published: May 2021

Most currently recommended therapies for metabolic dysfunction-associated fatty liver disease (MAFLD) involve diet control and exercise therapy. We searched PubMed and compiled the most recent research into possible forms of programmed cell death in MAFLD, including apoptosis, necroptosis, autophagy, pyroptosis and ferroptosis. Here, we summarize the state of knowledge on the signaling mechanisms for each type and, based on their characteristics, discuss how they might be relevant in MAFLD-related pathological mechanisms. Although significant challenges exist in the translation of fundamental science into clinical therapy, this review should provide a theoretical basis for innovative MAFLD clinical treatment plans that target programmed cell death.
MOCCA: a flexible suite for modelling DNA sequence motif occurrence combinatorics
Authors: Bredesen Bjørn André , Rehmsmeier Marc
Published: May 2021

Background

Cis-regulatory elements (CREs) are DNA sequence segments that regulate gene expression. Among CREs are promoters, enhancers, Boundary Elements (BEs) and Polycomb Response Elements (PREs), all of which are enriched in specific sequence motifs that form particular occurrence landscapes. We have recently introduced a hierarchical machine learning approach (SVM-MOCCA) in which Support Vector Machines (SVMs) are applied on the level of individual motif occurrences, modelling local sequence composition, and then combined for the prediction of whole regulatory elements. We used SVM-MOCCA to predict PREs in Drosophila and found that it was superior to other methods. However, we did not publish a polished implementation of SVM-MOCCA, which can be useful for other researchers, and we only tested SVM-MOCCA with IUPAC motifs and PREs.

Results

We here present an expanded suite for modelling CRE sequences in terms of motif occurrence combinatorics—Motif Occurrence Combinatorics Classification Algorithms (MOCCA). MOCCA contains efficient implementations of several modelling methods, including SVM-MOCCA, and a new method, RF-MOCCA, a Random Forest–derivative of SVM-MOCCA. We used SVM-MOCCA and RF-MOCCA to model Drosophila PREs and BEs in cross-validation experiments, making this the first study to model PREs with Random Forests and the first study that applies the hierarchical MOCCA approach to the prediction of BEs. Both models significantly improve generalization to PREs and boundary elements beyond that of previous methods—including 4-spectrum and motif occurrence frequency Support Vector Machines and Random Forests—, with RF-MOCCA yielding the best results.

Conclusion

MOCCA is a flexible and powerful suite of tools for the motif-based modelling of CRE sequences in terms of motif composition. MOCCA can be applied to any new CRE modelling problems where motifs have been identified. MOCCA supports IUPAC and Position Weight Matrix (PWM) motifs. For ease of use, MOCCA implements generation of negative training data, and additionally a mode that requires only that the user specifies positives, motifs and a genome. MOCCA is licensed under the MIT license and is available on Github at https://github.com/bjornbredesen/MOCCA.
Metabolome and transcriptome profiling reveals anthocyanin contents and anthocyanin-related genes of chimeric leaves in Ananas comosus var. bracteatus
Authors: Zhou Xuzixin , Xue Yanbin , Mao Meiqin , He Yehua , Adjei Mark Owusu , Yang Wei , Hu Hao , Liu Jiawen , Feng Lijun , Zhang Huiling , Luo Jiaheng , Li Xi , Sun Lingxia , Huang Zhuo , Ma Jun
Published: May 2021

Background

Ananas comosus var. bracteatus is a colorful plant used as a cut flower or landscape ornamental. The unique foliage color of this plant includes both green and red leaves and, as a trait of interest, deserves investigation. In order to explore the pigments behind the red section of the chimeric leaves, the green and red parts of chimeric leaves of Ananas comosus var. bracteatus were sampled and analyzed at phenotypic, cellular and molecular levels in this study.

Results

The CIELAB results indicated that the a* values and L* values samples had significant differences between two parts. Freehand sections showed that anthocyanin presented limited accumulation in the green leaf tissues but obviously accumulation in the epidermal cells of red tissues. Transcriptomic and metabolomic analyses were performed by RNA-seq and LC-ESI-MS/MS. Among the 508 identified metabolites, 10 kinds of anthocyanins were detected, with 6 significantly different between the two samples. The cyanidin-3,5-O-diglucoside content that accounts for nearly 95.6% in red samples was significantly higher than green samples. RNA-Seq analyses showed that 11 out of 40 anthocyanin-related genes were differentially expressed between the green and red samples. Transcriptome and metabolome correlations were determined by nine quadrant analyses, and 9 anthocyanin-related genes, including MYB5 and MYB82, were correlated with 7 anthocyanin-related metabolites in the third quadrant in which genes and metabolites showing consistent change. Particularly, the PCCs between these two MYB genes and cyanidin-3,5-O-diglucoside were above 0.95.

Conclusion

Phenotypic colors are closely related to the tissue structures of different leaf parts of Ananas comosus var. bracteatus, and two MYB transcription factors might contribute to differences of anthocyanin accumulation in two parts of Ananas comosus var. bracteatus chimeric leaves. This study lay a foundation for further researches on functions of MYBs in Ananas comosus var. bracteatus and provides new insights to anthocyanin accumulation in different parts of chimeric leaves.
A qualitative study of home care client and caregiver experiences with a complex cardio-respiratory management model
Authors: Schumacher Connie , Dash Darly , Mowbray Fabrice , Klea Lindsay , Costa Andrew
Published: May 2021

Background

Home care clients are typically older and have some degree of medical, physical, cognitive or social conditions that require formal or informal support to promote healthy aging in the community. Home care clients contribute a significant proportion of health service use, including emergency department visits. The DIVERT-CARE trial introduced a cardio-respiratory management model to improve client motivation, symptoms and rates of unwarranted health service use. Our objective was to explore the perceptions and experiences of individuals who participated in the DIVERT-CARE self-management support and education intervention.

Methods

A qualitative study was nested within a pragmatic randomized control trial and conducted following a 15-week multi-component cardio-respiratory intervention. A phenomenological descriptive design was employed using thematic analysis. Post-intervention, clients and their caregivers were invited to participate in a semi-structured telephone interview. Interview questions were designed to elicit the experience with the intervention components.

Results

A total of 29 interviews were completed from June 2018 to March 2020 from participants in Ontario, Newfoundland, and British Columbia. Three themes were identified; self-care trajectory and burden of responsibility, learning and behaviour change, and feeling connected pre-emptively to care providers, the information and medical advice, and connection through the therapeutic relationship.

Conclusions

Home care clients experience unique challenges in managing cardio-respiratory related chronic disease. Home-based interventions fostered a therapeutic relationship of connectedness while equipping clients with necessary knowledge and skills. These results inform recommendations for community nursing, and home-based self-management supports for older community-residing individuals.
The effect of sociodemographic factors on COVID-19 incidence of 342 cities in China: a geographically weighted regression model analysis
Authors: Zhang Huihui , Liu Yini , Chen Fangyao , Mi Baibing , Zeng Lingxia , Pei Leilei
Published: May 2021

Background

Since December 2019, the coronavirus disease 2019 (COVID-19) has spread quickly among the population and brought a severe global impact. However, considerable geographical disparities in the distribution of COVID-19 incidence existed among different cities. In this study, we aimed to explore the effect of sociodemographic factors on COVID-19 incidence of 342 cities in China from a geographic perspective.

Methods

Official surveillance data about the COVID-19 and sociodemographic information in China’s 342 cities were collected. Local geographically weighted Poisson regression (GWPR) model and traditional generalized linear models (GLM) Poisson regression model were compared for optimal analysis.

Results

Compared to that of the GLM Poisson regression model, a significantly lower corrected Akaike Information Criteria (AICc) was reported in the GWPR model (61953.0 in GLM vs. 43218.9 in GWPR). Spatial auto-correlation of residuals was not found in the GWPR model (global Moran’s I = − 0.005, p = 0.468), inferring the capture of the spatial auto-correlation by the GWPR model. Cities with a higher gross domestic product (GDP), limited health resources, and shorter distance to Wuhan, were at a higher risk for COVID-19. Furthermore, with the exception of some southeastern cities, as population density increased, the incidence of COVID-19 decreased.

Conclusions

There are potential effects of the sociodemographic factors on the COVID-19 incidence. Moreover, our findings and methodology could guide other countries by helping them understand the local transmission of COVID-19 and developing a tailored country-specific intervention strategy.
Retrospective analysis of real-world treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer starting first-line systemic therapy in the United Kingdom
Authors: Lester Jason , Escriu Carles , Khan Sarah , Hudson Emma , Mansy Talal , Conn Andrew , Chan Samuel , Powell Ceri , Brock Juliet , Conibear John , Nelless Lauren , Nayar Vaneet , Zhuo Xiaohui , Durand Adeline , Amin Amerah , Martin Peter , Zhang Xinke , Pawar Vivek
Published: May 2021

Background

The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom.

Methods

Electronic prescribing records of treatment-naive patients starting first-line (1 L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response.

Results

In all, 1003 patients were evaluated (median age, 68 years [range, 28–93 years]; 53.9% male). Use of 1 L IO monotherapy (0–25.9%) and targeted therapy (11.8–15.9%) increased during the study period, but chemotherapy remained the most common 1 L treatment at all time points (88.2–58.2%). Median OS was 9.5 months (95% CI, 8.8–10.7 months) for all patients, 8.1 months (95% CI, 7.4–8.9 months) with chemotherapy, 14.0 months (95% CI, 10.7–20.6 months) with IO monotherapy, and 20.2 months (95% CI, 16.0–30.5 months) with targeted therapy. In the 28.6% of patients who received second-line treatment, IO monotherapy was the most common drug class (used in 51.6%).

Conclusions

Although use of 1 L IO monotherapy for aNSCLC increased in the United Kingdom during the study period, most patients received 1 L chemotherapy. An OS benefit for first-line IO monotherapy vs chemotherapy was observed but was numerically smaller than that reported in clinical trials. Targeted therapy was associated with the longest OS, highlighting the need for improved treatment options for tumors lacking targetable mutations.
Dynamic change of serum CA19–9 levels in benign and malignant patients with obstructive jaundice after biliary drainage and new correction formulas
Authors: Zhao Bangbo , Cheng Qin , Cao Hongtao , Zhou Xingtong , Li Tianhao , Dong Liangbo , Wang Weibin
Published: May 2021

Background

CA19–9 is one of the most widely used tumor markers in biliary-pancreatic diseases. The measured value may not factually reflect the genuine CA19–9 level secreted by tumor, which affected by biliary obstruction. There is an urgent need of developing a correction formula of CA19–9 in biliary obstructive patients to guide clinical practice and avoid making improper clinical decision.

Methods

Clinical characteristics were collected among patients undergoing biliary drainage in our hospital between January 2014 and January 2019. By comparing the malignant and benign patients statistically, dynamic change trend of CA19–9 levels after biliary drainage was obtained. The correction formulas of CA19–9 were generated by means of linear regression.

Results

121 patients, including 102 malignant and 19 benign patients, were enrolled in this study. The baseline CA19–9 level of malignant patients is much higher than that of benign patients. Total bilirubin (TB) level was found to be not related with CA19–9 value (p = 0.109). The drop proportion of the average CA19–9 level in the malignant patients (39.2%, IQR -18.4-78.6%) was much lower than that in the benign patients (75.7%, IQR 58.1–86.6%) (p = 0.014). The correction formula, CA19–9True = 0.63 × CA19–9Measured - 20.3 (R2 = 0.693, p<0.001), was generated based on the linear relation between CA19–9 after drainage and CA19–9 before drainage in malignant patients, which had similar diagnostic value with true CA19–9 value.

Conclusions

Quantitative correction formulas of CA19–9 considering the effect of biliary decompression was first proposed in this study, aiming to provide a more accurate CA19–9 level to make more accurate clinical decision and avoid making improper therapeutic schedule.
A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker
Authors: Kelley Kristen C. , Grossman Kenneth F. , Brittain-Blankenship Mary , Thorne Kelli M. , Akerley Wallace L. , Terrazas Moises C. , Kosak Ken M. , Boucher Kenneth M. , Buys Saundra S. , McGregor Kimberly A. , Werner Theresa L. , Agarwal Neeraj , Weis John R. , Sharma Sunil , Ward John H. , Kennedy Thomas P. , Sborov Douglas W. , Shami Paul J.
Published: May 2021

Background

Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement.

Methods

Disulfiram 250 mg was administered daily in 28-day cycles. Four doses of copper gluconate were tested (2, 4, 6, and 8 mg of elemental copper) in a standard 3 + 3 dose escalation design. Patients were evaluated for dose limiting toxicities and response. ProteinS-glutathionylation was evaluated as a pharmacodynamic marker.

Results

Twenty-one patients were enrolled and 16 patients were evaluable for dose limiting toxicities. Among the 21 patients, there was a median of 4 lines of prior chemotherapy. Five Grade 3 toxicities were observed (anorexia, elevated aspartate aminotransferase or AST, elevated alkaline phosphatase, fever, and fatigue). Response data was available for 15 patients. Four patients had stable disease with the longest duration of disease control being 116 days. The median duration of treatment for evaluable patients was 55 days (range 28–124). Reasons for discontinuation included functional decline, disease progression, and disease-associated death. IncreasedS-glutathionylation of serum proteins was observed with treatment.

Conclusion

Disulfiram 250 mg daily with copper gluconate (8 mg of elemental copper) was well-tolerated in patients with solid tumors involving the liver and was not associated with dose limiting toxicities. While temporary disease stabilization was noted in some patients, no objective responses were observed. Treatment was associated with an increase inS-glutathionylation suggesting that this combination could exert a suppressive effect on cellular growth and protein function.

Trial registration

NCT00742911, first posted 28/08/2008.
Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma
Authors: Xu Yuanji , Wu Zijie , Ye Wangzhong , Xiao Youping , Zheng Wei , Chen Qinyan , Bai Penggang , Lin Zhizhong , Chen Chuanben
Published: May 2021

Background

To explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT).

Methods

A total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors.

Results

Univariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level.

Conclusion

The SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.